Approach

Lymphocutaneous/cutaneous sporotrichosis is not life threatening and has an excellent outcome. Conversely, extracutaneous forms of sporotrichosis may be life threatening, especially in patients with underlying immunocompromise, and response to treatment is variable depending on the host and the extent of the infection. Pregnant women require different treatment due to unsuitability of some antifungal drugs during pregnancy. Local hyperthermia is effective in pregnant women with fixed cutaneous (but not lymphocutaneous) sporotrichosis.

Lymphocutaneous and cutaneous sporotrichosis

Although spontaneous resolution of cutaneous lesions has rarely been reported, antifungal therapy is required.[1][36]

The duration of therapy is 2 to 4 weeks after all lesions have resolved, typically a total 3- to 6-month treatment course. Clinical improvement is usually seen within 4 weeks of therapy initiation.

Itraconazole is the treatment of choice. Response rates of 90% to 100% have been reported in several open nonrandomized treatment trials.[37]​[38][39]​​​ Itraconazole is well tolerated without adverse effects except for minor gastrointestinal (GI) intolerance.[36][37][38][39][40]

Itraconazole is available as a capsule and an oral solution. The capsule formulation is best absorbed with food; medications that decrease stomach acidity should be avoided. The oral solution is best absorbed with an empty stomach and, if tolerated without GI adverse effects, is the preferred formulation to treat sporotrichosis because of its favorable absorption characteristics.

For patients who do not respond to initial treatment, there are several alternative therapeutic regimens:

  1. A higher dose of itraconazole. Serum itraconazole levels should be monitored to ensure adequate drug absorption. Because of its long half-life and little serum level variation over a 24-hour period, drug levels can be drawn at any time point after dose administration. Serum levels of >1 microgram/mL are desirable.[36][37][38][39]

  2. Saturated solution of potassium iodide (SSKI). Response rates of 80% to 100% have been reported in one small randomized clinical trial, several open noncontrolled clinical trials, and in large case series from less developed areas of the world.[10][41][42]​​​ The solution has a bitter taste, and nausea is common. Over the 2 to 3 months of treatment, an acneiform nonpruritic rash over the upper torso and parotid gland swelling are common. However, results in cutaneous sporotrichosis are generally favorable.[10][36][41][42][43]

  3. High-dose terbinafine. A randomized blinded trial comparing 500 mg/day versus 1000 mg/day showed response rates of 52% and 87% respectively, and relapse rates of 21% and 0% respectively.[44]​ However, GI and neurologic adverse effects were seen in one third of treated patients, raising questions regarding the safety of this high-dose regimen. Liver function tests should be monitored on terbinafine therapy.[36][44] A study showed that treatment with a lower dose of terbinafine (250 mg/day) has comparable efficacy to therapy with low dose of itraconazole (100 mg/day). Specifically, cure rates exceeded 90%, and relapse was uncommon in both treatment arms, without significant side effects.[45] Hence, the discrepancy in response rates to terbinafine between the above studies requires future additional studies to determine the role of terbinafine therapy in the management of lymphocutaneous sporotrichosis.

  4. Fluconazole should be used only if all the above agents cannot be tolerated. Response rate with doses of ≥400 mg/day is only 63% to 71%.[36][46]

Ketoconazole and flucytosine are not recommended, as other medications are more efficacious and better tolerated. Amphotericin B, although effective, is not recommended because of its toxicity and because lymphocutaneous sporotrichosis is a localized non-life-threatening infection.[36]

Osteoarticular sporotrichosis

Owing to delayed diagnosis, recovery of joint function is uncommon.[36] Itraconazole is the treatment of choice. Response rates of >60% have been reported. At least 12 months of therapy are recommended; shorter treatment courses are associated with substantial relapse rates. Serum itraconazole levels should be monitored after a patient has received itraconazole for 2 weeks to ensure adequate drug levels. Levels of >1 microgram/mL are desirable.[36][37][47] Amphotericin B may be given as initial therapy (instead of itraconazole) in patients with extensive disease or in patients who are unresponsive to itraconazole. Response rates with amphotericin B are comparable to those with itraconazole but amphotericin B therapy is less well tolerated (i.e., renal impairment with azotemia, renal tubular acidosis, hypokalemia, and hypomagnesemia). After the patient has responded to amphotericin B therapy, step-down treatment with itraconazole for at least 12 months of total treatment duration can be given based on overall clinical response. Adjunctive surgical debridement may be helpful in certain occasions such as in drainage of septic joint, sequestrum resection, or synovectomy.

There are no studies comparing the efficacy of conventional amphotericin B deoxycholate with lipid formulations of amphotericin B, but lipid formulations are associated with considerably less renal toxicity. Intra-articular amphotericin B injections have occasionally been used, but are rarely indicated.[36] SSKI, terbinafine, and fluconazole are not effective.[36]

Pulmonary sporotrichosis

Prognosis of pulmonary sporotrichosis is usually poor.​[36]

For severe or life-threatening pulmonary sporotrichosis, amphotericin B is the recommended initial therapy. After the patient has responded to amphotericin B therapy, or after a cumulative amphotericin B dose of 1 to 2 is reached, step-down treatment with itraconazole for at least 3 to 6 months, or up to 12 months of total treatment duration, can be given based on overall clinical response.[48]

For less-severe disease, itraconazole given for at least 3 to 6 months, and for up to12 months is recommended based on overall clinical response. Serum itraconazole levels should be monitored after a patient has received itraconazole for 2 weeks to ensure adequate drug levels. Levels of >1 microgram/mL are desirable.[48]

Adjunctive surgical resection of affected lung tissue, whenever feasible, is recommended for localized pulmonary disease in combination with amphotericin B. However, many patients who develop pulmonary sporotrichosis have underlying COPD and cannot tolerate surgery. SSKI, terbinafine, and fluconazole are not effective.[36]

Meningeal sporotrichosis

Amphotericin B should be administered for a minimum of 4 to 6 weeks. After the patient has responded to amphotericin B therapy, step-down treatment with itraconazole for at least 12 months of total treatment duration can be given based on overall clinical response. Serum itraconazole levels should be monitored after a patient has received itraconazole for 2 weeks to ensure adequate drug levels. Levels of >1 microgram/mL are desirable.[7][36]

Combination of amphotericin B with fluconazole, itraconazole, or flucytosine is not recommended as it does not improve survival compared with amphotericin B monotherapy.[36] SSKI, terbinafine, and fluconazole are not effective.[36]

Disseminated sporotrichosis

Amphotericin B should be administered.[36][47] After the patient has responded to amphotericin B therapy, step-down treatment with itraconazole for at least 12 months of total treatment duration can be given. Serum itraconazole levels should be monitored after a patient has received itraconazole for 2 weeks to ensure adequate drug levels. Levels of >1 microgram/mL are desirable.

Combination antifungal therapy has not been studied in disseminated sporotrichosis and is not recommended.[36] Studies evaluating the combination of amphotericin B with azole antifungals (e.g., itraconazole, fluconazole) are lacking for severe cases of sporotrichosis, in which response rates to antifungal monotherapy are suboptimal.

Sporotrichosis in pregnant and nursing women

Amphotericin B is recommended for severe infections that require treatment during pregnancy.[36] It is preferable to wait until delivery to treat non life-threatening forms of sporotrichosis.

Azole antifungals are contraindicated due to their teratogenic potential. SSKI is contraindicated due to fetal thyroid toxicity. Terbinafine should not cause fetal toxicity, but because it passes to breast milk it could have an effect on nursing babies. Hence, the risk and benefits of using terbinafine in nursing and pregnant women should be thoroughly discussed with patients and treatment decisions should be individualized.

Local hyperthermia is effective with response rates of >70% in patients with fixed cutaneous (but not lymphocutaneous) sporotrichosis. More than 1-hour application of heat to lesions is required for several months on a daily basis. It may be used in pregnant women in whom the above antifungal agents are not safe.[36][49] The mechanism of action of hyperthermia in sporotrichosis is not well defined, but seems to relate both to the direct inhibition of thermo-intolerant Sporothrix strains[18] and to the enhancement of the killing rate of Sporothrix by polymorphonuclear leukocytes.[50]

Sporotrichosis in children

Children with lymphocutaneous/cutaneous sporotrichosis should be treated with itraconazole. Alternatively, SSKI can be used.[36] SSKI is especially poorly tolerated in children and one study comparing once-daily versus 3 times-daily SSKI therapy showed comparable response rates; hence, for children who do not tolerate the 3 times-daily regimen, once-daily SSKI may be reasonable. Fluconazole and terbinafine should not be used.

For severe sporotrichosis, amphotericin B is recommended. After the patient has responded to amphotericin B therapy, step-down treatment with itraconazole can be given. Itraconazole can also be used as chronic suppressive treatment in children with HIV.

Continuation treatment in immunocompromised patients

In patients with HIV and other immunocompromised patients, chronic suppressive therapy with itraconazole is recommended to prevent relapse after initial treatment for disseminated or meningeal sporotrichosis is complete.

In patients with meningeal sporotrichosis, lifelong suppression is necessary. In patients with disseminated sporotrichosis, discontinuation of suppressive treatment can be considered if their CD4 count remains above 200 cells/mm³ for >1 year and the patient has received >1 year of itraconazole therapy.

Monitoring during treatment

Serum itraconazole levels of >1 microgram/mL are desirable in patients with osteoarticular, pulmonary and meningeal sporotrichosis, and unresponsive cutaneous sporotrichosis.

Amphotericin B can cause renal dysfunction, therefore serum creatinine and blood urea nitrogen should be monitored during treatment. Liver function tests should be monitored in those on terbinafine.

Use of this content is subject to our disclaimer