Shwayder, T., Schneider, S. L., Icecreamwala, D., & Jahnke, M. N. (2019) - Longitudinal Observation of Pediatric Dermatology Patients.

Longitudinal Observation
of Pediatric Dermatology
Patients
Tor Shwayder
Samantha L. Schneider
Devika Icecreamwala
Marla N. Jahnke
123
Longitudinal Observation of Pediatric
Dermatology Patients
Tor Shwayder • Samantha L. Schneider
Devika Icecreamwala • Marla N. Jahnke
Longitudinal Observation
of Pediatric Dermatology
Patients
Tor Shwayder Samantha L. Schneider
Pediatric Dermatology Department of Dermatology
Henry Ford Hospital Henry Ford Hospital
Detroit, MI Detroit, MI
USA USA
Devika Icecreamwala Marla N. Jahnke

Icecreamwala Dermatology Department of Dermatology
Berkeley, CA Henry Ford Hospital
USA Detroit, MI
USA
ISBN 978-3-319-98100-0 ISBN 978-3-319-98101-7 (eBook)

https://doi.org/10.1007/978-3-319-98101-7
Library of Congress Control Number: 2018960271
© Springer Nature Switzerland AG 2019

This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of
the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation,
broadcasting, reproduction on microfilms or in any other physical way, and transmission or information
storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology
now known or hereafter developed.
The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication
does not imply, even in the absence of a specific statement, that such names are exempt from the relevant
protective laws and regulations and therefore free for general use.
The publisher, the authors, and the editors are safe to assume that the advice and information in this book
are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the
editors give a warranty, express or implied, with respect to the material contained herein or for any errors
or omissions that may have been made. The publisher remains neutral with regard to jurisdictional claims
in published maps and institutional affiliations.
This Springer imprint is published by the registered company Springer Nature Switzerland AG
The registered company address is: Gewerbestrasse 11, 6330 Cham, Switzerland
To my wife, Aimée, whose love, brilliance, and calm guidance
leads me through all of life’s amazing adventures.
– TAS
Introduction from the Senior Author (TAS)
Pediatric dermatology has been my life and passion for more than thirty years.
Seems like a long time looking forward, but it has gone by quickly. This book was
the brainchild of my (then) fellow Dr. Devika Patel Icecreamwala who recognized
in my vast library of images (many thousands) the kernel of a book to pass the accu-
mulated knowledge onto future generations. We have tended to illustrate the unusual
cases rather than the mundane. My thanks to Drs. Sam Schneider and Marla Jahnke
for their dogged contributions and editorial additions.
vii
Contents
Part I Eczematous Eruption of Childhood

1 Hyper IgE Syndrome �� 3
References�� 8
Part II Papulosquamous and Related Disorders
2 Psoriasis�� 11
References�� 16
Part III Hereditary Disorders of Cornification
3 Epidermolytic Ichthyosis�� 19

References�� 21
4 Nonbullous Congenital Ichthyosiform Erythroderma (CIE)�� 23
References�� 27
5 Lamellar Ichthyosis�� 29
5.1 Lamellar Ichthyosis�� 33
5.2 Harlequin Fetus�� 35
References�� 38
6 Netherton Syndrome�� 39
References�� 46
7 Conradi Hunermann Happle�� 47
References�� 50
8 Palmoplantar Keratoderma�� 51
Reference �� 53
ix
x Contents
9 Keratosis Follicularis Spinulosa Decalvans �� 55

References �� 57
10 Hypohidrotic Ectodermal Dysplasia�� 59
10.1 Hypohidrotic Ectodermal Dysplasia  �� 59
References �� 60
Part IV Disorders of Sebaceous and Sweat Glands
11 Familial Dysautonomia with Anhydrosis (Type IV) �� 63

Reference �� 65
Part V Cutaneous Tumors and Tumor Syndromes
12 Congenital Nevi�� 69

12.1 Halo Nevi�� 76
12.2 Congenital Nevus Photos�� 82
12.3 Congenital Nevus�� 86
12.4 More CNN Congenital Nevi �� 88
12.5 More Congenital Nevi�� 91
12.6 Congenital Nevi Surgical Outcomes�� 98
References�� 99
13 Brooke-Spiegler�� 101
References�� 102
14 Epidermal Nevus�� 103
14.1 Total Body Linear Epidermal Nevus�� 107
15 Basal Cell Nevus Syndrome�� 111
16 Mastocytoma�� 115
16.1 Urticaria Pigmentosa�� 117
Part VI Vascular Disorders of Infancy and Childhood
17 Infantile Hemangiomas �� 125

17.1 Hemangomas – Surgical Repair�� 134
18 Glomus Tumor�� 137
Contents xi
19 Phakomatosis�� 139
20 Vascular Malformations�� 143
21 Capillary Malformations�� 149
Reference �� 153
22 Venous Malformations�� 155
23 Macrocystic Lymphatic Malformations�� 161
24 Microcystic Lymphatic Malformation �� 165
Part VII Bullous Disorders of Childhood
25 Epidermolysis Bullosa Simplex�� 175

26 Junctional Epidermolysis Bullosa�� 193
26.1 Junctional EB Herlitz Variety�� 199
26.2 Junctional EB Non-Herlitz�� 203
27 Dystrophic Epidermolysis Bullosa�� 207
Part VIII Photosensitivity and Photoreactions
28 Actinic Prurigo �� 219

29 Hydroa Vacciniforme �� 223
30 Rothmund Thomson�� 229
31 Porphyria�� 231
32 Poikiloderma with Neutropenia�� 235
Part IX Vascular Diseases
33 Polyarteritis Nodosa�� 245

xii Contents
Part X Collagen Vascular Disorders
34 Discoid Lupus �� 251

35 Neonatal Lupus�� 255
36 Dermatomyositis�� 259
37 Morphea�� 265
Part I
Eczematous Eruption of Childhood
Chapter 1
Hyper IgE Syndrome
Hyper-immunoglobulin E (IgE) syndrome (HIES) is a rare clinical entity that was

first recognized by Davis in 1966 that affects 1:100,000 patients annually [1]. HIES
is a primary immunodeficiency, previously called Job syndrome. It is equally preva-
lent in men and women (Table 1.1).
HIES is characterized by eosinophilia, eczema, elevated IgE levels, and recurrent
cutaneous and pulmonary infections. Early cutaneous manifestations of HIES
include eczematous eruptions, recurrent abscesses, and chronic mucocutaneous
candidiasis. The abscesses are referred to as “cold abscesses” because they are non-
inflammatory and are typically caused by Staphylococcus aureus [2]. Diagnostically,
patients have eosinophilia and elevated IgE levels. Pulmonary findings mainly con-
sist of recurrent sinopulmonary infections with various bacterial, viral, and fungal
pathogens ultimately leading to the formation of bronchiectasis, pneumatoceles,
and parenchymal lung damage. Patients can present with abnormal craniofacial fea-
tures (i.e. characteristic facies, craniosynostosis, retained childhood dentition, and
high-arched palate), musculoskeletal abnormalities (i.e. hyperextensibility, scolio-
sis, and osteoporosis), vascular abnormalities (coronary artery dilatation, aneu-
rysms, and hypertension) as well as parenchymal brain lesions. Patients with HIES
are at increased risk of developing certain malignancies such as non-Hodgkin lym-
phoma [2].
The pathogenesis involves the JAK/STAT pathway, which is critical in mediating
the inflammatory cascade. Mutations in the STAT3 locus on chromosome 17 have
been identified in patients with HIES. Other mutations include DOCK8 and Tyk2
mutations.
The differential diagnosis of elevated serum IgE includes Wiscott-Aldrich,
Omenn, atypical complete DiGeorge, Netherton and polyendocrinopathy enteropa-
thy X-linked (IPEX) syndromes as well as immune dysregulation syndromes.
Prevention of skin and pulmonary infections is with prophylactic antibiotics and
antifungals. Eczema and skin abscesses can be mitigated with bleach baths and
chlorhexidine washes. Topical calcineurin inhibitors and topical corticosteroids
© Springer Nature Switzerland AG 2019 3

T. Shwayder et al., Longitudinal Observation of Pediatric Dermatology Patients,
https://doi.org/10.1007/978-3-319-98101-7_1
4
Table 1.1 Scoring system for Hyper IgE Syndrome (Job syndrome)
Clinical findings 0 1 2 3 4 5 6 7 8 10
Highest IgE (IU/mL) <200 200–500 501–1000 1001–2000 >2000
Total skin abscesses/boils None 1–2 3–4 >4
Total pneumonias None 1 2 3 >3
Parenchymal lung abnormalities None Bronchiectasis Pneumatocele
Other serious infection None Present
Fatal infection None Present
Highest eosinophils/uL <700 701–800 >800
Newborn rash None Present
Eczema (worst stage) None Mild Moderate Severe
Sinusitis/otitis (in worst year) 1–2 3 4–6 >6
Candidiasis None Oral, vaginal Fingernail Systemic
Retained primary teeth None 1 2 3 >3
Scoliosis (maximum curvature) <10 10-14 15–20 >20
Minimal trauma fractures None 1–2 >2
Hyperextensibility None Present
Characteristic face None Mild Present
Increased interalar distance <1 SD 1–2 SD >2 SD
High palate None Present
Congenital anomaly None Present
Lymphoma None Present
1 Hyper IgE Syndrome
1 Hyper IgE Syndrome 5
may help with the eczematous dermatitis. Certain patients with HIES may benefit
from immunoglobulin substitution therapy (i.e. IV IgG). Bone marrow transplanta-
tion has been attempted in several patients with mixed results making the utility of
this treatment less clear.
Many many patients with atopic dermatitis have high levels of IgE. The
query “is this Job’s Syndrome” comes up quite frequently. Now that we have
genetic testing for DOCK8 and STAT3 a firm diagnosis can be made. To my
surprise my last two patients did not have the long list of facial, brain, and
bone problems usually associated with HIES, rather they had persistent pus-
tules, hard to control eczema, and multiple staph infections. A nice check list
for HIES is:
• 8 or more ear infections in the past 12 months:
• 2 or more sinus infections in the past 12 months:
• Two or more months or antibiotics with little relief:
• Two or more pneumonias within 1 year:
• Failure of infant to gain weight or grow normally:
• Recurrent, deep skin or organ abscesses:
• Persistent thrush in mouth or elsewhere on skin, after age 1:
• Need IV antibiotics to clear infections:
• Two or more deep seated infections:
• Family history of immunodeficiency:
• Consanguineous parents:
• Dental abnormalities or missing teeth:
• Alopecia: Sparse hair on head or eyebrows:
• Does patient sweat or history of febrile seizures:
• Normal nail development:
• Any history of unexplained childhood deaths:
This is a shorthand from a very nice graph published by Rebecca Buckley

MD. This chart is helpful for STAT3 deficiency type IgE.
When I ask the above questions, I am tallying up the points from Table 1.1
for total of:
• >40 points likely
• 20–40 points uncertain
• <20 points unlikely HyperIgE syndrome.
6 1 Hyper IgE Syndrome
If I see a female patient with bad atopic dermatitis and recurrent skin viral
issues or any history of invasive viral infection or cervical cancer then I think
of DOC8 or TYK (tyrosine kinase) deficiencies.
All three deficiencies have elevated IgE levels and bad atopic dermatitis but a
“weird” infection history.
I usually end up ordering all of the other immunoglobulin levels and HIV to
make sure I’m not missing anything else.
Sometimes, I will also order flow cytometry to make sure they have function-
ing NK/T/B cell lines as well.
Patient presented at 5 weeks of age for pustules and crusting on her scalp. Genetic
testing revealed a positive STAT-3 mutation, which confirmed her diagnosis of
Hyper IgE Syndrome. She was initially treated with IV IgG infusions once a month
and daily trimethoprim-sulfamethoxizole as prophylaxis.
1 Hyper IgE Syndrome 7
Patient at several months of age who still has intermittent eczematous plaques
and sterile pustules on her face and scalp. She controls these flares with topical
calcineurin inhibitors and topical corticosteroids twice daily as needed. She is still
receiving monthly IV IgG infusions.
8 1 Hyper IgE Syndrome
Another patient presented during adolescence with predominantly eczematous

dermatitis who was found to have hyper-IgE syndrome.
References
1. Davis SD, Schaller J, Wedgwood RJ. Job's syndrome. Recurrent, "cold", staphylococcal
abscesses. Lancet. 1966;1(7445):1013–5.
2. Mogensen TH. STAT3 and the hyper-IgE syndrome: clinical presentation, genetic origin,
pathogenesis, novel findings and remaining uncertainties. JAKSTAT. 2013;2(2):e23435.
Part II
Papulosquamous and Related Disorders
Chapter 2
Psoriasis
Psoriasis is a common chronic inflammatory dermatologic condition that is com-

mon in childhood with approximately one third of cases presenting in this age group
[1, 2]. Psoriasis affects 0.5–2% of children with a mean age of onset of 7–11 years
[1, 3]. There is a slightly higher incidence of pediatric psoriasis in girls as well as a
strong genetic predisposition in cases of early onset psoriasis [1, 3]. The HLA-Cw6
susceptibility allele (also known as PSORS1) portends early onset psoriasis, more
extensive disease, and a strong family history [1].
The clinical presentation of pediatric psoriasis can vary greatly, as with adults.
Patients present with erythematous papules or plaques with shiny micaceous scale.
Lesions are classically on extensor surfaces but may be diffuse. Associated pruritus
often occurs. Myriad nail changes may include pitting, oil spots and onycholysis.
Most commonly, children present with plaque type psoriasis. Scalp psoriasis is
common in children and is often the first site of involvement. Guttate psoriasis is
significantly more common in the pediatric population but is still less common than
plaque psoriasis, representing just under half of pediatric cases and is often pre-
ceded by streptococcal pharyngitis. Guttate lesions typically resolve in most patients
within 3–4 months; up to 40% of patients, however, can evolve into chronic plaque
psoriasis. Rarer clinical variants include pustular psoriasis, erythrodermic psoriasis
and psoriatic arthritis. As with adults, nail psoriasis is more frequently associated
with severe disease and psoriatic arthritis [3]. Psoriatic arthritis occurs in 0.7–10%
of pediatrics cases with a peak onset between ages 9–12 [3]. Psoriatic arthritis is a
chronic inflammatory arthritis that causes destructive arthropathy and can lead to
permanent dysfunction.
In addition to psoriatic arthritis, there are other co-morbidities in patients with
psoriasis including obesity, metabolic syndrome, cardiac and cerebrovascular dis-
ease [3]. These co-morbidities are related to the chronic inflammation that is present
in psoriasis. Activation of T helper cells and Th-17 cells leads to a pro-inflammatory
state and upregulation of pro-inflammatory cytokines, which has many downstream
effects which are believed to increase the risk of metabolic syndrome and cardiovas-
cular disease. Because of the risk of these co-morbidities, different recommendations

https://doi.org/10.1007/978-3-319-98101-7_2
12 2 Psoriasis
for screening have been released for the pediatric population. Children should be
screened for obesity with body mass index (BMI) percentile starting at 2 years of
age [2]. The should undergo a fasting serum glucose every 3 years starting at age 10
or the onset of puberty if the patient is overweight and has two risk factors for dia-
betes mellitus (such as family history, high BMI or other conditions associated with
insulin resistance) and every 3 years starting at age 10 for obese patients [2]. For
dyslipidemia, patients should be screened with a fasting lipid panel between ages
9–11 and 17–21 years and with any additional cardiovascular risk factors outside of
those age ranges [2]. Screening for hypertension should begin yearly at 3 years of
age and for non-alcoholic fatty liver disease with alanine aminotransferase between
9 and 11 years of age. Mood disorders should be screened for annually [2].
Psoriasis can start at any age. One presentation that is often missed – a tiny
spot of psoriasis in the upper inner eye socket near the globella/inner eyebrow.
Often this is the first spot seen. Full plaque psoriasis is often acutely embar-
rassing for children. Do ask questions about school / peer acceptance, school
avoidance, bullying, etc.
My therapeutic ladder is usually: Topical steroids, topical vitamin D creams,

topical vitamin A creams, topical calcineurin inhibitors, natural sunlight, day
hospital. I still use old time treatments like sulfur or tar creams. Then I move
to oral methotrexate +/− cyclosporine depending on how bad the child’s skin
is. Oral vitamin A derivatives are more difficult in girls of child bearing age.
I have had disappointing results with the first generation of oral phosphodies-
terase inhibitors, but my numbers are low. Biologics can be a game changer,
especially the ones given three or four times a year. Don’t forget to ask about
joint pain. Psoriatic arthritis can occur very early on and is very destructive.
When found it pushes me to systemic therapies. I share these patients with my
colleagues in pediatric rheumatology.
Phototherapy is hard to do less than 10 years of age. The child just does not
stand still in the box, may remove their goggles, cries for their parent, etc.
The prognosis is a mixture of how much genetic input there is. IF one or both
parents have really bad psoriasis I cannot make any promises as to clearing.
And I warn the parent that the child will pass this along to half of their chil-
dren (never welcomed news).
2 Psoriasis 13
I make short term goals with the child. For example, “we will aim to have you
in shorts and T-shirt in four to six months.”
Don’t forget Camps for kids with skin diseases (Camp Discovery sponsored
by the American Academy of Dermatology) can be a game changer for these
children.
This patient initially presented during her early pre-teenage years with psoriatic
plaques diffusely on the body affecting ~15% body surface area with nail involve-
ment. She was managed with topical steroids.
14 2 Psoriasis
Same patient has greatly improved with respect to the scale and now has post-
inflammatory hyperpigmentation. She continues to use her topical corticosteroids as
needed.
This patient presented in childhood with psoriasis on the trunk and extremities as
well as a few small plaques on the face. The patient was managed with cyclosporine
and ultimately was transitioned to apremilast, which he did not tolerate due to the
gastrointestinal side effects. He was unable to come for phototherapy. Thus, he was
ultimately transitioned to a TNF-alpha inhibitor, ustekinumab, with improvement.
Throughout the entire course of therapy, the patient was continued on topical
corticosteroids.
2 Psoriasis 15
There are many treatment options available for patients with psoriasis with many
new treatments on the horizon. A definitive treatment ladder has been less well
established for pediatric patients. Compared to adults [1, 3] topical therapy for pso-
riasis tends to be successful in most cases. Most topical agents are not approved for
use in the pediatric population and are thus used off-label. Topical corticosteroids
serve as anti-inflammatory and anti-proliferative agents and help with pruritus. If
used for a prolonged period, patients may develop side effects including steroid
induced acne/rosacea, striae, hyper- or hypo-pigmentation, and telangiectasias.
Additionally, topical calcineurin inhibitors (tacrolimus and pimecrolimus) are ste-
roid sparing anti-inflammatory agents that can be used in more sensitive areas such
as the face, genitals and flexural areas. Some patients may report burning or stinging
with their application. Topical vitamin D analogues are another less commonly used
therapeutic option. Lastly, some patients use coal tar preparations but this is less
frequently utilized given the smell and staining [3].
In patients who are poorly controlled with topical treatments, have extensive
body surface area involvement or in cases compliance makes treatment difficult,
patients should be considered for phototherapy Narrowband UVB (NB-UVB) ther-
apy, which has both anti-inflammatory and anti-proliferative capabilities, is the pho-
totherapy of choice. Although there are no known strong malignancy risks, the real
risk of skin cancer remains an ongoing discussion due to a paucity of very long-term
studies ensuring its safety. As such, the maximum recommended treatments are 250
and annual skin examinations for any patients who have received greater than 150
treatments are recommended [3].
In cases where topical treatment alone or phototherapy fail, or even more impor-
tantly in cases of psoriatic arthritis, systemic medications are indicated. There are
many systemic agents available. Acitretin, methotrexate and cyclosporine are the
most common medications used in pediatric patients. It is important to remember
when treating patients with immune suppressing systemic medications, live vacci-
nations should be avoided. Biologic agents are the newest treatments added to the
armamentarium for psoriasis. Etanercept (a TNF-α inhibitor) is the only FDA-
approved biologic for pediatric psoriasis. All others are used off-label [3].
16 2 Psoriasis
References
1. Relvas M, Torres T. Pediatric Psoriasis. Am J Clin Dermatol. 2017;18:797.

2. Osier E, Wang AS, Tollefson MM, et al. Pediatric psoriasis comorbidity screening guidelines.
JAMA Dermatol. 2017;153:698.
3. Tangtatco JAA, Lara-Corrales I. Update in the management of pediatric psoriasis. Curr Opin
Pediatr. 2017;29:434.
Part III
Hereditary Disorders of Cornification
Chapter 3
Epidermolytic Ichthyosis
Epidermolytic ichthyosis (EI) is an example of a non-syndromic inherited ichthyo-

siform condition with a varied clinical appearance. Other names for the condition
include bullous congenital ichthyosiform erythroderma, epidermolytic hyperkerato-
sis and bullous ichthyosis [1]. This is a rare condition with a worldwide prevalence
of 1 in 200,000 to 300,000 [1]. It is transmitted as an autosomal dominant disorder
with complete penetration. The most common mutations occur in two keratin genes:
KRT1 or KRT10 [1, 2].
Clinically, it is characterized by blister formation and erythroderma at birth that
improves with age. As the patient approaches adulthood, they develop generalized
thickened skin, most prominent over the neck and in flexural areas. Patients with
mutations in KRT1 tend to have a more profound palmoplantar keratoderma.
Skin biopsy demonstrates epidermal acanthosis and hyperkeratosis and granular
degeneration is a striking histopathological feature [2].
In early infancy, the erythroderma with an impaired epidermal barrier can be life-
threatening requiring hospitalization for fluid and electrolyte management. Other
treatments are symptomatic, which in the older child and adult population revolve
around improving the hyperkeratosis. Treatment options for this include keratolytic
lotions, topical retinoids, topical adapalene, topical vitamin D preparations and oral
retinoids. Patients can also use gentle exfoliation and frequent moisturizing to
improve the texture and appearance of their skin. Additionally, bacterial infections
are frequent complications that should be addressed with topical or systemic antibi-
otics as needed [1]. Monitoring for dermatophyte infections and scabies is war-
ranted. In cases of scabies, treatment should be that of Norwegian scabies.

https://doi.org/10.1007/978-3-319-98101-7_3
20 3 Epidermolytic Ichthyosis
This patient has been treated with soriatane and tretinoin.
Topical Tretinoin to the face.

References 21
One week after starting oral soriatane.
References
1. Vahlquist A, Fischer J, Torma H. Inherited nonsyndromic ichthyoses: an update on pathophysi-

ology, diagnosis and treatment. Am J Clin Dermatol. 2018;19(1):51–66; PMID: 28815464.
2. Takeichi T, Akiyama M. Inherited ichthyosis: non-syndromic forms. J Dermatol.
2016;43(3):242–51.
Chapter 4
Nonbullous Congenital Ichthyosiform
Erythroderma (CIE)
Nonbullous congenital ichthyosiform erythroderma (CIE) is a clinical entity in the

category of autosomal recessive congenital ichthyoses (ARCIs) [1]. Other diagno-
ses that fall within this category include lamellar ichthyosis and harlequin ichthyo-
sis [1]. CIE is a rare condition with a prevalence of 1 in 100,000 to 200,000
individuals [2]. Nonbullous CIE can be caused by several mutations including
ALOX12B, ALOXE3,CERS3, CYP4F22, LIPN, NIPAL4/ICHTHYIN, PNPLA1,
TGM1, and ABCA12 [1, 2] all of which encode epidermal enzymes critical to the
processing of lamellar bodies. Mutations in these enzymes lead to inefficient cre-
ation of the cornified envelope and thus an impaired epidermal barrier [1].
Infants are commonly born as a collodion baby with or without eclabium and
ectropion. Classically, infants present with erythroderma with a powdery scale. In
most cases, the erythroderma resolves during infancy [2]. They may develop other
clinical features such as diffuse scaling, palmoplantar keratoderma, and onychodys-
trophy [1, 2]. When the palms and soles are severely affected, fissures are com-
monly present. Histopathology specimens are non-specific but demonstrate
hyperkeratosis with a normal to moderately thickened granular cell layer, slight
acanthosis and parakeratosis [2].
In the early days of life, treatment includes careful monitoring for electrolyte
disturbances in patients with collodion membranes and erythroderma. Babies
should remain well moisturized with ointment-based emollients in a humidified iso-
lette with careful measures to avoid infection until they shed a fair amount of the
membrane. As patients age, the various treatments may include oral retinoids for the
hyperkeratosis particularly with acitretin, which has been shown to ameliorate
ectropion [2]. Topical agents can also be utilized though can be a therapeutic chal-
lenge given the impaired epidermal barrier. Examples include topical vitamin D
derivatives and retinoids, such as tazarotene [2]. Patients should frequently moistur-
ize with thick emollients. Keratolytics may be helpful in cases of severe scalp and
palmoplantar involvement. Antihistamines can also play a role for itch. Regular

https://doi.org/10.1007/978-3-319-98101-7_4
24 4 Nonbullous Congenital Ichthyosiform Erythroderma (CIE)
bathing and manual exfoliation may also help. Additionally, it is important for these
patients to be evaluated by ophthalmology if ectropion is present. Otolaryngology
may also be helpful in patients who have persistent buildup of flaking skin in their
external auditory canal. Patients have an increased risk of cutaneous malignancy [1]
and thus should receive regular monitoring.
4 Nonbullous Congenital Ichthyosiform Erythroderma (CIE) 25
This family of three children all presented with CIE with collodion membrane at
birth and mild palmoplantar erythema and scale. Their diagnosis was confirmed by
genetics.
This patient presented at birth with erythema and “powdery” scale.

26 4 Nonbullous Congenital Ichthyosiform Erythroderma (CIE)
Several months later, she still has significant erythema but a reduction in scale.
References 27
Same child now age 5 years. She has been well-controlled on emollients and
bleach baths.
References
1. Jaju P, Novoa RA, Swetter SM, Sarin KY. Invasive melanoma in a patient with congenital
ichthyosiform erythroderma. Pediatr Dermatol. 2017;34(1):e35–6.
2016;43(3):242–51; PMID: 26945532.
Chapter 5
Lamellar Ichthyosis
Lamellar ichthyosis is a sub-type of non-bullous congenital ichthyosis. It can also

be classified as one of the non-syndromic autosomal recessive congenital ichthyosis
(ARCI) clinical manifestations [1]. Other ichthyoses within ARCI include congeni-
tal ichthyosiform erythroderma and harlequin ichthyosis. Many genes have been
implicated in the pathogenesis of lamellar ichthyosis including ABCA12, ALOXE3,
ALOX12B, CERS3, CYP4F22, NIPAL4/ICHTHYIN, PNPLA1, and TGM1 [2]. The
most common mutations include TGM1 and ABCA12. Lamellar ichthyosis is
uncommon occurring in 1 in 200,000 to 1 in 300,000 live births worldwide; how-
ever, it is more common in certain populations [1].
It is on a spectrum with harlequin ichthyosis; however, patients with lamellar
ichthyosis tend to present with milder clinical phenotypes. Like harlequin ichthyo-
sis, patients with lamellar ichthyosis are sometimes born as collodion babies.
Clinically, patients present with large thick grey / brown scales that cover a large
body surface area. The severity of presentation varies from patient to patient.
Classically, patients do not present with erythroderma though mild erythema is pos-
sible [2]. Other clinical manifestations include palmar-plantar keratoderma, alope-
cia, ectropion, nail dystrophy, and heat intolerance.
The diagnosis is generally made clinically but genetic testing is available for
patients with high suspicion. Histology is non-specific with findings such as ortho-
keratosis, acanthosis, and psoriasiform or papillomatous hyperplasia [1].
Patients with lamellar ichthyosis are managed as a neonate via aggressive sup-
portive care. Patients who present with collodion membranes and severe disease often
benefit from early systemic therapy with oral retinoids. Acitretin has been shown to
be effective with the hyperkeratosis and scale. Similar to other forms of ichthyosis,
topical therapies such as topical vitamin D3 derivatives, tazarotene, and keratolytics
may be effective but can be limited by their side effect profiles. Patients with heat
intolerance can benefit from frequent moisturizing, air conditioners, and humidifiers.
Patients with ectropion should be followed closely by ophthalmology [1].

https://doi.org/10.1007/978-3-319-98101-7_5
30 5 Lamellar Ichthyosis
Collodion babies are a very distinctive phenotype. Their outcome can be quite
variable so I do not make any predictions for the parents in the nursery.
Usually by 4–6 months I am reasonably sure and by the first year of life I
know. The one exception is epidermolytic hyperkeratosis (EI). These children
have large denudation of skin right after birth that scares the heck out of
everyone. This skin sloughing settles down fairly quickly and the child’s phe-
notype is obvious by 6 months of life or sooner.
Non bullous CIE can be quite variable with some children having a near nor-
mal skin and some being markedly red skin all their lives.
Lamellar ichthyosis can be debilitating and needs close following. Oral reti-
noids do help quite a bit but is a lifelong treatment.
She has improved with bleach baths, Amlactin 12% lotion and tretinoin 0.05%
cream. She was unable to take acitretin because she was planning a pregnancy.
5 Lamellar Ichthyosis 31
This young man presented with lamellar ichthyosis with thick plate-like scale
and erythema.
He improved with treatment with vitamin A derivatives but continues to have

lamellar scaling and thick palmar skin causing hand contractures. He is also strug-
gling with pruritus.
Same child 5 years later. His current regimen includes bleach baths every other
day, frequent Aquaphor applications, propylene glycol 20% to the palms and soles,
mupirocin ointment as needed and hydroxyzine as needed.
5.1 Lamellar Ichthyosis 33
5.1 Lamellar Ichthyosis
20 year old BM life long thick scaling.
Topical Vitamin A cream helps some. Note ectropion.

5.2 Harlequin Fetus 35
5.2 Harlequin Fetus
Harlequin fetus is a dramatic nursery arrival. The treatments are many and
intense. The fissured skin lets out moisture, electrolytes and nutrients and lets
in infection. Hypernatremic dehydration and kidney failure, systemic infec-
tion, feeding difficulties, contractures, eye care, are just a few issues. I have
treated them with both intensive cutaneous care plus nutritional support plus
or minus oral retinoids. The last three harlequin fetus I have treated have been
without oral retinoids and all have survived. We did frequent debridement of
thick skin, multiple applications of Vaseline based products, tube and IV feed-
ings, eye care, etc. These infants, if they survive, grow up to exhibit a pheno-
type of intense congenital ichthyosiform erythroderma.
Day zero.
Day 5.
5.3 Harlequin Fetus
Day 8.
Day 8.
Day 12.
5.4 Harlequin Fetus 37
Day 16.
5.4 Harlequin Fetus
Day 39.
Day 39.
Day 96.
Day 96.
References

2016;43(3):242–51.
2. Glick JB, Craiglow BG, Choate KA, Kato H, Fleming RE, Siegfried E, Glick SA. Improved
management of harlequin ichthyosis with advances in neonatal intensive care. Pediatrics.
2017;139(1). pii: e20161003. https://doi.org/10.1542/peds.2016-1003. Epub 2016 Dec 20.
Review. PMID: 27999114.
Chapter 6
Netherton Syndrome
Netherton Syndrome (NS) is an uncommon genodermatosis. It is caused by a loss-

of-function mutation in serine protease inhibitor of kazal type 5 (SPINK5). The
SPINK5 gene encodes lymphoepithelial kazal type related inhibitor type 5 (LEKTI),
which is a serine protease inhibitor that is expressed in all stratified epithelia as well
as in the thymus [1].
Clinically, patients with NS present with a classic triad of findings including
congenital ichthyosiform erythroderma, trichorrhexis invaginata (or bamboo hair)
and dermatitis (ichthyosis linearis circumflexa). Clinical phenotypes can vary; how-
ever the skin disease is often quite severe in newborn children. In older children and
adults, cutaneous infections can be a problem as well and require regular monitor-
ing and intertriginous areas can thicken and become a challenge to manage. Patients
can have severe food allergies associated with anaphylaxis [2].
Pathologically, biopsy specimens demonstrate epidermal acanthosis with elon-
gated rete ridges, hypogranulosis, and parakeratosis. Some cases may have an
inflammatory infiltrate in the dermis [1].
The treatment for patients with NS is predominantly symptomatic. Newborns and
infants are at high risk for metabolic abnormalities, fluid shifts, and dehydration due
to the impaired skin barrier function. Similarly, these patients are at increased risk of
infection and may have failure to thrive. Newborns and very young patients with NS
are at particularly high risk for life-threatening complications. These patients require
a multidisciplinary team to ensure that they are developing appropriately and receiv-
ing adequate nutrition. Throughout childhood, emollients are of utmost importance
due to the impaired skin barrier. Lesions consistent with atopic dermatitis may ben-
efit from topical corticosteroids or topical calcineurin inhibitors; however, caution
must be used to minimize systemic absorption given the impaired barrier function of
the skin. Pruritus and any atopy can be treated with oral antihistamines. As with
other ichthyosis patients, bathing and exfoliation can be helpful as well. For patients
with severe disease, IV IgG (0.4 g/kg/month) can be considered [3]. There have also
been case reports that TNF-α agents may be helpful [4]. Emergency epinephrine
should be provided for patients with anaphylactic food allergies.

https://doi.org/10.1007/978-3-319-98101-7_6
40 6 Netherton Syndrome
Newborn babies with netherton’s syndrome often are red and slightly scaly
either in the intertriginous areas and/or all over. The intertriginous redness
and mattering is life long and affects not only the armpits and groin, but also
behind the ears, the eyes, nose, chin, ear canals, nipples and umbilical recess.
One of my patient has intense redness and papillation in these areas especially
the groin with pus discharge, foul smell and pain.
The hair findings usually do not show up until terminal hairs start growing
(i.e. not the baby hair.)
Topical calcineurin inhibitors for the skin findings has been disappointing in
my hands.
This young boy presented shortly after birth with erythroderma and short hairs
on scalp and eyebrows.
This was after several years of treatment without much improvement in his
erythema.
6 Netherton Syndrome 41
The image of the foot demonstrates the characteristic ichthyosis linearis circum-
flexa with the annular erythematous lesions with parallel scale. He also began to
develop fungating vegetating plaques in the gluteal crease and folds that have not
been controlled with phototherapy, methotrexate, IVIgG, various topical antibiotics
or topical corticosteroids.
Now age 23y. Marked and persistent erythema and papillation in intertriginous
areas. Also note persistent plaque on chin. Multiple biopsies of groin and buttocks
read as psoriasiform dermatitis with positive HPV staining in focal areas.
This patient presented shortly after birth with erythema and scaling.
Same child age 7y.

This patient presented at birth with erythema and scaling skin.

As she has aged, the erythema as greatly improved but she still has the character-
istic short hairs seen in Netherton syndrome.
At age 5y, she has been using Aquaphor and bleach baths three times weekly as
maintenance therapy in addition to topical corticosteroids and topical calcineurin
inhibitors.
References
1. Hovnanian A. Netherton syndrome: skin inflammation and allergy by loss of protease inhibi-
tion. Cell Tissue Res. 2013;351(2):289–300.
2. Bolognia J, Jorizzo J, Schaffer J. Dermatology. 3rd ed. London: Elsevier; 2012.
3. Renner ED, Hartl D, Rylaarsdam S, et al. Comel-Netherton syndrome defined as primary
immunodeficiency. J Allergy Clin Immunol. 2009;124(3):536–43.
4. Fontao L, Laffitte E, Briot A, et al. Infliximab infusions for Netherton syndrome: sustained
clinical improvement correlates with a reduction of thymic stromal lymphopoietin levels in the
skin. J Invest Dermatol. 2011;131(9):1947–50.
Chapter 7
Conradi Hunermann Happle
Conradi-Hunermann-Happle (CHH) syndrome is a type of X-linked dominant ich-

thyosis. Other etiologies in this category include congenital hemidysplasia with ich-
thyosiform erythroderma and limb defects (CHILD syndrome). CHH is also known
as X-linked dominant chondrodysplasia punctata. As an X-linked dominant disor-
der, CHH is lethal in males except for males with XXY phenotype or in the case of
mosaicism. This disorder is exceedingly rare [1, 2].
CHH is caused by mutations in the EBP gene, which is located at Xp11.22-p11.23
[2]. This gene encodes an emopamil-binding protein (EBP) which ultimately leads
to dysfunctional cholesterol biosynthesis. Patients have increased levels of sterol
precursors including 8(9)cholesterol and 8-dehydrocholesterol [1, 2]. The pheno-
type is thought to arise due to this dysregulated cholesterol biosynthesis during key
moments of molecular development. To diagnose patients, genetic testing for the
EBP gene is available. Additionally, chondrodysplasia punctata can be identified on
x-ray imaging and accumulation of 8(9)cholesterol in the plasma can be detected by
mass spectrophotometry [1, 2].
CHH predominantly affects the skin, bone, and eyes. Patients typically first pres-
ent at birth with erythema and thick scale in a blaschkoid distribution. Over the first
few weeks to months of life, the erythema generally resolves. As patients age, they
typically develop atrophoderma particularly on the dorsal hands and forearms and
the ichthyosis often persists. If the scalp is involved, patients may develop alopecia.
Patients also can have nail changes including onychoschizia and flattening of the
nail plate. Teeth are normal. As the name suggests, patients also present with skel-
etal anomalies such as frontal bossing, malar hypoplasia, flat nasal bridge, short
neck, rhizomelic shortening of the limbs, and/or scoliosis. Most commonly, patients
develop chondrodysplasia punctata (or stippled epiphyses). This affects the long
bones as well as the trachea and vertebrae. It can be identified on x-ray and resolves
in adulthood (once the epiphysis has fused) [2]. Patients can additionally have oph-
thalmologic findings such as unilateral cataracts. Less often, patients also have con-
genital heart defects, sensorineural deafness, CNS malformations and/or congenital

https://doi.org/10.1007/978-3-319-98101-7_7
48 7 Conradi Hunermann Happle
renal anomalies. Patients have a normal life expectancy as well as normal mental
function.
There is no definitive treatment. Management consists of symptomatic relief.
Patients with persistent ichthyosis may benefit from emollients and keratolytics.
Given the concern regarding the bones as well as risk of cataracts, patients should
be concurrently followed by orthopedics and ophthalmology.
This young girl presented during infancy with macrocephaly, shortened limbs,
scoliosis, and club feet. At approximately three months of age, she developed an
erythematous eruption in the skin folds and across the trunk with scale.
Her diagnosis was confirmed by genetics. Both her mother and maternal grand-
mother have chondrodysplasia punctata associated with scoliosis, alopecia, ichthy-
osis, and dyspigmentation.
7 Conradi Hunermann Happle 49
50 7 Conradi Hunermann Happle
References
1. Takeichi T, Honda A, Okuno Y, Kojima D, Kono M, Nakamura Y, Tohyama M, Tanaka T, Aoyama

Y, Akiyama M. Sterol profiles are valuable biomarkers for phenotype expression of Conradi-
Hunermann- Happle syndrome with EBP mutations. Br J Dermatol. 2018;179(5):1186–8.
PMID: 29851033.
2. Canueto J, Giros M, Ciria S, et al. Clinical, molecular and biochemical characterization of
nine Spanish families with Conradi-Hunermann-Happle syndrome: new insights into X-linked
dominant chondrodysplasia punctata with a comprehensive review of the literature. Br J
Dermatol. 2012;166(4):830–8.
Chapter 8
Palmoplantar Keratoderma
The term palmoplantar keratoderma (PPK) refers to a diverse group of diseases that
result in hyperkeratosis on the palms and soles. PPKs can be acquired or inherited –
though acquired cases are more common.
Nomenclature is critical to understanding PPKs. Diffuse PPK describes lesions
that involve the entire surface of the palm and/or sole. This is in contrast to focal
PPK which predominantly demonstrates hyperkeratosis over pressure points. Within
focal PPK, there are two additional subtypes including nummular PPK (involving
ovoid lesions) and striate PPK (linear involvement). Lastly, there is punctate PPK,
which describes smaller keratotic papules on the palmoplantar surfaces. When eval-
uating patients with PPK, it is important to determine if they have any associated
cutaneous or extra-cutaneous signs of symptoms. This can help determine the type
of PPK that the patient may have [1].
Focal PPK can be inherited in an autosomal dominant inheritance pattern. There
are multiple genetic mutations in desmosomal and/or keratin components of the
skin that can be affected. The mainstay of treatment for isolated focal PPK is emol-
lients or keratolytics [1].
Treating PPK is a lifelong task and generally disappointing. The Keratolytics

help – but only a little. Scrubbing with a pumice stone is temporary. Oral reti-
noids can be a short term fix for the confluent type. Making sure the patient/
parent is aligned with your version of “treatment” is very important. Letting
the patient or parent know that the trait will be passed on to their children (or
grand children) is never welcomed news.

https://doi.org/10.1007/978-3-319-98101-7_8
52 8 Palmoplantar Keratoderma
This young girl presented during elementary school age with thickening of the
skin on the soles of her feet causing pain and occasionally deep painful fissures. She
is pictured here with her father who also has a plantar keratoderma. Their PPK type
appears to be a focal striate inherited PPK.
Reference 53
Over 10 years, her palmar-plantar keratoderma has worsened. She has used vari-
ous emollients with only minimal relief in her symptoms. Most recently, the patient
has found taclonex helpful.
Reference
1. Schiller S, Seebode C, Hennies HC, Giehl K, Emmert S. Palmoplantar keratoderma (PPK):

acquired and genetic causes of a not so rare disease. J Dtsch Dermatol Ges. 2014;12(9):781–8.
PMID: 25176457.
Chapter 9
Keratosis Follicularis Spinulosa Decalvans
Keratosis follicularis spinulosa decalvans (KFSD) is a genetic disorder within the

family of keratosis pilaris atrophicans. It is most commonly inherited as an x-linked
recessive mutation in MBTPS2 [1].
Clinically, patients present in childhood with the most commonly affected areas
including the face, scalp, trunk and limbs. Patients can demonstrate erythematous
follicular papules with central keratotic core that ultimately leads to a scarring alo-
pecia of the scalp, eyebrows, and eyelashes. Patients also have evidence of keratosis
pilaris [1].
Treatment for patients with KFSD primarily involves symptomatic relief with
emollients or keratolytic agents. Many of the articles on therapy are anecdotal; how-
ever, there is a case report of a patient improving on an oral retinoid [2]. The authors
recommend 6–12 months of treatment for optimal response [2].

https://doi.org/10.1007/978-3-319-98101-7_9
56 9 Keratosis Follicularis Spinulosa Decalvans
This young man presented in childhood with evidence of keratosis pilaris on the
upper extremities as well as scaring of the lateral eyebrows and vertex scalp. At
birth, genetic testing confirmed keratosis follicularis spinulosa decalvans and hypo-
hidrotic ectodermal dysplasia. He did have missing teeth on his lower jaw but no
nail abnormalities.
As he approached puberty, the inflammation became more calm but the scarring
alopecia remained. He did not have any efficacious results from isotretinoin,
minocycline, doxycycline, cyclosporine or mycophenolate mofetil. He declined to
take pioglitazone (Actos).
References 57
References
1. Zhang J, Wang Y, Cheng R, Ni C, Liang J, Li M, Yao Z. Novel MBTPS2 missense mutation

causes a keratosis follicularis spinulosa decalvans phenotype: mutation update and review of
the literature. Clin Exp Dermatol. 2016;41(7):757–60. PMID: 27663151.
2. Gupta D, Kumari R, Bahunutula RK, Thappa DM, Toi P, Parida PK. Keratosis follicularis
spinulosa decalvans showing excellent response to isotretinoin. Indian J Dermatol Venereol
Leprol. 2015;81(6):646–8.
3. Sgontzou T, Armyra K, Kouris A, Bokotas C, Kontochristopoulos G. Repeated salicylic acid
peels for the treatment of hyperplastic sebaceous glands in hypohidrotic ectodermal dysplasia.
J Cosmet Laser Ther. 2014;16(6):293–5.
Chapter 10
Hypohidrotic Ectodermal Dysplasia
8 Mon WM with Ectodermal dysplasia Showing classic peri-ocular changes and

the pegged incisors.
10.1 Hypohidrotic Ectodermal Dysplasia
Hypohidrotic ectodermal dysplasia is a rare genodermatosis that is most commonly

X-linked with a mutation in the HED gene. It occurs in approximately 1:10,000
male infants [1].

https://doi.org/10.1007/978-3-319-98101-7_10
60 10 Hypohidrotic Ectodermal Dysplasia
At birth, patients can present with a collodion membrane or profound scaling.

Clinically presents with sparse or absent hair, missing or peg shaped teeth, and a
decreased ability to sweat. The nails are usually unaffected. Atopic dermatitis is a
very common co-morbid condition in these patients affecting approximately 2/3 of
individuals.
Given their phenotype, these patients often require a multidisciplinary
approach to their management. These patients have profound dental problems
and require close monitoring and interventions by pediatric dentistry. Patients
should be followed closely by their pediatricians to ensure that they are growing
and developing normally. Should a patient also have concomitant atopic derma-
titis, topical steroids, topical calcineurin inhibitors, bleach baths, antihistamines,
and emollient use should be encouraged. Some patients may require antibiotics
for secondary impetiginization. Though less common, some patients can develop
sebaceous hyperplasia as a component of their hypohidrotic ectodermal dyspla-
sia. This phenotype can be managed with salicylic acid chemical peels to aid in
cosmesis [2].
References
1. Huang SX, Liang JL, Sui WG, Lin H, Xue W, Chen JJ, Zhang Y, Gong WW, Dai Y, Ou ML.
EDA mutation as a cause of hypohidrotic ectodermal dysplasia: a case report and review of the
literature. Genet Mol Res. 2015;14(3):10344–51. PMID: 26345974.
2. Sgontzou T, Armyra K, Kouris A, Bokotas C, Kontochristopoulos G. Repeated salicylic acid
peels for the treatment of hyperplastic sebaceous glands in hypohidrotic ectodermal dysplasia.
J Cosmet Laser Ther. 2014;16(6):293–5.
Part IV
Disorders of Sebaceous and Sweat Glands
Chapter 11
Familial Dysautonomia with Anhydrosis
(Type IV)
Familial dysautonomia with anhidrosis type IV is a very rare cause of anhidrosis. It

has an autosomal recessive inheritance. The diagnosis is suspected clinically in
patients who present with anhidrosis and repetitive trauma; however, a histamine
flare test can be performed. These patients will not produce a flare [1]. Once clini-
cally suspected, genetic testing can confirms an abnormal NTRK1 (TRKA) gene,
located on chromosome 1 [1]. This gene encodes for a neurotropic tyrosine kinase
receptor type 1, which plays an important role in the nerve growth factor pathway
ultimately leading to the failure to thrive of unmyelinated fibers and some small
myelinated fibers [1].
Clinically, patients present with anhidrosis with recurrent fevers. Additionally,
patients demonstrate repetitive self-mutilation and dreadful injuries due to their
insensitivity to pain. They also are insensitive to extremes of temperature as well.
Developmental delays can also occur.
On histology, patients do not have innervation to their eccrine sweat glands pro-
viding the phenotype of anhidrosis. This can be confirmed with immunohistochemi-
cal staining and even electron microscopy.
This is an exceedingly rare entity that can be confused with child abuse.
These cases are quite rare – I have seen two in 30 years. But do think of it
when you have none healing wounds in pressure bearing areas in children.

https://doi.org/10.1007/978-3-319-98101-7_11
64 11 Familial Dysautonomia with Anhydrosis (Type IV)
She presented in early childhood with chronic insensitivity to pain and hypohi-
drosis. She has suffered multiple broken bones and many skin lesions due to lack of
pain.
The lesion on her coccyx presented because of chronic pressure and lack of sen-
sation. The first metatarsal lesion presented due to repeated trauma. Treated with
excision and tissue rotation.
Reference 65
Reference
1. van den Bosch GE, Baartmans MG, Vos P, Dokter J, White T, Tibboel D. Pain insensitivity
syndrome misinterpreted as inflicted burns. Pediatrics. 2014;133(5):e1381–7.
Part V
Cutaneous Tumors and Tumor Syndromes
Chapter 12
Congenital Nevi
Congenital nevi (CN) are benign melanocytic proliferations presenting at birth or

soon after and can evolve and progress over time. CN are subdivided based on their
size into small lesions (<1.5 cm), medium (1.5–19.9 cm) and large (≥20cm) [1, 2].
The majority of lesions fall into the small or medium categories. The incidence of
large CN is approximately 1 in 20,000 people [2].
With congenital nevi, the risk of development of a melanoma is a real concern.
The size of the lesion predicts the risk of malignant transformation into a mela-
noma. The overall risk of melanoma for patients with congenital nevi has been
estimated at 1–2% [2]. Small and medium sized congenital nevi have a very low risk
(~<1%) [1]. For patients with large congenital nevi, the risk has been reported as
high as 10–15% with a large proportion of patients developing a melanoma in the
central nervous system as opposed to in the skin alone [2].
In addition to characterization by size, lesions have been sub-classified by their
phenotype. Classic proliferative nodules describe congenital nevi with a well-
defined round or ovoid border. A second lesion is termed nevoid overgrowth. These
clinically present with ill-defined borders and are generally much larger than classic
proliferative nodules. These lesions are also much softer than classic proliferative
nodules and occur preferentially on the flanks [2].
There are many genes implicated in the development and progression of con-
genital nevi. They are proposed to occur initially due to a somatic mutation during
embryogenesis that progresses through the cell line. Multiple mutations have been
proposed including NRAS, BRAF, MC1R, TP53, and GNAQ [2].
The monitoring schedule for patients with congenital nevi is controversial given
the albeit relatively low risk of melanoma development but more frequent monitor-
ing, such as every 3 months, in the first 5 years of life should be considered with
those with giant CN and 2 or more medium CN. Clinical photography can be help-
ful to determine changing lesions over time when concerns arise. Dermoscopy can
be helpful as well but in larger CN, dermosocopy is less helpful given that mela-
noma tends to arise from the dermis. Examination with visual inspection and palpa-
tion is the most important part of the exam. Imaging is somewhat controversial.

https://doi.org/10.1007/978-3-319-98101-7_12
70 12 Congenital Nevi
Screening magnetic resonance imaging (MRI) of the brain and spine have been
recommended before the age of 1 year. This provides a baseline examination should
a child develop progressive disease or neurologic changes. Melanoma of the skin,
eye and CNS and neurologic disease are associated with giant CN, although the risk
is likely less than 5% in spite of literature suggesting higher numbers.
Any concerning changes should be biopsied for evaluation by an experience der-
matopathologist. Additional ancillary tests can aid in the sensitivity of diagnosing
melanomas such as fluorescent in situ hybridization or genetic testing [2]. One of
the main diagnostic challenges both clinically and histopathologically with CN is
proliferative nodules, which can mimic melanoma.
In general, these lesions do not need to be treated. Excision, dermabrasion and
laser are all potential treatments to improve the appearance. If a patient is diagnosed
with a melanoma, a multidisciplinary approach should guide therapy. Aside from
the risk of developing melanoma, patients can also rarely develop other tumors such
as rhabdomyosarcoma [2].
Most CN are present at birth. However in very fair Caucasians it might take
months (or even a few years) to darken up enough to make the diagnosis. I
have patients whose chart notes say: Café au lait macule vs congenital mela-
nocytic nevus for several visits.
Small CN I do not worry about in terms of malignant degeneration. The risk

is unknown because the denominator is unknown.
Medium sized CN are more of a cosmetic nuisance than a melanoma risk.
IN giant CN the risk of melanoma exists but is small but real (2-4% by my
reading of the literature.) I have had one patient die, and one paralyzed in 30
years. There is no standardized way to follow them. My gestalt is that there is
a bimodal risk curve with melanoma showing up 0–5y, then a low level risk as
an adult. I follow the children 3–4 times a year until kindergarten then once or
twice a year after that.
12 Congenital Nevi 71
Leptomeningeal melanocytosis is rare but real. Who and whether we screen

the CN children for this condition is controversial. If the MRI is negative-
great. If it is positive, does it affect our treatments? Perhaps sharing the child
with neurology/neurosurgery sooner? Personally I would like to know. Any
child with a giant CN, or two or more medium sized ones I will suggest a
scan. The earlier you get it the easier it is for the radiologist to tell leptomen-
ingeal melanocytosis from normal brain myelin.
I do not recommend removing CN. Certainly I do NOT recommend removing

the giant ones. The scars left behind are horrendous.
Proliferative nodules and their histopathology can provoke many paragraphs

of equivocating verbiage by the pathologist. Make sure your pathologist
knows the entity and has seen it before s/he misdiagnoses a proliferative nod-
ule as a melanoma.
This young boy presented with a congenital nevus on his right knee. He had a
biopsy performed when he was an infant that showed a compound melanocytic
proliferation with severe atypia. He had a repeat biopsy at two years of age that
showed a compound nevus, congenital type but there was no discussion of atypia or
malignant potential. He does have leg length discrepancy.
At five years, a third biopsy showed dermal fibrosis with focal melanocytic
proliferation.
He has been followed closely for seven years without any malignant transforma-
tion within his congenital nevus.
This patient first presented for evaluation of this congenital nevus during her
elementary school years.
She returned for re-evaluation seven years later without any concerning features.
This patient presented with a congenital nevus on her dorsal right hand with a
halo around it.
She was noted to have vitiligo elsewhere on her body.
Her vitiligo progressed and her nevus continued to fade over time.
This is a second patient with vitiligo on the body and surrounding a congenital
nevus on the right inner buttocks. The nevus disappears over time.
12.1 Halo Nevi
4 y WF.
Same child now age 12 y.

12.1 Halo Nevi 77
14 y WF what it looks like when mole goes away completely.
This young man presented with a medium congenital nevus on the left upper
posterior thigh. There were terminal hairs present in the lesion.
The hairs grew longer and darker over time.
This patient presented in infancy for evaluation of a small congenital nevus. It

remained remarkably stable over his youth.
12.1 Halo Nevi 79
This patient’s congenital nevus remained stable in size and shape over time but
had darkening of the pigment.
This patient’s medium congenital nevus had terminal hairs present as well as a
few erythematous and brown papules. It remained stable over time.
This patient has a medium to large congenital nevus on his right upper back. Per
the family, it has been growing with him. He is developing normally without any
seizures, headaches, or movement issues. He did have a biopsy performed that was
consistent with a congenital nevus. No further biopsies or imaging studies have
been performed.
This patient presented with a large congenital nevus on the upper back extending
into the scalp with variable colors and raised borders. The nevus also had dark hairs
within it.
12.1 Halo Nevi 81
This young man presented for continued surveillance of a giant congenital nevus.
He has been followed since birth now 26 y old.
He had 22 biopsies in the past that were all consistent with a congenital nevus;
however, he had one biopsy that resulted as “markedly atypical dermal melanocytic
proliferation, biologically indeterminant.” Due to this biopsy, the patient had the
lesion excised with appropriate margins.
This patient presented at birth with a giant congenital melanocytic nevus with
concomitant neurocutaneous melanosis.
Throughout his youth, he had approximately 12 lesions excised from the spinal
cord, which ultimately resulted in paraplegia. However, he has continued to grow
and develop normally without seizures or other neurologic deficits.
He has been treated with mekinist (trametnib) as well as oxybutynin but his dis-
ease as progressed rendering him unable to walk.
12.2 Congenital Nevus Photos
10 mon WF – note proliferative nodules.

12.2 Congenital Nevus Photos 83
3 week old WM.
16 week old WF.

10 y HM.
4 y WF scalp CNN Note thickened hair texture.

12.2 Congenital Nevus Photos 85
8 y WM Note advanced Pubic hair development.

12.3 Congenital Nevus
11week WF labial CNN.
26 w WM penile CNN.
12.3 Congenital Nevus 87
15 y BM face CNN. The light streaks are similar to halo phenomenon.
1y WM of age scalp and forehead nevus.
Same child age 2 y.

10 mon WF scalp CNN.
12.4 More CNN Congenital Nevi
1 week old WF.

12.4 More CNN Congenital Nevi 89
Same child 24 months old.
3 week old, this child gets an Mri to r/o Leptomeningeal melanocytosis.

1 month WM.
Same child 4 ½ years old.
6 week WF old amalgam of hemangioma and cnn.

12.5 More Congenital Nevi 91
12.5 More Congenital Nevi
4 ½ y WF CNN eyelid.
6 day old BM.
Same child now 37 months old.

10 day old WM.
Same child now 8 ½ y old.

Now 11 y old.
Now 17 y old.
18 y old.
12 y boy.
Same child now 16 y.
Same child now 20 y.

10 y WM scalp nevus.
1 day old WM.

12.6 Congenital Nevi Surgical Outcomes
Balloon expansion stage one.
3 y WM. Had nevus “removed” at age 6 weeks Shows marked nevus recurrens.

References 99
3 week old IF.
Same child now 3 y after surgery.
References
1. Lee MS, Jun HJ, Cho SH, Lee JD, Kim HS. Intense pulsed light alone and in combina-
tion with Erbium Yttrium-Aluminum-Garnet Laser on small-to-medium sized congenital
Melanocytic Nevi: single center experience based on retrospective chart review. Ann Dermatol.
2017;29(1):39–47.
2. Kinsler VA, O'Hare P, Bulstrode N, et al. Melanoma in congenital melanocytic naevi. Br J
Dermatol. 2017;176(5):1131–43.
Chapter 13
Brooke-Spiegler
Brooke-Spiegler syndrome refers to a syndromic presentation of benign adnexal

tumors such as cylindromas, eccrine spiradenomas, and trichepitheliomas [1].
Patients can also present with major and minor salivary gland tumors and rarely
with mammary cylindromas [2, 3]. The cause is a genetic mutation in the CYLD
gene, a tumor suppressor gene, and is inherited in an autosomal dominant fashion
with variable penetrance [1–3]. Patients commonly present with tumors during ado-
lescence but continue to develop lesions into adulthood [2, 3].
Patients should be considered for genetic testing if they (1) have multiple cylin-
dromas, spiradenomas, or trichoepitheliomas, (2) have a single lesion with an
affected first-degree family member or (3) have an asymptomatic family member
with a known mutation in the family.
Clinically, the tumors most commonly appear on the head and neck. In Brooke-
Spiegler syndrome, cylindromas are more common in women than in men (6-9:1)
[2]. Cylindromas occur most commonly on the scalp as asymptomatic, smooth pink
nodules. They can present as solitary lesions or in clusters. Spiradenomas, on the
other hand, tend to be tender dermal nodules often with a dark blue to black discol-
oration. Trichoepitheliomas tend to occur on the face with a concentration in the
nasolabial folds and the medial eyebrows.
Confirmation of these different appendageal tumors occurs via histopathology.
On histology, cylindromas present as well-circumscribed nests of monomorphic
blue cells in the dermis with an eosinophilic outline. The nodules are nested together
such that they resemble jigsaw puzzle pieces [2]. Spiradenomas present as well-
demarcated blue basaloid nests of cells in the dermis with intermixed paler cells and
lymphocytes. There may also be hyaline droplets present [3]. Trichoepitheliomas
present as cribiform basaloid cells with follicular papillae in the stroma, which rep-
resent the papillary mesenchymal bodies. There are also spindled fibroblasts present
[3]. Patients can have overlapping entities on histology, which more strongly sug-
gests that they may have a syndromic presentation.
Malignant transformation has been reported in 10–15% of patients [3]. As such,
clinical monitoring is paramount. As the tumors can be cosmetically disfiguring,

https://doi.org/10.1007/978-3-319-98101-7_13
102 13 Brooke-Spiegler
treatment is often requested. Lesions can be excised or treated with other destructive
methods such as cryosurgery or fractional ablative carbon dioxide laser. There is a
high recurrence rate of all types of tumors.
This patient has facial trichoepitheliomas as part of Brooke Spiegler syndrome.

Her father also has the same genetic syndrome.
She has continued to develop new lesions as well as enlarging older lesions. She
was treated with shave excision; however, many lesions recurred. Most recently, she
was treated with fractional carbon dioxide laser with good cosmetic results.
References
1. Dubois A, Wilson V, Bourn D, Rajan N. CYLD genetic testing for Brooke-Spiegler syndrome,
familial cylindromatosis and multiple familial trichoepitheliomas. PLoS Curr. 2015;7. pii:
ecurrents.eogt.45c4e63dd43d62e12228cc5264d6a0db. https://doi.org/10.1371/currents.eogt.4
5c4e63dd43d62e12228cc5264d6a0db.
2. Guardoli D, Argenziano G, Ponti G, et al. A novel CYLD germline mutation in Brooke-Spiegler
syndrome. J Eur Acad Dermatol Venereol. 2015;29(3):457–62.
3. Kazakov DV. Brooke-Spiegler syndrome and phenotypic variants: an update. Head Neck
Pathol. 2016;10(2):125–30.
Chapter 14
Epidermal Nevus
Epidermal nevi typically occur shortly after birth, usually within the first year of life
although some patients report occurrence later in life as they likely do not notice
small and flat lesions as early. It is estimated to occur in 1 in 1000 infants with both
genders equally affected. Epidermal nevi most commonly occur sporadically, how-
ever, they can also be inherited.
Epidermal nevi are hamartomas of the epidermis and papillary dermis as they
represent an overgrowth of this normally occurring tissue. It has been proposed that
they arise in a common progenitor cell in the epidermis during development.
Multiple mutations have been identified in epidermal nevi including KRT1, KRT 10,
ATP2A2, FGFR3, PIK3CA, HRAS and KRAS [1].
Clinically, patients commonly present with hyperkeratotic, hypo- or hyper-
pigmented plaques in a blaschkoid distribution. Lesions can sometimes be oriented
in a linear fashion. Over time, lesions may thicken and appear increasingly verru-
cous. Patients can also present with epidermal nevus syndromes, which involves
epidermal nevi in combination with neurologic or musculoskeletal anomalies.
On histology, epidermal nevi commonly demonstrate papillomatosis, acanthosis,
and hyperkeratosis. These are benign lesions and as such do not require treatment.
Lesions can be removed surgically but most also remove the papillary dermal com-
ponent or risk recurrence. Other therapies with mixed efficacy include retinoic acid,
corticosteroids, tar, anthralin, 5-fluorouracil, and podophyllin [2]. Treatment with
various ablative lasers can also aid cosmesis though it may lead to scarring.
Most EN are present at birth, but I have seen them come up as late as 18 years
of age. Early on the differential diagnosis is usually nevus sebaceous of
Jadassohn.

https://doi.org/10.1007/978-3-319-98101-7_14
104 14 Epidermal Nevus
Small ones can be left alone. If removal is needed the cream mixture of
Tretinoin and 5-FU does a reasonable job. Other treatments that have helped
me include: curretage, destructive lasers, topical acids, etc.
Large ones are very difficult because there is no quick treatment. Questions
regarding is the child avoiding school, bullying, depression etc. should be
asked.
Signs and symptoms of “Epidermal Nevus Syndrome” should be asked if the

nevus is extensive. Simple questions regarding the age of walking and talk-
ing, and of seizures or developmental delays exist are quick screens.
If my patient is a boy with a large epidermal nevus whose pathology shows

epidermolytic hyperkeratosis, what is the risk when he grows up and fathers a
child that the offspring will have total body epidermolytic hyperkeratosis ich-
thyosis? The answer depends on whether gonads are involved. If male, and we
can identify mutation in patient’s nevus, we can check sperm to see if that
mutation has been passed along.
If my patient is a girl - grows up and gets pregnant - what is the risk of total
body epidermolytic hyperkeratosis ichthyosis in her offspring? Again it
depends on whether her gonads are involved. However you can’t check her
eggs unless you pull them out in a petri dish. One could check embryos.
Does the risk have anything to do with the extent of the nevus? Probably. The
more widespread it is the earlier the mutation probably occurred, so it is more
likely to have contributed to the gonad.
Does the risk have anything to do with the location of the nevus on the child
(i.e. arm vs abdomen?) Unknown but probably not.
14 Epidermal Nevus 105
This patient has a linear epidermal nevus in the axilla.

He was treated with topical fluorouracil cream and electrodessication and curettage
with good results.
This patient has a linear epidermal nevus that has been present since birth in the
left arm. As she aged, she developed additional lesions on her central chest, lower
abdomen, and left axilla. She also has seizures, indicating an “epidermal nevus
syndrome”.
This patient has a linear epidermal nevus on the right chest extending into the
right axillary vault. It has been present since birth. No neurologic issues.
Trial of laser vaporization with reasonable results.

14.1 Total Body Linear Epidermal Nevus 107
14.1 Total Body Linear Epidermal Nevus
15 y. Note lines of Blaschko.

LEN 15 y old continued.
42 y BF life long L.E.N.

References 109
Linear Epidermal Nevus- 8 month old wm.
References
1. Asch S, Sugarman JL. Epidermal nevus syndromes: new insights into whorls and swirls.
Pediatr Dermatol. 2018;35(1):21–9. https://doi.org/10.1111/pde.13273. Epub 2017 Oct 16.
Review. PMID: 29044700.
2. Kim JJ, Chang MW, Shwayder T. Topical tretinoin and 5-fluorouracil in the treatment of linear
verrucous epidermal nevus. J Am Acad Derm. 2000;43(1Pt 1):129.
Chapter 15
Basal Cell Nevus Syndrome
Basal Cell Nevus Syndrome (BCNS) (also known as Gorlin Syndrome) is a rare
autosomal dominant disorder associated with basal cell skin cancers and other fea-
tures. The incidence of BCNS reportedly varies from 1 in 57,000 to 1 in 256,000
[1]. The mutation associated with BCNS is in the PTCH1 gene, a tumor suppressor
gene, which plays an important role during embryogenesis affecting cell prolifera-
tion, differentiation and cell fate. PTCH mutations have high penetrance but vari-
able phenotypic expression [1, 2].
Basal cell carcinomas may occur as early as 3–4 years of age but the average age
of presentation is 25 years old [1]. Dermoscopy can be helpful in the identification
of BCCs in these patients [3]. Palmoplantar pits are a unique clinical finding with
BCNS. They occur in up to 80% of patients by 15 years of age with the palms more
often affected than soles [1]. Multiple odontogenic keratocysts are a specific sign of
BCNS with 90% of BCNS patients affected. These can be identified clinically but
also as lytic bone lesions on radiographic imaging [1]. Other anomalies may include
skeletal abnormalities, craniofacial dysmorphism, and macrocephaly. Calcification
of the falx cerebri may occur and medulloblastoma, meningiomas, ovarian fibro-
mas, ovarian cancer and cardiac fibromas are among various tumors associated with
BCNS.
The diagnostic criteria for BCNS includes both major and minor criterion. Patients
must meet two major and one minor criterion or one major and three minor criterion.
The major criteria include at least five BCCs or one BCC before age 30, odontogenic
keratocysts, greater than 2 palmoplantar pits, lamellar calcification of the falx cere-
bri, or a first degree relative with BCNS. The minor criteria include macrocephaly,
congenital malformations (i.e. cleft lip/palate, frontal bossing, coarse facies, hyper-
telorism), polydactyly, radiologic vertebral or rib anomalies (i.e. bifid, splayed or
extra ribs), ovarian or cardiac fibroma, medulloblastoma, ocular anomalies (i.e. cata-
ract, coloboma, microphthalmia) or lymphomesenteric or pleural cysts [1].
The work-up of these patients begins with the clinical examination. Patients
should also be referred for radiographic imaging. There are molecular tests for
BCNS; however, only a limited number of mutations can be identified.

https://doi.org/10.1007/978-3-319-98101-7_15
112 15 Basal Cell Nevus Syndrome
Evaluation and treatment of patients with BCNS should utilize a multidisci-

plinary approach. Close clinical monitoring for the development of BCCs is very
important. In prepubescent children, the BCCs tend to follow a benign course,
whereas aggressive treatment is indicated in adulthood. Many of these patients have
innumerable lesions and excision and Mohs may be difficult. Photodynamic therapy
(PDT) could be considered for larger affected areas. PDT has also been hypothe-
sized to have a chemoprotective effect [1]. Other treatments for BCC include
destruction via ablative laser, pulsed dye laser, cryotherapy, topical 5- fluorouracil,
or topical imiquimod [1, 3]. Furthermore, systemic mediations which inhibit the
sonic the hedgehog pathway may be utilized [1, 4]. Overall, BCNS has a good prog-
nosis with low metastatic potential for BCC and medulloblastomas.
In the first two decades of life the BCNS children get tiny skin tag like growths
in the intertriginous areas, the neck and armpits especially. Diagnosis of BCC
made by snipping one of these off. In subtle cases the diagnosis is made by
putting together the history of dental jaw cysts, or bifid ribs and seeing these
little skin tags. I have had disappointing results using topical treatments for
the BCC. I usually bring the kids in twice a year to remove these grows under
local anesthesia. Do not forget to get the neurologist involved, you do not
want to miss brain cancer.
This young patient presented in early childhood for his condition. He had a his-
tory of a cleft lip and palate surgically repaired and rhinoplasty for re-revision. He
also had a bone graft for lost teeth. He does have difficulties with speech.
References 113
He has had excision of 8 basal cell carcinomas that present as flesh colored
pedunculated papules. He has also been treated with 5% imiquimod cream nightly.
He wears photoprotection.
References
1. Lam C, JC O, Billingsley EM. “PTCH”-ing it together: a basal cell nevus syndrome review.
Dermatol Surg. 2013;39(11):1557–72.
2. Coulombe C, Gagnon LP, Larouche V, Dionne MC. Infantile-onset palmo-plantar basal cell
carcinomas and pits in Gorlin syndrome. JAAD Case Rep. 2018;4(7):662–4. https://doi.
org/10.1016/j.jdcr.2018.06.017.
3. Sorensen A, Wolter S, Patel N, Hansen R, Price H. Dermoscopy for identification of basal
cell carcinomas in basal cell nevus syndrome during carbon dioxide laser surgery. Pediatr
Dermatol. 2016;33(1):109–11.
4. Tang JY, Ally MS, Chanana AM, et al. Inhibition of the hedgehog pathway in patients with
basal-cell nevus syndrome: final results from the multicentre, randomised, double-blind, pla-
cebo-controlled, phase 2 trial. Lancet Oncol. 2016;17(12):1720–31.
Chapter 16
Mastocytoma
Mastocytosis represents a spectrum of disease presentations. In pediatric patients,

this broad category includes solitary mastocytomas, diffuse cutaneous mastocyto-
sis, and urticaria pigmentosa [1, 2]. Presentation before puberty defines childhood
mastocytosis. The majority of pediatric patients present with mastocytosis by
2 years of age. Both genders are affected equally. Mastocytosis is a disorder of mast
cells leading to increased histamine release. Many pediatric cases of mastocytosis
have a mutation in the c-KIT gene, which when activated promotes cell growth and
survival [1].
Solitary mastocytomas appears as a solitary tan/brown macule or papule.
Mastocytomas have a predilection for the lower extremities. When there are multi-
ple tan/brown macules, the diagnosis is more consistent with urticaria pigmentosa
[1, 2]. Lesions commonly present during early childhood on the trunk. Lesions may
urticate with heat such as in a warm bath or friction. In clinic, rubbing a lesion with
a blunt object to induce urtication is known as Darier’s sign.
The clinical features of mastocytosis directly reflect the results of histamine
release. Patients can present with pruritus, flushing, abdominal pain, diarrhea, pal-
pitations, dizziness, and syncope. Patients with extra-cutaneous disease may also
present with symptoms such as fever, night sweats, malaise, weight loss, bone pain,
abdominal pain and difficulty with mentation. Fortunately, deaths are rare. Given
that the disease is mediated by histamine release, factors such as alcohol, narcotics,
salicylates, non-steroid anti-inflammatory medications, polymyxin B and anticho-
linergic medications may exacerbate symptoms [1].
Patients may have spontaneous resolution of their disease but this does not com-
monly occur before adolescence [2]. Treatment is predominantly symptomatic.
Patients should attempt to avoid mast cell degranulators and any known triggers.
Patients can obtain symptomatic relief of specific cutaneous lesions with topical or
intralesional corticosteroids [3]. Systemic agents can be used if necessary for wide-
spread cutaneous flares or for systemic symptoms with oral antihistamines, cromo-
lyn sodium, corticosteroids, and phototherapy. Those patients with severe disease
may consider interferon-α-2b, cladribine, or imatinib mesylate (a KIT inhibitor).

https://doi.org/10.1007/978-3-319-98101-7_16
116 16 Mastocytoma
This patient presented in early childhood with urticaria pigmentosa. Fortunately, he

did not have systemic involvement.
28 week old widespread U.P. and marked Darrier’s sign.
Same child 4 y later.

16.1 Urticaria Pigmentosa 117
This patient also presented as a toddler for urticaria pigmentosa. Again, fortunately
for her, she did not have systemic involvement.
She was treated with topical corticosteroids and oral antihistamines.
16.1 Urticaria Pigmentosa
11 week WM Marked Darrier Sign.

118 16 Mastocytoma
16 week WM widespread U.P.
7w WM solitary bullous lesion left flank.

12 weeks now – treated with topical steroids an oral antihistamines.
5 y WF unusal plaque type U.P.

120 16 Mastocytoma
5 y WM widespread U.P.
122 16 Mastocytoma
References
1. Meni C, Bruneau J, Georgin-Lavialle S, Le Sache de Peufeilhoux L, Damaj G, Hadj-Rabia S,

Fraitag S, Dubreuil P, Hermine O, Bodemer C. Paediatric mastocytosis: a systematic review of
1747 cases. Br J Dermatol. 2015;172(3):642–51; PMID: 25662299.
2. Heinze A, Kuemmet TJ, Chiu YE, Galbraith SS. Longitudinal Study of Pediatric Urticaria
Pigmentosa. Pediatr Dermatol. 2017;34(2):144–9.
3. Patrizi A, Tabanelli M, Neri I, Virdi A. Topical corticosteroids versus “wait and see” in the
management of solitary mastocytoma in pediatric patients: a long-term follow-up. Dermatol
Ther. 2015;28(2):57–61.
Part VI
Vascular Disorders of Infancy and
Childhood
Chapter 17
Infantile Hemangiomas
Infantile hemangiomas (IH) represent the most common soft tissue tumor of infancy.
These neoplasms are more common in females (2–5:1) and affect 4–5% of infants
[1]. Risk factors for the development of IH include premature or low-birth weight
infants, mothers who underwent chorionic villus sampling, or multiple gestation
infants [1].
IH is a benign neoplasm of the vascular endothelial cells. The pathogenesis is
still being elucidated. Several somatic mutations in these cell populations have been
identified including those in vascular endothelial growth factor (VEGF) as well as
other pathways that regulate vascular proliferation [1]. Hypoxia is thought to be a
contributor to IH development particularly given the higher risk of IH development
in low-birth weight babies. Hypoxia leads to the upregulation of GLUT1 and VEGF
allowing for proliferation of progenitor endothelial cells [1].
Clinically, lesions follow a relatively predictable course with an initial prolifera-
tive phase over several months followed by stabilization then gradual involution
over years. At birth, IH are generally not present but precursor lesions including
telangiectasias, pallor or bruise like lesions may occur. IH then proliferate in the
first days to months postnatally. Hemangiomas can be defined as both superficial,
deep and mixed with superficial hemangiomas comprising the majority of cases [1].
More superficial lesions appear brighter red and can appear finely lobulated. Larger
segmental hemangiomas also appear red in color and over time develop into a
plaque with papules on the surface. Deep hemangiomas are difficult to visualize at
first but eventually develop an ill-defined deep blue color without overlying skin
changes [1]. Mixed hemangiomas will have superficial red discoloration overlying
a background of blue.
While the vast majority of IH follow a benign course toward involution, there are
a few notable concerns. Up to 10% of IH can ulcerate, which is the most common
complication noted with hemangiomas. IH located near mucosa (i.e. the lips or
anogenital) and larger lesions have the highest risk for ulceration. Additionally,
periocular and large lesions over the ear can have functional consequences. Lesions
over the tip of the nose, cartilaginous ear, lips, nipple can particularly be concerning

https://doi.org/10.1007/978-3-319-98101-7_17
126 17 Infantile Hemangiomas
in terms of the normal development of these sites as permanent destruction can

occur.4 Furthermore, those involving the parotid gland can also be slow to improve.
Additionally, lesions in a beard distribution on the face or neck place patients at risk
for airway involvement and otolaryngology evaluation may be required. Patients
with 6 or more IH should have abdominal ultrasound to evaluate for liver involve-
ment, which is often benign and may not require intervention.
There are several syndromes to consider that include infantile hemangiomas.
These are considered when IH present with a segmental sub-type and occur at cer-
tain anatomical sites such as over a large area on the face or over the lumbosacral
region. Segmental IH on the face could be concerning for PHACE(S) Syndrome,
which represents a collection of findings. P: posterior fossa and other structural
brain malformations; H: hemangioma; A: arterial anomalies of cervical and cerebral
vessels; C: cardiac defects (i.e. coarctation of the aorta); E: eye anomalies [1]. Some
add an “S” for sternal abnormalities. Large segmental lesions on the lower body,
particularly over the lumbosacral area, can represent a similar syndrome named
LUMBAR. L: lumbosacral hemangioma and lipomas or other cutaneous anomalies,
U: urogenital anomalies and ulceration; M: myelopathy (spinal dysraphism); B:
bony deformities; A: anorectal and arterial anomalies; R: renal anomalies [1].
The histology of these lesions varies depending on the whether the lesion is in
the proliferative versus the involuting phase. While proliferating, there is evidence
of endothelial cell hyperplasia, mast cells, and a prominent basement membrane
around lobules. During the involuting phase, fibrofatty tissue becomes present in the
lesion with decreasing numbers of mast cells. The lesions are GLUT1 position with
immunohistochemical staining, which helps differentiate IH from other vascular
malformations [1].
IH can begin to involute over the first year of life and continue for several years
thereafter with 90% of hemangiomas resolved by 9 years of age. Involuted IH may
heal without residual defects in the skin or patients may have atrophic, fibrofatty or
telangiectatic lesions. Treatments for IH should be tailored to the patient and the
phenotype of the IH with consideration for the family’s wishes. Most lesions require
minimal to no interventions but others will require treatment, even a multidisci-
plinary approach to management. Highest consideration for treatment should be
considered for those at risk for functional impairment as well as those with concern
for permanent cosmetic deformity. The mainstay of topical and oral treatment is
with beta-blockers. Other treatments include topical, intralesional, or systemic cor-
ticosteroids, topical imiquimod, vascular laser, or surgical excision [1–3].
The discovery of oral propranolol has really revolutionized my treatment of

infantile hemangiomas. It has markedly reduced the number of children with
ulcerating, obstructing, and destructive hemangiomas. The tipping point to
start oral propranolol is an amalgam of how comfortable the parents are, the
physician is with an oral medicine, combined with, the location of the
17 Infantile Hemangiomas 127
hemangioma, the size, and whether it is breaking open and causing problems.
Ones that are blocking the eyes, nose, on the lips, genitals, anus tend to get
propranolol right away. Ditto ones that are breaking down and bleeding. I do
not hospitalize infants to start propranolol. I do not contact cardiology. If the
child is very small and less than 6 weeks old I will give the first dose in the
clinic and monitor vitals for 30–60 minutes after the dose. That is all.
Wedge shaped hemangiomas of the head, and irregular reticulated hemangio-

mas of the pelvis region both get imaged to rule out PHACE or PELVIS syn-
drome respectively.
Hemangiomas involving the temples, jaw line and anterior neck should be
evaluated by ENT to rule out “beard” syndrome. The risk is the trachea being
occluded by the growing hemangioma.
This patient presented with a hemangioma of her right calf. Over time, the lesion
involuted and became atrophic but does cause her discomfort. She did have imaging
performed that did not show a deep component.
Same child age 10y.

She did not receive any treatment for her hemangioma aside from compression.
She presented in infancy for multiple hemangiomas on the eyelids, eyebrows,

forehead, left ear, chest and back.
Over her childhood, the hemangiomas receded; however, she does have a slight
ptosis in her left eyelid.
The left side of her face was treated with cryotherapy and the right side with
vascular laser with good success.
As part of PHACE syndrome, the patient also has an aberrant right subclavian
artery and intra cardiac holes (that self-resolved). Additionally, she is missing a seg-
ment of the anterior communicating artery and has an aberrant circle of Willis.
Hemangioma treated with occlusion only (before propranolol).
Back hemangioma - 3 month old.

4 month old.
7 mon old.
12 month old.
4 years old.
10 years old.
PELVIS Syndrome Child with Hemangioma, Lipomyelomeningocoele, bifid
scrotum, ambiguous genitalia, hypospadias, tethered cord.
17 weeks.
PELVIS Syndrome – Now 1 y old. Porpranolol for 11 months orally and surgical
repairs of scrotum and cord.
17.1 Hemangomas – Surgical Repair
2 ½ y BM large globella hemangioma.
3 y now – 2 months after surgery.

References 135
References
1. Bolognia J, Jorizzo J, Schaffer J. Dermatology. 3rd ed. Elsevier; 2012.

2. Chinnadurai S, Sathe NA, Surawicz T. Laser treatment of infantile hemangioma: a systematic
review. Lasers Surg Med. 2016;48(3):221–33.
3. Janmohamed SR, van Oosterhout M, de Laat PC, van Rosmalen J, Madern GC, Oranje
AP. Scoring the therapeutic effects of oral propranolol for infantile hemangioma: a prospective
study comparing the Hemangioma Activity Score (HAS) with the Hemangioma Severity Scale
(HSS). J Am Acad Dermatol. 2015;73(2):258–263. Jahnke MN. Vascular Lesions. Pediatr
Ann. 2016;45(8):e299–305.
Chapter 18
Glomus Tumor
A glomus tumor is a benign neoplasm composed of glomus cells. Glomus tumors

are subdivided into two main categories including glomus tumors and glomuvenous
malformations (also known as glomangiomas) [1].
Glomus tumors present most commonly in adolescence as solitary painful pap-
ules typically located on extremities with a predilection for the subungual location.
Many are small (<2 mm) and have a blue-red appearance. Both genders are affected
equally, however, women have a stronger preponderance of subungual lesions. On
histology, the lesion is composed of monomorphic glomus cells associated with
vascular proliferation [1].
Glomangiomas present at a younger age than glomus tumors, usually in infancy
or early childhood, with multiple asymptomatic lesions. The papules are often blue
in appearance and may be clustered together. They may become darker blue over
time. These represent a smaller proportion of glomus tumors overall. Although
these lesions are less tender than glomus tumors, they may become tender with
palpation or with menstruation and pregnancy. Most cases are sporadic, however,
familial cases have been reported with a loss-of-function mutation in the glomulin
gene (GLMN). On histology, these lesions resemble a venous malformation lined by
glomus cells [1].
Most cases are benign. Treatments are directed predominantly toward symptom-
atic relief and cosmesis. For solitary lesions, surgical excision is a viable option.
Other treatment options include electrodessication, sclerotherapy, and laser surgery
[2]. Recurrence is a concern with any residual untreated lesions [1].

https://doi.org/10.1007/978-3-319-98101-7_18
138 18 Glomus Tumor
This patient presented as a teenager for painful glomangiomas on her left flank.
She received a trial therapy of sodium tetradecyl sulfate sclerotherapy but it is

unclear if this helps. She is planning to try pulsed dye laser next.
References
1. Bolognia J, Jorizzo J, Schaffer J. Dermatology. 3rd ed. London/New York: Elsevier; 2012.
2. Trost J, Buckley C, Smidt AC. Long-pulsed Neodymium-doped Yttrium Aluminum Garnet
laser for Glomuvenous malformations in adolescents. Pediatr Dermatol. 2015;32(5):e217–8.
Chapter 19
Phakomatosis
Phakomatosis Pigmentovascularis describes a group of rare sporadic genodermato-

ses that have cutaneous, neurovascular, and ophthalmological abnormalities. All
five subtypes have variable combinations of vascular and pigmentary lesions. The
first subtype is phakomatosis Ia/b which makes up a minority of cases. It is charac-
terized by an epidermal nevus presenting with a nevus flammeus. Type IIa/b phako-
matosis (also known as phakomatosis cesioflammea), the most common type,
demonstrates dermal melanocytosis and a nevus flammeus. Patients can also present
with nevus anemicus, hypotrichosis, lipohypoplasia and hypoplastic nails. The third
type is III a/b (or phakomatosis spilorosea), which includes a macular nevus spilus
in combination with a nevus flammeus. Similarly, patients can also present with
nevus anemicus and hypotrichosis as well as lymphedema. Type IVa/b (phakomato-
sis pigmentovascularis, unclassifiable) presents with a nevus flammeus, hypermela-
nosis, and a nevus spilus in addition to nevus anemicus, nevoid hyper- or
hypopigmentation and nevus sebaceous. Lastly, type V a/b (phakomatosis cesio-
marmorata) combines dermal melanocytosis with cutis marmorata telangiectatica
congenita [1, 2].
Patients with phakomatoses can have extracutaneous manifestations. Some can
be concerning such as scleral or intraocular melanocytosis, glaucoma or intracranial
abnormalities that can represent a nidus for seizures. Some patients have presented
with overgrowth phenotypes. Most concerning is that patients have presented with
concomitant melanoma [1, 3].
Although the pathogenesis of phakomatoses is not completely clear, recent
research has demonstrated certain genetic mutations. Mutations in GNAQ and
GNA11 were identified in the pigmentary or vascular lesions in patients with phako-
matoses but were not present in the blood. This finding suggests that these muta-
tions may be post-zygotic [3].
Given the large degree and potential severity of extra-cutaneous manifestations.
These patients should have a multidisciplinary approach that includes radiographic
imaging, ophthalmology and neurology to evaluate for concomitant findings [2].

https://doi.org/10.1007/978-3-319-98101-7_19
140 19 Phakomatosis
She presented with phakomatosis pigmentokeratotica in association with nevus

sebaceous, epidermal nevi, nevus spilus, and spitz nevi.
The lesion in the left ear pinna and lobe had a velvet appearance that was bother-
some to the patient. She was treated with a fractional carbon dioxide laser.
References 141
References
1. Bolognia J, Jorizzo J, Schaffer J. Dermatology. 3rd ed. London/New York: Elsevier; 2012.
2. Al Robaee A, Banka N, Alfadley A. Phakomatosis pigmentovascularis type IIb associated with
Sturge-weber syndrome. Pediatr Dermatol. 2004;21(6):642–5.
3. Thomas AC, Zeng Z, Riviere JB, et al. Mosaic activating mutations in GNA11 and GNAQ
are associated with Phakomatosis Pigmentovascularis and extensive dermal melanocytosis.
J Invest Dermatol. 2016;136(4):770–8.
Chapter 20
Vascular Malformations
Vascular malformations (VM) include capillary, venous, arteriovenous, lymphatic

and combined malformations. These lesions represent errors in vascular morpho-
genesis. Both genders are equally affected. They differ from hemangiomas in that
these lesions are usually present at birth, present throughout life, and are GLUT1
negative on histology. Because these lesions persist over the life of the patient, it is
important to identify the type of lesion to help guide management.
Various imaging studies can help differentiate the types of vascular malforma-
tions. Arteriography is helpful in diagnosis an arteriovenous malformation.
Ultrasound, computed tomography and magnetic resonance imaging can help iden-
tify lymphatic, venous, and arteriovenous malformations. Capillary malformations
can be challenging to identify with imaging. Vascular malformations are exceed-
ingly difficult to manage but a multidisciplinary approach is critical to optimize
patient care.
Often making the diagnosis of VM versus an hemangioma can be difficult

early on. Hemangiomas usually show up in the first month. VM are present
right at birth but may be subtle. They grow slowly with age. Radiology exami-
nation is often not of help because most radiologists call everything an “hem-
angioma” and fail to or unable to distinguish VM from hemangiomas. It takes
a well-trained radiologist who has had exposure to multiple VM to make the
distinction.
Having a good vascular anomalies team is a boon to managing these difficult

cases. Interventional radiologists are the key members of these teams.

https://doi.org/10.1007/978-3-319-98101-7_20
144 20 Vascular Malformations
6 month WF with capillary malformation and limb size descrepancy.

20 Vascular Malformations 145
6 y BM with large venous abnormality of the leg.

146 20 Vascular Malformations
20y WM with large venous malformation of the arm.

20 Vascular Malformations 147
24 y WF large mixed arterio-venous malformation of the chest and neck that

included mediastinal structures and enlarged tongue.
Chapter 21
Capillary Malformations
Capillary malformations represent the most common type of vascular malforma-

tion. These malformations can be inherited or sporadic. There are various types of
capillary malformations including ataxia telangiectasia, capillary malformation –
arteriovenous malformation, cerebral capillary malformations, hereditary hemor-
rhagic telangiectasia (Osler-Weber-Rendu) and juvenile polyposis with hereditary
hemorrhagic telangiectasia [1]. When inherited, each of these presentations can
have different genetic mutations.
The two main types of capillary malformations include port-wine stains (PWS)
and telangiectasias. As a generality, capillary malformations tend to be red and mac-
ular during infancy. A PWS is often present at birth as well-circumscribed ery-
thematous macules and/or patches. These lesions grow as the child develops. When
a PWS occurs on the face, it commonly follows the distribution of the trigeminal
nerve: V1 (ophthalmic), V2 (maxillary) or V3 (mandibular). As the child ages, the
PWS often becomes darker in color – even approaching purple – and can have tex-
tural changes as well including thickening and nodularity.
Patients can have genetic syndromes associated with capillary malformations
including Sturge-Weber, Klippel-Trenaunay, Proteus, CLOVES (congenital lipoma-
tous (fatty) overgrowth, vascular malformations, epidermal nevi and scoliosis/skel-
etal/spinal anomalies), CLAPO (capillary malformation of the lower lip, lymphatic
malformation of the face and neck, asymmetry and partial/generalized overgrowth)
and macrocephaly-capillary malformation.
Telangiectasias are dilated capillary blood vessels in the upper dermis that pres-
ent as red lesions at various anatomic sites. Similar to PWS, telangiectasias can be
associated with syndromes such as cutis marmorata telangiectatica congenital,
hereditary hemorrhagic telangiectasia, and ataxia-telangiectasia.

https://doi.org/10.1007/978-3-319-98101-7_21
150 21 Capillary Malformations
15y WF with Ataxia Telangiectasia. Prominent enlarged telangiectasias of the ear

pinnae and sclera can be a key to making this diagnosis.
Six week old WF with CMTC.

21 Capillary Malformations 151
Seven week old WM with CMTC.
Discoloration from capillary malformations can be treated with laser interven-

tions especially the pulsed dye laser (PDL). PDL helps predominantly with cosme-
sis by improving the color and preventing textural changes to PWS. It is important
to note that PWS on the central face and distal limbs do not tend to response to
treatment as well as other anatomic locations. For syndromic cases, a multidisci-
plinary approach to management is paramount. PEARLS: Capillary malformations
are a very broad range of diagnoses. The diagnosis is a combination of: pattern
recognition at birth and as the mark grows together with MRI and X-ray results.
More and more genetic testing helps us narrow the differential. Simple stains can be
lasered to reduce the redness. I laser treat them starting a few months of age using
swaddling and topical numbing creams. We use oral tylenol, ice packs before and
after plus sucrose to suck on. Lastly I laser quickly and efficiently. The larger spot
sizes help cover more realestate quickly.
152 21 Capillary Malformations
Four year old WM Port Wine Stain of the face. He was treated with candela pulsed
dye laser.
Five week old segmental PWS leg.

Reference 153
Six year old WF PWS shin.
Reference
1. Rozas-Muñoz E, Frieden IJ, Roé E, Puig L, Baselga E. Vascular stains: proposal for a clinical
classification to improve diagnosis and management. Pediatr Dermatol. 2016;33(6):570–84.
PMID: 27456075.
Chapter 22
Venous Malformations
There are various types of venous malformations including cutaneous and mucosal
venous malformations and glomuvenous malformations (glomangiomas, as dis-
cussed previously). Clinically, venous malformations present with a dark blue hue
representing the venules in the dermis. The lesions tend to be soft, freely compress-
ible, and may increase in size and darken in color with dependency [1]. The best
imaging modality to identify a venous malformation is a T2-weighted MRI, which
can help guide the remainder of the treatment based on anatomic location and depth
and extent of the lesion [2].
Cephalic venous malformations may lead to overgrowth of various facial fea-
tures or of the cranium. Patients with lesions on the head and neck should have
evaluation for parapharyngeal and laryngeal involvement to avoid any life-
threatening complications. Venous malformations on the trunk and extremities may
similarly lead to overgrowth of various anatomic areas (i.e. limb overgrowth). These
can be cosmetically and functionally debilitating lesions. Additionally, lesions on
the trunk and extremities can extend deep into the muscles and skeletal system.
Patients with venous malformations may have a genetic syndrome and thus
should be evaluated as such. Examples include familial cutaneous and mucosal
venous malformation, blue rubber bleb nevus syndrome, glomuvenous malforma-
tion, or Maffucci syndrome.
The management of patients with vascular malformations should have a multi-
disciplinary approach. Patients may need to avoid trauma to the areas such as
through aggressive sports. Certain lesions may be amenable to treatment with
sclerotherapy [3]. Other treatments to consider include surgical excision or laser
surgery.

https://doi.org/10.1007/978-3-319-98101-7_22
156 22 Venous Malformations
This patient presented at 4 months of life with a lesion on her tongue.
She has had two treatments with sclerosants performed by interventional radiology
unfortunately the lesion recurred.
22 Venous Malformations 157
This patient presented with a venous malformation on the left flank. He had mag-
netic resonance imaging showing involvement of chest wall structures
This young boy presented with a right sided venous malformation that was con-
firmed with MRI.
22 Venous Malformations 159
He was advised to use compression garments; however, the child complained of

discomfort with the therapy.
At birth, this infant was unable to open her right eye preciptating imaging stud-
ies, which confirmed a vascular malformation.
She was treated with propranolol for a year without improvement.

She had a partial excision of the lesion during childhood.
MRI from several years later demonstrated a large vascular malformation thought to
be a veno-lymphatic entity extending from the eye to the masseter muscles of the
cheek.
References
1. Boon LM, Mulliken JB, Enjolras O, Vikkula M. Glomuvenous malformation (glomangioma)

and venous malformation. Arch Dermatol. 2004;140(8):971–6.
2. Rozas-Munoz E, Frieden IJ, Roe E, Puig L, Baselga E. Vascular stains: proposal for a clinical
classification to improve diagnosis and management. Pediatr Dermatol. 2016;33(6):570–84;
PMID: 27456075.
3. Ali S, Mitchell S. Outcomes of venous malformation sclerotherapy: a review of study method-
ology and long-term results. Semin Interv Radiol. 2017;34(03):288–93.
Chapter 23
Macrocystic Lymphatic Malformations
Macrocystic lymphatic malformation represents a type of lymphatic vascular mal-

formation. There are many subtypes of lymphatic vascular malformations including
familial congenital lymphedema (Milroy disease), lymphedema-distichiasis syn-
drome, hypotrichosis-lymphedema-telangiectasia, Hennekam lymphangiectasia-
lymphedema syndrome, hereditary lymphedema, and lymphedema-choanal
atresia [1].
Macrocystic lymphatic malformations most commonly occur on the neck, axilla
and lateral chest wall. Clinically, they resemble large subcutaneous masses without
overlying epidermal change. These lesions occur in utero and can sometimes be
diagnosed through fetal ultrasound monitoring. Additional imaging studies such as
ultrasound, CT or MRI may be useful in diagnosis as can aspiration of the fluid with
cytology studies. Histologically, they present as a large group of lymphatic channels
lined by a thin endothelium.
Macrocystic lymphatic malformation are associated with several genetic disor-
ders including Down, Turner and Noonan syndromes. Treatment of macrocystic
lymphatic malformations is best with sclerotherapy and lesions with few larger cys-
tic spaces appear to respond the best. Other options include surgical excision. There
are high rates of recurrence.

https://doi.org/10.1007/978-3-319-98101-7_23
162 23 Macrocystic Lymphatic Malformations
The patient presented as a toddler with a cystic hygroma. It was treated with drain-
age and absolute alcohol to induce sclerosis; however, it recurred approximately 7
years later.
Patient now 21 y old

Reference 163
Cystic hygroma
21 month old
Reference
1. Damaskos C, Garmpis N, Manousi M, et al. Cystic hygroma of the neck: single center experi-
ence and literature review. Eur Rev Med Pharmacol Sci. 2017;21(21):4918–23.
Chapter 24
Microcystic Lymphatic Malformation
Microcystic lymphatic malformation (also known as lymphangioma circumscrip-

tum) presents as a collection of poorly defined, small lymphatic channels that appear
as clear or hemorrhagic vesicles. Lymphangioma circumscriptum can evolve over
time with various distributions and colors of the vesicles. The lesions can present
clinically anywhere on the body but have a predilection for the proximal limbs,
chest, and the mouth. Bleeding and crusting of the lesions can complicate the
course. Rarely, infection may occur.
Small lesions are best treated with surgical excision; however, the lesions are
often larger than anticipated during surgical planning, which can lead to incomplete
excisions and recurrence around the scar. Other treatment options include laser ther-
apy, radiofrequency ablation, cryosurgery or sclerotherapy [1, 2].
The microcystic type has a very distinctive frogs eggs on the surface.
Treatment is very difficult. Surgical excision leads to near 100% recurrence in
my experience. Topical rapamycin (a.k.a. Sirolimus) has had some interesting
reports that it may help. Case reports with various destructive and fraxel lasers
are also intriguing. Don’t let the surgeons cut these patients!

https://doi.org/10.1007/978-3-319-98101-7_24
166 24 Microcystic Lymphatic Malformation
This patient presented with lympangioma circumscriptum without any sign of

infection.
She was treated with 5% imiquimod cream three times weekly with minimal results.
Lymphangiomas
12 y WM Lymphangioma of penis
24 Microcystic Lymphatic Malformation 167
Dermoscopy of the lesion

Lymphangiomas
6 y WF calf
6 ½ y right breast
Lymphangiomas
7 y WF note clear fluid filled vesicles

Lymphangiomas and recurrence after surgery
12 y WM. Had been surgically removed age 6, skin grafted. Now all recurred. Not
an uncommon sight in my clinic.
Lymphangioma recurrences after surgery
14 BM removed age 5 now returned

16 y WF removed age 1y.

Lymphangiomas recurring after surgery
4y WM removed aged 2.
This 4 month BF had an enormous macro cystic lymphangioma of her left leg it lead
to her untimely death due to hemodynamic issues.
References
1. Sun RW, Tuchin VV, Zharov VP, Galanzha EI, Richter GT. Current status, pitfalls and
future directions in the diagnosis and therapy of lymphatic malformation. J Biophotonics.
2018;11(8):e201700124. https://doi.org/10.1002/jbio.201700124. Epub 2017 Nov 5. Review.
PMID: 28851128.
2. Patel GA, Schwartz RA. Cutaneous lymphangioma circumscriptum: frog spawn on the skin.
Int J Dermatol. 2009;48(12):1290–5.
Part VII
Bullous Disorders of Childhood
Chapter 25
Epidermolysis Bullosa Simplex
Epidermolysis bullosa simplex (EBS) is a mechanobullous disorder where the skin

fragility affects the epidermis. There are both basal and suprabasal subtypes depend-
ing on where the blister occurs. It is inherited predominantly in an autosomal domi-
nant fashion. Multiple genes have been implicated in EBS including PKP-1 and
DSP for suprabasilar lesions and KRT5, KRT14, PLEC1, ITGA6, ITGB4, and DST
for basilar lesions. These gene mutations correlate to proteins such as plakophilin-1,
desmoplakin, keratin-5, keratin-14, plectin, alpha-6 beta-4 integrin, and dystonin,
respectively [1].
The localized phenotype, called EBS-localized (previously called EBS, Weber-
Cockayne) presents in childhood with blisters in areas of trauma. This subtype of
EBS rarely leads to scarring. It is the most common presentation of EBS. EBS-
Dowling Meara is a subtype that presents with a herpetiform orientation of vesicles
that often leads to scars [1]. Patients with EBS tend to have a normal life span.
Patients must avoid triggers for their blisters as best they can and have good wound
care when lesions develop. A few rarer subtypes of EBS have less favorable prog-
noses such as EBS with pyloric atresia or EBS with muscular dystrophy [1]. EBS
with mottled pigmentation is a rare subtype of EBS. Patients often present with EBS
that ultimately heals with dyspigmentation as well as photosensitivity and dental
issues. Blisters develop during infancy and decrease as the child ages whereas the
reticulated dyspigmentation develops later in childhood and tends to persist [2].
Neonates presenting with blistering has a short differential. However I have

been humbled trying to predict which type of EB will come of these neonates.
I used to wait until they “declared” their phenotype – often a year. Nowadays
genetic testing makes this journey a lot quicker. I have seen severe simplex
and mild junctional types. Dystrophic types present the greatest challenges.
Multi-disciplinary clinics are helpful. In recessive dystrophic variants death
from squamous cell carcinoma creeps up on them in the 20–30 s.

https://doi.org/10.1007/978-3-319-98101-7_25
176 25 Epidermolysis Bullosa Simplex
This patient has a history of biopsy confirmed epidermolysis bullosa simplex.

25 Epidermolysis Bullosa Simplex 177
He has developed multiple epidermolysis bullosa nevi.

This patient has a history of epidermolysis bullosa simplex with localized blisters
on his bilateral soles.
This patient presented at birth with congenital absence of skin on both extremi-
ties. He subsequently began to develop blisters on his heels and ankles.
Originally labeled: “Bart syndrome”, which is now known to progress to many dif-
ferent subtypes of EB. This child had epidermolysis bullosa simplex.
This patient presented during infancy with epidermolysis bullosa simplex.

This patient presented during childhood with epidermolysis bullosa simplex and
axillary hyperhidrosis.
This patient presented during infancy with epidermolysis bullosa simplex with mot-
tled pigmentation.
References
1. Intong LR, Murrell DF. Inherited epidermolysis bullosa: new diagnostic criteria and classifica-
tion. Clin Dermatol. 2012;30(1):70–7.
2. Echeverria-Garcia B, Vicente A, Hernandez A, et al. Epidermolysis bullosa simplex with mot-
tled pigmentation: a family report and review. Pediatr Dermatol. 2013;30(6):e125–31.
Chapter 26
Junctional Epidermolysis Bullosa
Junctional epidermolysis bullosa (JEB) induces skin fragility slightly deeper in the
basement membrane zone affecting the lamina lucida. It is most commonly inher-
ited in an autosomal recessive manner. Mutations include LAMA3, LAMB3, LAMC2,
COL17A1, ITGA6, ITGB4 corresponding to the proteins laminin-332, type XVII
collagen, and alpha-6 beta-4 integrin [1].
Herlitz-type JEB has a very severe phenotype that is often fatal. These patients
have a complete lack of laminin-332 which greatly impairs the barrier integrity of
the skin. Patients present in infancy with a large surface area of erosions. Additionally,
there can be involvement of ocular, tracheolaryngeal, gastrointestinal, genitouri-
nary, and renal systems. Other phenotypes of JEB tend to have a more favorable
prognosis due to mutations (as opposed to complete absence) in the aforementioned
proteins leading to decreased expression. These patients present with skin fragility
as well as hair, nail, and tooth enamel defects [1].

https://doi.org/10.1007/978-3-319-98101-7_26
194 26 Junctional Epidermolysis Bullosa
26 Junctional Epidermolysis Bullosa 195
26 Junctional Epidermolysis Bullosa 197
This patient presented during infancy with biopsy proven junctional epidermolysis
bullosa, non-lethal type.
26.1 Junctional EB Herlitz Variety 199
This patient presented with junctional epidermolysis bullosa.
26.1 Junctional EB Herlitz Variety

12 days of age.
26.1 Junctional EB Herlitz Variety 201
Same child 26 weeks old, died one week later.

6 week old WM – died 4 weeks later at age 10 weeks.

26.2 Junctional EB Non-Herlitz 203
26.2 Junctional EB Non-Herlitz

Reference 205
32 y WF with Junctional non-herlitz EB, cerebral palsy and wheel chair bound.
Reference
Chapter 27
Dystrophic Epidermolysis Bullosa
Dystrophic epidermolysis bullosa (DEB) is the most severe presentation of epider-

molysis bullosa with skin fragility occurring in the sublamina densa region. DEB is
the second most common presentation of EB after EBS. There are two subtypes of
DEB. The first is the dominant dystrophic phenotype (DDEB) and the second is the
recessive dystrophic phenotype (RDEB). Both subtypes have mutations in COL7A1,
which correlates to type VII collagen [1, 2].
DDEB patients have reduced expression of type VII collagen portending a better
prognosis than RDEB. Similar to other subtypes of EB, patients present with skin
fragility and blistering in areas of friction or trauma. Clinically, these lesions heal
with scarring, milia, and/or loss of nails [1].
On the other hand, RDEB patients tend to have near complete loss of type VII
collagen expression. RDEB-generalized severe (previously called Hallopeau-
Siemens) is such a presentation. Patients develop generalized blistering in infancy
that leads to scarring and pseudosyndactyly. The mucous membranes are also
involved which leads to difficulties with swallowing, urination and defecation.
Furthermore, the large surface area affected by impaired barrier function can lead to
anemia, infection, malnutrition, delayed puberty, osteoporosis, and failure to thrive.
Patients with RDEB have a decreased lifespan often into the fourth decade of life as
these patients are prone to develop renal complications or aggressive squamous cell
carcinoma [3]. Other sub-types of RDEB tend to have a better prognosis and are not
as prone to squamous cell carcinoma [1].

https://doi.org/10.1007/978-3-319-98101-7_27
208 27 Dystrophic Epidermolysis Bullosa
27 Dystrophic Epidermolysis Bullosa 209
This patient presented during childhood with dominant dystrophic epidermolysis

bullosa.
This young woman has recessive dystrophic epidermolysis bullosa with frequent
bullae formation and scarring. She has also had several squamous cell carcinomas
that were treated with photodynamic therapy and Mohs micrographic surgery.
References 215
Right hand had release surgery.
This young woman has recessive dystrophic epidermolysis bullosa. She follows
regularly with ophthalmology, gastroenterology, ENT and endocrinology.
References
2. Uitto J, Christiano AM. Molecular basis for the dystrophic forms of epidermolysis bullosa:
mutations in the type VII collagen gene. Arch Dermatol Res. 1994;287(1):16–22.
3. Pourreyron C, Cox G, Mao X, Volz A, Baksh N, Wong T, Fassihi H, Arita K, O’Toole EA,
Ocampo-Candiani J, Chen M, Hart IR, Bruckner-Tuderman L, Salas-Alanis JC, McGrath
JA, Leigh IM, South AP. Patients with recessive dystrophic epidermolysis bullosa develop
squamous-cell carcinoma regardless of type VII collagen expression. J Investig Dermatol.
2007;127(10):2438–44.
Part VIII
Photosensitivity and Photoreactions
Chapter 28
Actinic Prurigo
Actinic prurigo is a photodermatosis most commonly seen in Native Americans

(more commonly Mestizo patients) but can occur in all ethnicities. It more com-
monly affects female patients (2:1) and it commonly occurs in families. There is a
strong HLA association with HLA-DR4. It has been hypothesized to be a variant of
polymorphous light eruption (PMLE) [1, 2].
Patients often present in childhood with pruritic crusted papules with concomi-
tant conjunctivitis and cheilitis. Actinic prurigo more often occurs in patients with
darker phototypes [2]. As a photodermatosis, ultraviolet light exposure is a critical
precipitating factor. Patients often experience flares in the spring and summer. While
lesions are most often present on exposed skin, uncovered skin can become affected.
Patients can present with excoriations leading to hemorrhagic crusting or lichenifica-
tion. Commonly, the eruption resolves by adolescence though it can persist [1, 2].
Histopathology of these cutaneous lesions reveals epidermal spongiosis, acan-
thosis, and perivascular monocytic inflammation. The inflammation may also have
eosinophils and mast cells. As opposed to PMLE, papillary dermal edema is not
often observed in actinic prurigo [2]. Biopsy specimens of the oral mucosa for the
cheilitis can be more specific for actinic prurigo as the germinal centers present in
these specimens are diagnostic [1].
Patients can undergo photo testing, which is abnormal for either UVB, UVA or
both in most cases. Management of actinic prurigo consists of vigorous photo pro-
tection with broadband sunscreens, protective clothing, hats and sunscreen.
Additionally, patients can use topical calcineurin inhibitors or topical corticoste-
roids. Patients can also be treated with phototherapy such as NB-UVB or PUVA
with the goal of disease hardening. For more severe disease, providers can consider
oral thalidomide at 50–100 mg nightly over several weeks. The main concerns with

https://doi.org/10.1007/978-3-319-98101-7_28
220 28 Actinic Prurigo
thalidomide include teratogenicity and drug-induced peripheral neuropathy. Other

systemic agents that have been used in actinic prurigo include oral corticosteroids,
azathioprine, and cyclosporine. Other reported therapies include vitamin E,
beta-carotene, tetracycline, antimalarial medications, and antihistamines, however,
these have variable efficacies [1, 2].
This condition is very itchy as the name says. The curious thing is it appears/
persists in the winter, so don’t let that throw you.
This patient presented with actinic prurigo on his face. She had been treated with
hydroxychloroquine with success. Currently, she is practicing photoprotection and
applying high potency topical steroids as needed for any outbreaks.
References 221
Five years later, the actinic prurigo is quiet.
References
1. Naka F, Shwayder TA, Santoro FA. Photodermatoses: Kids are not just little people. Clin
Dermatol. 2016;34(6):724–35.
2. Rodriguez-Carreon AA, Rodriguez-Lobato E, Rodriguez-Gutierrez G, et al. Actinic Prurigo.
Skinmed. 2015;13(4):287–95; quiz 296
Chapter 29
Hydroa Vacciniforme
Hydroa vacciniforme is another photodermatosis that most often affects children. It

is exceedingly rare. Affected patients tend to have lighter phototypes and it affects
male patients slightly more frequently than female patients. There has been a pro-
posed association between hydroa vacciniforme and the Epstein-Barr virus (EBV).
Although this is a scarring photodermatosis, the active lesions often resolve by early
adulthood [1, 2].
As a photodermatosis, lesions develop more often during the spring and summer
months and they more frequently affect the face and dorsal hands. Patient present
with symmetric erythematous macules with a burning sensation. These ultimately
develop into papules and plaques that progress to umbilicated vesicles. The lesions
ultimately have severe hemorrhagic crusting and varioliform scaring. The lesions
appear on sun-exposed skin [1, 2].
Histopathology can aid in diagnosis. Lesions present with progressive epidermal
spongiosis with the pathognomonic triad of findings: keratinocyte degeneration,
formation of intraepidermal vesicles with inflammatory cells, and confluent epider-
mal necrosis [1]. Cases that have co-infection with EBV can also demonstrate atypi-
cal lymphocytes on histology [1].
Treatment of hydroa vacciniforme is extremely challenging and many cases are
refractory. Management of these patients requires avid photo protection with broad-
band sunscreens, photo protective clothing, broad brimmed hats and sunglasses.
Other reported treatments include phototherapy (NB-UVB or PUVA), beta-carotene,
antimalarials, azathioprine, thalidomide, cyclosporine, antibiotics, anti-virals, corti-
costeroids, and fish oil supplementation [1, 2]. Patients with severe disease may
need a hematopoietic stem cell transplant [1].

https://doi.org/10.1007/978-3-319-98101-7_29
224 29 Hydroa Vacciniforme
This patient presented because he was developing a rash on the face and ears with
sun-exposure that was healing with scarring. His biopsy was highly suggestive of
hydroa vacciniforme. He was treated with hydroxychloroquine, topical corticoste-
roids, and photoprotection with improvement.
29 Hydroa Vacciniforme 225
This patient has both hydroa vacciniforme with evidence of scarring and post-
inflammatory hyperpigmentation.
She has been managed predominantly with photoprotection.

226 29 Hydroa Vacciniforme
This patient has marked vesicular hydroa vacciniforme with high EBV titers.
He has been managed medically with hydroxychloroquine and photoprotection.

References 227
References
1. Levoska MA, Cohen JI, Manoli I, et al. Recurrent scarring papulovesicular lesions on sun-
exposed skin in a 22-year-old man. J Am Acad Dermatol. 2018;78(3):637–42.
2. Nitiyarom R, Wongpraparut C. Hydroa vacciniforme and solar urticaria. Dermatol Clin.
2014;32(3):345–353, viii.
Chapter 30
Rothmund Thomson
Rothmund-Thomson syndrome is a rare genodermatosis with the prominent feature

of poikiloderma. It is inherited in an autosomal recessive manner and has a mutation
in the gene RECQL4. This gene encodes an adenosine triphosphate-dependent DNA
helicase, which is ultimately involved in DNA repair [1]. Both genders are equally
affected and most patients present in the first year of life.
Clinically, patients have a typical appearance often with short stature, frontal
bossing, saddle nose, and prognathism. At initial presentation, infants with
Rothmund-Thomson have erythema, edema, and vesicles on the face. Over time,
this generalizes to the extremities and the buttocks ultimately progressing to poiki-
lodermatous lesions. Patients can also have cataracts, hypogonadism, hypodontia,
and thin hair. Musculoskeletal abnormalities such as absent or hypoplastic thumbs
or malformed forearms are common. Patients do have an increased risk of malig-
nancy including osteosarcoma and squamous cell carcinoma [1]. Osteosarcomas
have been reported in as many as 30% of patients [1].
Management of these patients should be multifactorial to assess the patients’
skeletal, ophthalmologic, and malignant predispositions. Bothersome cutaneous
lesions can have telangiectasias addressed with a pulsed dye laser. Patients
should be counseled about vigorous photo protection to prevent cutaneous
malignancies [1].

https://doi.org/10.1007/978-3-319-98101-7_30
230 30 Rothmund Thomson
This patient was born with this genodermatosis. She continued to have hyperkera-
totic growths on her scalp, body, arms, and legs with accentuation over her palms
and soles. She also had cicatricial alopecia and joint contractures.
She died of lymphoma.
Reference
1. Yang JY, Sohn YB, Lee JS, Jang JH, Lee ES. Rare presentation of Rothmund-Thomson syn-
drome with predominantly cutaneous findings. JAAD Case Rep. 2017;3(3):172–4.
Chapter 31
Porphyria
Porphyria refers to a class of diseases related to dysfunctional heme biosynthesis.

Porphyrias can be sub-divided based on clinical presentation (cutaneous versus
extra-cutaneous manifestations), enzymes affected (erythropoietic or hematopoi-
etic) or time course (acute versus chronic).
Transient neonatal porphyria is a very rare presentation of porphyria. There are
few cases reported in the literature and much remains to be understood about the
entity. Patients present in infancy almost immediately after birth with high plasma
porphyrins of unknown etiology. It has been hypothesized that some patients had
hepatic dysfunction whereas others may have degradation of erythrocyte precur-
sors, which have higher levels of porphyrins than mature red blood cells. In all
cases, it has been hypothesized that the transient porphyrinemia leads to photosen-
sitivity in these patients [1, 2].

https://doi.org/10.1007/978-3-319-98101-7_31
232 31 Porphyria
This patient was seen in the neonatal intensive care unit. She was started on bili-
lights shortly after birth and developed transient porphyrinemia.
The eruption resolved on its own with photoprotection and maturation of the liver.
31 Porphyria 233
Erythropoetic Protoporphyria is the most common porphyria abnormality one will

see in a pediatric clinic. It is due to a partial enzyme activity of ferrochelatase. This
blockage causes protoporphyrins to accumulate in the stool and blood (but not the
urine). The skin findings are more insidious. The usual story is an infant taken for
the first stroll on a sunny day becoming fussy and crying accompanied by red swol-
len skin in the exposed areas. This can also occur through window glass. So the
story may be applicable to sunlight through a nursery or car windows. Actual blis-
ters rarely appear. It is only the realization that the red swollen skin occurs in sun
exposed areas that the diagnosis can be approached. Serum screen will show ele-
vated proto-porphyrins. With repeated exposure the skin becomes leathery and
wrinkled, especially over the nose and knuckles. Treatment is sun protection from
the visible wavelengths (so clothing and hats will work, but sun blocks will not).
Depending on the amount of ferrochelatase the child has working in their liver the
child’s tolerance to sunlight can be minutes to hours. Old treatments include things
that bind the bile salts or help bind and/or excrete porphyrins from the GI track, and
also beta carotene. There is not good science why beta carotenes would work. New
treatments include injectables that increase the melanin in the skin (afamelanotide)
Long term consequences include liver damage in approximately 10% of the patients.
9y WF face, note horizontal thickened skin over the nose.

234 31 Porphyria
Knuckles
References
1. By CC, Owens A, Wesson SK. Purpuric eruption in a transfused neonate receiving photo-
therapy. Pediatr Dermatol. 2014;31(6):e152–3.
2. Boer B, Tisack A, Shwayder T. Transient porphyrinemia in a neonate: a case report. Pediatr
Dermatol. 2016;33(6):e375–6.
Chapter 32
Poikiloderma with Neutropenia
Poikiloderma with neutropenia is also known as “Navajo poikiloderma.” There are

only a couple dozen known cases of this rare genodermatosis with autosomal reces-
sive inheritance. Patients present with mutations in C16orf57. Both genders are
equally affected. It was recently described in 2011 and found to have a predomi-
nance in the Navajo Indian population.
Patients present in the first year of life with typical clinical characteristics.
Initially, their cutaneous manifestations appear on the peripheral extremities with
progression to the upper extremities, trunk, face and earlobes, which is the opposite
of the poikiloderma progression seen in Rothmund Thomson [1]. As opposed to
Rothmund Thompson, another genodermatosis with poikiloderma, poikiloderma
with neutropenia tends not to have photosensitivity. As their disease progresses,
their clinical lesions develop into poikiloderma, which is a combination of atrophy,
telangiectasias, and dyspigmentation. Other cutaneous manifestations include pal-
moplantar keratoderma, keratotic papules on the face and forearms and recurrent
cutaneous infections. Patients often have short stature, midfacial hypoplasia, and
nail dystrophy.
Patients with Navajo poikiloderma also commonly have neutropenia, which
explains the other name for this condition: poikiloderma with neutropenia. This
laboratory finding can be cyclical in nature. These pediatric patients can also develop
recurrent sinopulmonary infections, lacrimal duct obstruction and dental caries.
Some patients may have developmental delay. Patients have a normal life span.
Patients benefit from a multidisciplinary approach to management. Squamous cell
carcinoma has recently been reported in sun exposed areas in one of my 14 y
Hispanic patient (TAS).

https://doi.org/10.1007/978-3-319-98101-7_32
236 32 Poikiloderma with Neutropenia
This patient was diagnosed with Navajo poikiloderma (Clericuzio Poikiloderma

with Neutropenia) at nine years of age. Around the time of diagnosis, she was devel-
oping dystrophic calcifications in the skin.
32 Poikiloderma with Neutropenia 237
32 Poikiloderma with Neutropenia 239
Left foot
Right foot
Same child now age 14y. Note progression of poikiloderma. She has developed two
squamous cell carcinomas on her heels (see figure). She now practices diligent
photoprotection.
These Indian brothers presented with poikiloderma and neutropenia. They had
genetic testing performed that was positive for C16orf57 which confirmed their
disease of poikiloderma with neutropenia.
They have recently started to develop calcified subcutaneous nodules concerning

for dystrophic calcification versus calcinosis cutis.
Reference 241
Reference
1. Chantorn R, Shwayder T. Poikiloderma with neutropenia: report of three cases including one
with calcinosis cutis. Pediatr Dermatol. 2012;29(4):463–72.
Part IX
Vascular Diseases
Chapter 33
Polyarteritis Nodosa
Polyarteritis nodosa (PAN) is a medium vessel vasculitis. Men tend to be more fre-
quently affected than women (4:1). All ages can be affected but most commonly
patients present as middle-aged adults. Patients can present with isolated cutaneous
disease or disease with systemic symptoms – called classic PAN. Cutaneous disease
tends to have a more benign, though persistent, course. It affects approximately
10% of patients. Progression from cutaneous PAN to classic PAN is uncommon.
Pediatric patients tend to present with cutaneous PAN [1].
Multiple etiologies have been proposed for the pathogenesis of PAN including
infections, inflammatory diseases, malignancies and medications. Infections associ-
ated with PAN include hepatitis B and C, streptococcal, parvovirus B19 and HIV
infections. Streptococcal infections are a common precipitating factor in pediatric
patients [1].
Cutaneous findings include livedo racemosa, palpable purpura, retiform purpura,
subcutaneous nodules, ulcers, or peripheral gangrene. Systemic symptoms may
include fever, arthralgias, myalgias, paresthesias, abdominal pain, orchitis and
hypertension. Cutaneous disease can have minor systemic symptoms such as fever
and arthralgias. Patients with cutaneous PAN have a positive anti-neutrophil cyto-
plasmic antibody (ANCA) in up to 20% of cases [1].
Diagnosis of cutaneous PAN is classically performed by histopathology. On histo-
pathology, biopsies of PAN demonstrate a necrotizing vasculitis of medium-sized
arteries. The arteries involved in PAN tend to be deep, which should be considered
before obtaining a biopsy. Direct immunofluorescence (DIF) of this entity may dem-
onstrate C3, IgM, and fibrin within or around vessel walls [1]. It has been suggested
that non-invasive imaging technologies such as Doppler ultrasound or computed
tomography angiography could similarly be used to aid in the diagnosis [1].
Management of cutaneous PAN involves symptomatic relief. The most common
treatments include topical or intralesional corticosteroids. If patients are not
responding, one could consider oral corticosteroids. Some patients respond to non-
steroidal anti-inflammatory agents. Other treatment considerations include treating
any precipitating infection and/or discontinue any precipitating medications. Other

https://doi.org/10.1007/978-3-319-98101-7_33
246 33 Polyarteritis Nodosa
reported medications include methotrexate, dapsone, IV IgG, pentoxifylline, col-

chicine, azathioprine, mycophenolate mofetil, or TNF-alpha inhibitors [2].
References 247
This patient was found to have biopsy proven polyarteritis nodosa as well as livedo
reticularis without any associated systemic disease.
He has been well-controlled on methotrexate and cyclosporine.
References
1. Ozcakar ZB, Fitoz S, Yildiz AE, Yalcinkaya F. Childhood polyarteritis nodosa: diagnosis with
non-invasive imaging techniques. Clin Rheumatol. 2017;36(1):165–71.
2. Inoue N, Shimizu M, Mizuta M, Ikawa Y, Yachie A. Refractory cutaneous polyarteritis nodosa:
successful treatment with etanercept. Pediatr Int. 2017;59(6):751–2.
Part X
Collagen Vascular Disorders
Chapter 34
Discoid Lupus
Lupus erythematosus is a broad disease category. It can be subdivided into multiple

categories including systemic and cutaneous manifestations. Cutaneous lupus can
be further subdivided into acute cutaneous lupus, subacute cutaneous lupus and
chronic cutaneous lupus. Discoid lupus erythematosus (DLE) is a further subcate-
gory of chronic cutaneous lupus and it is the most common lupus presentation [1].
Approximately 3% of patients develop DLE before 10 years of age [1, 2]. In
pediatric patients older than 10 years of age, women are more frequently affected
[2]. In adults, the progression from DLE to SLE is uncommon, however, it is thought
to be more likely in pediatric patients and has been reported to be as high as 50%.
The average age of progression from DLE to SLE was 11 years old and the greatest
risk of progression occurred 1 year after diagnosis [1].
Clinically, patients present with hyperpigmented patches or thin plaques with
central pink atrophy, follicular plugging, scarring alopecia and scarring on the skin.
Lesions are commonly on the head and neck with a predominance of lesions on the
scalp and the conchal bowls [1].
DLE can be localized to the head and neck or generalized. Among adult patients,
those with nephropathy, arthralgias, and elevated antinuclear antibody titers may
shower higher rates of progression to SLE. Among pediatric patients, it is unclear if
generalized disease portends a higher risk of progression to SLE [1].
Patients should be followed to evaluate for progression to systemic disease.
Work-up includes history and physical examination, skin biopsy, and laboratory
testing including complete blood count with differential, renal function, liver func-
tion, urinalysis and antinuclear antibody [2].
Histopathology of DLE lesions demonstrates follicular plugging, interface or
vacuolar dermatitis, perivascular lymphocytic inflammation, and basement mem-
brane thickening [3]. Depending on the work-up, more specific antibodies for lupus
can be considered including anti-dsDNA, anti-Ro/sSA, anti-La/SSB, anti-Smith,
and anti-snRNP. Treatment options include topical corticosteroids, topical calcineu-
rin inhibitors and photoprotection as first line therapies. The initial systemic medi-
cations used for DLE are anti-malarial medications such as hydroxychloroquine.

https://doi.org/10.1007/978-3-319-98101-7_34
252 34 Discoid Lupus
Hydroxychloroquine decreases the risk of disease progression from skin only to

systemic lupus and should be initiated in patients with cutaneous lupus first line. In
recalcitrant cases, one can consider intralesional or systemic corticosteroids or other
immunosuppressive agents [2].
This patient presented with cutaneous lupus affecting the left cheek and left chest
that was confirmed with biopsy.
She received treatment with hydroxychloroquine; however, she developed transami-

nitis so the treatment was discontinued. She was treated with high potency topical
steroids and topical calcineurin inhibitor as well as photoprotection with success.
34 Discoid Lupus 253
Same child now age 17 years. Was restarted on daily plaquenil without liver issues.
No cutaneous rashes.
254 34 Discoid Lupus
Five years WF with sudden onset erythematous scaly eruption cheeks, nose, upper
V of neck and outer arms after sun exposure. Biopsy consistent with lupus.
References
1. Arkin LM, Ansell L, Rademaker A, et al. The natural history of pediatric-onset discoid lupus
erythematosus. J Am Acad Dermatol. 2015;72(4):628–33.
2. Timpane S, Brandling-Bennett H, Kristjansson AK. Autoimmune collagen vascular diseases:
kids are not just little people. Clin Dermatol. 2016;34(6):678–89.
3. Bangert JL. Subacute cutaneous lupus erythematosus and discoid lupus erythematosus. Arch
Dermatol. 1984;120(3):332.
Chapter 35
Neonatal Lupus
Neonatal lupus erythematosus (NLE) falls into the category of subacute cutaneous
lupus erythematosus (SCLE). It presents at birth in infants whose mothers have a
diagnosis of systemic lupus erythematosus (SLE) in approximately 1 in 20,000
births [1]. Diagnostically, patients have a positive anti-Ro/SSA antibody as this
antibody was obtained from the mother through transplacental passage [1, 2]. If a
mother has had one child affected, there is an ~25% chance of having another
affected infant [1].
Clinically, lesions present as erythematous annular patches predominantly on the
head and neck but can spread to the upper trunk. Infants are also frequently photo-
sensitive. Histologically, these lesions are identical to SCLE with vacuolar interface
dermatitis, few apoptotic keratinocytes, and epidermal atrophy. The lesions resolve
over time without any residual scarring, however, dyspigmentation can take several
months to resolve. Some patients do have persistent telangiectasias.
Of utmost concern with NLE are the internal findings. Cardiovascular manifesta-
tions remain the most serious. Patients have a high likelihood of presenting with
congenital heart block (i.e. third-degree heart block) with or without cardiomyopa-
thy, which is most often apparent at birth. Congenital heart block in the setting of
NLE has a high mortality rate approaching 20% with the majority of patients requir-
ing a pacemaker. Other systemic manifestations include hepatobiliary disease, ane-
mia or thrombocytopenia, which tend to resolve over a few months as the maternal
IgG antibodies dissipate [1].
Given the severity and risk of internal disease in the setting of NLE, patients who
present with cutaneous lesions should have an extensive work-up including physical
examination, electrocardiogram, complete blood count, and liver function tests.
Patients diagnosed with NLE should be followed over the first year of life to ensure
that clinical findings resolve. Additionally, follow-up with a pediatric cardiologist is
important for those infants with congenital heart block [1].

https://doi.org/10.1007/978-3-319-98101-7_35
256 35 Neonatal Lupus
This patient presented in the neonatal period with signs of neonatal lupus. Her cuta-
neous eruption self-resolved with post-inflammatory hypopigmentation. Cardiac
screening was negative/normal.
The post inflammatory hypopigmentation improved over time.
References 257
References
1. Shiiya C, Ota M. Facial rash, fever, and anemia in a newborn. JAMA. 2017;317(20):2125–6.
2. Lee LA, Frank MB, McCubbin VR, Reichlin M. Autoantibodies of neonatal lupus erythemato-
sus. J Investig Dermatol. 1994;102(6):963–6.
Chapter 36
Dermatomyositis
Dermatomyositis (DM) consists of both cutaneous and musculoskeletal manifesta-

tions. The incidence is higher in women than in men. DM is thought to result from
an immune-mediated process.
Proposed triggers include malignancy, medications and infectious agents
although malignancy is very rare in juvenile DM. Juvenile DM has an HLA correla-
tion with HLA-DR3 and HLA-B8. Japanese patients with juvenile DM may have an
HLA phenotype of HLA-DRB1*15021 [1]. Approximately, a quarter of patients
with juvenile DM will have a positive anti-p155/140 or anti-p140 antibody. Less
common antibodies in juvenile DM include anti-aminoacyl-tRNA synthetases (i.e.
anti-Jo-1), anti-SRP, or anti-Mi-2 [2].
Patients present with inflammation in the musculature leading to weakness pre-
dominantly in the proximal muscles. Parents may describe the weakness as diffi-
culty raising from a chair or brushing their hair. In younger children, the changes
may be more subtle and less noticeable. They may notice the child appears “lazy”
or refuses to participate in activities. In addition, patients often demonstrate cutane-
ous findings such as the poikiloderma, heliotrope rash, Gottren papules or erythema,
periungual erythema or telangiectasias, ragged cuticles, or shawl sign. Heliotrope
rash refers to the violaceous patches on the upper eyelids with periorbital edema.
Gottren papules/erythema describes the pink macules and papules overlying the
knuckles. Shawl sign similarly describes the pink to erythematous patches overly-
ing the shoulders. Patients can present with isolated symptoms of myositis, which is
referred to as polymyositis. Similarly, patients can present without myositis and just
cutaneous findings, which is referred to as amyopathic dermatomyositis but weak-
ness often develops over time [3].
Juvenile DM portends a much higher risk of calcinosis cutis than adults DM,
particularly overlying pressure points such as joints. This manifestation presents in
up to 30% of pediatric patients and commonly within the first 3 years after diagno-
sis. Pediatric patients also have an increased risk of small-vessel vasculitis. Unlike
the adult counterpart, juvenile DM is not associated with an increased risk of

https://doi.org/10.1007/978-3-319-98101-7_36
260 36 Dermatomyositis
alignancy. Pulmonary findings such as interstitial lung disease are another associ-
m
ated concern, which is more frequently encountered in adult patients [3].
The diagnostic criteria for DM includes symmetric proximal muscle weakness,
muscle biopsy evidence of myositis, increase in serum skeletal muscle enzymes,
characteristic electromyography pattern or typical cutaneous eruption. The likeli-
hood of disease depends on how many criteria the patient meets. Skin biopsy can
aid in diagnosis, however, it demonstrates the same histopathologic findings as cuta-
neous lupus so the differential diagnosis must be considered clinically. Laboratory
work-up should include muscle enzyme levels, myositis antibodies and antinuclear
antibodies. Non-invasive imaging procedures such as magnetic resonance imaging
or ultrasound have been used to identify myositis most often replacing the role of
muscle biopsy [3].
The goal of treatment is to rapidly decrease inflammation to minimize symptoms
and prevent morbidity. Treatment for patients with juvenile DM includes systemic
corticosteroids – most commonly prednisone 2 mg/kg. Patients are often started on
a concomitant steroid-sparing agent that increases as the corticosteroid is tapered.
Immunosuppressants include methotrexate, azathioprine, or mycophenolate mofetil.
Recalcitrant disease may be treated with high-dose intravenous corticosteroids,
intravenous immunoglobulin, cyclophosphamide, cyclosporine, rituximab, or anti-
TNF alpha medications. Cutaneous disease should also be treated with topical cor-
ticosteroids or topical calcineurin inhibitors and photoprotection. Additionally,
hydroxychloroquine may help with cutaneous manifestations. Calcinosis cutis can
be difficult to treat, which is why early treatment to minimize inflammation is rec-
ommended [3–5].
This patient presented at age two with concern for dermatomyositis with calcinosis
cutis. Several of the affected areas resolved with intralesional corticosteroid injec-
tions but the patient was left with cutaneous depressions and hyperpigmentation.
36 Dermatomyositis 261
The nasal lesion was surgically excised. She was also managed with IV IgG and is
currently being weaned off oral prednisone.
262 36 Dermatomyositis
11 y WM dermatomyositis showing classic changes of the elbows.
Face.
References 263
Hands and knees.
Looped capillaries of the nail folds.
References
1. Tomono N, Mori M, Nakajima S, et al. HLA-DRB1*15021 is the predominant allele in

Japanese patients with juvenile dermatomyositis. J Rheumatol. 2004;31(9):1847–50.
2. Gunawardena H, Betteridge ZE, McHugh NJ. Myositis-specific autoantibodies: their clinical
and pathogenic significance in disease expression. Rheumatology. 2009;48(6):607–12.
3. Batthish M, Feldman BM. Juvenile dermatomyositis. Curr Rheumatol Rep. 2011;13(3):216–24.
4. Timpane S, Brandling-Bennett H, Kristjansson AK. Autoimmune collagen vascular diseases:
kids are not just little people. Clin Dermatol. 2016;34(6):678–89.
5. Papadopoulou C, Wedderburn LR. Treatment of juvenile dermatomyositis: an update. Paediatr
Drugs. 2017;19:423–34.
Chapter 37
Morphea
Morphea is an inflammatory skin disease that ultimately results in sclerotic plaques.

It has been divided into several classifications including plaque-type morphea
(which is also known as localized scleroderma). linear morphea (linear sclero-
derma), and deep morphea (or morphea profundus) [1]. Linear morphea also
includes the subtypes en-coup-de-sabre and progressive hemifacial atrophy [1]. The
prevalence of morphea is approximately 0.4–1 per 100,000 patients and it is more
common in females compared to men (2–3:1) [1]. The mean age of onset for pedi-
atric patients with morphea is 7 years of age.
Lesions present as slightly elevated, erythematous, violaceous or hyperpig-
mented plaques that feel indurated. As the lesion progresses centrifugally, the cen-
tral aspect becomes sclerotic and white contrasting with a more violaceous
discoloration on the periphery of the lesion. The lilac discoloration of the periphery
is a sign of disease activity.
Plaque type morphea is the most common subtype of morphea in the general
population and is most common on the trunk [1]. In pediatric patients, linear mor-
phea is the most common subtype and more frequently affects the head/face [1]. En
coup de sabre (or blow with a single edged sword) is a term to describe linear mor-
phea on the forehead or scalp. It can rarely affect the meninges and brain creating a
nidus for seizures. Additionally, progressive hemifacial atrophy is a morphea vari-
ant known as Parry-Romberg Syndrome. This syndrome affects the distribution of
the trigeminal nerve leading to progressive loss of subcutaneous fat with little or no
true sclerosis. Linear morphea can affect the trunk or the limbs causing local restric-
tive disease and limb length discrepancies. An additional morphea variant is atro-
phoderma of Pasini and Pierini, which may appear to be a superficial form of plaque
morphea versus a “burnt-out” phenotype of morphea. In this variant, hyperpig-
mented lesions are more commonly evident on the trunk.
Patients with morphea have an increased prevalence of anti-single stranded
DNA (ssDNA), anti-topoisomerase IIα, anti-phospholipid, anti-fibrillin-1 and
anti-histone. Additionally, pediatric patients with linear morphea and patients
with generalized morphea tend to have high titers of anti-nuclear antibodies

https://doi.org/10.1007/978-3-319-98101-7_37
266 37 Morphea
(ANA). Additional laboratory findings include elevated rheumatoid factor and

eosinophilia [1].
Morphea can overlap with other connective tissue diseases such as lichen sclero-
sus et atrophicus, systemic lupus erythematosus, rheumatoid arthritis, Sjogren’s
syndrome, juvenile dermatomyositis, polymyositis, or eosinophilic fasciitis. The
clinical course of morphea can last an average of 3–5 years but patients can have
reactivation of their disease [2].
Morphea tends to be a clinical diagnosis but can be confirmed histologically.
A biopsy of normal and abnormal skin may be needed for comparison of the collagen
quality. On hematoxylin and eosin, the appearance of the biopsy specimen depends
upon the age of the lesion, the depth biopsied, and the area biopsied. The most infor-
mative part of the biopsy is at the junction of the deep dermis and subcutaneous tissue
necessitating a deep biopsy. At the inflammatory border of a lesion, the endothelial
cells appear edematous and small capillaries are surrounded by a predominantly lym-
phocytic inflammatory infiltrate. As the disease progresses and becomes more scle-
rotic, the inflammatory infiltrate dissipates. There may be an effaced dermal-epidermal
junction with a reduced number of capillaries and densely packed collagen in the deep
dermis. Eccrine glands may appear closely surrounded by this dense collagen [1].
The treatment of morphea depends upon the extent of the disease. Mild superfi-
cial disease can be treated with topical corticosteroids, topical calcineurin inhibitors
or topical calcipotriene. Systemic therapies for morphea include methotrexate, sys-
temic corticosteroids, calcitriol, and hydroxychloroquine. Patients with en coupe de
sabre require rapid initiation of systemic therapies with IV steroids and methotrex-
ate. Furthermore, patients with rapidly progressing disease or joint involvement
warrant early systemic therapy. If a patient has developed linear morphea affecting
a joint, physical therapy is a critical component of their treatment plan. Once the
disease has stabilized, patients can pursue various laser treatments to even the skin
discoloration and texture as well as hyaluronic acid filler to improve the depressed
scars. Other patients have pursued fat transplant to correct depressed areas.
Localized small spots of morphea don’t cause much difficulties. Beware of

ones that are linear and cross joints. They can cause permanent contractures.
I treat these with pulse steroids and 2 years of methotrexate plus/minus UVA-1
treatments.
37 Morphea 267
This patient presented at 8 years of age for scarring and white discoloration on the
chin extending onto the jawline. She had a biopsy that was consistent with morphea
and concomitant extra-genital lichen sclerosus.
She was initially treated with high potency topical steroids and calcineurin inhibi-
tors, which improved the morphea but did not improve the indentation present on
the chin.
The patient returned for follow-up several years later out of concern for the scarring
on her chin. She had hyaluronic acid filler injected into the depressed scar.
268 37 Morphea
She subsequently underwent fractional carbon dioxide laser.
Patient presented at age 10 with firmness of his face that was first identified by his
dentist who noted bone resorption and a receding gingiva via dental x-rays. He was
noted to have morphea of the left maxilla and overlying skin as well as the left lat-
eral periocular region.
His disease is currently well-controlled on methotrexate, mycophenolate mofetil

and high potency topical steroids.
37 Morphea 269
270 37 Morphea
This patient presented at age 11 for white hardened skin that started on the bilateral
anterior shins and was continuing to progress. On examination, she had signifi-
cantly reduced range of motion of the ankles and knees. Her biopsy was consistent
with localized scleroderma. She was started on IV methylprednisolone monthly for
six months and methotrexate weekly with good improvement.
This is an example of linear morphea.
After two times three doses of IV corticosteroids (a month apart), the patient was
transitioned to narrow-band UVB light therapy in addition to two years of oral
methotrexate as well as several months of physical therapy. Her range of motion as
37 Morphea 271
improved greatly and her disease is now in remission – controlled with topical
corticosteroids.
This young child presented at 4 years of age for thickening of the skin over the nape
of her neck, shoulder, right upper arm, and right leg. She was initially treated with
high-potency topical corticosteroids on the weekdays and topical calcineurin inhibi-
tors on the weekends.
This is an example of plaque type morphea.
272 37 Morphea
Her disease has remained in remission and the affected areas have softened and
lightened in color.
This patient presented at 10 years of age for hyperpigmented atrophic plaques on
his flank and back. A biopsy was performed that confirmed morphea.
His lesions appear hyperpigmented with slight dermal atrophy on the trunk making
this a possible Atrophoderma of Pasini and Pierini variant of morphea.
37 Morphea 273
He was initially treated with topical corticosteroids without much improvement. He

was then started on UVA1 phototherapy as well as methotrexate. This regimen led
to improvement in his atrophoderma.
Perry-Rhomberg, En coup de Sabre
6 years WM early stages of the disease

274 37 Morphea
6½ years
Same child now 7¾ years WM marked facial atrophy

37 Morphea 275
Now 8 2/12 years s/p three boluses of IV steroids and 1½ years of methotrexate
9 3/12 years, On methotrexate for more than 2 years

276 37 Morphea
10 years, Fat reconstruction 2 1/3 months before
References
1. Browning JC. Pediatric morphea. Dermatol Clin. 2013;31(2):229–37.

2. Christen-Zaech S, Hakim MD, Afsar FS, Paller AS. Pediatric morphea (localized scleroderma):
review of 136 patients. J Am Acad Dermatol. 2008;59(3):385–96.

Shwayder, T., Schneider, S. L., Icecreamwala, D., & Jahnke, M. N. (2019) - Longitudinal Observation of Pediatric Dermatology Patients.

Transféré par

Informations du document

Titre original

Copyright

Formats disponibles

Partager ce document

Partager ou intégrer le document

Options de partage

Avez-vous trouvé ce document utile ?

Ce contenu est-il inapproprié ?

Droits d'auteur :

Formats disponibles

Shwayder, T., Schneider, S. L., Icecreamwala, D., & Jahnke, M. N. (2019) - Longitudinal Observation of Pediatric Dermatology Patients.

Transféré par

Droits d'auteur :

Formats disponibles

Longitudinal Observation

Devika Icecreamwala Marla N. Jahnke

ISBN 978-3-319-98100-0 ISBN 978-3-319-98101-7 (eBook)

Library of Congress Control Number: 2018960271

© Springer Nature Switzerland AG 2019

Part I Eczematous Eruption of Childhood

Part II Papulosquamous and Related Disorders

Part III Hereditary Disorders of Cornification

3 Epidermolytic Ichthyosis������������������������������������������������������������������������ 19

9 Keratosis Follicularis Spinulosa Decalvans ������������������������������������������ 55

Part IV Disorders of Sebaceous and Sweat Glands

11 Familial Dysautonomia with Anhydrosis (Type IV) ���������������������������� 63

Part V Cutaneous Tumors and Tumor Syndromes

12 Congenital Nevi���������������������������������������������������������������������������������������� 69

Part VI Vascular Disorders of Infancy and Childhood

17 Infantile Hemangiomas �������������������������������������������������������������������������� 125

Part VII Bullous Disorders of Childhood

25 Epidermolysis Bullosa Simplex�������������������������������������������������������������� 175

Part VIII Photosensitivity and Photoreactions

28 Actinic Prurigo ���������������������������������������������������������������������������������������� 219

Part IX Vascular Diseases

33 Polyarteritis Nodosa�������������������������������������������������������������������������������� 245

Part X Collagen Vascular Disorders

34 Discoid Lupus ������������������������������������������������������������������������������������������ 251

Hyper-immunoglobulin E (IgE) syndrome (HIES) is a rare clinical entity that was

© Springer Nature Switzerland AG 2019 3

This is a shorthand from a very nice graph published by Rebecca Buckley

Another patient presented during adolescence with predominantly eczematous

Psoriasis is a common chronic inflammatory dermatologic condition that is com-

© Springer Nature Switzerland AG 2019 11

My therapeutic ladder is usually: Topical steroids, topical vitamin D creams,

1. Relvas M, Torres T. Pediatric Psoriasis. Am J Clin Dermatol. 2017;18:797.

Epidermolytic ichthyosis (EI) is an example of a non-syndromic inherited ichthyo-

© Springer Nature Switzerland AG 2019 19

This patient has been treated with soriatane and tretinoin.

Topical Tretinoin to the face.

One week after starting oral soriatane.

1. Vahlquist A, Fischer J, Torma H. Inherited nonsyndromic ichthyoses: an update on pathophysi-

Nonbullous congenital ichthyosiform erythroderma (CIE) is a clinical entity in the

© Springer Nature Switzerland AG 2019 23

This patient presented at birth with erythema and “powdery” scale.

Lamellar ichthyosis is a sub-type of non-bullous congenital ichthyosis. It can also

© Springer Nature Switzerland AG 2019 29

He improved with treatment with vitamin A derivatives but continues to have

5.1 Lamellar Ichthyosis

20 year old BM life long thick scaling.

Topical Vitamin A cream helps some. Note ectropion.

5.2 Harlequin Fetus

5.3 Harlequin Fetus

5.4 Harlequin Fetus

1. Takeichi T, Akiyama M. Inherited ichthyosis: non-syndromic forms. J Dermatol.

Netherton Syndrome (NS) is an uncommon genodermatosis. It is caused by a loss-­

© Springer Nature Switzerland AG 2019 39

Same child age 7y.

This patient presented at birth with erythema and scaling skin.

Conradi-Hunermann-Happle (CHH) syndrome is a type of X-linked dominant ich-

© Springer Nature Switzerland AG 2019 47

1. Takeichi T, Honda A, Okuno Y, Kojima D, Kono M, Nakamura Y, Tohyama M, Tanaka T, Aoyama

Treating PPK is a lifelong task and generally disappointing. The Keratolytics

© Springer Nature Switzerland AG 2019 51

1. Schiller S, Seebode C, Hennies HC, Giehl K, Emmert S. Palmoplantar keratoderma (PPK):

Keratosis follicularis spinulosa decalvans (KFSD) is a genetic disorder within the

© Springer Nature Switzerland AG 2019 55

Part I Eczematous Eruption of Childhood

Part II Papulosquamous and Related Disorders

Part III Hereditary Disorders of Cornification

3 Epidermolytic Ichthyosis�� 19

9 Keratosis Follicularis Spinulosa Decalvans �� 55

Part IV Disorders of Sebaceous and Sweat Glands

11 Familial Dysautonomia with Anhydrosis (Type IV) �� 63

Part V Cutaneous Tumors and Tumor Syndromes

12 Congenital Nevi�� 69

Part VI Vascular Disorders of Infancy and Childhood

17 Infantile Hemangiomas �� 125

Part VII Bullous Disorders of Childhood

25 Epidermolysis Bullosa Simplex�� 175

Part VIII Photosensitivity and Photoreactions

28 Actinic Prurigo �� 219

Part IX Vascular Diseases

33 Polyarteritis Nodosa�� 245

Part X Collagen Vascular Disorders

34 Discoid Lupus �� 251

5.1 Lamellar Ichthyosis

5.2 Harlequin Fetus

5.3 Harlequin Fetus

5.4 Harlequin Fetus

Netherton Syndrome (NS) is an uncommon genodermatosis. It is caused by a loss-

10.1 Hypohidrotic Ectodermal Dysplasia

12.1 Halo Nevi

12.2 Congenital Nevus Photos

12.3 Congenital Nevus

12.4 More CNN Congenital Nevi

12.5 More Congenital Nevi

12.6 Congenital Nevi Surgical Outcomes

14.1 Total Body Linear Epidermal Nevus