Dermatite de Interface Revisao

Interface Dermatitis
A. Neil Crowson, MD; Cynthia M. Magro, MD; Martin C. Mihm, Jr, MD
Interface dermatitis can be classified based upon the cell

type that dominates the infiltrate (ie, neutrophilic, lymphocytic, or lymphohistiocytic) or by the intensity of the
interface inflammation. Regarding lymphocytic interface
dermatitis, there are 2 broad categories: cell-poor interface
dermatitis, when only a sparse infiltrate of inflammatory
cells is present along the dermoepidermal junction, or cell
rich, which typically occurs as a heavy bandlike infiltrate
that obscures the basal layers of the epidermis. In the case
of lymphocytic interface dermatitis, the latter is often
termed a lichenoid interface dermatitis. This review focuses
upon the mononuclear cell-predominant forms of interface
dermatitis.
(Arch Pathol Lab Med. 2008;132:652666)
he term interface dermatitis refers to the finding in a skin

biopsy of an inflammatory infiltrate that abuts or obscures the dermoepidermal junction (DEJ). Historically, interface dermatitis has been classified based in part upon
the cell type that dominates the infiltrate (ie, neutrophilic,
lymphocytic, or lymphohistiocytic). Interface dermatitis
can also be classified by the intensity of the interface inflammation; regarding lymphocytic interface dermatitis,
there are 2 broad categories in our classification scheme.
These include cell-poor interface dermatitis (Table 1),
when only a sparse infiltrate of inflammatory cells is present along the DEJ, or cell rich (Table 2). The infiltrate in
lesions of cell-rich lymphocytic interface dermatitis typically occurs as a heavy bandlike process that obscures the
basal layers of the epidermis; this is often termed a lichenoid interface dermatitis.
CELL-POOR INTERFACE DERMATITIS: THE
DERMATOPATHOLOGY OF CONNECTIVE TISSUE
DISEASE AND ITS MIMICS
Cell-poor vacuolopathic interface dermatitis is defined
by basilar keratinocyte and subepithelial vacuolopathy un-
Accepted for publication October 9, 2007.

From the Departments of Dermatology, Pathology and Surgery, University of Oklahoma and Regional Medical Laboratories, St John Medical Center, Tulsa, Okla (Dr Crowson); the Department of Pathology
and Laboratory Medicine, Weill Medical College, Cornell University,
New York, NY (Dr Magro); and the Departments of Dermatology and
Pathology, Harvard Medical School, Massachusetts General Hospital,
Boston (Dr Mihm).
The authors have no relevant financial interest in the products or
companies described in this article.
Presented in part at the 28th Annual Course, Current Concepts in
Surgical Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, November 2006.
Reprints: A. Neil Crowson, MD, Regional Medical Laboratories, St
John Medical Center, 1923 S Utica Ave, Tulsa, OK 74104 (e-mail:
ncrowson@sjmc.org).
652 Arch Pathol Lab MedVol 132, April 2008
accompanied by a significant inflammatory infiltrate. Usually, there is some lymphocyte tagging along the DEJ
pointing to the immunopathogenetic basis, namely, cellular cytotoxicity, either in the context of a type 4 immune
reaction or of antibody-dependent cellular cytotoxicity, or
a type 2 immune reaction, when autoantibodies target
components of the basement membrane zone to trigger an
antibody-dependent cellular cytotoxicity reaction.
The prototypic differential diagnoses of a cell-poor interface dermatitis include erythema multiforme; autoimmune connective tissue disease, particularly systemic lupus erythematosus, dermatomyositis, and mixed connective tissue disease; graft-versus-host disease (GVHD);
morbiliform viral exanthem; and morbiliform drug reaction (Table 1).
There are a variety of more recently described entities
that also manifest a lymphocytic interface inflammatory
infiltrate, such as the human immunodeficiency virus
(HIV)related dermatoses, the cutaneous eruption of lymphocyte recovery, and the superantigen id reaction. Cutaneous T-cell dyscrasias and cutaneous T-cell lymphoma
can be associated with a combination of interface inflammation and basal layer epidermal colonization, and thus
they enter into the differential diagnosis of interface dermatitis.1,2 Specifically, so-called interface parapsoriasis (or
cutaneous lymphoid dyscrasia of the hypopigmented interface type), pityriasis lichenoides,3 and patch or early
plaque-stage lesions of mycosis fungoides may manifest
this histomorphology.2,3 Furthermore, there are additional
forms of autoimmune connective tissue disease (CTD) that
have been associated with an interface dermatitis, including Sjogren syndrome, vitiligo, 4,5 and autoimmune
thryoiditis.6
ERYTHEMA MULTIFORME
Introduction/Clinical Features
Erythema multiforme is a distinctive clinical pathologic
entity with a wide variety of underlying causes. The classic lesion has a targetoid morphology with a peripheral
rim of erythema and a central zone of pallor. Some lesions
manifest a dusky or violaceous appearance with no true
central clearing. Blisters may be observed. As the pathogenetic basis of erythema multiforme is one of cellular cytotoxicity, the sites of predilection are those where antigenic processing is maximal, which includes the palms
and soles, but lesions may occur elsewhere and may become widespread.
Histopathology
Common to cases of drug- or infectious-based etiology
are focal areas of basilar vacuolopathy accompanied by
Interface DermatitisCrowson et al
Table 1.
Prototypes of Cell-Poor Interface Dermatitis
Erythema multiforme
Autoimmune connective tissue disease, particularly
Systemic lupus erythematosus
Dermatomyositis
Mixed connective tissue disease
Graft-versus-host disease
Morbiliform viral exanthem
Morbiliform drug reaction
lymphocyte tagging along the DEJ; suprabasilar lymphocytosis around degenerating keratinocytes also may be
seen (Figure 1). In those cases mediated by infection, one
typically observes a fairly brisk angiocentric superficial
and deep lymphocytic infiltrate, along with a cell-poor interface dermatitis with minimal epidermal injury. In contrast, cases of drug-based etiology may show a less intense
dermal-based inflammatory cell infiltrate, often with tissue eosinophilia but with more pronounced degenerative
epithelial changes, including discrete zones of confluent
epidermal necrosis (Figure 2). Focal areas of basilar vacuolopathy accompanied by lymphocyte tagging along the
DEJ are the hallmarks; suprabasilar lymphocytosis around
degenerating keratinocytes also may be seen. In drugbased erythema multiforme, acrosyringeal accentuation of
these interface inflammatory and degenerative epithelial
changes is typical. There may be streak dyskeratosis,
whereby basilar keratinocytes acquire an elongated cigarshaped morphology with hypereosinophilic condensed
cytoplasms and pyknotic elongated nuclei. As most clinicians biopsy acute lesions, the epidermis is typically of
normal thickness and is surmounted by a basket weave
pattern of orthokeratosis. Lesions of active herpes not infrequently show areas of interface dermatitis resembling
erythema multiforme; characteristic viral cytopathic
changes of herpes, however, may be observed.
Differential Diagnosis
The main consideration is that of acute autoimmune
CTD, typically as seen in the setting of systemic CTD syndromes. In our experience, in lesions of systemic lupus
erythematosus (SLE) (Figure 3) or dermatomyositis (Figure 4), the presence of striking dermal mucin deposition
is a helpful distinguishing feature. As well, the degree of
epithelial injury in such cases is usually less than that observed in erythema multiforme. Acrosyringeal accentuation, as seen in drug-associated erythema multiforme, is
not present in lesions of acute systemic collagen vascular
disease. Although tissue eosinophilia may be observed in
drug-associated erythema multiforme, eosinophilis in lesions of CTD are uncommon outside of a few specific settings, such as drug-induced SLE and bullous SLE. In erythema multiforme there usually is no alteration of the
stratum corneum, pointing to the transient and acute nature of the eruption. In contrast, in the interface dermatitis
of CTD, hyperkeratosis and parakeratosis are frequent.
Also, a function of the transient and acute nature of erythema multiforme is the unaltered architecture of the epidermis with preservation of the retia, in contrast to CTD,
where one typically observes an atrophying interface dermatitis with retiform effacement. Furthermore, pauci-inflammatory mucin deposition is highly characteristic for
lesions of collagen vascular disease.
Arch Pathol Lab MedVol 132, April 2008
Table 2.
Prototypes of Cell-Rich Interface Dermatitis
Idiopathic lichenoid disorders

Lichen planus
Lichen nitidus
Lichen striatus
Lichenoid autoimmune connective tissue disease, particularly
Discoid lupus erythematosus
Anti-ROpositive systemic lupus erythematosus
Mixed connective tissue disease
Lichenoid and granulomatous dermatitis
Lichenoid purpura
Lichenoid and fixed drug reaction
The distinction of erythema multiforme from acute

GVHD (Figure 5) may be difficult. There are, however, 3
useful morphologic clues: (1) in acute GVHD, the interface
change is characteristically very focal, with accentuation
at tips of rete ridges; (2) there is a dearth of tissue eosinophilia; and (3) follicular involvement is very common and
at times can be the anatomic structure manifesting the
brunt of interface change. A recent study demonstrated
that intraepidermal bile pigment deposition can be seen
in biopsies of GVHD specimens and correlates with hyperbilirubinemia and/or liver involvement. While this
finding is only observed in a minority of cases of GVHD,
it is a highly specific finding; it is not observed in erythema multiforme unless, of course, there is unrelated liver
disease. We have never found this a useful morphologic
clue.
Autoimmune progesterone dermatitis is temporally associated with the menstrual period. The manifestations
are polymorphous and include urticaria, erythema multiforme, and eczema, although we have even encountered
erythema nodosumlike lesions. Histologically, the cases
show a variable histomorphology dependent on the clinical presentation. Cases resembling erythema multiforme
show a vacuolar interface dermatitis with varying degrees
of keratinocyte necrosis. During each cycle, the eruptions
may appear at previously affected sites, hence mimicking
the clinical features of a fixed drug eruption. This rare
phenomenon is attributed to an autoimmune reaction to
female sex hormones. The condition can improve with tamoxifen, which suppresses ovulation and the postovulation rise in endogenous progesterone levels. In extreme
cases, an oophorectomy is performed.
Pathogenesis
Erythema multiforme is a type 4 cellular cytotoxic reaction. Provocation of lesions is typically related to ingestion of drugs or to infection with viruses or microbial
pathogens, such as Mycoplasma sp7 or herpes, including in
the context of recurrent herpes labialis. Classical targetoid
lesions are more common in patients whose erythema
multiforme is triggered by herpes simplex. The disease is
typically self-limited, but it may recur. Drug-induced
forms of erythema multiforme can be quite severe. When
the eruption is extensive, there may be severe oral mucosal
involvement, which defines Stevens-Johnson syndrome
(SJS). In SJS, more than 10% of the body surface is affected
by epidermal necrosis and detachment, in a fashion reminiscent of, but less marked than, toxic epidermal necrolysis (TEN), in which more than 30% of the skin surface
is so affected.8 Case fatality rates are 1% to 5% in the forInterface DermatitisCrowson et al
653
Table 3.
Lupus Erythematosus: Comparison of Clinical and Direct Immunofluorescence Manifestations by Subtype*

Feature
Lesion character
Scale
Follicular atrophy
Photodistribution
Scarring
Atrophy
Pigmentary alteration
Telangiectasia
SLE
SCLE
DLE
Fine, easily detached

Absent
Present
Absent
Usually absent
Slight
Present
Fine, easily detached

Absent
Marked
Absent
Usually absent
Slight
Present
Thick, adherent
Present
Present
Present
Present, often marked
Often marked
Present
4 ACR criteria for SLE (incidence)

100%
40%
Positive lupus band test
90%
60%
Lesional skin
Active disease 90%
30%
Nonlesional sun-protected skin
Inactive disease 30%
* SLE indicates systemic lupus erythematosus; SCLE, subacute cutaneous lupus erythematosus; DLE, discoid
American College of Rheumatology. After Crowson and Magro.17
mer instance and 25% to 35% in the latter, where management in a dedicated burn unit is necessary.9 Genetic
factors appear to predispose patients to SJS, at least in
certain populations.10 A viral etiology is rarely implicated
for these severe forms of erythema multiforme. There are
rare reports of erythema multiforme following allergic
contact dermatitis with nickel and poison ivy (ie, Rhus
dermatitis). Eruptions mimicking TEN also have been described in the setting of drug-induced linear immunoglobulin (Ig) A disease, paraneoplastic pemphigus, and
GVHD. In all of these aforesaid conditions where the clinical features are truly indistinguishable from true druginduced TEN, the baseline morphology would capture
features unique to each of the disorders, such as areas of
neutrophilic interface in IgA disease, acantholysis in the
setting of pemphigus, and striking follicular involvement
in the setting of GVHD. The epidermal necrosis in erythema multiforme is mediated by cytotoxic T cells of the
TC1/TC2 subsets11 through provocation of apoptosis and
by acting through interaction between circulating soluble
Fas and its receptor, FasL.12 This feature is the logic behind
the therapeutic application of intravenous immunoglobulin, which binds soluble Fas in the peripheral blood stream
and has thus been thought to have a potential role in the
treatment of TEN.8 Synergistic action with helper T cells,
including those of the TH2 subset, is implied by demonstration of the thymus- and activation-regulated chemokine.13
As mentioned above, herpes-associated erythema multiforme occurs in association with recurrent herpes simplex infection. Herpes DNA polymerase gene (Pol) and pol
gene expression have been shown in recurrent erythema
multiforme lesions in this setting, the latter through immunohistochemistry using antibody directed against pol
in lesional skin of patients with herpes-associated erythema multiforme. In addition, the T-cell receptor variable
chain repertoire in such patients is composed primarily of
V2 chainpositive cells, suggesting a selective homing of
lymphocytes to sites of viral antigen expression.14
Antibodies directed against desmosomal plaque proteins desmoplakins 1 and 2 have been described in a subset of patients with erythema multiforme major. Such
studies suggest a humoral-based etiology in the propagation of lesions of erythema multiforme in these patients.
The epitope is localized at the carboxy-terminal domain
of desmoplakin and is responsible for the assembly of keratin filaments with desmosomes. Purified human anti654 Arch Pathol Lab MedVol 132, April 2008
10%
90%
010%
lupus erythematosus; and ACR,
body directed against the carboxy terminus of desmoplakins 1 and 2 when injected into newborn mice produces a constellation of changes that resembles erythema
multiforme, suggesting a role for these antibodies in a
subset of patients with erythema multiforme.15,16
THE CONNECTIVE TISSUE DISEASES
Introduction
The manifestations of connective tissue disease in the
skin encompass vasculopathy and vasculitis of leukocytoclastic, granulomatous, and lymphocytic subtypes; panniculitis; and dermal and epidermal infiltrates. The vasculitides and panniculitides are not considered in this review. With respect to the epidermal and dermal findings,
the characteristic morphology seen in most skin lesions of
lupus erythematosus, dermatomyositis, relapsing polychondritis (C.M.M. and A.N.C., personal observation,
1998), Sjogren syndrome, perniosis, and mixed connective
tissue disease comprises a variable superficial or superficial and deep lymphocytic infiltrate in concert with a lymphocytic interface dermatitis ranging from a subtle cellpoor vacuolopathic injury pattern to a lichenoid infiltrate.1724 The hallmark of the cell-poor interface dermatitis
is a sparse number of lymphocytes scattered along the DEJ
with concomitant degenerative epithelial changes manifested by basilar vacuolopathy and dyskeratosis.
Relatively specific to the connective tissue diseases are
hyperkeratosis with follicular and acrosyringeal plugging,
epidermal atrophy, basement membrane zone thickening,
and prominent dermal mucinosis. In those cases of cellpoor interface dermatitis owing to hypersensitivity reactions, where the insult is acute, no alteration of the stratum
corneum or of the basement membrane zone is seen, nor
is dermal mucinosis conspicuous. Chronic vasculopathic
changes defined by reduplicated capillary and venular
basement membranes imparting a hyaline appearance to
the structure in concert with vascular ectasia also are useful morphologic clues.
With respect to the subclassification of connective tissue
disease, a skin biopsy processed for both routine microscopy and for immunofluorescence analysis can provide information of essential value in support of the clinical diagnosis. However, knowledge of the clinical findings (Table 3), including in the context of extracutaneous disease
and serology (Table 4), must be carefully integrated to arrive at a correct diagnosis. The pathologist is in a powerful
position to positively influence this process.
Table 4.
ANA
Seropositivity by Connective Tissue Disease Classification*
ssDNA
dsDNA
Sm
SSA/Ro
SSB/La
nRNP
Histone
Scl 70
SLE
95100
010
70
70
30
40
1020
4050
30
0
SCLE
70
0
1020
0
0
6080
10
0
0
0
DLE
2030
1020
1020
0
1020
10
0
0
0
CRST
90
90
0
0
0
0
0
0
0
0
PSS
70
10
1020
0
0
10
10
20
0
30
MCTD
95100
0
30
0
05
0
0
100
0
0
* Seropositivity is expressed as percentage of cases. ANA indicates antinuclear antibody; C, complement; ssDNA, single-stranded DNA; dsDNA,
double stranded DNA; Sm, Smith; nRNP, nuclear ribonucleoprotein; SLE, systemic lupus erythematosus; SCLE, subacute cutaneous lupus erythematosus; DLE, discoid lupus erythematosus; CRST, CREST syndrome; PSS, progressive systemic sclerosis/scleroderma; and MCTD, mixed connective
tissue disease. After Crowson and Magro.17
Dependent upon ethnicity.
CELL-POOR INTERFACE DERMATITIS OF AUTOIMMUNE

CONNECTIVE TISSUE DISEASE
Introduction
The 2 main connective tissue disease syndromes characterized by a cell-poor vacuolar interface dermatitis are
systemic lupus erythematosus17 and dermatomyositis.19
Dermatologists apply the designation acute lupus erythematosus to the macular erythematous lesions of sudden
onset in patients with SLE. In such acute lesions, the
changes are subtle: the epidermis and the stratum corneum may not show any appreciable alterations, save for a
focal and often subtle basilar vacuolopathy with a few
lymphocytes tagging along the DEJ.17 Patchy parakeratosis
often is seen, and when the lesions have been present for
a few weeks or more, there may be atrophy with attentuation of the retiform pattern. What is more striking are
alterations of the dermis comprising splaying of the collagen fibers by mucin, along with superficial vascular
plexus ectasia. Critical to the diagnosis is the presence of
clinical signs and symptoms that fulfill the American College of Rheumatology criteria for SLE.25 The differential
diagnosis of this particular reaction pattern includes dermatomyositis, which will be discussed on the following
page. We also have observed exactly this morphology in
patients with constitutional symptoms simulating SLE in
the setting of parvovirus B19 infection and Lyme disease.26,27 In any patient who presents with (1) an acute
symptom complex characterized by a skin rash with arthralgia and constitutional symptoms and (2) a skin biopsy histomorphologically resembling acute lupus erythematosus as defined by the criteria above, we recommend
that consideration be given to the possibility of parvovirus
B19 infection and Lyme disease, the latter particularly if
the patient is from an endemic area.
LUPUS ERYTHEMATOSUS
Clinical Features
Lupus erythematosus (LE) is an autoimmune disorder
affecting skin, hematopoietic, and lymphoreticular organs,
joints, kidney, lung, serosa, and cardiovascular structures
in concert or in isolation. Lupus erythematosus is subdivided clinically into systemic (SLE), subacute cutaneous
(SCLE), and discoid (DLE) forms, each with its own characteristic skin findings (Table 5).17,18,25,28,29 A diagnosis of
SLE is based on the presence of 4 or more of the criteria
of the American College of Rheumatology.25 Patients with
SCLE manifest photodistributed, annular, papulosquamous eruptions accompanied by extracutaneous manifestations that, if present, are mild in nature, such as microArch Pathol Lab MedVol 132, April 2008
hematuria or arthralgia.17,18 In DLE, disease is restricted

to a cutaneous expression as one or more scaling plaques
in photodistributed areas, typically involving the head
and neck region.
Histopathologic Features
Some authors aver that light microscopy has limitations
in the subclassification of LE29 and that the differences between subtypes reflect lesional age, a position to which
we emphatically do not subscribe. Although it is true that
a sparse lymphocytic interface infiltrate in the incipient
lesion of DLE may mimic the more ominous systemic form
and that discoid lesions may be seen in SLE patients, the
pattern of disease progression, seen in some 5% of patients, is from DLE to SLE and not vice versa.17,18 Certain
features prove particularly helpful in subclassification.17,18
Lesions of SLE, for example, show a pauci-inflammatory
interface dermatitis with subtle basal layer vacuolopathy
and no basement membrane zone thickening, keratotic follicular plugging, or acanthosis (Figure 3). Skin biopsies
from patients with SCLE demonstrate suprabasilar exocytosis of lymphocytes with satellitosis to necrotic keratinocytes, slight or absent thickening of the basement membrane zone or follicular plugging, and no significant deep
perivascular or periadnexal infiltrate. Atrophy is variable
but usually is present in lesions of SLE and SCLE. Lesions
of DLE generally manifest a heavier superficial and deep
perivascular and periappendageal lymphocytic infiltrate,
basement membrane zone thickening, keratotic follicular
plugging, and variable acanthosis and atrophy.17,18
The differential diagnosis is that of lymphocytic interface dermatitis and embraces dermatomyositis, Sjogren
syndrome, drug-related lupus erythematosuslike eruptions, polymorphous light eruption, perniosis, Jessner lymphocytic infiltrate, vitiligo, erythema multiforme, and certain delayed-type hypersensitivity and id reactions and
viral exanthemata.19,20,22,3032 Kikuchi necrotizing lymphadenitis can produce skin lesions with a lymphocytic vasculopathy and cell-poor interface dermatitis identical to
that seen in SLE,33 but these may in turn reflect a forme
fruste of SLE. The idiopathic lichenoid eruptions lichen
planus, lichen nitidus, and lichen striatus can be problematic if parakeratosis and atrophy are seen.32 Another pitfall
is the distinction of lichenoid actinic keratoses from lesions
of DLE in sun-damaged skin. Correlation with clinical,
serologic, and direct immunofluorescence findings is
therefore imperative. A clinician may be advised to submit
a fresh biopsy of lesional or nonlesional skin, depending
655
Table 5.
Grade 0
Grade 1
Grade 2
Grade 3
Grade 4
Grades of Graft-Versus-Host Disease
No pathologic change
Basal vacuolization
Basal vacuolization, keratinocyte necroses, and
dermal inflammation
Confluence of basal vacuoles
Separation of epidermis from dermis
upon the clinical situation, in a physiologic medium such

as normal saline or Michel transport medium for a lupus
band test (LBT).17,31
Direct Immunofluorescence: The LBT and Its Implications for Pathogenesis of Connective Tissue Diseases. The examination by fluorescence microscopy of frozen sections cut from lesional or nonlesional sun-exposed
or nonsun-exposed skin received fresh, in saline, or in
transport medium and incubated with fluorescein-conjugated antibodies monospecific for IgG, IgA, IgM, and
complement constitutes the LBT.17,31 The definition of a
positive LBT is controversial, with differences in applicable criteria partly explaining the disparate results from
various series. To be considered a positive LBT, deposition
of IgM in sun-exposed skin should assume a continuous
band over at least 50% of the width of the biopsy specimen
and be at least moderate in intensity.17,31 Weak IgM decoration along the DEJ is common in sun-exposed skin of
patients who do not have LE, including in the context of
normal skin specimens from healthy young adults; one
study showed weak interrupted linear and granular IgM
and Clq deposition along the DEJ in 25% of such samples,34,35 whereas deposition of IgG, IgA, and C3 was seen
in less than 5%.17,31 In sun-protected skin, an interrupted
band of IgM of at least moderate intensity is sufficient for
designation as a positive LBT. The deposition of IgG is
usually less intense than that of IgM, but false-positive
results are rare. Thus, even an interrupted weak band of
IgG deposition in sun-exposed skin.17,18,31 can be considered a positive LBT. Concomitant IgA deposition enhances
the specificity of the assay.
Sun-exposed lesional skin should be used to substantiate an initial diagnosis of LE so as to avoid a false-negative result due to reduced sensitivity in sun-protected
skin. After the diagnosis of LE is made, a biopsy of nonlesional skin may be performed to further assist in subclassification and prognostication; a positive LBT in sunprotected skin is predictive of systemic disease in the context of renal and other organ involvement. Although a skin
lesion less than 2 months old may give negative direct
immunofluorescence results, a positive LBT is seen in 90%
of lesional skin biopsies from DLE and SLE patients. A
negative LBT is almost invariably seen in nonlesional skin
of DLE patients, whereas more than 80% of nonlesional
skin biopsies show a positive LBT in SLE patients.36 The
LBT is positive in more than 90% of sun-exposed nonlesional skin biopsies from SLE patients with active disease
versus only one third of patients with inactive disease.36
Patients with SCLE manifest a positive LBT in only 30%
to 50% of cases.18
Indirect Immunofluorescence: The Membrane Attack
Complex of Complement and Its Putative Pathogenetic
Role. An indirect immunofluorescence methodology to
detect the presence of the membrane attack complex of
complement (C5b-9) in frozen sections may be a helpful
adjunct to the LBT.18 Keratinocyte fluorescence for C5b-9
correlates with seropositivity for antibodies to extractable

nuclear antigens Smith (Sm), Ro/SSA, La/SSB, or RNP.
Patients with such antibodies often manifest distinctive
clinical features and may be seronegative for antinuclear
antibody.18 Antibodies to La correlate with SICCA syndrome, and in the setting of SCLE may be predictive of a
higher incidence of pulmonary disease, whereas patients
with SLE who have antibodies to Ro are at greater risk
for photosensitive skin eruptions, interstitial pneumonitis,
myositis, myocarditis, and complete heart block.37,38 Patients with antibodies to RNP frequently have Raynaud
disease, sclerodactyly, and myopathy.39 The Ro, La, Sm,
and RNP antigens are small ribonucleoprotein macromolecules resident in nuclei and, in the case of Ro, the cytoplasms of all eukaryotic cells.39 Binding of the Ro autoantibody may be dependent on relocation of nuclear and
cytoplasmic Ro antigens to the cell surface, an event that
follows UV light exposure, viral infection, or estrogen
therapy.4042 The presence of the membrane attack complex
of complement in the basement membrane zone of skin
lesions of patients with SLE and DLE and of renal tubules
in patients with lupus nephritis, coupled with its absence
in uninvolved skin, suggests its pathogenic role.18,43 The
surface binding of anti-Ro antibodies may allow adherence of C5b-9, the latter forming plasmalemmal pores that,
in concert with antibody-dependent cellular cytotoxicity,
may be an important mechanism of keratinocyte injury.18,43,44
Vascular deposition of C5b-9 is seen in dermatomyositis,
in mixed connective tissue disease (MCTD), and in SLE
patients who possess the lupus anticoagulant, antibodies
to Ro, or biopsy-proven lymphocytic vasculitis.18,19,38,45,46
Vasculitis has been shown in skeletal muscle biopsy specimens of LE patients with anti-Ro and anti-La antibodies,
perhaps reflecting localization of the Ro antigen to endothelia, as has been shown in vitro.38,40,47 In addition to myositis, SLE patients with anti-Ro antibodies manifest cutaneous lesions virtually identical to those seen in dermatomyositis.38
DERMATOMYOSITIS
Clinical Features
Dermatomyositis combines an inflammatory myopathy
with characteristic skin lesions: the often-subtle heliotrope
rash, the Gottron papule, a violaceous or hypopigmented
papule over the joints of the fingers, erythema of the upper back (the shawl sign), extensive erythema of the
extensor surfaces of the arms, scaly alopecia, and cuticular
overgrowth with periungual telangiectasias.19,4850 Although myositis usually eventuates, skin involvement may
be unaccompanied initially by objective evidence of muscle disease; such cases are referred to as amyopathic dermatomyositis or dermatomyositis sine myositis.51 In adult populations, roughly one third of patients have an underlying
malignancy, with statistical correlation demonstrated to
lymphoma and to carcinomas of ovary, lung, pancreas, colon, and stomach.48,52 Other manifestations include arthritis, myocarditis, and esophageal and pulmonary disease.
Dermatomyositis appears to represent an aberrant immune response directed principally at endothelia in an
immunogenetically predisposed individual following antigenic stimuli, such as neoplasms, drugs, or infections.
With respect to the latter, it has been demonstrated that
symptomatology in some cases of dermatomyositis reInterface DermatitisCrowson et al
Figure 1. Erythema multiforme. A, There is a superficial and middermal perivascular lymphocytepredominant infiltrate that extends into the
basal layers of the epidermis, where a lymphocytic interface injury pattern is seen. At the outset, this pattern is cell poor, becoming more robust
over time, as in this example (original magnification 100). B, As the lesions age, or in severe cases as exemplified by Stevens-Johnson syndrome,
keratinocyte necrosis may become more confluent. This is particularly true for drug-induced examples which, as in this case, may show significant
tissue eosinophilia (original magnification 100).
Figure 2. Toxic epidermal necrolysis. The full thickness of the epidermis is necrotic and shows detachment from the dermis (original magnification
100).
Figure 3. Acute lupus erythematosus. As typifies most of the skin lesions in patients with systemic lupus erythematosus, this biopsy shows a cellpoor lymphocytic injury pattern (original magnification 100).
Figure 4. Dermatomyositis. A, There is a subtle lymphocytic interface infiltrate that extends into the basal layer of the epidermis. The blood
vessels of the superficial vascular plexus show ectasia (original magnification 100). B, The ectatic blood vessels (straight arrow) are either devoid
of endothelia or are lined by hyperchromatic (curved arrow), degenerating, and/or proplastic endothelia, and there is loss of dermal papilla
capillaries (original magnification 600).
657
Figure 5. Acute graft-versus-host disease. There is a very subtle cell-poor lymphocytic interface injury pattern (arrow) that often shows accentuation
in the adnexal structures (original magnification 100).
Figure 6. Pityriasis lichenoides chronica. A, An interface dermatitis pattern is visible from scanning and intermediate magnifications. Confluent
parakeratosis is classical (original magnification 100). B, The pattern of epidermal percolation is a haphazard pattern, accompanied by only
slight or no spongiosis reflecting the pathobiology of the infiltrate: a clonally restricted cutaneous T-cell dyscrasia (original magnification 200).
flects the presence of endotheliotropic viruses, such as

parvovirus B19, that may alter endothelial antigenicity.26,53
reactions, do not typically produce the same vascular injury patterns.
MIXED CONNECTIVE TISSUE DISEASE
Although some observers doubt that histologic criteria

exist to distinguish dermatomyositis from other connective tissue diseases, such as SLE, SCLE, and MCTD, a constellation of light microscopic and immunofluorescent features, in concert with modern serology, is virtually pathognomonic for each of these entities.1721 Skin lesions of
dermatomyositis manifest an atrophying cell-poor lymphocytic interface dermatitis accompanied by dermal mucinosis and vascular alterations that vary according to the
age of the lesion biopsied and the presence or absence of
myopathy: in patients with myopathic dermatomyositis, a
characteristic injury pattern comprising a variably cellpoor, often thrombogenic lymphocytic vasculopathy
mainly affecting the dermal papillae capillaries is seen.
Clinical Features
Immunofluorescence
The immunofluorescent profile of dermatomyositis
comprises a negative LBT in conjunction with membrane
attack complex (C5b-9) deposition along the DEJ and within
blood vessels.19 Similar vascular deposition is seen in the
setting of SLE with antibodies to Ro and MCTD in the
setting of antibodies to RNP.21,38 All 3 conditions manifest
myopathy, interstitial lung disease, and vasculitis, perhaps
reflecting the common localization of antibodies to endothelial RNA antigens, the expression of which is up-regulated owing to endogenous or exogenous triggers.
The differentiating points of dermatomyositis from
most cases of LE include active vascular injury characterized by endothelial cell necrosis and intraluminal fibrin
deposition along with the end sequelae of vasculopathy,
namely, reduction of vascular density and vascular ectasia
(Figure 4). Hypovascularity is more conspicuous in cases
of myopathic versus amyopathic dermatomyositis, implying that cutaneous vascular changes mirror those in muscle, whereby a critical reduction in vascular density is necessary to generate objective evidence of myopathy.19,54,55 In
MCTD, a lymphocytic interface injury pattern in concert
with a lymphocytic vasculopathy can closely mimic dermatomyositis. Sclerodermoid tissue alterations are fairly
common in the former but rare in the latter. Eosinophils
are observed in biopsies of dermatomyositis in approximately 10% to 20% of cases (A.N.C. and C.M.M., personal
observation, 2000) but are rare in idiopathic LE and
MCTD, possibly reflecting a pathogenic role for aberrant
delayed-type hypersensitivity in a minority of cases. The
other causes of cell-poor vacuolopathic interface dermatitis, such as certain viral exanthems and hypersensitivity
Mixed connective tissue disease was first defined by

Sharp et al56 as a distinct rheumatic disease syndrome associated with high titers of antibody to an extractable nuclear antigen (nRNP). The typical features include Raynaud phenomenon, polyarthritis, polyserositis, myositis,
sclerodactyly, restrictive lung disease, lymphadenopathy,
and esophageal dysfunction. The cutaneous manifestations include SLE-like malar erythema, discoid plaques, an
SCLE-like photodistributed eruption, swollen hands,
sclerodactyly, and vasculitis.
Biopsies of the photodistributed eruptions show a cellpoor or lichenoid interface dermatitis with suprabasilar
exocytosis around necrotic keratinocytes in the absence of
deep periadnexal or perivascular extension or conspicuous
follicular plugging.21
Immunofluorescence
Nuclear keratinocyte immunoreactivity with IgG and
C5b-9 is demonstrated in all cases studied, accompanied by
a positive LBT in roughly one half of cases. The in vivo
speckled nuclear staining for IgG observed within keratinocytes of lesional and nonlesional skin correlates with
antibodies to nRNP, the serologic hallmark of MCTD.
Granular vascular deposition of immunoreactants, including C5b-9, also is seen.21
The histopathology of MCTD mimics SCLE by virtue of
the lymphocytic interface dermatitis, but it differs by
showing vasculopathic alterations comprising ectasia, hypovascularity, and luminal thrombosis confined to the superficial vascular plexus, and sometimes by a concomitant
sclerodermoid tissue reaction.21 As mentioned, distinction
from dermatomyositis can be problematic. Perniosis can
demonstrate a similar pattern of interface injury with associated lymphocytic vasculopathy, but the exocytosis of
lymphocytes in perniosis tends to be directed to retia and
acrosyringia.22 The interface dermatitis of erythema multiforme often is accompanied by pronounced papillary
dermal edema, tissue eosinophilia, and epidermal colloid
body formation in the absence of atrophy, vascular density
reduction, or alterations of the stratum corneum.
Acute GVHD. Clinical Features. Acute GVHD manifests as erythematous patches occurring classically within
30 days following bone marrow transplantation. The skin
is the most common site of involvement of GVHD, al-
Figure 7. Lichen planus. A, The prototypic biopsy shows compact orthohyperkeratosis, wedge-shaped thickening of the granular cell layer, a
sawtooth pattern of acanthosis, and a heavy, bandlike lymphoid infiltrate, unaccompanied by tissue eosinophilia, that obscures the dermoepidermal
junction and is unassociated with deep extension. This is the definition of a lichenoid infiltrate (original magnification 100). B, A heavy lymphoid
infiltrate unaccompanied by tissue eosinophilia obscures the basal keratinocytes, which show apoptosis with cytoid (colloid or Civatte) body
formation (arrow). Postinflammatory pigment incontinence is the result (original magnification 200).
Figure 8. Lichen nitidus. A circumscribed lymphohistiocytic infiltrate is present. It splays apart the adjacent rete ridges (original magnification
100).
659
though other organ systems, such as the liver and gastrointestinal tract, also are involved frequently. The erythematous patches are typically acral in location and may form
blisters in severe examples. Rarely, acute GVHD will develop in patients who receive autologous blood transfusions of nonirradiated blood or blood products that have
not been subjected to leukopheresis.
Histopathology. Acute GVHD produces a cell-poor lymphocytic interface inflammatory process that is often accentuated in the acrosyringia or in the terminations of hair
follicles within the epidermis (Figure 5).4 A grading
scheme has been produced (Table 5). Damage to the epidermis results in loss of keratinocyte nuclear polarity, often attributed to the injection or administration of antineoplastic agents. These changes, in concert with individual cell necrosis of keratinocytes, occurring within 3
weeks of transplantation are more likely to be a sequel of
the administration of cytoreductive agents than to acute
GVHD. Eosinophils are sometimes present in lesions of
acute GVHD. The most severe form of GVHD is indistinguishable from toxic epidermal necrolysis.
Differential Diagnosis. The differential diagnosis of
acute GVHD is that of the cell-poor interface dermatitides
discussed at the onset of this review.
Interface Dermatitis of HIV Infection. Clinical Features. HIV infection may be associated with a variety of
inflammatory dermatoses ranging from eosinophilic folliculitis to seborrheic dermatitis. Patients also may develop
a peculiar multifocal plaque and patchlike erythema with
scaling that becomes violaceous over time and is associated with pronounced hyperpigmentation. This eruption
is often itchy and often shows a photodistribution with
accentuation in the face and neck.
Histopathologic Features. Common to the biopsies from
many of these different pathophysiologic entities is a
mononuclear cell interface dermatitis lateral to the main
area of tissue pathergy. The infiltrate is typically lymphocytic with deep extension and accompanied by admixed
eosinophils, histiocytes, and plasma cells.
Differential Diagnosis. The differential diagnosis includes both cell-poor and cell-rich interface dermatitis of
diverse ideology. This entity is included in the section on
cell-poor interface dermatitis, as that is the classic and
most common histomorphology of the interface inflammatory infiltrate in such lesions.4
VITILIGO
Clinical Features
Vitiligo is an acquired disorder in which an autoinflammatory lymphocytic infiltrate targets melanocytes in various locations, typically resulting in loss of pigment in
skin, mucous membranes, and/or hair.5 It appears that
there is a complex interplay of genetic and environmental
factors. Although there are case reports of vitiligo and hair
pigment loss concurrent with the presence of underlying
central nervous system tumors and with exacerbation of
multiple sclerosis, case control studies fail to confirm a
statistically significant increase of vitiligo in the latter setting.57 Other autoimmune disorders of a systemic nature,
including perncious anemia and type 1 diabetes mellitus,
have been shown to have a statistical link to vitiligo, as
does an increased incidence of alopecia areata and hypothyroidism.58 On occasion, the areas of skin depigmentation in cases of vitiligo manifest a blaschkolinear distri660 Arch Pathol Lab MedVol 132, April 2008
bution, implying a role for genetic mosaicism in the expression of the disease.59 Triggering of the autoimmune
diathesis by hepatitis C virus is implied by one case report
in which the vitiligo lesions improved with antiviral therapy in a hepatitis C patient.60
At the advancing edge of a vitiligo lesion, skin biopsy
shows a lymphocytic interface dermatitis that is variably
cell poor. In the older center of such a lesion, postinflammatory melanophage accumulation may be seen in concert
with a decrease or absence of melanocytes.
PITYRIASIS LICHENOIDES
Clinical Features
Pityriasis lichenoides is a self-limited dermatosis that
usually presents in the first to third decades of life and
shows a predilection for males. The onset ranges from an
acute eruption termed pityriasis lichenoides et varioliformis
acuta (PLEVA) to a chronic eruption, pityriasis lichenoides
chronica (PLC), which tends to heal with postinflammatory
hyperpigmentation. Lesions number from dozens to hundreds and frequently affect the anterior trunk and flexor
aspects of the proximal extremities preferentially. The etiologic basis has long been postulated to be viral in nature,
based in part on the clinical behavior and in part on phenotypic studies that show a characteristic infiltrate comprising CD8 lymphocytes admixed with a minor populace of Langerhans cells or indeterminate cells. Although
there are rare case reports of the detection of cytomegalovirus in endothelia of cases of PLEVA,61 larger series
have shown clonal restriction in lesions of PLEVA1,3,6264
and PLC.1,3,6264 The T-cell populations in both forms of pityriasis lichenoides show deletion of postthymic T-lineage
markers, indicating that the process represents a true lymphoid dyscrasia.63 Recently, we have shown relative defects in activity of the CD4/CD25 T-regulatory cell population.3
In PLEVA, the DEJ often is obscured by a pure population of lymphocytes associated with basal layer vacuolopathy, colloid body formation, and variable but sometimes
confluent epidermal necrosis. Intraepidermal hemorrhage,
endothelial swelling, papillary dermal edema, bleeding,
and wedge-shaped superficial and deep dermal lymphoid
infiltrates are characteristic.1 The parakeratotic scale often
contains neutrophils. A rare extreme expression of the disease is the ulceronecrotic variant, in which necrotizing
lymphocytic vasculitis produces confluent epidermal necrosis.65 Parakeratosis often is confluent and epidermal injury less striking in PLC (Figure 6).66 The epidermis may
show superficial pallor, and melanophages often are present in the papillary dermis, reflecting basal layer injury.
As PLEVA and PLC represent poles of a spectrum of injury, not all cases can be comfortably classified as one or
the other; some authorities sign out most cases simply as
pityriasis lichenoides without further qualification.16
The differential diagnosis includes pityriasis rosea, in
which discrete mounds of parakeratin overlie foci of epidermal spongiosis, and small-plaque parapsoriasis, where
the degree of epithelial injury generally is less and the
infiltrate more sparse.66 The common viral exanthem patInterface DermatitisCrowson et al
tern may mimic PLEVA by virtue of a perivascular and

interface lymphocytic infiltrate accompanied by basilar
vacuolopathy with scattered cytoid bodies and streak dyskeratosis, but the epidermis usually is surmounted by a
basket-weave pattern of orthokeratinization, and the lymphocytic infiltrate is usually only superficial. Similar features also typify evolving lesions of erythema multiforme,
which may show eosinophils in the dermal inflammatory
populace, a finding that helps to enable distinction. Secondary syphilis merits consideration, but it usually has a
significant plasma cell component, which is at variance
with the pure lymphoid populace of pityriasis lichenoides.
Connective tissue diseases with pronounced keratinocyte
degeneration, such as SCLE, can be problematic if a superfical shave biopsy is submitted and the deep infiltrates
of pityriasis lichenoides, which would enable distinction,
cannot be assessed. Large plaque parapsoriasis may be
considered, as it manifests an interface pattern of colonization with a wiry pattern of horizontal collagen fiber
thickening typically absent in lesions of PLEVA but common in lesions of PLC.63
HYPOPIGMENTED INTERFACE VARIANT OF
PRELYMPHOMATOUS CUTANEOUS
LYMPHOID DYSCRASIA
Introduction
This entity has fallen under the appellation hypopigmented mycosis fungoides and manifests a characteristic race,
sex, and age predilection.1 Patients are usually younger
and of African American extraction; there is a female predilection. The lesions often involve truncal areas similar
to typical mycosis fungoides. While hypopigmented mycosis fungoides has been described, a hypopigmented variant of large plaque parapsoriasis as a precursor state has
not been specifically alluded to in the literature. There is,
however, a form of interface parapsoriasis. Many of the
cases of hypopigmented mycosis fungoides described in
the literature do not manifest a clinical course or a histology specimen diagnostic of fully evolved mycosis fungoides, and are thus better characterized as a form of cutaneous lymphoid dyscrasia falling under the designation
of hypopigmented large plaque parapsoriasis and/or hypopigmented epitheliotropic T-cell dyscrasia.
The histology comprises a low-density epitheliotropic
lymphocytic infiltrate with characteristic colonization of
the basal layer unaccompanied by significant destructive
epithelial changes. The lack of epithelial injury distinguishes this process from a true immunologically mediated interface dermatitis. There is often a haphazard single-cell pattern of lymphocyte migration into the upper
layers of the epidermis. Pautrier microabscesses are not
seen; the presence of such discrete aggregates of neoplastic lymphocytes in the epidermis would warrant categorization as mycosis fungoides. Many of the cells in the
epidermis have a distinctly cerebriform appearance; a
small celldominant infiltrate predominates. There may be
some accentuation of migration to involve hair follicles
and acrosyringia.
Phenotypic Studies
There is a significant reduction in CD7 and CD62L expression; often CD62L shows a greater loss than CD7.
From a phenotypic perspective, there is a predominance
of CD8 lymphocytes over those of the CD4 subset.1 If the

CD8 lymphocytes are reactive and induce lesional resolution and/or contribute to immunologic surveillance to
prevent disease progression, one would expect to see
greater epithelial injury of bystander keratinocytes as the
basis for the leucoderma.
Molecular Studies
We have studied similar cases and have observed the
same restricted oligoclonal T-cell repertoire between biopsies, adding credence to the designation of these cases
as forms of cutaneous lymphoid dyscrasia.
CELL-RICH INTERFACE DERMATITIS: THE LICHENOID
TISSUE REACTION
Introduction
Cell-rich interface dermatitis is defined by us as an inflammatory infiltrate along the DEJ that is of sufficient
intensity that it obscures, at least focally, the basilar keratinocytes. When this process is bandlike in character it
may be termed lichenoid. Interface dermatitis can comprise
a mainly lymphocytic population, a mainly lymphohistiocytic infiltrate, or a granulocyte-predominant interface injury pattern. The latter may, in turn, be classified as a neutrophil-predominant pattern, as seen, for example, in linear IgA disease or bullous lupus erythematosus, or an eosinophil-predominant pattern, as seen in bullous
pemphigoid. The granulocyte-predominant injury pattern
is beyond the scope of this review, which confines itself to
the lymphocyte-predominant interface injury pattern. Lichenoid interface dermatitis is seen in numerous conditions, including lichen planus, lichenoid hypersensitivity
reactions of drug- or contact-based etiology, lichenoid reactions in the setting of hepatobiliary disease,67 secondary
syphilis, and autoimmune CTD. Lichenoid pigmentary
purpura of Gougerot and Blum is a form of pigmented
purpuric dermatosis which often is associated with a
drug-based etiology and is discussed in more detail below. Most of the foregoing will be considered with a specific emphasis on distinctive light microscopic features.
When a lichenoid interface dermatitis is present, the onus
is on the clinician to consider, to investigate, and to exclude, where appropriate, these various disorders. The idiopathic lichenoid disorders include lichen planus, lichen
nitidus, and lichen striatus. The prototype is lichen planus.32
LICHEN PLANUS
Clinical Features
Considered an idiopathic dermatosis, lichen planus
manifests as violaceous, itchy, flat-topped, polygonal papules covered by a reticulated surface scale termed Wickham
striae. Lesions typically manifest on the volar aspect of the
forearms and other flexural surfaces of acral parts; genitalia are often involved. Lesions may be widespread. Oral
changes accompany the cutaneous eruption in roughly
one half of cases, and these manifest as linear or reticulate
whitish plaques and as lacy white patches along the occlusal lines of the buccal mucosa and elsewhere. Nail
changes are frequently seen and manifest as dystrophies
with ridging and splitting of the distal aspect of the nail
plate. Variants of lichen planus include the atrophic form
(lichen planus actinicus), hypertrophic lichen planus, bullous lichen planus, and linear lichen planus. Hypertrophic
661
lichen planus is particularly problematic diagnostically, as

significant pseudoepiltheliomatous hyperplasia occurs in
response to chronic rubbing and irritation, classically on
the shins, and closely mimics well-differentiated squamous cell carcinoma histologically. Scarring alopecia may
be seen in association with lichen planus; this is termed
lichen planopilarias. A lichen planuslike eruption can be
seen in patients infected with hepatitis C virus or hepatitis
B virus68; case control studies show conflicting data regarding the significance of the association, but most observers accept that one exists.69,70
Histopathology
Compact orthohypokeratosis overlying an epidermis
that shows wedge-shaped thickening of the granular cell
layer and a sawtooth pattern of acanthosis is prototypic
for lichen planus (Figure 7). A dense, bandlike lymphocytic infiltrate obscures the DEJ; in our lexicon, this is the
defining feature of a lichenoid dermatosis. There is no
deep extension of the infiltrate in idiopathic lichen planus,
and eosinophils should number no more than 1 to 3 per
any given tissue section of a 4-mm punch biopsy specimen. As they undergo destruction, the basal keratinocytes
release melanin into the dermis with compensatory accumulation of dermal melanophages to cause postinflammatory hyperpigmentation clinically. Repair of the basal
layers of the epidermis is associated with the squamotization of the basal layer, with replacement of the normal
cuboidal progenitor cells in that anatomical location. Cleftlike spaces may form between the undersurface of the epidermis and dermis; these are termed Max-Joseph spaces.
This process may eventuate in clinically evident bullous
lesions (ie, bullous lichen planus).
As lesions of lichen planus are itchy, they may be
rubbed and chronically irritated; parakeratosis may supervene. With persistent rubbing and irritation, pseudoepitheliomatous change may be superimposed to generate
hypertrophic lichen planus. End-stage lesions may show
compact orthohyperkeratosis with slight thickening of the
epidermis but lack the significant inflammatory component, therefore having a nondiagnostic histomorphology.
Biopsies from mucosal sites similarly show a bandlike
lymphocytic and histocytic infiltrate obscuring the epithelial-submucosal interface, but in mucosal sites, tissue eosinophilia is often profound. Atrophic lichen planus
(sometimes called lichen planus actinicus) has atrophy with
attenutation of the retiform pattern.
From a pathophysiologic perspective, the lymphoid cells
are T cells expressing CD3 and CD4. Increased numbers
of T cells are often present along the DEJ; this is a form
of T lymphocyte that is only a minor fraction of circulating
T cells in humans and responds to a broad array of microbial pathogens, including in the context of those with
superantigen properties. This is one clue to the possible
infection-triggered etiology of lichen planus, including in
the context of the hepatitis Ctriggered lesions.68
If significant tissue eosinophilia is present in the lichenoid inflammatory process, a lichenoid drug eruption or
fixed drug eruption should be suspected.71 Solitary lesions
of benign lichenoid keratosis or lichenoid actinic keratosis
show a dome-shaped contour with a peripheral actinic
lentigo in the former instance and basal layer crowding
and atypia in the latter. Furthermore, benign lichenoid keratosis occurs typically on the trunk in the clinical setting
of a suspect basal cell carcinoma, whereas lichenoid actinic
keratosis is seen in the setting of dermatoheliosis and is

frequently a multifocal process. A clinician should always
specify when a lichenified dermatosis, as opposed to a
solitary lesion, is biopsied.
LICHEN NITIDUS
Lichen nitidus classically presents clinically as miliary
papules involving the arms, trunk, and penis,7275 and histologically as a superficial lymphocytic and granulomatous infiltrate that imparts a ball in claw appearance to
the epidermis and subjacent dermal papillae (Figure 8).32
LICHEN STRIATUS
The presentation of lichen striatus is as a linear eruption
involving an extremity, biopsies of which prototypically
show a hybrid lichenoid and ezcematous dermatitis with
suprabasilar dyskeratosis. The lesions initially manifest a
spongiotic dermatitis histologically, with the lichenoid
mononuclear cell infiltrate supervening and then being
followed by fibrosis with horizontal papillary dermal fibrosis. In our hands, lichen striatus has proven to be one
of the disorders manifesting a lichenoid and granulomatous morphology. An additional and characteristic finding
in our series was lymphocytic eccrine hidradenitis and
erythrocyte extravasation.32
LICHENOID AND GRANULOMATOUS DERMATITIS
AS AN ENTITY SUI GENERIS
Introduction and Clinical Features
In 2000, we described 40 patients in whom biopsies
showed a lichenoid and granulomatous dermatitis associated clinically with a variety of disorders. The individual
lesions presented most frequently as lichenoid papules
which, in roughly 20% of the cases, ultimately were held
to be examples of the idiopathic lichenoid eruptions lichen
nitidus, lichen striatus, and even lichen planus. Other cases
were held to represent a reflection of underlying systemic
autoimmune disrders, microbial id reactions, and drug
eruptions. Implicated drug classes included lipid-lowering
agents, -blockers, ACE inhibitors, H2 antagonists, plaquenil, and antibiotics, several of which are known to provoke lichenoid eruptions.32 Some of these patients had underlying medical illnesses with proven associations with
cutaneous granulomatous infiltrates, such as thyroiditis,
diabetes mellitus, hepatitis C, rheumatoid arthritis, and
Crohn disease,32,76 suggesting a form of granulomatous
Koebnerization of a lichenoid drug reaction. With respect
to the infectious associations, these included patients with
active infection or an id response to nonviable microbial
antigen. The organisms were among those with superantigen properties, namely, viruses, mycobacterial and treponemal species, and streptococci. Superantigens are microbial proteins that interact with the variable region of
the T-cell receptor and the conserved residues of class II
antigen-presenting cells, thereby stimulating a much larger percentage of the T-cell repertoire than do traditional
bacterial oligopeptides.30,7783 Follicular inflammation, lymphocytic eccrine hidradenitis, and perineural infiltrates
are also characteristic, particularly in postherpetic lesions.
The defining histomorphology is a bandlike infiltrate of
lymphocytes and histiocytes closely applied to the undersurface of the epidermis and obscuring the DEJ. Additional light microscopic features in the drug-associated cases
Figure 9. Fixed drug eruption. A, This is a variant of the lichenoid drug eruption but is associated with accentuation of the injury pattern in the
biologically plastic tips of the retia. Tissue eosinophils are usually present (original magnification 100). B, There are clusters of colloid bodies
around the retia with pigment incontinence that will be reflected clinically as postinflammatory hyperpigmentation (original magnification 200).
Figure 10. Atypical pigmentary purpura. A, There is a heavy, bandlike infiltrate of lymphocytes in the upper dermis associated with horizontal
fibrosis. The infiltrate does not obscure the dermoepidermal junction, and is thus not lichenoid in character (original magnification 100). B, The
epidermis shows focal percolation by lymphocytes that have smaller nuclear diameters than do their dermal counterparts; this is an important
clue that the patient does not have a plaque-stage lesion of mycosis fungoides (original magnification 200).
included parakeratosis, keratinocyte necrosis, acrosyringeal accentuation, a lichenoid pigmentary purpura-like reaction pattern, granulomatous vasculitis, tissue eosinophilia, plasmacellular infiltrates, and sparing of the deep
dermis. Some cases manifested lymphoid atypia in the setting of ingestion of drugs with immune-dysregulating
properties.
LICHENOID CTD SYNDROMES
Introduction
The prototypic lichenoid connective tissue disease syndromes include SCLE, anti-Roassociated SLE, and
MCTD.
Clinical
The lichenoid connective tissue disease syndromes have
in common a polycyclic annular and/or papulosquamous
photodistributed eruption involving the head, neck, arms,
and the v of the chest and upper back. In SCLE, there
are no significant extracutaneous stigmata of collagen vascular disease. Serologic testing reveals anti-Ro antibodies
in the majority of cases. Some cases of SCLE are of drugbased etiology, where the main implicated drugs include
calcium channel blockers,23 Griseofulvin, thiazides, and
antihistamines.24 In anti-Roassociated SLE, while the cutaneous eruption may be morphologically indistinguishable from SCLE, there are other extracutaneous stigmata
indicative of a systemic CTD syndrome, including renal
dysfunction, musculoskeletal complaints, pulmonary disease, and central nervous system manifestations.38 Also,
the patients may have cutaneous and extracutaneous stigmata indicative of vascular compromise, as manifested by
ulceration, digital infarcts, palpable purpura, mononeuritis multiplex, gastrointestinal ulcerations, and myocardial
infarction. In MCTD, the patients have a constellation of
characteristic extracutaneous manifestations, which include Raynaud phenomenon, sclerodactyly, and pulmonary hypertension.21 In MCTD, while patients may have a
skin rash that resembles SCLE, other characteristic features allow the distinction, namely, anti-RNP antibodies,
sclerodactyly, variable myositis, Raynaud phenomenon,
and pulmonary hypertension.
663
Histopathology
The prototypic histomorphology of the lichenoid CTD
syndromes is one of variable epidermal hyperplasia and
atrophy accompanied by an interface dermatitis that ranges in quality from being lichenoid in nature to a cell-poor
vacuolar dermatitis. There is variable middermal and deep
dermal perivascular extension of the infiltrate. Dermal
mucinosis is ubiquitous. Also characteristic is the presence
of suprabasilar dyskeratosis, with lymphocyte satellitosis
around degenerating keratinocytes. Other concomitant inflammatory cell elements, such as epithelioid histiocytes,
plasma cells, and eosinophils, are uncommon, although it
is emphasized that in a small minority of cases of drugassociated SCLE, eosinophils and granulomata may be observed.23,24,71 It has been our experience that a significant
vasculopathy is not present in SCLE. In contrast, in both
anti-Roassociated SLE and MCTD, a microangiopathy
similar to that encountered in dermatomyositis is a frequent finding. In particular, one may observe zones of vascular density reduction, endothelial cell necrosis, and variable luminal fibrin deposition.38
LICHENOID DRUG ERUPTION
Clinical Features
Lichenoid drug eruptions are caused by a variety of
medications ranging from thiazide diuretics to antihistaminics and antihypertensive agents with -blocking and
ACE inhibitor properties.24,71 As mentioned above, the lichenoid drug eruption is characterized by deep extension
of an infiltrate that includes eosinophils but has other features typical for lichen planus morphologically at both a
clinical and histologic level.
FIXED DRUG ERUPTIONS
Clinical Features
The fixed drug eruption is characterized by the recurrence of one or a few plaques of macular erythema that
manifest a persistent or slowly expanding lesion at one or
a few anatomical locations in association with the repeated
ingestion of a drug of a particular class or a similar class.
These lesions typically form a violaceous hue and leave
significant postinflammatory hyperpigmentation. Certain
classes of antibiotics and nonsteroidal anti-inflammatory
agents taken on an over-the-counter basis by patients are
frequently included.71
The morphology of the fixed drug eruption is characterized by a heavy bandlike infiltrate, which may be
patchy and is associated with particular homing of the
lymphoid infiltrate to the retia; clusters of colloid (Civatte)
bodies around the tips of rete ridges are a characteristic
finding. Full-thickness necrosis due to confluent colloid
body formation may be seen. The infiltrates often include
scattered tissue eosinophils, and postinflammatory hyperpigmentation at a histologic level is often significant. On
occasion, a neutrophilic fixed-drug eruption with abundant karryorhectic debris may be seen.
LICHENOID PURPURA OF GOUGEROT AND BLUM
Introduction and Clinical Features
The pigmentary purpuras are a heterogeneous group of
dermatoses defined by specific clinicopathologic features
but sharing dermal lymphocytic infiltrates and hemor664 Arch Pathol Lab MedVol 132, April 2008
rhage at the light microscopic level. The prototype,

Schanmberg disease, manifests as a purpuric macular
eruption of the shins in middle-aged patients. A variety
of other forms are described, including the eczematoid
purpura of Doucas and Kapetanikus, the annular purpura
of Majochi, and 3 variants that produce a bandlike and
often heavy infiltrate in the upper dermis. These latter variants include lichen aureus, the lichenoid pigmentary purpura of Gougerot and Blum, and atypical pigmentary purpura,84 a term applied by us to cases of pigmentary purpura in which individual lesions, although clinically presenting as pigmentary purpura, show lymphoid atypia by
light microscopy. Previous reports suggest that the pigmented purpuric dermatoses with heavy lymphoid infiltration may presage fully evolved mycosis fungoides. A
drug-based etiology is clearly implicated in some one
third of cases of atypical pigmentary purpuras, the culprit
agents being calcium channel blockers, lipid-lowering
agents, -blockers, ACE inhibitors, antihistamines, antidepressants, or analgesics.84,85 Although these atypical and
lichenoid pigmentary purpuras may express clonal restriction of T cells, showing loss of panT-cell markers in a
fashion identical to mycosis fungoides, most are reversible
with appropriate drug modulation, or remain biologically
stable. We consider them a forme fruste of lymphoproliferative disease which, in the vast majority of cases, has an
indolent course.
Histologic Features
Although lesions of drug-related atypical pigmentary
purpura may mimic mycosis fungoides or idiopathic atypical pigmentary purpura histologically, the cytomorphology of the intraepidermal populace, when more atypical
than the dermal based populace, is predictive of mycosis
fungoides versus drug-related or idiopathic cases.
LICHENOID GVHD
In lesions of chronic GVHD, a lichenoid morphology
supervenes.4 Ultimately, chronic inflammation in this setting may result in a sclerodermoid tissue reaction. We
have seen accelerated variants of lichenoid GVHD in the
setting of peripheral blood stem cell transplantation.
LICHENOID MYCOSIS FUNGOIDES
This is an unusual variant that shows true lichenoid destructive interface change exactly recapitulating classic lichen planus. However, almost invariably there are areas
of haphazard lymphocyte migration into the epidermis
that are indistinguishable from those morphologic changes encountered in typical mycosis fungoides. Other discriminating features are enhanced cytologic atypia.
CONCLUSION
Interface dermatitis can be broadly broken down into
cell-poor and cell-rich inflammatory processes and addressed as well by the character of the cellular infiltrate.
A bandlike inflammatory infiltrate that obscures the DEJ,
that is, a lichenoid inflammatory process, calls to mind a
set of differential diagnostic considerations that is distinct
from those that flow from a cell-poor interface injury pattern. A comprehension of the pathobiology of the different
entities that fall into these broad categories of injury will
point the astute pathologist toward a recognition of distinctive histomorphologic features which can, with cliniInterface DermatitisCrowson et al
copathologic correlation, enable a precise etiopathologic

diagnosis and so promote an enhancement of patient care.
References
1. Magro CM, Guitart J, Crowson AN. Precursor lesions of cutaneous T cell
lymphoma. In: Magro CM, Crowson AN, Mihm MC, eds. The Cutaneous Lymphoid Proliferations. New York, NY: John Wiley and Sons; 2007:93140.
2. Magro CM, Mihm MC, Crowson AN. Mycosis fungoides. In: Magro CM,
Crowson AN, Mihm MC, eds. The Cutaneous Lymphoid Proliferations. New York,
NY: John Wiley and Sons; 2007:267299.
3. Magro CM, Crowson AN, Morrison C, Li J. Pityriasis lichenoides chronica:
stratification by molecular and phenotypic profile. Hum Pathol. 2007;38:479
490.
4. Horn TD. Interface dermatitis. In: Barnhill R, Crowson AN, eds. Textbook
of Dermatopathology. 2nd ed. New York, NY: McGraw-Hill Co; 2004:3560.
5. Spritz RA. The genetics of generalized vitiligo and associated autoimmune
diseases. Pigment Cell Res. 2007;20:271278.
6. Cheng W, Gilliam AC, Castrovinci A, Pazirandeh M. Anti-thyroid autoantibody-associated interface dermatitis in individuals with undifferentiated connective tissue diseasean unrecognized subset of autoimmune disease? J Rheumatol.
2007;34:8188.
7. Schalock PC, Dinulos JG, Pace N, Schwarzenberger K, Wenger JK. Erythema
multiforme due to Mycoplasma pneumoniae infection in two children. Pediatr
Dermatol. 2006;23:546555.
8. French LE. Toxic epidermal necrolysis and Stevens Johnson syndrome: our
current understanding. Allergol Int. 2006;55:916.
9. Gravante G, Delogu D, Marianetti M, Trombetta M, Esposito G, Montone
A. Toxic epidermal necrolysis and Steven Johnson syndrome: 11-years experience
and outcome. Eur Rev Med Pharmacol Sci. 2007;11:119127.
10. Ueta M, Sotozono C, Tokunaga K, Yabe T, Kinoshita S. Strong association
with HLA-A*0206 and Stevens-Johnson syndrome in Japanese. Am J Ophthalmol.
2007;143:367368.
11. Nishio D, Izu K, Kabashima K, Tokura Y. T cell populations propogating in
the peripheral blood of patients with drug eruptions. J Dermatol Sci. 2007;48:
2533.
12. Stur K, Karlhofer EM, Stingle G. Soluble Fas ligand: a discriminating feature
between drug-induced skin eruptions and viral exanthems. J Invest Dermatol.
2007;127:802807.
13. Quaglino P, Caproni M, Antiga E, et al. Serum levels of the Th1 promoter
IL-12 and the Th2 chemokine TARC are elvated in erythema multiforme and Stevens-Johnson syndrome/toxic epidermal necrolysis and correlate with soluble Fas
ligand expression: an immunoenzymatic study form the Italian Group of Immunopathology. Dermatology. 2007;214:296304.
14. Kokuba H, Imafuku S, Huang S, Aurelian L, Burnett JW. Erythema multiforme lesions are associated with expression of herpes simplex virus (HSV) gene
and qualitative alterations in the HSV-specific T-cell response. Br J Dermatol.
1198;138:952964.
15. Fukiwake N, Moroi Y, Urabe K, Ishii N, Hashimoto T, Furue M. Detection
of autoantibodies to desmoplakin in a patient with oral erythema multiforme. Eur
J Dermatol. 2007;17:238241.
16. Crowson AN. Superficial and deep perivascular dermatitis. In: Barnhill R,
Crowson AN, eds. Textbook of Dermatopathology. New York, NY: McGraw-Hill
Co; 2004:7996.
17. Crowson AN, Magro CM. The cutaneous pathology of lupus erythematosus: a review. J Cutan Pathol. 2001;28:123.
18. Magro CM, Crowson AN, Harrist TJ. The use of antibody to C5b-9 in the
subclassification of lupus erythematosus. Br J Dermatol. 1996;134:855862.
19. Crowson AN, Magro CM. The role of microvascular injury in the pathogenesis of cutaneous lesion of dermatomyositis. Hum Pathol. 1996;1926:1419.
20. Teramoto N, Katayama I, Arai H, et al. Annular erythema: a possible association with Sjogrens syndrome. J Am Acad Dermatol. 1989;20:596601.
21. Magro CM, Crowson AN, Regauer S. The dermatopathology of mixed connective tissue disease. Am J Dermatopathol. 1997;19:205212.
22. Crowson AN, Magro CM. Idiopathic perniosis and its mimics: a clinical
and histological study of 38 cases. Hum Pathol. 1997;28:478484.
23. Crowson AN, Magro CM. Subacute cutaneous lupus erythematosus arising
in the setting of calcium channel blocker therapy. Hum Pathol. 1997;28:6773.
24. Crowson AN, Magro CM. Lichenoid and subacute lupus erythematosuslike dermatitis associated with antihistamine therapy. J Cutan Pathol. 1999;26:95
99.
25. Tan EM, Cohen AS, Fries JF, et al. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1982;25:12711277.
26. Magro CM, Dawood MR, Crowson AN. The cutaneous manifestations of
human parvovirus B19 infection. Hum Pathol. 2000;31:488497.
27. Crowson AN, Magro CM, Dawood MR. A causal role for parvovirus B19
infection in adult dermatomyositis and other autoimmune syndromes. J Cutan
Pathol. 2000;27:505515.
28. David-Bajar KM. Subacute cutaneous lupus erythematosus. J Invest Dermatol. 1993;100:2S8S.
29. Jerdan MS, Hood AF, Moore GW, Callen JP. Histopathologic comparison
of the subsets of lupus erythematosus. Arch Dermatol. 1990;126:5255.
30. Magro CM, Crowson AN. Interface and granulomatous dermatitis as a
manifestation of antecedent microbial infection: the superantigen id reaction. J
Cutan Pathol. 1998;25:538544.
31. Magro CM, Crowson AN. The application of immunofluorescence testing

in diagnostic dermatopathology. Adv Dermatol. 1999;15:441486.
32. Magro CM, Crowson AN. Lichenoid and granulomatous dermatitis: a novel
cutaneous reaction pattern. Int J Dermatol. 2000;39:126133.
33. Crowson AN, Allen P, Cornelison R, et al. Kikuchis histiocytic necrotizing
lymphadenitis with skin involvement: a clinicopathologic study. Lab Invest. 2002;
82:97A.
34. Leibold AM, Bennion S, David-Bajar K, Schleve MJ. Occurrence of positive
immunofluorescence in the dermoepidermal junction of sun-exposed skin of normal adults. J Cutan Pathol. 1994;21:200206.
35. Weigand DA. Lupus band test: anatomic regional variations in discoid
lupus erythematosus. J Am Acad Dermatol. 1986;14:426428.
36. Jaworsky C. Connective tissue diseases. In: Elder DE, Johnson BE, Elenitsas
R, Johnson BE, Murphy GF, eds. Levers Histopathology of the Skin. 9th ed. Philadelphia, Pa: JB Lippincott Co; 2005:293322.
37. Ben-Chetrit E. The molecular basis of the SSA/Ro antigens and the clinical
significance of their autoantibodies. Br J Rheumatol. 1993;32:396402.
38. Magro CM, Crowson AN. The cutaneous pathology associated with seropositivity for antibodies to Ro/SSA: a clinicopathological study of 23 adult patients
without subacute cutaneous lupus erythematosus. Am J Dermatopathol. 1999;21:
129137.
39. McCauliffe DP, Sontheimer RD. Molecular characterization of the Ro/SSA autoantigens. J Invest Dermatol. 1993;100:73S79S.
40. Furukawa F, Kahihara-Sawami M, Lyons MB, Norris DA. Binding of antibodies to ENA SS-A/Ro and SS-B/La is induced on the surface of human keratinocytes by UVL: implications for the pathogenesis of photosensitive cutaneous
lupus. J Invest Dermatol. 1990;94:7785.
41. Tesar JT, Armstrong J. Expression of Ro/SSA and La/SSB antigens on epithelial cell surface following in vitro adenovirus (AV) infection [abstract]. Arthritis
Rheum. 1986;S74:C20.
42. Norris DA. Pathomechanisms of photosensitive lupus erythematosus. J Invest Dermatol. 1993;100:58S68S.
43. Helm KF, Peters MS. Deposition of membrane attack complex in cutaneous
lesions of lupus erythematosus. J Am Acad Dermatol. 1993;28:687691.
44. Crowson AN, Magro CM. C5b-9 deposition at the dermoepidermal junction
in lupus erythematosus [letter]. J Am Acad Dermatol. 1994;31:515516.
45. Magro CM, Crowson AN. The immunofluorescence findings in cutaneous
lesions of dermatomyositis: a comparative study versus lupus erythematosus. J
Cutan Pathol. 1997;24:543552.
46. Lim KL, Abdul-Wahab R, Lowe J, Powell RJ. Muscle biopsy abnormalities
in systemic lupus erythematosus: correlation with clinical and laboratory parameters. Ann Rheum Dis. 1994;53:178182.
47. Lanto B, Bohm F, Maffert W, Sonnichsen N. The cytotoxic effect of antiRo- (SS-A) antibodies and UVA light on human endothelial cells in vitro. Dermatol Monatsschr. 1990;176:305311.
48. Kovacs SO, Kovacs C. Dermatomyositis. J Am Acad Dermatol. 1998;39:
899920.
49. Callen JP. Dermatomyositis. Lancet. 2000;355:5357.
50. Sontheimer RD, Costner MI. Dermatomyositis. Chap 157. In: Wolff K,
Goldsmith L, Katz S, Gilchrest B, Paller A, Leffell D, eds. Dermatology in General
Medicine. 7th ed. New York, NY: McGraw-Hill. In press.
51. Euwer RL, Sontheimer RD. Amyopathic dermatomyositis: a review. J Invest
Dermatol. 1993;100:124S127S.
52. Hill CL, Zhang Y, Sigurgeirsson B, et al. Frequency of specific cancer typesin dermatomyositis and polymyositis: a population-based study. Lancet. 2001;
357:96100.
53. Magro CM, Crowson AN, Dawood M, Nuovo GJ. Parvoviral infection of
endothelial cells in cutaneous lesionspossible role in vasculitis and autoimmune diseases. J Rheumatol. 2002;29:12271235.
54. Kissel JT, Halterman RK, Rammohan KW, Mendell JR. The relationship of
complement-mediated microvasculopathy to the histological features and clinical
duration of disease in dermatomyositis. Arch Neurol. 1991;48:2630.
55. Emslie-Smith AM, Engel AG. Microvascular changes in early and advanced
dermatomyositis: a quantitative study. Ann Neurol. 1990;27:343356.
56. Sharp GC, Irwin WS, Tan EM, Gould RG, Holman JR. Mixed connective
tissue disease: an apparently distinct rheumatic disease syndrome associated with
a specific antibody to an extractable nuclear antigen. Am J Med. 1972;52:148
159.
57. Ramagopalan SV, Dyment DA, Valdar W, et al. Autoimmune disease in
families with multiple sclerosis: a population-based study. Lancet Neurol. 2007;
6:604610.
58. Gopal KV, Rama Rao GR, Kumar YH, et al. Vitiligo: a part of a systemic
automimmune process. Indian J Dermatol Venereol Leprol. 2007;73:162165.
59. Schallreuter KU, Kruger C, Rokos H, Hasse S, Zothner C, Panske A. Basic
research confirms co-existence of acquired Blaschkolinear vitiligo and acrofacial
vitiligo. Arch Dermatol Res. 2007;299:225230.
60. Taffaro M, Pyrsopoulos N, Cedron H, et al. Vitiligo improvement in a hepatitis C patient after treatment with PEG-interferon alpha 2A and ribavirin: a case
report [published online ahead of print April 12, 2007]. Dig Dis Sci.
61. Tsai KS, Hsieh HJ, Chow KC, Lin TY, Chiang S, Huang HH. Detection of
cytomegalovirus infection in a patient with febrile ulceronecrotic Mucha-Habermanns disease. Int J Dermatol. 2001;40:694698.
62. Dereure O, Levi E, Kadin ME. T-cell clonality in pityriasis lichenoides et
varioliformis acuta: a heteroduplex anaylsis of 20 cases. Arch Dermatol. 2000;
136:483486.
665
63. Magro CM, Morrison C, Kovatich A, Burns F, Crowson AN. Pityriasis lichenoides is a cutaneous T-cell dyscrasia: a clinical, genotypic, and phenotypic
study. Hum Pathol. 2002;33:788795.
64. Shieh S, Mikkola DL, Wood GS. Differentiation and clonality of lesional
lymphocytes in pityriasis lichenoides chronica. Arch Dermatol. 2001;137:305
308.
65. Lopez-Estebaranz JL, Vanaclocha F, Gil R, et al. Febrile ulceronecrotic Mucha-Habermann disease. J Am Acad Dermatol. 1993;29:903906.
66. Benmaman O, Sanchez JL. Comparative clinicopathological study on pityriasis lichenoides chronica and small plaque parapsoriasis. Am J Dermatopathol.
1988;10:189196.
67. Magro CM, Crowson AN, Mihm MC. Cutaneous manifestations of gastrointestinal disease: In: Elder DE, Johnson BE, Elenitsas R, Johnson BE, Murphy GF,
eds. Levers Histopathology of the Skin. 9th ed. Philadelphia, Pa: JB Lippincott
Co; 2005:419434.
68. Crowson AN, Nuovo G, Ferri C, Magro CM. The dermatopathological
manifestations of hepatitis C infection: a clinical, histologic and molecular assessment of 35 cases. Hum Pathol. 2003;6:573579.
69. de Mattos Camargo Grossman S, de Aguiar MC, Teixeira R, do Carmo MA.
Oral lichen planus and chronic hepatitis C: a controversial association. Am J Clin
Pathol. 2007;127:800804.
70. Noam Y, Dagon N, Shinar E, Meir G. Association between hepatitis C virus
infection and oral lichen planus in Israeli patients. Isr Med Assoc J. 2007;9:370
372.
71. Crowson AN, Brown TJ, Magro CM. Progress in the understanding of the
pathology and pathogenesis of cutaneous drug eruptions: implications for management. Am J Clin Dermatol. 2003;4:407428.
72. Ellis FA, Hill WF. Is lichen nitidus a variety of lichen planus? Arch Dermatol
Syph. 1938;38:569573.
73. Senea FE, Caro MA. Lichen striatus. Arch DermatolSyph. 1941;43:116
133.
74. Lee H. Lichen striatus. Lancet. 1951;1:615617.

75. Staricco RG. Lichen striatus: a study of 15 new cases with special emphasis
on the histopathological changes and review of the literature. Arch Dermatol.
1959;79:311324.
76. Magro CM, Crowson AN. Drug-induced immune- dysregulation as a cause
of atypical cutaneous lymphoid infiltrates: a hypothesis. Hum Pathol. 1996;26:
125132.
77. Dellabona P, Peccoud J, Kappler J, Marrack P, Benoist C, Mathis D. Superantigens interact with MHC class II molecules outside of the antigen groove.
Cell. 1990;62:11151121.
78. Mollick JA, Miller GG, Musser JM, Cook RG, Grossman D, Rich RR. A
novel superantigen isolated from pathogenic strains of Streptococcus pyogenes
with aminoterminal homology to staphylococcal enterotoxins B and C. J Clin
Invest. 1993;92:710719.
79. Reda KB, Kapur V, Mollick JA, Lamphear JG, Musser JM, Rich RR. Molecular characterization and phylogenetic distribution of the streptococcal superantigen gene (ssa) from Streptococcus pyogenes. Infect Immun. 1994;62:1867
1874.
80. Drake CG, Kotzin BL. Superantigens: biology, immunology, and potential
role in disease. J Clin Immunol. 1992;12:149162.
81. Ohmen JD, Barnes PF, Grisso CL, et al. The T cell receptors of human
gamma delta T cells reactive to Mycobacterium tuberculosis are encoded by
specific V genes but diverse V-J junctions: M tuberculosis contains a superantigen
[abstract]. J Immunol. 1993;150:94A.
82. Abe J, Takeda T, Watanabe Y, et al. Evidence for superantigen production
by Yersinia pseudotuberculosis. J Immunol. 1993;151:41834188.
83. Cole BC, Atkin CL. The mycoplasma arthritidis T-cell mitogen, MAM: a
model superantigen. Immunol Today. 1991;12:271276.
84. Crowson AN, Magro CM. Atypical pigmentary purpura: a clinical, pathological and genotypic study of 40 cases. Hum Pathol. 1999;30:11041112.
85. Magro CM, Crowson AN. Drug induced immune-dysregulation as a cause
of atypical lymphoid infiltrates. Hum Pathol. 1996;27:125132.

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Interface Dermatitis

A. Neil Crowson, MD; Cynthia M. Magro, MD; Martin C. Mihm, Jr, MD

Interface dermatitis can be classified based upon the cell

he term interface dermatitis refers to the finding in a skin

Accepted for publication October 9, 2007.

Prototypes of Cell-Poor Interface Dermatitis

Prototypes of Cell-Rich Interface Dermatitis

Idiopathic lichenoid disorders

The distinction of erythema multiforme from acute

Lupus Erythematosus: Comparison of Clinical and Direct Immunofluorescence Manifestations by Subtype*

Fine, easily detached

Fine, easily detached

4 ACR criteria for SLE (incidence)

Seropositivity by Connective Tissue Disease Classification*

CELL-POOR INTERFACE DERMATITIS OF AUTOIMMUNE

hematuria or arthralgia.17,18 In DLE, disease is restricted

Grades of Graft-Versus-Host Disease

upon the clinical situation, in a physiologic medium such

correlates with seropositivity for antibodies to extractable

658 Arch Pathol Lab MedVol 132, April 2008

flects the presence of endotheliotropic viruses, such as

reactions, do not typically produce the same vascular injury patterns.

MIXED CONNECTIVE TISSUE DISEASE

Although some observers doubt that histologic criteria

Mixed connective tissue disease was first defined by

tern may mimic PLEVA by virtue of a perivascular and

of CD8 lymphocytes over those of the CD4 subset.1 If the

lichen planus is particularly problematic diagnostically, as

keratosis is seen in the setting of dermatoheliosis and is

rhage at the light microscopic level. The prototype,

copathologic correlation, enable a precise etiopathologic

Arch Pathol Lab MedVol 132, April 2008

31. Magro CM, Crowson AN. The application of immunofluorescence testing

666 Arch Pathol Lab MedVol 132, April 2008

74. Lee H. Lichen striatus. Lancet. 1951;1:615617.

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