Sporothrix schenckii (Sporotrichosis)
Authors:Carol A. Kauffman, M.D.
MICROBIOLOGY
Sporotrichosis is caused by infection with the dimorphic fungus Sporothrix schenckii. The organism is distributed worldwide, and is found mostly in soil, decaying vegetable matter, and sphagnum moss (18). S. schenckiigrows as a mold in the environment and at temperatures below 35°C; the organism assumes the yeast form in vivo and at temperatures above 35°C.
EPIDEMIOLOGY
Sporotrichosis occurs throughout the world from temperate to tropical regions. A preponderance of cases has been reported from the Americas and Japan.
Infection occurs primarily by percutaneous inoculation of the conidia of S. schenckii; in a few patients, inhalation of the conidia leads to pulmonary infection. Most infections are sporadic and often associated with scratches from rose bushes, hay, wood splinters, or conifer needles. Contaminated soil and sphagnum moss used as packing material around plants have been associated with outbreaks of sporotrichosis (9, 12). Infection can also be secondary to scratches or bites from animals, including armadillos, cats, and rodents (8, 24, 27). An extensive outbreak of cat-associated sporotrichosis, occurring mostly in women and children who care for domestic cats, is ongoing in Rio de Janiero, Brazil (3).
CLINICAL MANIFESTATIONS
The most common manifestations of sporotrichosis are cutaneous or lymphocutaneous infections of the extremities (15). Much less common is osteoarticular involvement, which can take the form of osteomyelitis, tenosynovitis, septic arthritis, or bursitis, and appears to be more common in alcoholics (15). Pulmonary sporotrichosis is another uncommon manifestation of infection, occurring most often in men with underlying chronic obstructive pulmonary disease (23). Disseminated sporotrichosisis rare and described mostly in those who have HIV infection or are on immunosuppressive therapy (1, 4, 5, 11, 22, 29). Meningeal sporotrichosis can occur as an isolated chronic meningitis or as one manifestation of disseminated infection (15, 29)
LABORATORY DIAGNOSIS
The diagnosis of sporotrichosis is best made by culture of exudate from ulcerated lesions or by culture and histopathological examination of tissue biopsies. Rarely, S. schenckii has been grown from blood (1, 2). Serological assays are not standardized and at this time, are not useful for diagnosis of sporotrichosis.
PATHOGENESIS
S. schenckii is relatively avirulent. Those strains that do cause infection appear to contain melanin, a known virulence factor for other fungi (9). Neutrophils and macrophages are able to ingest and kill S. schenckii yeast forms in the absence of antibody. Cell mediated immunity appears to be important in controlling infection, as noted with more severe disease in patients with HIV infection and in T-cell deficient mice.
SUSCEPTIBILITY IN VITRO AND IN VIVO
Susceptibility testing has not been standardized for S. schenckii, but several studies have shown susceptibility to itraconazole and amphotericin B, but not to voriconazole or echinocandins (10, 20). Interestingly, saturated solution of potassium iodide (SSKI), an effective treatment for lymphocutaneous sporotrichosis, does not inhibit growth of S. schenckii in vitro (26). Clinical experience has been the major determinant for the choice of antifungal therapy for this infection.
ANTIMICROBIAL THERAPY
General
Guidelines for the management of sporotrichosis have been recently published by the Infectious Diseases Society of America (17). Itraconazole has become the drug of choice for lymphocutaneous and cutaneous infection withS. schenckii. Response rates of 90-100% can be expected with 100-200 mg of itraconazole daily for 3-6 months (14, 25,28). Improved absorption occurs when the oral suspension is used rather than the capsule formulation. The oral solution is taken between meals. The capsules must be taken with food, and gastric acid-lowering agents should not be used.
Special Situations
For patients who have pulmonary, severe osteoarticular, meningeal, or disseminated infection, amphotericin B may be required for initial therapy. The IDSA Guidelines recommend use of a lipid formulation of amphotericin B at 3-5 mg/kg daily until the patient’s condition has stabilized. Amphotericin B deoxycholate, 0.7-1 mg/kg daily, is an alternative, but is associated with more side effects.
Osteoarticular Infections
Osteoarticular sporotrichosis is best treated with itraconazole at a total dosage of 400 mg daily, given as two divided doses (17, 28, 30). The response rate is approximately 70%, but relapses are common. Therapy should be continued for at least 1 year in an attempt to prevent relapse.
Pulmonary Infection
Pulmonary sporotrichosis is difficult to treat (14, 17, 23). If the patient is not acutely ill, therapy can be started with 200 mg twice daily of itraconazole and continued for at least one year. For patients with life-threatening pulmonary sporotrichosis, amphotericin B should be given, with step-down to itraconazole therapy after the patient has shown a favorable response.
Disseminated Sporotrichosis
Amphotericin B, preferably a lipid formulation at 3-5 mg/kg daily is recommended for disseminated infection (17). After the patient has improved, therapy can be switched to itraconazole, 200 mg twice daily, for at least one year. For immunosuppressed patients, life-long itraconazole, 200 mg daily, may be required.
Sporotrichal Meningitis
The IDSA Guidelines recommend a lipid formulation of amphotericin B at a dosage of 5 mg/kg daily for 4-6 weeks, followed by itraconazole, 200 mg twice daily for at least one year. For immunosuppressed patients, life-long itraconazole, 200 mg daily, may be required (17).
Alternative Therapies
Cutaneous and Lymphocutaneous Disease
SSKI is a reasonable alternative for cutaneous and lymphocutaneous sporotrichosis (6, 17, 21). The response rate for SSKI is generally over 90%. The drug is clearly less costly than any other agent and is used preferentially in developing countries (6, 21). The major drawback to the use of SSKI is its toxicity, which includes anorexia, nausea, salivary gland swelling, metallic taste, rash, and fever. The dosage initially is 5 drops three times daily; this is increased by 5 drops per dose every week up to a maximum dosage of 40-50 drops three times daily. Once daily administration of the daily dose has been used in children (6). Fluconazole is a reasonable alternative for cutaneous and lymphocutaneous sporotrichosis. A dosage of 400-800 mg daily should be prescribed for 6 months (17, 16), and the response is often slower than that noted with itraconazole. Terbinafine has been reported to be effective in the treatment of cutaneous and lymphocutaneous sporotrichosis at a dosage of 500 mg twice daily (7).
Osteoarticular and Visceral Sporotrichosis
Few options other than itraconazole and amphotericin B exist for pulmonary, osteoarticular, meningeal, and disseminated sporotrichosis. SSKI, fluconazole, and terbinafine should not be used for these forms of sporotrichosis. There is no clinical experience with voriconazole, and in vitro, this agent appears to be inactive against S. schenckii. Posaconazole may have in vitro activity against S. schenckii (10), but no clinical use has been reported.
ADJUNCTIVE THERAPY
Surgery is suggested as an adjunct for patients with pulmonary sporotrichosis (23). However, severe chronic obstructive pulmonary disease and extensive bilateral infection, present in many of these patients, often preclude surgical intervention (17).
For the occasional patient who has cutaneous sporotrichosis and who may be pregnant or for some other reason cannot take a systemic antifungal agent, local application of heat may lead to resolution of infection (13, 19).
ENDPOINTS FOR MONITORING THERAPY
The therapeutic response is measured by improvement in cutaneous lesions, which generally take several months to regress. Therapy should continue for a few weeks after the lesions have resolved totally or only residual scar tissue is present. Pulmonary sporotrichosis is measured by clinical, microbiological, and radiographic improvement. Resolution of pulmonary infiltrates is slow, and it is often difficult to tell residual fibrosis from active infection. Sputum should no longer yield S. schenckii. Sporotrichal arthritis is followed by clinical and microbiological parameters; synovial fluid cell counts should revert to normal, and culture should show no growth. Clinical and radiographic resolution of osteomyelitis is slow. Abnormalities in CSF parameters should return to normal as meningeal sporotrichosis is treated.
VACCINES
No vaccines are available.
PREVENTION
Because sporotrichosis is acquired from the environment, the most effective preventive measure is avoidance of activities that predispose to inoculation of the organism from soil, plant matter, or animals. For high risk occupations or avocations that involve sphagnum moss and plants that have sharp spikes or material with sharp edges, such as rose gardening, conifer planting, and topiary, wearing gloves, long-sleeved shirts, and long pants will help decrease the risk (12). Veterinarians should be careful to avoid aerosols and direct cutaneous inoculation when handling cats that have ulcerated lesions caused by S. schenckii (24).
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None.
What's New
Bonifaz A, et al. Sporotrichosis in Childhood: Clinical and Therapeutic Experience in 25 Patients. Pediatr Dermatol 2007;24:369-372.
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Adhikari P, Mietzner T. Cell Mediated Immunity. 2008.
Kauffman CA, et al. Clinical Practice Guidelines for the Management of Sporotrichosis: 2007 Update by the Infectious Disease Society of America. Clin Infect Dis 2007;45:1255-65.
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