Dermatologic Manifestations of

Sporotrichosis

1. OVERVIEW

Background
Sporotrichosis is a subcutaneous or systemic infection caused
by Sporothrix schenckii, a rapidly growing dimorphic fungus. The
organism derives its name from R B Schenck, who first reported the
infection in 1898. Sporothrix species typically exist as a saprophytic mold
on vegetative matter in humid climates worldwide. A dimorphic fungus,
the organism exhibits mycelial forms at 25°C and a yeast form at
37°C. [1, 2, 3]
Cutaneous infection often results from a puncture wound involving
infected cats, thorns or other plant matter. Other more unusual reported
causes include insect stings, squirrel bites, and trauma induced by
liposuction. [4, 5] Any compromise of the skin barrier with subsequent
seeding could potentially cause infection. Sporotrichosis usually occurs
sporadically as isolated cases. Occasionally, groups of individuals are
infected after being exposed to the organism. [6, 7, 8]
Since approximately the beginning of the 21st century, an outbreak of
increasing numbers of cases has been occurring in Rio de Janeiro, Brazil.
From 1998-2004, 759 culture-proven cases have been identified and
treated, predominantly among women at a median age of 39 years and
predominantly among those with domiciliary or professional contact with
infected cats. [6]
An outbreak in the United States in 1988 affected 84 people who handled
sphagnum moss. [8] An unusually large outbreak occurred in Africa in the
1940s in more than 3000 miners who had frequent physical contact with
wood timber supports. This contributed significantly to the current
understanding of Sporothrix schenckii, its growth patterns, and its
mechanisms of dissemination.
Pathophysiology
Sporotrichosis infections can be either cutaneous or extracutaneous.
Cutaneous infections are most common and are subclassified into fixed
cutaneous and lymphocutaneous. A few authors refer to a rarely included
third subclass of cutaneous sporotrichosis in which diffuse cutaneous
involvement occurs.
Fixed cutaneous infections occur at the site of inoculation and remain
confined entirely to the skin. Lymphocutaneous disease results from
lymphangitic spread of an infection. Satellite lesions develop along the
path of the lymphatic vessels (sporotrichoid spread) and associated
lymphadenopathy occurs. Extracutaneous, or disseminated
sporotrichosis, can present as pyelonephritis, orchitis, mastitis, synovitis,
meningitis, or osseous infection. [1, 2, 3, 9, 10]
Sporotrichosis can cause a monoarthritis, typically involving the
knee. [11, 12]Many affected individuals are immunosuppressed by
alcoholism or HIV infection. [13, 14, 15] Pulmonary involvement is rare. [2, 3]
Under study is the mechanism of pathogen-host interaction, including a
70-kd (Gp70) glycoprotein from the cell wall of S schenckii, which is
involved in fungal adherence to the dermal extracellular matrix. [16] This
protein shows promise as a possible target for passive immunity
therapies. [17]
Epidemiology
Frequency
United States
The incidence of sporotrichosis is unknown. As an unreported, sporadic
disease, its incidence is difficult to estimate. The mold itself is endemic to
the Missouri and the Mississippi River Valleys. [2, 3]
International
Sporotrichosis is the most common subcutaneous mycosis in South
America. [18,19] Most reported cases occur in Mexico, followed by the
remaining Americas, Australia, Asia, and Africa. Sporotrichosis is rare in
Europe. [2, 3] However, it has been described as endemic in northeast
China. [20]
Sex
In the past, males were affected more often than females due to
occupational-related risks for puncture wounds. With the 1998 outbreak in
Rio de Janeiro, Brazil, women with exposure to infected cats currently
account for the predominant number of new cases. [2, 3]
Age
Sporotrichosis may occur in any age, but it typically affects adults,
reflecting their more frequent participation in veterinary care, gardening,
woodworking, and occupational situations in which puncture wounds may
occur. [2, 3, 6, 7, 8]
Prognosis
Localized disease responds well to treatment. The morbidity of cutaneous
infections is generally low, although therapy can be prolonged and can
have potentially serious adverse effects. Scarring can result at ulcerated
sites. [1]Systemic infections can be life threatening, especially in the
immunocompromised host. [2, 13, 14, 15] Systemic disease requires
prolonged treatment with potentially toxic systemic therapy.
Patient Education
For excellent patient education resources, visit
eMedicineHealth's Infections Center. Additionally, see eMedicineHealth's
patient education article Sporotrichosis.

2. PRESENTATION

History
Most patients relate a history of a recent prick injury at the site of
infection. Clinical disease usually becomes apparent within 3 weeks of
injury; however, the interval from injury to apparent infection may be as
long as 6 months. The injuries are attributed to a variety of causes,
including rose thorns, hay, sphagnum moss, conifer needles, mine
timbers, and infected cats. The characteristic skin lesion is a dermal or
subcutaneous nodule that may ulcerate. As the infection spreads along
the regional lymphatic chain, satellite nodules develop along with
associated regional lymphadenopathy. The infection may disseminate to
cause systemic disease. [1, 2, 3]
Physical
Lymphocutaneous sporotrichosis is the most common presentation.
Symptoms usually arise within 3 weeks of injury. A subcutaneous nodule
develops at the site of inoculation and may ulcerate as the result of
central abscess formation. Satellite lesions form along the associated
lymphatic chain and lymphadenopathy subsequently develops. [1, 2, 3, 6, 7]
 Close-up of an ulcerated nodule reveals the satellite lesions characteristic of
lymphangitic (sporotrichoid) spread.

Fixed cutaneous disease also is known as nonlymphatic sporotrichosis. This

appears as a scaly, acneform, verrucous or ulcerative nodule that remains
localized. Satellite lesions and lymphadenopathy do not occur in this form of
sporotrichosis. Fixed cutaneous lesions may rarely resemble pyoderma, rosacea,
pyoderma gangrenosum, and keratoacanthomas. [1, 2, 3, 6, 7, 21]
Disseminated disease can result in pyelonephritis, orchitis, mastitis, arthritis,
synovitis, meningitis, osseous infection, or, rarely, pulmonary disease. Cutaneous
lesions can occur in the setting of disseminated infection. [1, 2, 3, 6, 7]
Clinical signs and symptoms may be blunted in the presence of elevated
glucocorticoid states or systemic steroid therapy. Sporotrichosis in this setting has
resembled erysipeloid cellulitis. [13]
Causes
Sporotrichosis is caused by S schenckii, a dimorphic fungus. [1]

3. DDx

Differential Diagnoses
 Mycobacterium Marinum Infection of the Skin
 Leishmaniasis
  Pediatric Nocardiosis
 Pediatric Syphilis

4. WORKUP

Laboratory Studies
Fungal cultures
S schenckii readily grows on Sabouraud dextrose agar at 25 º C as a
lobated, smooth or verrucous, moist, cream-colored colony with
occasional aerial mycelium, maturing to a black leathery colony. Yeast
growth at 37 º C must be demonstrated to confirm Sporothrix. Inform the
laboratory that sporotrichosis is clinically suspected. The organisms are
characteristically scarce in tissue and may not be detected with tissue
stains alone; therefore, cultures are essential.
Mycobacterial cultures
Perform cultures to rule out mycobacterial infection. The laboratory
should be alerted to the possibility of an atypical mycobacterial infection,
particularly if Mycobacterium marinum is suspected, to ensure that
appropriate cultures are performed.
Tissue Gram stain
Gram stain is performed to rule out other infective or foreign body
processes.
Acid-fast stain
Staining of tissue or purulent discharge may assist in the evaluation of
possible mycobacterial infection. The paucity of organisms in such
infections necessitates the use of cultures if infection is clinically
suspected; a negative acid-fast bacillus (AFB) stain does not adequately
rule out infection.

Imaging Studies
Perform chest radiography if pulmonary symptoms are present.

Other Tests
Intradermal skin testing using sporotrichin as an antigen to diagnose
sporotrichosis is not routinely used because of its high false-positive and
false-negative rates.
Urine, semen, and cerebral spinal fluid cultures, as well as fine-needle
aspirate or tissue biopsy cultures are indicated based on suspicion of
systemic disease.

Procedures
Obtain appropriate tissue for hematoxylin and eosin, tissue cultures,
Gram stain, Fite stain, and fungal stains.

Histologic Findings
A nonspecific granulomatous reaction with pseudoepitheliomatous
hyperplasia is typically present. Rarely, periodic acid-Schiff staining
reveals the round to oval, cigar-shaped spores within the granuloma. The
rare extracellular asteroid bodies of eosinophilic spicules surrounding a
central yeast are specific for sporotrichosis, as asteroid bodies seen in
other granulomatous reactions are intracellular, filamentous myelin
figures that contain lipid. [2, 22]

5. TREATMENT

Medical Care
Systemic antifungal agents are the mainstay of treatment. Antifungal
agents are used for fungicidal or fungistatic eradication of the infective
organism S schenkii. [23, 24] An increase in cutaneous induration, redness,
and local lymphadenopathy may be expected after treatment is started,
resulting from an increased immune response to the antigenic challenge
of the killed fungus. Thermal adjuvant therapy to systemic antifungals
may be beneficial, as S schenckii does not survive above
39°C. [23, 24] Passive immunization with monoclonal antibody against a 70-
kd putative adhesin of S schenckii induces protection in murine
sporotrichosis, giving promise for future therapies for this and similar
deep-space fungal infections. [17]

Surgical Care
Surgery combined with antifungals for localized pulmonary disease has
proven beneficial. [24]

Consultations
Consultations may include an infectious disease specialist and/or an
internist and subspecialists as indicated by organ system involvement.
 6. GUIDELINES

Clinical Practice Guidelines

Infectious Disease Society of America (IDSA) Clinical Practice
Guidelines for the Management of Sporotrichosis [24]
Per the IDSA Website, these guidelines are current as of October
2014. [25]
Lymphocutaneous/cutaneous sporotrichosis
Administer itraconazole at 200 mg/d.
In patients who do not respond, administer itraconazole at 200 mg twice
daily, 500 mg twice daily, or add potassium iodide (see below).
In patients intolerant of itraconazole, administer fluconazole at 400-800
mg/d or local hyperthermia.
Osteoarticular sporotrichosis
Administer amphotericin B and switch to itraconazole after therapeutic
response.
Administer amphotericin B lipid formulation at 3-5 mg/kg/d.
Administer amphotericin B deoxycholate at 0.7-1.0 mg/kg/d.
Administer itraconazole at 200 mg twice daily for at least 12 months.
Confirm serum therapeutic levels after 2 weeks.
Pulmonary sporotrichosis
Antifungals are administered for localized disease after surgery, and this
is also for initial therapy for severe infections.
Administer amphotericin B and switch to itraconazole after therapeutic
response.
Administer amphotericin B lipid formulation at 3-5 mg/kg/d.
Administer amphotericin B deoxycholate at 0.7-1.0 mg/kg/d.
Administer itraconazole at 200 mg twice daily for at least 12 months.
Confirm serum therapeutic levels after 2 weeks.
Meningeal and disseminated (systemic) sporotrichosis
Administer amphotericin B and switch to itraconazole after therapeutic
response.
Administer amphotericin B lipid formulation at 3-5 mg/kg/d.
Administer amphotericin B deoxycholate at 0.7-1.0 mg/kg/d.
Administer itraconazole at 200 mg twice daily for at least 12 months.
Confirm serum therapeutic levels after 2 weeks.
Pregnancy
Administer amphotericin B lipid formulation at 3-5 mg/kg/d.
Administer amphotericin B deoxycholate at 0.7-1.0 mg/kg/d.
Avoid azoles.
Pediatric cutaneous sporotrichosis
Administer potassium iodide, 1 drop 3 times daily, increasing as tolerated
to a maximum of 1 drop/kg or 40-50 drops 3 times daily, which ever is
lowest.
Pediatric disseminated sporotrichosis
Administer amphotericin B deoxycholate at 0.7 mg/kg/d, followed by
itraconazole at 6-10 mg/kg, not to exceed 400 mg/d.

7. MEDICATION

Medication Summary
The goals of pharmacotherapy are to reduce morbidity and prevent
complications. Continue systemic therapy until clinical resolution is
achieved, typically 4-6 months.
Antifungal agents
Class Summary
These agents are used for fungicidal or fungistatic eradication of the
infective organism S schenkii.
Amphotericin B (AmBisome)
 View full drug information
Amphotericin B is produced by a strain of Streptomyces nodosus; it can
be fungistatic or fungicidal. Amphotericin B binds to sterols, such as
ergosterol, in the fungal cell membrane, causing intracellular components
to leak with subsequent fungal cell death. This is the drug of choice for
systemic disease, although more recent literature indicates itraconazole
or terbinafine may replace amphotericin B as the drug of choice for
systemic sporotrichosis.
Itraconazole (Sporanox)
 View full drug information
Itraconazole is a synthetic triazole antifungal agent that slows fungal cell
growth by inhibiting cytochrome P-450-dependent synthesis of ergosterol,
a vital component of fungal cell membranes. Itraconazole is the drug of
choice for cutaneous disease and second drug of choice (likely to soon
be first DOC) for systemic disease. It is available as a 100-mg capsule.
Potassium iodide (SSKI, Pima)
 View full drug information
Potassium iodide is a saturated solution containing approximately 142 g
potassium iodide in 100 mL water. It inhibits thyroid hormone secretion.
The mechanism of action against Sporothrix is unknown. It is the third
drug of choice for cutaneous disease. Potassium iodide is not effective for
systemic disease. It contains 8 mg of iodide per drop and may be mixed
with juice or water for intake.
Fluconazole (Diflucan)
 View full drug information
Fluconazole is a synthetic oral antifungal (broad-spectrum bistriazole) that
selectively inhibits fungal cytochrome P-450 and sterol C-14 alpha-
demethylation. It is the fourth drug of choice for systemic disease,
modestly effective and thus reserved for itraconazole-intolerant patients.
Terbinafine (Lamisil)
 View full drug information
Terbinafine is a synthetic allylamine hypothesized to act by inhibiting
squalene epoxidase, thus blocking synthesis of ergosterol, a vital
component of fungal cell membranes. Terbinafine is an alternative for
cutaneous disease, with promise for systemic disease.