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Inoculated
Immune System
Diagnosis and reasoning

This young man has presented with a solitary, painless, erythematous, non-healing ulcer on his le thumb for six weeks - an
interesting clinical conundrum; the di erential diagnoses can be broadly classified into infectious and non-infectious etiologies.
With respect to the former, the key diagnoses to consider include cutaneous leishmaniasis, given his travel history;
sporotrichosis, due to his occupation as a gardener; and cutaneous tuberculosis, which is a common cause of chronic cutaneous
ulcers.
Key non-infectious causes include neoplasms such as basal and squamous cell carcinoma, so tissue sarcoma, and
keratoacanthoma.
Given the possibility of leishmaniasis, microscopic examination of skin scrapings is a good first test, as it is easy and fast, with
minimal invasiveness. However, the negative result seen here does not confirm or exclude this possibility.
A skin biopsy is a logical next step; here, the histopathological findings suggest at granulomatous inflammation, favoring a
chronic infection, although the possibility of tuberculosis still remains.
Cultures of the biopsy specimens are now reasonable; these reveal the causative agent to be Sporothrix schenckii, clinching the
diagnosis. Note that the clinical findings in this patient show this to be the fixed cutaneous form of sporotrichosis.
It should be appreciated that there is no clear rationale for an autoimmune screen, given the absence of systemic symptoms
which would point towards such an etiology.
Neither is there justification for a chest x-ray; pulmonary sporotrichosis is mainly encountered in immunocompromised
individuals, and if present here, would have been accompanied by respiratory and constitutional symptoms.
Itraconazole is the treatment of choice for uncomplicated cutaneous sporotrichosis; the preferred dose is 200 mg per day, and
the drug should be continued for 2 to 4 weeks following the resolution of the lesion.
Note that amphotericin B is indicated for the treatment of disseminated cutaneous sporotrichosis, extracutaneous
sporotrichosis, and in immunodeficient and pregnant patients; it should not be employed here.
Meglumine antimoniate is used to treat cutaneous leishmaniasis, while corticosteroids might have been considered if an
autoimmune condition were suspected.
Discussion
Sporotrichosis, also known as rose gardener’s disease, is an infection caused by the dimorphic fungus Sporothrix schenckii; it is
encountered worldwide, with focal regions of hyperendemicity.
In the United States, the incidence is ~1 to 2 cases per million persons per year, with no predilection for gender, age, or race.
S. schenckii is a saprophyte found in soil, decaying wood, hay, and sphagnum moss; it typically causes infection in humans
following traumatic implantation from contaminated plant materials.
Individuals who frequently handle plants, such as gardeners, are at a higher risk of contracting the disease; however, zoonotic
transmission from cats, human-to-human spread by wound contamination from infected dressings, and contraction from topical
herbal medications have also been described.
The average incubation period is three weeks; subsequently, a small, indurated papulonodular lesion appears at the site of
inoculation, gradually enlarges, and may even ulcerate.
Following this, the presentation varies depending on the clinical subtype of the infection; these include the lymphocutaneous,
fixed cutaneous, disseminated cutaneous, and extracutaneous forms.
The lymphocutaneous form is the most common type, accounting for 70% to 80% of cutaneous cases; it usually a ects the
extremities.
In this, following development of the primary ulcerative nodule, similar nodules develop along the course of the proximal
lymphatics; these may so en and ulcerate to discharge seropurulent material.
The lesions are usually asymptomatic but may itch or be painful in some patients. Regional lymphadenopathy may also be
present.
The fixed cutaneous form is characterized by a localized lesion at the inoculation site; this most frequently a ects the face, and
may appear as a papule, papulopustule, nodule, verrucous plaque, non-healing ulcer, or small abscess.
Disseminated cutaneous disease is defined by the presence of three or more lesions a ecting two di erent anatomical sites; it is
usually due to cutaneous dissemination following multiple traumatic implantations or, less o en, due to hematogenous spread
in an otherwise healthy patient.
The extracutaneous variant occurs in immunocompromised individuals and may a ect various organs. Typical manifestations
include sinusitis, central nervous system infections, ocular infections, osteoarticular disease, and pulmonary disease.
Where sporotrichosis is suspected, histopathology and microbiological studies are the key investigations of diagnostic value.
Microscopy of biopsy material is o en non-specific, showing features resembling granulomatous disease. However, application
of the periodic acid-Schi or Grocott's methenamine silver stains allows identification of fungal elements such as budding-yeast-
like cells, cigar-shaped cells, and asteroid bodies.
Fungal cultures remain the gold standard microbiological test, with sabouraud-dextrose agar the culture medium of choice. The
fungus can be identified by its characteristic colony morphology, microscopic appearance, and thermal dimorphism with mold
formation at 25°C and yeast at 37°C.
Polymerase chain reaction (PCR) may be useful in the diagnosis of disseminated or extracutaneous sporotrichosis; serological
testing for fungal antigens is also available now.
Spontaneous resolution of sporotrichosis is rare, with most patients requiring treatment. In this respect, the Infectious Diseases
Society of America (IDSA) recommends itraconazole for uncomplicated cutaneous sporotrichosis and osteoarticular
sporotrichosis.
For patients with pulmonary, meningeal, and disseminated sporotrichosis, liposomal amphotericin B is the mainstay of
treatment; due to the teratogenicity of azole drugs, this agent should also be used to treat severe sporotrichosis in pregnant
women.
In resource-poor countries, saturated solution of potassium iodide given orally is an alternative treatment for cutaneous
sporotrichosis; however, this has numerous side e ects ranging from gastrointestinal irritation to hypothyroidism, while it is also
contraindicated in pregnancy.
Treatment for cutaneous sporotrichosis should continue until 2 to 4 weeks following resolution of the skin lesion. For
extracutaneous sporotrichosis, treatment should persist for at least 12 months, so as to completely eradicate the infection.
Note also that persons at high risk of contracting sporotrichosis should wear gloves and heavy boots to prevent accidental skin
puncture; zoonotic transmission from cats can be avoided by taking proper preventive measures such as isolation of infected
cats and declawing.
Take home messages

1. Sporotrichosis is a known cause of chronic cutaneous ulcers, and should be considered if the patient has been in contact with
soil or plant matter.
2. Most cases occur following traumatic implantation, although the a ected individual may not necessarily recall this.
3. Staining of histological specimens may reveal fungal structures; however, it is cultures which are the gold standard for
diagnosis.
4. Itraconazole is the drug of choice for cutaneous disease, while amphotericin B is preferred in disseminated disease,
immunocompromise, and pregnancy.
References
1. MAHAJAN VK. Sporotrichosis: An Overview and Therapeutic Options Dermatol Res Pract [online] 2014 Dec 29:272376
[viewed 13 October 2016] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4295339
2. BURNS MJ, KAPADIA NN, SILMAN EF. Sporotrichosis West J Emerg Med [online] 2009 Aug, 10(3):204 [viewed 13 October
2016] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2729227
3. BARROS MB, DE ALMEIDA PAES R, SCHUBACH AO. Sporothrix schenckii and Sporotrichosis Clin Microbiol Rev [online] 2011
Oct, 24(4):633-654 [viewed 13 October 2016] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3194828
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Inoculated

Diagnosis and reasoning

Take home messages

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