Effect of Different Itraconazole Dosing Regimens on Cure Rates, Treatment Duration, Safety, and Relapse Rates in Adult Patients With Tinea Corporis/Cruris: A Randomized Clinical Trial.

Importance: With worldwide emergence of recalcitrant and resistant dermatophytosis, itraconazole is increasingly being used as the first-line drug for treatment of tinea corporis/cruris (TCC). Apparent inadequacy with low doses has led to empirical use of higher doses and antifungal combinations. Objective: To compare cure rates, treatment durations, safety profiles, and relapse rates of itraconazole 100, 200, and 400 mg/d for the treatment of TCC. Design, Setting, and Participants: This double-blind randomized clinical trial included adult patients with treatment-naive TCC involving at least 5% body surface area. Patients were recruited from the dermatology outpatient department of a tertiary care hospital in New Delhi, India between March 1, 2020, and August 31, 2021. Interventions: Patients were randomized to 1 of the 3 treatment groups. Biweekly blinded assessments were performed until cure or treatment failure. Posttreatment follow-up of at least 8 weeks was conducted to detect relapses. Main Outcome and Measures: Cure rates, treatment durations, safety profiles, and relapse rates were assessed. Secondary outcomes included comparison of rapidity of clinical response and cost-effectiveness between groups. Results: Of the 149 patients assessed, the mean (SD) age was 34.3 (12.2) years, 69 patients (46.4%) were women, and 80 patients (53.6%) were men. The difference in cure rate between the 100- and 200-mg groups was statistically nonsignificant (hazard ratio [HR], 1.44; 95% CI, 0.91-2.30; P = .12), while the difference between the 100- and 400-mg groups (HR, 2.87; 95% CI, 1.78-4.62; P < .001) and between the 200- and 400-mg groups (HR, 1.99; 95% CI, 1.28-3.09; P = .002) was statistically significant. Mean (SD) treatment durations were statistically significantly different between the 100- and 400-mg groups (7.7 [4.7] weeks vs 5.2 [2.6] weeks; P = .03) and between the 200- and 400-mg groups (7.2 [3.8] weeks vs 5.2 [2.6] weeks; P = .004), but the difference between the 100- and 200-mg groups was not statistically significant. A total of 55 patients (47.4%) relapsed after treatment. Relapse rates were comparable across groups. No patient discontinued treatment due to adverse effects. Treatment with the 200-mg dose incurred a 63% higher cost and 400 mg a 120% higher cost over 100 mg in achieving cure. Conclusions and Relevance: In this randomized clinical trial, high overall efficacy was observed among the 3 itraconazole doses for treatment of TCC, but with prolonged treatment durations and considerable relapse rates. Treatment with the 200- and 100-mg doses did not differ significantly in efficacy or treatment durations, while 400 mg scored over the other 2 on these outcomes. Considerable additional cost is incurred in achieving cure with the 200- and 400-mg doses. Trial Registration: Clinical Trials Registry of India Identifier: CTRI/2020/03/024326.

Predicting a therapeutic cut-off serum level of itraconazole in recalcitrant tinea corporis and cruris-A prospective trial.

BACKGROUND: With rising resistance to terbinafine, and consistently high MICs to fluconazole and griseofulvin, itraconazole is being increasingly used as a first line drug for tinea corporis/cruris. However, inadequate clinical responses are often seen with it in spite of in vitro susceptibility. This is possibly related to a variable pharmacokinetic profile of itraconazole. The drug serum levels associated with the therapeutic outcome have not been defined in dermatophytic infections. METHODS: Forty treatment naïve patients with tinea corporis/cruris were randomised to one of the three dose groups (100, 200 and 400 mg/day) of itraconazole. The drug serum levels of 21 of these patients were obtained after 2 weeks of treatment and correlated with the final clinical outcome and in vitro antifungal susceptibility data. RESULTS: Trichophyton indotineae was identified by sequencing of ITS region of rDNA and TEF1α. All isolates were sensitive to itraconazole (Minimum Inhibitory Concentration (MICs) range: 0.06-0.5 µg/ml), while MICs to terbinafine were uniformly high (range 8-32 µg/ml). Thirty-seven patients (92.5%) achieved complete cure, while three failed treatment. Serum levels achieved with 400 mg/day were significantly higher than levels with 100 or 200 mg dose. All patients with itraconazole serum levels of >0.2 µg/ml were cured, while two out of the 10 patients with serum levels <0.2 µg/ml failed treatment. CONCLUSIONS: Therapeutic failures are uncommon with itraconazole, and the prevalent strain in India has low itraconazole MICs. Treatment failure is likely with itraconazole serum levels of <0.2 µg/ml, while levels >0.2 µg/ml are consistently associated with a positive therapeutic outcome.

A prospective study on patterns of topical steroids self-use in dermatophytoses and determinants predictive of cutaneous side effects.

Nonprescription use of topical corticosteroids (TCS) is a significant concern. This can lead to cutaneous adverse effects, altered morphology of skin disorders and chronicity of cutaneous infections. To record and analyze the patterns of TCS use in patients with tinea corporis/cruris and analyze factors determining the development of cutaneous side effects. Hundred patients with a clinical diagnosis of tinea corporis/cruris who could recall the TCS preparation/s used were included. The TCS usage patterns were recorded and analyzed. Most patients had used very potent TCS (n = 66). Most reported using TCS intermittently for duration ranging from 1 to 4 weeks (n = 78). Relapse of symptoms occurred within 1 to 2 weeks of stopping TCS, triggering reuse. Cutaneous adverse effects were present in 44 patients (striae [n = 29], hypo/depigmentation [n = 11], skin thinning [n = 8], hypertrichosis [n = 1], tinea pseudoimbricata [n = 1]). There was a significant correlation between presence of cutaneous adverse effects and the total duration of TCS use (P = .0016), duration of disease (P = .016), and total amount of TCS used (P = .012). Use for >60 days and of >32 g were associated with 89% and 96.3% (respectively) probability of developing cutaneous adverse effects. Self-use of TCS is a worrisome trend. Intermittent use is a plausible reason for development of cutaneous side effects in only 44% patients.