Chapter 303. Sporotrichosis

Sporotrichosis is an uncommon, chronic mycosis caused by Sporothrix schenckii. This ubiquitous plant saprophyte is a dimorphic fungus that grows as a mold at room temperature and as a yeastlike form in tissue. Although distributed worldwide, it is found most commonly in warm, highly humid regions and in temperate climates. Mexico, other parts of Central America, Asia, the United States, Canada, and France are endemic areas. Infection is characterized by isolated cutaneous or subcutaneous necrotizing nodules associated with the indolent development of suppurating nodules along the course of the proximal lymphatics. Extracutaneous and pulmonary forms of the disease occur infrequently. The histopathologic findings of primary cutaneous disease combine features of both granulomatous and pyogenic inflammation. Granulomatous lesions consist of aggregations of epithelioid histiocytes with central areas of necrosis and neutrophils or zones of Langhans giant cells associated with fibroblasts and lymphocytes. Occasionally, areas of microabscesses unassociated with granulomatous reaction may be seen. In chronic disease, pseudoepitheliomatous hyperplasia may be extensive and mimic neoplasm. A common histopathological feature is the asteroid body, a round basophilic, yeastlike structure surrounded by rays of eosinophilic material thought to represent antigen-antibody complexes. The asteroid body may also be seen in other mycoses.

In 95% of cases, the organism is percutaneously inoculated by contaminated thorns, tree bark, splinters, or animal bites.1 Rare cases of human-to-human transmission have been reported. Sporotrichosis has been reported in many areas of the United States but is most common along the Mississippi River Valley and in the Plains states. Most cases are sporadic, but outbreaks have been attributed to a single source.2-4 Infection occurs in all age groups; about 10% to 25% of cases occur in children.

Clinical Manifestations

The spectrum of clinical findings in sporotrichosis can be divided into lymphocutaneous, fixed cutaneous, extracutaneous (localized or multifocal), and pulmonary. Cutaneous infection is most common in children; documented localized extracutaneous infections are rare.

Lymphocutaneous sporotrichosis accounts for 75% of infections. Following inoculation, the average incubation period is 3 weeks but ranges from 5 days to 6 months. Lesions usually involve the upper extremities but may occur on the face and trunk.5 The primary lesion is a firm, mobile, nontender subcutaneous nodule that enlarges and becomes discolored (Fig. 303-1). After 2 weeks, it undergoes necrosis, leaving a painless ulcer. During the next several weeks, additional lesions develop along the proximal lymphatics; intervening lymphatic channels become thickened, with overlying cutaneous erythema (Fig. 303-2). Lesions can persist for months to years. Few heal spontaneously, with scarring of the ulcers. Systemic symptoms are absent or mild.

Fixed cutaneous disease accounts for 20% to 25% of cases and is common in children. Infection is limited to the site of inoculation and consists of ulcerative, plaquelike, or maculopapular lesions. They can resolve spontaneously, persist for years, or resolve and recur.

Extracutaneous disease accounts for less than 1% of cases and may occur as localized or multifocal disease. Osteoarticular manifestations are common and include destructive arthritis, tenosynovitis, chronic osteomyelitis, and periostitis. Localized extracutaneous infections may result from hematogenous dissemination, spread from contiguous skin lesions, or from direct inoculation. The tibiae and the bones of the hands are often affected. Arthritis is slowly progressive, and symptoms include pain, swelling, and impaired function. Osteoarticular disease usually remains localized but can spread to contiguous structures; dissemination is rare.

Multifocal extracutaneous disease results from hematogenous spread, is rare in children, and occurs in immunocompromised patients.

In adults, predisposing conditions include AIDS, malignancy, diabetes, sarcoidosis, alcoholism, and long-term corticosteroid therapy. Sporotrichal meningitis is a rare but severe manifestation of disseminated disease primarily seen in immunocompromised patients and has a very poor prognosis. Primary pulmonary sporotrichosis, seen mainly in adults, follows inhalation of spores. It may affect the lung parenchyma or remain localized to the hilar nodes. There is usually no extracutaneous site of infection. Apical portions of the lung are involved, and chronic cavitary lesions may result. Lesions can be progressive and fatal. Another pulmonary presentation involves the hilar lymph nodes only and may mimic tuberculosis and histoplasmosis. This manifestation can remain stable for long periods and often resolves spontaneously.

Diagnosis

Painless papulovesicular, ulcerative, or nodular lesions that fail to respond antibiotics should prompt consideration of sporotrichosis. The differential diagnosis includes infection with Nocardia species, Francisella tularensis, nontuberculous mycobacteria, Treponema pallidum, and Leishmania. Nodular lymphangitis can also be seen with infections caused by pyogenic bacteria Pseudomonas species; Bacillus anthracis; and other mycoses, including blastomycosis, chromoblastomycosis, coccidioidomycosis, cryptococcosis, and histoplasmosis. Nodular lymphangitis can be seen with mycetoma, which may be caused by bacteria or fungi. A careful travel and exposure history helps differentiate these entities.

The laboratory diagnosis of sporotrichosis is problematic because histopathologic findings of pyogranulomatous inflammation are not diagnostic, few organisms are found in tissue, and their morphology may not be typical. Using methodology appropriate for fungi, S schenckii can be isolated from exudate or biopsied tissue, and conversion of the mold to yeast forms is confirmatory.6 The organism is more readily recovered from synovial fluid than from cutaneous lesions. In cases of meningitis, the cerebrospinal fluid typically shows a mild pleocytosis with a majority of lymphocytes, elevated protein, and hypoglycorrhachia.

Serological testing has not proved useful for the diagnosis of sporotrichosis and is not commercially available.7

Treatment

Guidelines for the treatment of sporotrichosis have been published.8 Iodide therapy is effective treatment of cutaneous disease and is often utilized as a therapeutic agent in developing countries because it is inexpensive and available. The mechanism by which iodide therapy works is unknown. Five drops of a saturated solution of potassium iodide mixed in water, milk, or juice is given 3 times daily; each dose is increased by 5 drops weekly until a maximum of 40 to 50 drops 3 times daily for adults is reached. Maximum dosing in children is 40 to 50 drops 3 times daily or 1 drop per kilogram of body weight, whichever is lower. Treatment continues for 6 to 8 weeks after the resolution of the lesions. Side effects include anorexia, nausea, a metallic taste, rash, fever, and swelling of the salivary glands. The extended length and inconvenience of treatment with iodide often leads to poor compliance. Iodide therapy cannot be used in pregnancy.

Itraconazole is currently the recommended treatment for cutaneous and localized lymphocutaneous sporotrichosis for adults and children (see Table 247-1). Response rates are excellent and side effects are few. However, treatment is expensive. Care must be taken to avoid drug interactions. The liquid preparation of itraconazole is preferred. Serum concentrations should be documented to confirm absorption (available through Miravista Diagnostics, Indianapolis, IN). Lesions usually resolve within 1 month of beginning treatment; treatment should be continued for several months after the lesions have healed to decrease the likelihood of relapse. Itraconazole is also the treatment of choice for isolated osteoarticular disease. Therapy should continue for 1 to 2 years. Itraconazole may be used for treating subacute or chronic pulmonary disease.

Fluconazole is considered effective but less active and can be used if first-tier therapy is not tolerated.

Local hyperthermia has been effective for treating cutaneous lesions because S Schenckii is growth impaired at temperatures exceeding 42°C and may be considered for patients who cannot tolerate the recommended drugs or during pregnancy. Local hyperthermia may not be readily tolerated in children.

Amphotericin B is used to treat progressive disseminated and pulmonary sporotrichosis or in initial treatment of osteoarticular disease. In adults, most clinical experience has involved deoxycholate amphotericin B; however, new treatment guidelines prefer lipid formulations of amphotericin B because of fewer adverse effects. Amphotericin B is preferred during pregnancy because the azoles should be avoided. Data in children is lacking, but deoxycholate amphotericin B is recommended for initial treatment of disseminated disease followed by itraconazole. Treatment in AIDS patients is problematic because progressive infection has been described in patients receiving amphotericin B, and the relapse rate is high. Therefore, as with other systemic fungal infections in AIDS patients, lifetime prophylaxis with itraconazole is recommended, although discontinuation of treatment after 1 year if CD4 counts recover may be considered. Amphotericin B is the preferred treatment for infections of the central nervous system.