Deep dermatophytosis and inherited CARD9 deficiency.

BACKGROUND: Deep dermatophytosis is a severe and sometimes life-threatening fungal infection caused by dermatophytes. It is characterized by extensive dermal and subcutaneous tissue invasion and by frequent dissemination to the lymph nodes and, occasionally, the central nervous system. The condition is different from common superficial dermatophyte infection and has been reported in patients with no known immunodeficiency. Patients are mostly from North African, consanguineous, multiplex families, which strongly suggests a mendelian genetic cause. METHODS: We studied the clinical features of deep dermatophytosis in 17 patients with no known immunodeficiency from eight unrelated Tunisian, Algerian, and Moroccan families. Because CARD9 (caspase recruitment domain-containing protein 9) deficiency has been reported in an Iranian family with invasive fungal infections, we also sequenced CARD9 in the patients. RESULTS: Four patients died, at 28, 29, 37, and 39 years of age, with clinically active deep dermatophytosis. No other severe infections, fungal or otherwise, were reported in the surviving patients, who ranged in age from 37 to 75 years. The 15 Algerian and Tunisian patients, from seven unrelated families, had a homozygous Q289X CARD9 allele, due to a founder effect. The 2 Moroccan siblings were homozygous for the R101C CARD9 allele. Both alleles are rare deleterious variants. The familial segregation of these alleles was consistent with autosomal recessive inheritance and complete clinical penetrance. CONCLUSIONS: All the patients with deep dermatophytosis had autosomal recessive CARD9 deficiency. Deep dermatophytosis appears to be an important clinical manifestation of CARD9 deficiency. (Funded by Agence Nationale pour la Recherche and others.).

Review of antifungal therapy and the severity index for assessing onychomycosis: part I.

This review outlines recent data on treatment modalities and outcomes with antifungal therapy in onychomycosis. Included are topical, mechanical, chemical and systemic treatments or a combination thereof. Topical treatments, or transungual drug delivery systems (TUDDS), including ciclopirox and amorolfine were shown to be effective if used alone for mild-moderate nail involvement. Specifically, superficial white onychomycosis (SWO) restricted to the dorsum of the nail plate and moderate distal lateral subungual onychomycosis (DLSO). Mechanical treatments were mostly effective as adjuncts to topical therapy which include nail avulsion and abrasion. In particular, partial nail avulsion aids topical therapy in DLSO and partial subungual onychomycosis for a more effective therapy. Chemical avulsion is a painless method of debridement which uses a keratinolysis formula that is effective only in limited and early disease. Systemic therapies have been shown to be effective with terbinafine and itraconazole is suggested as being the most cost-effective therapy. Systemic therapies require consideration of side effects and monitoring by both patient and physician prior to treatment application. An effective suggestion is the use of a topical with debridement for mild-moderate onychomycosis and systemic (terbinafine) plus topical for severe onychomycosis. Most treatment modalities will require long-term use from 3 to 9 months to be most effective, with strategies presented in Part II of this review.

Health workers' agreement in clinical description of filarial lymphedema.

Severity of lymphedema and presence of entry lesions are risk factors for acute bacterial dermatolym-phangioadenitis (ADLA) in those with filarial lymphedema. Recurrent ADLA causes acute morbidity and progression of lymphedema severity; however, there is little work assessing the ability of health workers to reliably stage disease severity and identify risk entry lesions. This knowledge is important in initiation of management and assessing interventions. We evaluated inter-rater reliability with two independent health workers rating both legs of 17 patients using a questionnaire and the Dreyer classification of lymphedema. The health workers could reliably stage lymphedema with high agreement (RMAC weighted kappa of 0.89) and identify nail, interdigital, and other skin lesions. However, there was less consistency in identifying the clinical nature of skin lesions. This indicates that the Dreyer classification can be a replicable way to stage lymphedema and a questionnaire can deliver high observer agreement on the presence of risk lesions.

Outbreaks of sporotrichosis.

This article examines the reasons for clusters of cases or outbreaks of sporotrichosis such as the Brazilian outbreak described in this issue of Current Opinion in Infectious Diseases. It highlights areas that require elucidation such as the infectivity of yeast phase fungi in relation to other outbreaks. It then describes phenotypic variations seen with Sporothrix schenckii that could contribute to pathogenesis and enhanced infectivity of fungi in the environment.

Review of antifungal therapy, part II: treatment rationale, including specific patient populations.

This portion of the antifungal review focuses on treatment rationale and suggestions, including special populations such as the elderly, children, and pregnant and immunocompromised individuals. In elderly individuals, the pathogen may be associated with certain comorbidities; treatment should begin with local treatments such as debridement (mechanical or chemical) and a topical. In children, the pathogen most commonly isolated is Trichophyton rubrum. Children should be examined for concomitant tinea and treatment options can begin with a chemical debridement (non-painful) and a topical, with non-responders being treated with combination therapy as in adults. It is suggested that blood tests are monitored at baseline and every 4-8 weeks in children on systemic therapy. Terbinafine is the only systemic in category B and local therapies should be the primary treatment modalities in pregnancy. Prevalence of onychomycosis is high in immunocompromised patients with higher relapse rates after treatment. The same fungal infections that are seen in healthy populations are usually represented in the immunocompromised host. There is a stepwise approach that is suggested in the treatment of onychomycosis. Before treatment, several factors should be determined, which include risk for failure and compliance issues. Strategies for therapy include monotherapy, combination therapy, supplemental therapy, and intermittent therapy. Topical monotherapy is effective in early distal nail disease and for the prevention of reinfection of the cured nail. Combination therapy is an appropriate progression of therapy for patients who failed monotherapy or are at risk for failure. Combined therapies are shown to increase cure rates. Mechanical interventions are essential in reducing fungal burdens to allow other modalities to penetrate, especially in dermatophytomas and onycholysis.