Characterization of Recalcitrant Dermatophytosis in a Multicenter Study in Sri Lanka.

A changing clinical scenario of dermatophytosis has been observed in Sri Lanka during the past few years. In keeping with the trend described in India, an increase in the number of chronic, relapsing, and recalcitrant infections has been noted. The objective of our study was to assess the therapeutic response of dermatophytosis to standard antifungal treatment in Sri Lanka and to identify possible contributory factors in cases showing inadequate therapeutic response. A descriptive, observational, cross-sectional study was carried out in nine hospitals, representing each province. Over 6 months, patients with dermatophytosis on glabrous skin were included. All subjects underwent skin scrapings for mycological studies and were treated with a standard course of antifungals for a specific period. In those patients who achieved complete clearance, recurrences were noted. The study included 796 patients, of whom 191 (24%) had symptoms for more than 3 months at presentation. A total of 519 patients (65.2%) had multiple-site involvement, and 503 (63.2%) had evidence of prior use of topical steroids. Skin scrapings were positive for fungal elements in the direct smears of 659 patients (82.8%), and the predominant dermatophyte isolated was Trichophyton mentagrophytes (65.6%). Partial responders after 10 weeks of treatment and recurrences after complete clearance were significantly greater in the group that used topical steroids before presentation (P < 0.001). This study highlights the magnitude of the threat of an inadequate therapeutic response in dermatophytosis in Sri Lanka, and identifies steroid misuse, and the shift of the predominant fungal species to T. mentagrophytes as possible causative factors.

Cutaneous leishmaniasis in Sri Lanka: effect on quality of life.

BACKGROUND: The quality of life in many patients is affected by skin lesions. Cutaneous leishmaniasis (CL), the commonest form of leishmaniasis, is no exception. In Sri Lanka, CL is an emerging parasitological condition with over 3,000 cases within the last decade. Lesions are often seen on exposed parts of the body which may cause social stigma, and hence a study was done to assess the changes in quality of life of CL patients. METHOD: A total of 294 patients (200 civilians and 94 army personnel) answered a previously validated Sinhala self-administered Dermatology Life Quality Index (DLQI) questionnaire and an interviewer-administered questionnaire. RESULTS: From the majority of the civilian population, 47% had no effect on their quality of life due to CL lesions, 33.5% were affected in a small way, 12.5% were affected moderately, 6.5% suffered in a large way, and 0.5% (one patient) were extremely affected due a large ulcerative lesion being on the face. The effect on quality of life was negligible in the majority of army patients as well (35.1% no effect, 31.9% small effect), with a few patients affected moderately and very largely (22.3 and 10.6%, respectively). The most affected domain in patients was symptoms and feeling 1.27 ± 1.400 (mean ± SD), and the least was the relationships domain 0.27 ± 0.625. CONCLUSION: CL does not seem to affect the quality of life in the majority of Sri Lankan patients when compared to CL in other parts of the world or other skin diseases.

Efficacy, Safety and Cost-Effectiveness of Thermotherapy in the Treatment of Leishmania donovani-Induced Cutaneous Leishmaniasis: A Randomized Controlled Clinical Trial.

Leishmania donovani causes cutaneous leishmaniasis (CL) in Sri Lanka. Standard treatment is multiple, painful doses of intralesional sodium stibogluconate (IL-SSG). Treatment failures are increasingly reported, hence the need to investigate alternatives. Efficacy, safety, and cost-effectiveness of thermotherapy were assessed for the first time for L. donovani CL. A single blinded noninferiority randomized controlled trial was conducted on new laboratory-confirmed CL patients with single lesions (N = 213). Selected patients were randomly assigned to 1) test group (N = 98; single session of radiofrequency-induced heat therapy (RFHT) given at 50°C for 30 seconds) and 2) control group (N = 115; 1-3 mL IL-SSG given weekly, until cure/10 doses). Patients were followed-up fortnightly for 12 weeks to assess clinical cure. Cost of treatment was assessed using scenario building technique. Cure rates by 8, 10, and 12 weeks in RFHT group were 46.5%, 56.5%, and 65.9% as opposed to 28%, 40.8%, and 59.4% in IL-SSG group, with no major adverse events. Cure rate by RFHT was significantly higher at 8 weeks (P = 0.009, odds ratio [OR]: 2.236, confidence interval [CI]: 1.217-4.108) and 10 weeks (P = 0.035, OR: 1.881, CI: 1.044-3.388), but comparable thereafter. Cost of RFHT was 7 times less (USD = 1.54/patient) than IL-SSG (USD = 11.09/patient). A single application of RFHT is safe, cost-effective, and convenient, compared with multiple doses of IL-SSG in the treatment of L. donovani CL. Therefore, RFHT would be considered noninferior as per trial outcome when compared with standard IL-SSG therapy with multiple benefits for the patient and the national health care system.

Nonresponsiveness to standard treatment in cutaneous leishmaniasis: A case series from Sri Lanka.

Leishmaniasis is caused by parasitic protozoa of the genus Leishmania. Cutaneous leishmaniasis (CL) is endemic in Sri Lanka with over 3000 cases during the last decade and numbers are increasing. Treatment options available in Sri Lanka for CL include intralesional/intramuscular sodium stibogluconate and cryotherapy. Eight cases of treatment failure with standard therapy are reported from the Dermatology Clinic, Teaching Hospital Anuradhapura. Therapeutic regimes aim for clinical healing, these patients responded poorly to anti-leishmanial therapy, indicating the need for close monitoring, explore alternative treatment options and to investigate for drug resistance in parasites.

Filaggrin-null mutations are associated with increased maturation markers on Langerhans cells.

BACKGROUND: Mutations in the gene encoding filaggrin (FLG), an epidermal structural protein, are the strongest risk factor identified for the development of atopic dermatitis (AD). Up to 50% of patients with moderate-to-severe AD in European populations have FLG-null alleles compared with a general population frequency of 7% to 10%. OBJECTIVE: This study aimed to investigate the relationship between FLG-null mutations and epidermal antigen-presenting cell (APC) maturation in subjects with and without AD. Additionally, we investigated whether the cis isomer of urocanic acid (UCA), a filaggrin breakdown product, exerts immunomodulatory effects on dendritic cells. METHODS: Epidermal APCs from nonlesional skin were assessed by using flow cytometry (n = 27) and confocal microscopy (n = 16). Monocyte-derived dendritic cells from healthy volunteers were used to assess the effects of cis- and trans-UCA on dendritic cell phenotype by using flow cytometry (n = 11). RESULTS: Epidermal APCs from FLG-null subjects had increased CD11c expression. Confocal microscopy confirmed this and additionally revealed an increased number of epidermal CD83(+) Langerhans cells in FLG-null subjects. In vitro differentiation in the presence of cis-UCA significantly reduced costimulatory molecule expression on monocyte-derived dendritic cells from healthy volunteers and increased their ability to induce a regulatory T-cell phenotype in mixed lymphocyte reactions. CONCLUSIONS: We show that subjects with FLG-null mutations have more mature Langerhans cells in nonlesional skin irrespective of whether they have AD. We also demonstrate that cis-UCA reduces maturation of dendritic cells and increases their capacity to induce regulatory T cells, suggesting a novel link between filaggrin deficiency and immune dysregulation.