Published on 19/03/2015 by admin
Filed under Dermatology
Last modified 19/03/2015
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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
Coccidioidomycosis is an endemic systemic mycosis caused by inhalation of dimorphic fungi of the genus Coccidioides (C. immitis and C. posadasii). It is endemic in desert regions of southwestern United States, Central and South America. Primary pulmonary disease is usually sub-acute and self-limiting. The immunocompromised are particularly susceptible to chronic pulmonary disease. One percent progress to disseminated disease, and again, those with impaired cell-mediated immunity are at greater risk of this. Coccidioidomycosis is an opportunistic infection with advanced HIV infection and CD4 counts less than 250. Solid-organ transplant recipients, patients with hematologic malignancies, and those on long-term immunosuppressants, including corticosteroids and TNF-α antagonists, are also at risk. Extrapulmonary haematogenous dissemination can affect almost any organ but most frequently involves the skin, lymph nodes, skeletal system, and meninges. Dissemination to the skin can give rise to ulcerative and verrucous lesions with a predilection for the nasolabial area. Subcutaneous abscesses, sinus tracts and fistulae can develop as a result of coccidioidal infection in neighbouring lymph nodes, bones, or joints. Other dermatological manifestations include erythema nodosum and erythema multiforme associated with primary pulmonary infection. Primary infection of the skin is rare.
Dermatologists should be aware that the combination of atypical skin lesions, pulmonary infiltrates, and a history of travel to endemic areas of the disease may represent disseminated infection with coccidioidomycosis.
Treatment depends on disease extent and predisposing factors. Those with primary pulmonary infection and no risk factors require only periodic assessments for 2 years to ensure that the infection is self-limiting. Some clinicians prefer to treat with oral azoles to prevent any risk of progression, although there are no trial data to support this. Antifungal therapy is indicated for severe or chronic pneumonia, progressive or disseminated infection. Itraconazole (200–600 mg daily) and fluconazole (400–800 mg daily) have replaced amphotericin B as the initial choice of therapy for most chronic pulmonary and disseminated infections. Ketoconazole (400 mg daily) shows comparable efficacy to the other azoles, but is associated with a higher risk of adverse effects with long-term use. Parenteral amphotericin B (amphotericin B deoxycholate 0.5–1.5 mg/kg/day or lipid formulations of amphotericin B 2.0–5.0 mg/kg/day) is now recommended for those with severely acute infection with respiratory failure, those with rapidly progressive and disseminated infection, and women during pregnancy. Published reports of its use, however, are still limited to small numbers of patients treated in open-label, non-randomized studies. There have been no clinical trials assessing the efficacy of lipid formulations of amphotericin B. Newly available antifungal agents that may be used for refractory infection include the triazoles, posaconazole and voriconazole, in vitro studies having demonstrated their efficacy. However, there have been no comparative studies as yet evaluating their efficacy against the established azoles used for treating coccidioidomycosis. There are early reports too of the successful use of caspofungin, an echinocandin, although results of in vitro susceptibility studies have varied widely.
In addition to drug therapy, surgery is sometimes indicated for the removal of focal infection such as pulmonary cavities, focal osseous infection, or the debridement of soft tissue. Long-term prophylaxis with azoles is indicated for the immunocompromised, and meningeal infection requires lifelong azole therapy in order to prevent recurrence. Recovery from infection confers lifelong immunity and provides the rationale for the ongoing development of a possible vaccine.
Direct microscopy
Culture
Serological tests
Imaging studies (chest and bone radiography)
Serology for HIV/AIDS infection (where relevant)
The characteristic globular spherules may be seen in potassium hydroxide mounts of infected material: sputum, cerebrospinal fluid, or pus. Culture is the definitive method of establishing the diagnosis. Coccidioides spp. grow rapidly on most media within 5 days. In the mycelial form, the fungus is highly infectious, so cultures should be handled with care. Serological tests are useful and can be used to assess response to therapy.
The NIAID Mycoses Study Group. Galgiani JN, Catanzaro A, Cloud GA, Higgs J, Friedman BA, Larsen RA, Graybill JR. Ann Intern Med 1993; 119: 28–35.
Uncontrolled clinical trial which included 50 patients with coccidioidal meningitis. Forty-seven patients were evaluated. Twenty-five had received no previous treatment, and nine were HIV positive. Thirty-seven of 47 patients (79%) responded to treatment. Response rates were similar in patients who had or had not received previous therapy.
Fluconazole demonstrates efficacy in the treatment of coccidioidal meningitis.
Treatment of Skin Disease Comprehensive Therapeutic Strategies 4e
Fluconazole
Itraconazole
