Sporotrichosis: A brief review

Etiopathogenesis

S. schenckii, a common saprophyte of soil, decaying wood, hay, and sphagnum moss, is a complex of at least six cryptic species viz. S. globosa (in India, the UK, Spain, Italy, China, Japan, and the USA), S . mexicana (environmental, in Mexico), S. albicans, S. brasiliensis (in Brazil), S. luriei, and S. schenckii sensu stricto.^[8,9] These show distinct biochemical properties (dextrose, sucrose, and raffinose assimilation), geographical distribution, virulence, disease patterns, and therapeutic response. S. globosa is the commonest isolated strain in India and evidently responsible for most cases of treatment failure.^[10,11]

Cutaneous infection occurs following traumatic implantation of S. schenckii into the skin from contaminated thorns/ needles, hay stalks, soil, splinters, and contaminated bizarre injuries. However, only 10%–62% of patients could recall history of trauma in most reports with few exceptions as it is mostly forgotten being innocuous and happened few weeks/ months earlier.^[1-7] Zoonotic transmission attributed to insect/ bird/animal(s) bites, fish handling, etc. are because of wound contamination from infected dressings or indigenous/ herbal poultices and so is human-to-human spread.^[2] Although animals are not significant source of human infection, cats have been important vehicle in dissemination of S. schenckii in a long-lasting epidemic in Brazil.^[12]

Since disease occurrence depends upon the fungus in the environment and its portal of entry, professionals handling plants or plant material (farmers, gardeners, florists, foresters, nursery workers) are at risk of getting infection without any predilection for age, gender, or race. The reported preponderance of males or females and individuals aged between 30 and 50 years is perhaps from their high occupational exposure risk.^[7]

Clinical spectrum

The incubation period varies from a few weeks to few months (average 3 weeks). The portal of entry, the size, and the depth of the inoculums, virulence, and thermal tolerance of the fungus, and the host immune status have been suggested to influence the subsequent manifestations.^[13] Sporotrichosis primarily involves the skin and surrounding lymphatics without systemic symptoms. A small, indurated, progressively enlarging papulo-nodule (primary lesion) evolves at inoculation site, which may ulcerate (sporotrichotic chancre), develop few similar satellite lesions with or without transient adenopathy.^[13] It may remain as such or progress into one of the clinical forms listed in Table 2 [Figure 1]. Lymphocutaneous sporotrichosis, involvement of upper limb, dominant hand in particular, and face especially in children remain the commonest clinical presentation.

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Figure 1:

(a) Fixed cutaneous sporotrichosis: A small crusted plaque develops at inoculation site seen here over cheek of a child. This form is common in children and responds better to treatment. Small lesion at the periphery of primary lesion indicates destabilization of the lesion because of trauma from self manipulation, surgery, or biopsy.

(b) An ulcerated lesion of fixed cutaneous sporotrichosis mimicking pyoderma ganrenosum.

(c) Lymphocutaneous sporotrichosis: An ulcerative lesion (sporotrichotic chancre) has developed at inoculation site over dorsal hand with a string of ulcerative plaques along the proximal lymphatics characterizes this form and the diagnosis is fairly easy.

(d) Healing of lymphocutaneous sporotrichosis lesions 8 weeks after treatment with saturated solution of potassium iodide.

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Diagnosis

Clinical suspicion is paramount for early diagnosis. Cutaneous leishmaniasis, cutaneous tuberculosis, atypical mycobacteriosis, nocardiosis, and other mycobacteriosis, mycobacteriosis, nocardiosis, and other subcutaneous mycoses remain major differentials. Ulcerated lesions can mimic pyoderma gangrenosum.^[14]

Histopathology

The histologic features remain variable. In lymphocutaneous sporotrichosis these vary from acute on chronic inflammation with characteristic zonation, chronic epithelioid cell granuloma with foreign body or Langhans’ giant cells to non-specific chronic granulomatous inflammatory cell infiltrate in dermis.^[2] The major histopathologic features of fixed cutaneous sporotrichosis include central ulceration of epidermis with hyperkeratosis at the edge, acanthosis and pseudoepitheliomatous hyperplasia. Dense mixed granulomatous cellular infiltrate in upper and mid dermis comprises lymphocytes, plasma cells, and variable number of epithelioid histiocytes, giant cells, and eosinophils with or without fibrocapillary proliferation. Cigar-shaped or asteroid bodies, oval-to-round or single budding forms of the yeast within the cytoplasm of giant cells or in the centre of asteroid bodies, or Splendore-Hoeple phenomenon is visualized occasionally.

Causative fungus

Identification of S. schenckii in direct examination of pus or biopsy specimen is not always possible and laboratory culture of S. schenckii from clinical samples is confirmatory. Its growth on Sabouraud’s glucose agar at 25°C becomes visible within days. The initial cream-colored colonies turn brown/black after few weeks due to melanin production.

Subcultures on blood glucose-cystene agar or brain-heart infusion broth at 37°C yields yeast form. In practice demonstration of this temperature dimorphism along with colony characteristics helps in its identification [Figure 2].^[6,13]

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Figure 2

Sporothrix schenckii and temperature dimorphism.

(a) Culture on Sabouraud’s glucose agar at 25°C. The initial cream colored colony;

(b) Turns brown black as it matures.

(c) Sporothrix schenckii isolate from subculture on brain heart infusion agar at 37°C. The budding yeast cells (blue arrows) and cigar-shaped yeast cells (green arrows) are seen interspersed between spores (Grams’ stain, × 100).

(d) Sporothrix schenckii from culture on SDA at 25°C. The delicate branching, yeast form, and pyriform conidia in a characteristic sleeve-like pattern (black arrows) and flower-like arrangement (red arrows), (Stain, lactophenol cotton blue, × 40).

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Other diagnostic tools

The diagnostic utility of intradermal tests using sporotrichin or peptide-rhamnomannan antigen in practice remains limited because of false positive (in cured or healthy persons in endemic areas) or false negative (in severe or disseminated sporotrichosis) results.^[1,13] Serodiagnostic and molecular diagnostic techniques are useful for research and diagnosing rare extracutaneous forms.^[13] A favorable therapeutic response to saturated solution of potassium iodide (SSKI) is also nearly diagnostic.^[13,15]

Treatment

Most of the treatment recommendations are based on small case series or case reports. Any treatment found effective needs to be extended for 2–4 weeks after lesions have healed. Itraconazole (100–200 mg/d, PO) remains first-line treatment for all forms.^[16] However, SSKI is still preferred for uncomplicated cases in developing countries with limited resources, and when itraconazole have failed. It is given orally in a starting dose of 5 drops thrice daily (t.i.d.) mixed with milk or fruit juice to make it palatable. The dose is increased daily by 5 drops t.i.d. up to a maximum 30 to 40 drops t.i.d. Metallic taste necessitates dosage adjustment at a lower level.^[13]

It is not useful in extracutaneous forms and remains contraindicated in patients who develop hypersensitivity (intolerable metallic taste, flu-like symptoms) or have preexisting thyroid disorders because of defective autoregulation mechanism (as from surgery or radioactive iodide therapy for Graves’ disease, Hashimoto’s thyroiditis).^[17]

An adequate control with intravenous amphotericin B (3–5 mg/kg of lipid formulation) is recommended in systemic sporotrichosis patients when the treatment cannot be deferred or before initiating long-term itraconazole therapy or when other drugs are contraindicated (as in pregnancy).^[13]

Terbinafine (125 to 1000 mg/day given for 4–37 weeks) has been used effectively to treat cutaneous sporotrichosis when itraconazole had failed or remains contraindicated.^[13] A combination of SSKI and itraconazole or terbinafine shows better efficacy than either drug used alone.^[7]

In in-vitro studies posaconazole has shown good activity against five species of S. schenckii but activity of ravuconazole against S. brasiliensis is limited; both remain understudied clinically.^[13] Echinocandins and voriconazole are not effective in sporotrichosis treatment.^[18,19]

The daily application of heat (42°–43°C) to the lesion for weeks using heat compresses, infrared heater, or hand-held pocket warmer is useful as an adjunct or for treating small cutaneous lesions pending specific therapy.