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Sporotrichosis
Evidence Levels: A Double-blind study B Clinical trial ≥ 20 subjects C Clinical trial < 20 subjects D Series ≥ 5 subjects E Anecdotal case reports
Sporotrichosis is a deep, cutaneous fungal infection caused by several species of Sporothrix of which the most common in S. schenckii , a rapidly growing dimorphic saprophytic fungus found in soil and plant matter. It can affect both humans and animals and is prevalent worldwide, but is more common in the Tropics. Sporadic zoonotic transmission (most commonly with cats) is now also well recognized. Cutaneous lesions develop following traumatic inoculation of S. schenckii. Infection is therefore more common in some occupations, such as horticulturists, carpenters, and miners; 15% of cases occur in children less than 10 years of age. The initial lesion appears at the site of injury as an erythematous, ulcerated, or verrucous nodule. Lesions can be localized and are known as fixed-type sporotrichosis. The more common presentation is the lymphocutaneous form, where there is nodular lymphangitic spread. Pulmonary and disseminated infection following inhalation is uncommon. It is a risk in the immunocompromised and an emerging problem in those with advanced HIV infection. Infection is usually sporadic, but outbreaks may occur due to contaminated soil and wood.
Management Strategy
Although there have been cases describing the spontaneous remission of sporotrichosis, it is common practice to treat the disease. Treatment includes localized physical therapies, saturated solution of potassium iodide (SSKI), azoles, terbinafine, and amphotericin B. Historically, uncomplicated lymphangitic and fixed forms of sporotrichosis have been treated with high-dose SSKI initiated with five drops three times daily and increased as tolerated to 10–50 drops three times daily (equivalent to 250 mg to 1 g three times daily). Treatment is continued for 3–4 weeks after clinical cure. The mechanism of action of potassium iodide is not known but it is highly effective, with reported cure rates ranging from 80% to 100%. It is also inexpensive, and is first-line treatment for sporotrichosis in most developing countries. However, it is inconvenient to administer and side effects are common, although not serious, and include metallic taste, nausea, abdominal pain, and salivary gland enlargement.
Itraconazole is first-line therapy in countries where it is affordable. It should be initiated at a loading dose of 200 mg three times daily for 3 days, followed by 100–400 mg daily, depending on disease severity. It may be administered continuously or intermittently (pulse). Cure rates for cutaneous and lymphocutaneous infection are high, generally 90%–100%. Terbinafine (250–1000 mg daily) produces similar efficacy. Fluconazole (400–800 mg daily) therapy gives response rates of 63%–71% and therefore is recommended for second-line therapy only. Ketoconazole is ineffective for the treatment of sporotrichosis. Drug therapies are sometimes combined in order to increase efficacy. There are limited case reports of the use of physical therapies, which have been used either alone or in combination with drug therapy. These include thermotherapy (using infrared wavelengths to heat tissues to 42–43°C), photodynamic therapy, laser (Nd:YAG), cryotherapy, and electrosurgery. Physical therapies may have a useful role as monotherapy in those for whom systemic therapies are contraindicated.
There are no clinical trials to guide therapy for disseminated or meningeal sporotrichosis, which can occur with immunosuppression. Based on case reports, parenteral amphotericin B (AmB) is the preferred treatment (AmB deoxycholate 0.7 mg/kg daily, or as a lipid formulation 3.0–5.0 mg/kg daily). A lipid formulation of AmB is recommended for meningeal infection. Following AmB induction therapy, itraconazole (200 mg twice daily) is given as maintenance therapy.
Clinical Practice Guidelines for the Management of Sporotrichosis: 2007 Update by the Infectious Diseases Society of America
Kauffman CA, Bustamante B, Chapman SW, et al. Clin Infect Dis 2007; 45(10): 1255–65.
For cutaneous and lymphocutaneous infection in developed countries, first-line recommended therapy is with itraconazole 200 mg daily, which is continued for 2–4 weeks after all lesions have resolved. Usually a 3–6 month course of treatment is recommended. Patients who fail to respond can be given either high-dose itraconazole 200 mg twice daily, terbinafine 500 mg twice daily, or saturated solution of potassium iodide (SSKI initiated at a dose of five drops three times daily and increased as tolerated to 40–50 drops thrice daily). Children can be treated with the same drugs at a dose of 6–10 mg/kg for itraconazole (maximum 400 mg daily) and a maximum of one drop/kg of SSKI. Fluconazole should only be used in patients who cannot tolerate any of these treatments. Thermotherapy can be used for fixed lesions in those in whom oral therapy is contraindicated, such as pregnant women. Amphotericin B is recommended first-line therapy for severe pulmonary or osteoarticular infection, and disseminated and meningeal sporotrichosis. After initial response, itraconazole is recommended as stepdown therapy and should be given to complete a total of at least 12 months of therapy. Amp B is also the drug of choice for severe infection in pregnancy.
Future updated guidelines will need to incorporate recent data demonstrating the efficacy of lower doses of itraconazole and terbinafine for sporotrichosis.
Direct microscopy of infected material is futile because the infective organisms are scarce in tissue. Culture is the most sensitive means of diagnosis, and is characteristically rapid, with growth usually seen within 1 week in 90% of cases. In the remaining 10% it may take up to 4 weeks to achieve a positive result on Sabouraud agar culture. The diagnosis is confirmed by demonstrating dimorphism, or conversion to the yeast phase. Suitable material for culture may include lesion swab, aspirate, or biopsy. Histopathology reveals a mixed granulomatous and pyogenic inflammatory response with pseudoepitheliomatous hyperplasia. The fungus is sometimes visualized with periodic acid–Schiff staining and is associated with extracellular Sporothrix asteroid bodies, consisting of yeast surrounded by radiating eosinophilic spicules. There is only limited data for polymerase chain reaction, and it requires further clinical validation.
Immunity and treatment of sporotrichosis
Garcia Carnero LC, Lozoya Perez NE, Gonzalez Hernandez SE, et al. J Fungi (Basel) 2018; 4(3): 100.
Given the limitations of current drug therapies and the acquisition of antifungal drug resistance, this review discusses passive and active immunological responses as a topic of growing interest in the development of a potential anti- Sporothrix vaccine
Sporotrichosis in immunocompromised hosts
Queiroz-Telles F, Buccheri R, et al. J Fungi (Basel) 2019; 11(5): 8.
This reviews the presentation of opportunistic sporotrichosis in several different immunosuppressive states including diabetes, alcoholism, transplantation, hematological malignancies, HIV, and iatrogenic immunosuppression. It discusses how higher doses of antifungals and more prolonged courses are usually required. Therapy was generally started with amphotericin formulations, which were switched to itraconazole after the initial improvement.
The impact of sporotrichosis in HIV-infected patients: a systematic review
Moreira JAS, Freitas DF, et al. Infection 2015; 43(3): 267–76.
This is a systematic review of reported cases of HIV-associated sporotrichosis found via PubMed (1984–2013). A total of 39 papers were included, and 58 patients’ data analyzed; 56.9% of cases were from Brazil and 31% from the US. The median CD4 cell count was 97 cells/mm 3 . The most common clinical forms were disseminated and disseminated cutaneous affecting 56.9% and 17.5% of patients, respectively. Mortality was 30% and significantly higher in those with central nervous system involvement and death.
In this group of patients, AmB was usually the drug of choice and itraconazole was used as maintenance therapy.
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