D. Roseeuw

Antifungal Pulse Therapy for Onychomycosis: A Pharmacokinetic and Pharmacodynamic Investigation of Monthly Cycles of 1-Week Pulse Therapy With Itraconazole

BACKGROUND AND DESIGN In the treatment of onychomycosis, oral therapies have generally been given as a continuous-dosing regimen. For example, the suggested dose of itraconazole for the treatment of onychomycosis has thus far been 200 mg/d for 3 months. Based on the advances in our understanding of the pharmacokinetics of itraconazole, we investigated the efficacy and nail kinetics of intermittent pulse-dosing therapy with oral itraconazole in patients who were suffering from onychomycosis. Fifty patients with confirmed onychomycosis of the toenails, predominantly Trichophyton rubrum, were recruited and randomly assigned to three (n = 25) or four (n = 25) pulses of 1-week itraconazole therapy (200 mg twice daily for each month). Clinical and mycological evaluation of the infected toenails, and determination of the drug levels in the distal nail ends of the fingernails and toenails, were performed at the end of each month up to month 6 and then every 2 months up to 1 year. RESULTS In the three-pulse treatment group, the mean concentration of itraconazole in the distal ends of the toenails ranged from 67 (month 1) to 471 (month 6) ng/g, and in the distal ends of the fingernails, it ranged from 103 (month 1) to 424 (month 6) ng/g. At month 11, the drug was still present in the distal ends of the toenails at an average concentration of 186 ng/g. The highest individual concentrations of 1064 and 1166 ng/g were reached at month 6 for toenails and fingernails, respectively. At end-point follow-up, toenails in 84% of the patients were clinically cured with a negative potassium hydroxide preparation and culture in 72% and 80% of the patients, respectively. In the four-pulse treatment group, the mean concentration of itraconazole in the distal ends of the toenails ranged from 32 (month 1) to 623 (month 8) ng/g, and in the distal ends of the fingernails, it ranged from 42 (month 1) to 380 (month 6) ng/g. The highest individual concentrations of 1549 and 946 ng/g were reached at month 7 for toenails and at month 9 for fingernails, respectively. At month 12, the drug was still present in the distal ends of the toenails at an average concentration of 196 ng/g. At end-point follow-up, toenails in 76% of the patients were clinically cured with a negative potassium hydroxide preparation and culture in 72% and 80% of the patients, respectively. There were no significant intergroup differences between the three- and four-pulse treatment groups for the primary efficacy parameters. The drug was well tolerated with no significant side effects in either patient group. CONCLUSIONS Following pulse therapy with itraconazole (400 mg/d given for 1 week each month for 3 to 4 months), the drug has been detected in the distal ends of nails after the first pulse, and it has reached therapeutic concentrations with further therapy. After stopping the last pulse, the drug remains in the nail plate at levels above 300 ng/g for several months. Clinical cure rates between 76% and 84% and negative mycological examination findings between 72% and 80%, respectively, were observed in toenail onychomycosis. The data suggest that pulse therapy with itraconazole is an effective and safe treatment option for onychomycosis.

Posttreatment itraconazole levels in the nail: New implications for treatment in onychomycosis

BACKGROUND A problem in the treatment of onychomycosis is the lengthy duration of therapy. The pharmacokinetics of itraconazole suggest a potential for briefer treatment. OBJECTIVE This study was designed to investigate itraconazole nail kinetics in 39 patients with onychomycosis in relation to their therapeutic outcome. METHODS All patients received itraconazole for 3 months at a dose of 100 or 200 mg daily. Itraconazole levels of distal nail clippings were determined during a 6-month posttherapy period. RESULTS Therapeutic itraconazole concentrations were found in the nail plates of fingernails and toenails for up to 6 months after treatment. Cure of the toenails was observed in 79% of the patients treated with the 200 mg dosage and in 26% of those treated with 100 mg at 6 months after therapy. CONCLUSION The data suggest that the drug reaches the nail via incorporation into the matrix and by diffusion from the nail bed and is eliminated with regrowth of the nail after discontinuation of treatment.

Acute generalized exanthematous pustulosis induced by paracetamol. A case with severe hemodynamic disturbances.

We report on a 28-year-old Bangladesh man with acute generalized exanthematous pustulosis, induced by paracetamol. The patient presented with an erythematous and pustular eruption after taking 1 tablet of paracetamol for a sore throat. After intravenous administration of propacetamol hydrochloride (which is a prodrug of paracetamol), the rash became worse, showing a toxic epidermal necrolysis-like appearance and the patient suffered from severe hemodynamic disturbances. After discontinuation of propacetamol hydrochloride, the eruption cleared within 2 days. Prick testing performed in the patient revealed a positive reaction for propacetamol hydrochloride.

Recurrent Contagious Ecthyma (Orf) in an Immunocompromised Host Successfully Treated with Cryotherapy

A 48-year-old patient under immunosuppressive therapy for renal transplantation had contagious ecthyma which relapsed after excision. Stable healing was obtained by cryotherapy.

Aleukemic Leukemia cutis

A patient with acute myelomonocytic leukemia is reported. He had presented erythroderma and atypical cellular infiltration of the skin 4 months prior to the detection of leukemia in the peripheral blo

Subcorneal Pustular Dermatosis Treated with PUVA Therapy

Background: Subcorneal pustular dermatosis (SPD) is a chronic recurrent pustular dermatosis of unknown etiology. Many treatments have been proposed, none of which has been uniformly successful. Objective: Our purpose is to report a patient with SPD successfully treated by PUVA and to review the literature concerning phototherapy treatment of SPD. Methods: A patient suffering from SPD resistant to diaminodiphenylsulphone (dapsone) responded well to a combination therapy consisting of dapsone and PUVA. He received 50 mg/day and 3 PUVA sessions a week. Photographs were taken at baseline and after 15 sessions. Results: The lesions were virtually cleared after 15 sessions. The patient remained free of lesions with a maintenance therapy of dapsone (50 mg/ day) and 1 PUVA session a week. Conclusion: The therapeutic value of phototherapy for the treatment of SPD still has to be confirmed and could be a valuable alternative for treatment-resistant patients.

Trichothiodystrophy-like hair abnormalities in a child with keratitis ichthyosis deafness syndrome.

Abstract:  Keratitis ichthyosis deafness syndrome is a rare congenital ectodermal disorder. It appears to be genetically heterogeneous and may be caused by mutations in the connexin 26 (Cx26) gene (GJB2) or in the connexin 30 gene. It is characterized by the association of ichthyosis‐like skin lesions, hearing loss, and vascularizing keratitis. We report the clinical and molecular findings in a 5‐year‐old girl with keratitis ichthyosis deafness syndrome. DNA sequencing in our patient revealed a p.Ser17Phe mutation in GJB2. Besides the typical clinical features of keratitis ichthyosis deafness syndrome, a peculiar intriguing finding not previously described in the literature in this condition was that polarizing light microscopy of the scalp hair in our patient revealed striking bright and dark bands as seen in trichothiodystrophy. Amino acid analysis of the hair sample also disclosed a reduced cysteine index. We emphasize that it would be of great benefit to examine hair shafts in other patients with keratitis ichthyosis deafness syndrome for trichothiodystrophy‐like abnormalities.