Published on 18/03/2015 by admin
Filed under Dermatology
Last modified 22/04/2025
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Mahreen Ameen and Wanda Sonia Robles
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 Sporothrix schenckii, a rapidly growing dimorphic saprophytic fungus found in soil and plant matter, occurring worldwide, but more commonly in the tropics. Disseminated and internal infection is a risk in the immunocompromised and in advanced HIV infection. Cutaneous lesions develop following traumatic inoculation of S. schenckii. It is more common in some occupations such as horticulturists, carpenters, and miners due to inoculation with infected soil or wood. 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.
Although there have been cases describing the spontaneous remission of sporotrichosis, it is common practice to treat the infection. Treatment includes local measures (thermotherapy), 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 to 50 drops three times daily (equivalent to 250 mg to 1 g three times daily). Treatment is continued for 3 to 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, starting at a loading dose of 200 mg three times daily for 3 days followed by 100–400 mg daily. 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.
There are no clinical trials to guide therapy for disseminated or meningeal sporotrichosis which can occur with immunosuppression. On the basis of 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, iItraconazole (200 mg twice daily) is given as maintenance therapy. Thermotherapy (using infrared and far infrared wavelengths to heat tissues to 42–43°C) is known to be effective although there are few reports of its use. It has a useful role in those for whom systemic therapies are contraindicated. There is limited clinical data demonstrating the potential of cryotherapy as an adjuvant to systemic therapy.
Culture
Polymerase chain reaction
Serology for HIV infection (where relevant)
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. Culture is the most sensitive means of diagnosis, and is characteristically rapid, with growth usually seen within 3 to 5 days. Infected material is inoculated onto Sabouraud’s dextrose agar at 25°C. The colonies are initially white or creamy with a wrinkled surface, which becomes progressively darker to a brown or black color. The diagnosis is confirmed by demonstrating dimorphism, or conversion to the yeast phase, achieved by incubation at 37°C on brain–heart infusion agar, which produces oval or cigar-shaped yeasts. Polymerase chain reaction is able to detect the fungus even in lesions with few organisms.
Al-Tawfiq JA, Wools KK. Clin Infect Dis 1998; 26: 1403–6.
There are a growing number of reports of S. schenckii infection in the HIV-infected population. Disease usually starts as a localized cutaneous lesion which subsequently disseminates. This article presents a case report of disseminated sporotrichosis in an HIV-infected patient followed by a review of the literature and discussion of treatment options for HIV-infected patients.
The authors revised the treatment of sporotrichosis in AIDS patients, suggesting amphotericin B as the drug of choice, and itraconazole for use as maintenance therapy.
Sterling JB, Heymann WR. J Am Acad Dermatol 2000; 43: 691–7.
This article reviews the pharmacology and adverse effects of potassium iodide as a therapeutic agent. It discusses contraindications to its use, which include a history of thyroid or kidney disease, and pregnancy.
Gottlieb GS, Lesser CF, Holmes KK, Wald A. Clin Infect Dis 2003; 37: 838–40.
A male adult patient developed disseminated infection following treatment with multiple immunosuppressants, including etanercept and infliximab for inflammatory arthritis. He was subsequently treated with a lipid formulation of amphotericin B.
With the increasing availability and use of anti-TNF-α agents, there is an increased risk of sporotrichosis presented with disseminated infection rather than indolent cutaneous lesions only.
Gutierrez-Galhardo MC, do Valle AC, Fraga BL, Schubach AO, Hoagland BR, Monteiro P, et al. Mycoses 2010; 53: 78–80.
This is an increasingly recognized phenomenon. This report describes two cases of disseminated sporotrichosis developing in HIV-infected individuals after the initiation of anti-retroviral therapy. Both were successfully treated with amphotericin B in combination with itraconazole.
Vásquez-Del-Mercado E, Arenas R, Padilla-Desgarenes C. Clin Dermatol 2012; 30: 437–43.
In this recent review article the authors recommend itraconazole as the treatment of choice for localized disease. They recognize that in resource-poor regions potassium iodide is an acceptable alternative. For systemic and disseminated cases amphotericin B is the treatment of choice.
de Lima Barros MB, Schubach AO, de Vasconcellos Carvalhaes de Oliveira R, Martins EB, Teixeira JL, Wanke B. Clin Infect Dis 2011; 52: e200–6.
This is the largest study of sporotrichosis (68.1% with lymphocutaneous form and 23.1% with fixed form) treated with itraconazole 50–400 mg/day. There was a 94.6% cure rate in the 619 patients who completed treatment (547 with 100 mg/day, 59 with 200–400 mg/day, and four children with 50 mg/day). Treatment was given until cure and the median treatment duration was 12 weeks (range, 2–64 weeks). Lymphocutaneous and disseminated forms required approximately 2 weeks longer to achieve cure than the fixed form. The most frequent clinical adverse effect was nausea; 12.4% required further courses of treatment because of relapse. These were mainly those treated with the lower dose of 100 mg/day. One patient failed, despite dose escalation of itraconazole to 400 mg/day, and was cured only after switching to potassium hydroxide.
This study demonstrated that 100 mg daily dose is highly effective in the vast majority of patients with fixed or lymphocutaneous disease although it was sometimes associated with a higher risk of relapse. This is important as it makes itraconazole a more affordable option in resource-poor regions.
Song Y, Zhong SX, Yao L, Cai Q, Zhou JF, Liu Y, et al. J Eur Acad Dermatol Venereol 2011; 25: 302–5.
This randomized controlled trial comparing pulse itraconazole 200 mg twice daily for 1 week every month (n=25, mean course of treatment 2.65 ± 0.81 pulses) with continuous itraconazole 100 mg twice daily (n=25, mean course of treatment 2.8 ± 2.33 months) demonstrated cure rates at 48 weeks of 81.8% and 95.8%, respectively. Side effects in the pulse therapy and continuous therapy groups were 4.5% vs 16.7%, respectively.
Pulse therapy has the advantages of lower cost and fewer adverse effects although this small trial demonstrates higher efficacy with the continuous itraconazole regimen.
Mahajan VK, Sharma NL, Sharma RC, Gupta ML, Garg G, Kanga AK. Mycoses 2005; 48: 25–31.
A total of 103 cases of the lymphocutaneous and fixed cutaneous varieties of sporotrichosis are described during the period 1990–2002. Potassium iodide was used as first-line treatment, and in 93% of patients healing of lesions occurred in 4 to 32 weeks (average 8.7 weeks) without significant side effects. Itraconazole was used in 12 patients, and was also highly effective.
This study demonstrates that the efficacy of potassium iodide is comparable to itraconazole.
Bonifaz A, Saúl A, Paredes-Solis V, Fierro L, Rosales A, Palacios C, et al. Pediatr Dermatol 2007; 24: 369–72.
The mean age of this cohort of affected children was 9.3 years. Two-thirds were affected with the lymphocutaneous form, and the upper limbs and face were most commonly affected. Nineteen children were cured clinically and mycologically with potassium iodide, three with itraconazole, and one with heat therapy.
Chapman SW, Pappas P, Kauffmann C, Smith EB, Dietze R, Tiraboschi-Foss, et al. Mycoses 2004; 47: 62–8.
This was a multicentre, randomized, double-blind trial evaluating the safety and efficacy of oral terbinafine for the treatment of cutaneous and lymphocutaneous sporotrichosis. Patients were treated with either 500 mg daily (n=28) or 1000 mg daily (n=35) for a maximum period of 24 weeks. Cure was significantly higher in the higher dose treatment group (87% vs 52%,p=0.004) with no relapses 24 weeks after treatment cessation. By contrast, there were six relapses in the lower dose group.
Terbinafine has fungicidal activity and therefore continuing treatment beyond mycological cure may not be required although studies have yet to demonstrate this.
Francesconi G, Valle AC, Passos S, Reis R, Galhardo MC. J Eur Acad Dermatol Venereol 2009; 23: 1273–6.
Of 50 cases of sporotrichosis treated with terbinafine 250 mg daily, 96% (n=48) were cured after a mean treatment period of 14 weeks with no recurrence after a mean follow-up period of 37 weeks. One patient discontinued drug therapy because of the development of a skin rash.
Standard doses of terbinafine have adequate efficacy and sporotrichosis does not generally require high dose terbinafine therapy. One of the advantages of terbinafine is that it has fewer drug–drug interactions than itraconazole.
Francesconi G, Francesconi do Valle AC, Passos SL, de Lima Barros MB, de Almeida Paes R, Curi A, et al. Mycopathologia 2011; 171: 349–54.
Itraconazole 100 mg daily and terbinafine 250 mg given to 249 and 55 patients, respectively, with culture-proven sporotrichosis demonstrated almost equal cure rates in both group of 92–93% within a similar mean period of time (11.5–11.8 weeks). Adverse effects were equally frequent with both drugs occurring in approximately 7% of those treated and were generally mild except in two patients receiving itraconazole who had to discontinue treatment.
Further evidence for the efficacy of lower doses of itraconazole or terbinafine therapy; terbinafine is perhaps better tolerated.
Vilela R, Souza GF, Fernandes Cota G, Mendoza L. Rev Iberoam Micol 2007; 24: 161–3.
A case report from Brazil of a patient with advanced HIV infection who presented with multiple, ulcerated nodules. S. schenckii was isolated from the skin as well as spinal fluid. Treatment consisted of amphotericin B (1.0 mg/kg/day) and a total dose of 650 mg was given. The skin lesions and neurological condition improved within 1 week of treatment.
Diaz M, Negroni R, Montero-Gei F, Castro LG, Sampaio SA, Borelli, et al. Clin Infect Dis 1992; 14(Suppl 1): S68–76.
An open label multicentre trial of fluconazole administered at a dose of 200–400 mg daily to 19 patients with sporotrichosis produced a 63% cure rate. The vast majority of patients required a 400 mg daily dose. Treatment was well tolerated.
Kauffman CA, Pappas PG, McKinsey DS, Greenfield RA, Perfect JR, Cloud G, et al. Clin Infect Dis 1996; 22: 46–50.
This clinical trial involved 14 patients with lymphocutaneous infection and 16 with osteoarticular or visceral sporotrichosis. Eleven of the 30 patients had previously been treated with other forms of antifungal therapy without success. Most patients were treated with fluconazole 400 mg/day. Four patients received fluconazole 200 mg/day and another four received 800 mg/day. 71% of patients (10 of 14) with lymphocutaneous sporotrichosis were cured. However, only 31% (5 of 16) with osteoarticular or visceral sporotrichosis responded to treatment.
Fluconazole was only modestly effective for the treatment of sporotrichosis, and perhaps should be considered second-line therapy in patients who are unable to take itraconazole.
Hiruma M, Kawada A, Noguchi H, Ishibashi A, Conti Díaz IA. Mycoses 1992; 35: 293–9.
Pocket warmers and infrared and far infrared rays were used to treat 14 cases of sporotrichosis, seven in children and seven in adults. Daily applications of heat were applied to the lesions and the devices warmed tissues to 42–43°C. All lesions treated with pocket warmers were facial lesions in children. Infrared and far infrared rays generated more heat than pocket warmers allowing the length of a single treatment to be reduced by three-quarters to only a single 15-minute treatment daily. The overall cure rate was 71%.
The efficacy for this form of treatment has not been satisfactorily evaluated. However, it has an important role in the treatment of infection in those who are unable to take systemic therapy.
Ferreira CP, Galhardo MC, Valle AC. Braz J Infect Dis 2011; 15: 181–3.
Nine patients with one or two lesions of sporotrichosis which persisted despite completing drug therapy with either of itraconazole, potassium iodide or terbinafine were then treated with cryotherapy given monthly as two cycles of 15 seconds with a halo of 5 mm. The patients required one to four cryotherapy sessions to achieve cure.
The study has demonstrated the efficacy of cryotherapy and its ability to speed up disease resolution. By acting as an adjunctive therapy it has the potential to decrease the duration of chemotherapy.
Kauffman CA, Bustamante B, Chapman SW, Pappas PG. Clin Infect Dis 2007; 45: 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 to 4 weeks after all lesions have resolved. Usually a 3- to 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 1 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, disseminated, and meningeal sporotrichosis. After initial response, itraconazole is recommended as step-down therapy and should be given to complete a total of at least 12 months of therapy. Amphotericin 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.
Treatment of Skin Disease Comprehensive Therapeutic Strategies 4e
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Itraconazole
Terbinafine
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Amphotericin B (for disseminated sporotrichosis)
Fluconazole
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