Richard B. Odom

Allergic Contact Hypersensitivity to Nickel, Neomycin, Ethylenediamine, and Benzocaine: Relationships Between Age, Sex, History of Exposure, and Reactivity to Standard Patch Tests and Use Tests in a General Population

A study population of 1,158 paid adult volunteers was obtained. Prior to patch testing, a history of previous exposure to four allergens also was obtained. Prevalence of positive reactions to patch tests was nickel, 5.8%; neomycin, 1.1%; ethylenediamine, 0.43%; and benzocaine, 0.17%. Nine percent of women reacted to nickel compared with 0.9% of men. There was a strong correlation of nickel sensitivity with a history of pierced ears, earlobe rash, and jewelry rash. Ten of 12 neomycin-positive subjects used neomycin for one week or longer on an inflammatory dermatosis, compared with six of 36 age-, race-, and sex-matched controls. By history, 85% were exposed to benzocaine, 48% to neomycin, and 15% to Mycolog (ethylenediamine). Of 127 patients referred to clinics for evaluation of contact dermatitis, 11% yielded positive tests to nickel, 6.3% to neomycin, 3.1% to ethylenediamine, and 1.6% to benzocaine. Data obtained from testing contact dermatitis patients are not applicable to the general population.

The allopurinol hypersensitivity syndrome

Hypersensitivity reactions to allopurinol, a drug commonly used in the treatment of hyperuricemia, are being reported with increasing frequency. Of thirty-eight patients reviewed herein (including seven from our hospital and thirty-one from a review of the literature), ten deaths (26%) were related to complications of allopurinol hypersensitivity. Preexisting renal disease was present in 97% of patients, and, in the majority of these, the dosage of allopurinol was not reduced despite instructions contained in the package insert for this drug. At least 78% of patients were taking a thiazide diuretic prior to starting allopurinol therapy. Over 60% of patients had received allopurinol for asymptomatic hyperuricemia. Hallmarks of this hypersensitivity syndrome include a prolonged illness initially manifested by fever, a prominent cutaneous reaction, eosinophilia, hepatic abnormalities, and acute renal failure. Other involvement such as gastrointestinal bleeding is common. The mechanism of the hypersensitivity reaction is not clear, but it may represent an immune complex disease prolonged by the persistence of a currently undefined antigen. Treatment with systemic corticosteroids, often for several months, is usually necessary for the gradual resolution of this potentially fatal syndrome.

Once-weekly fluconazole (150, 300, or 450 mg) in the treatment of distal subungual onychomycosis of the fingernail.

BACKGROUND Onychomycosis is a prevalent infection of the nail caused primarily by dermatophytes. Fluconazole is active in vitro against the most common pathogens of onychomycosis, penetrates into the nail bed, and is clinically effective in the treatment of a wide variety of superficial fungal infections. OBJECTIVE The purpose of this study was to compare the efficacy and safety of three different doses of fluconazole (150, 300, and 450 mg) given orally once weekly to that of placebo in the treatment of distal subungual onychomycosis of the toenail caused by dermatophytes. METHODS In this multicenter, double-blind study, 362 patients with mycologically confirmed onychomycosis were randomized to treatment with fluconazole, 150, 300, or 450 mg once weekly, or placebo once weekly for a maximum of 12 months. To enter the study, patients were required to have at least 25% involvement of the target nail with at least 2 mm of healthy nail from the nail fold to the proximal onychomycotic border. Patients who were clinically cured or improved at the end of treatment were further evaluated over a 6 month follow-up period. At both the end of therapy and the end of follow-up, clinical success of the target nail was defined as reduction of the affected area to less than 25% or cure. RESULTS At the end of therapy, 86% to 89% of patients in the fluconazole treatment groups were judged clinical successes as defined above compared with 8% of placebo-treated patients. Clinical cure (completely healthy nail) was achieved in 28% to 36% of fluconazole-treated patients compared with 3% of placebo-treated patients. Fluconazole demonstrated mycologic eradication rates of 47% to 62% at the end of therapy compared with 14% for placebo. The rates at the end of follow-up were very similar, indicating that eradication of the dermatophyte was maintained over the 6-month period. All efficacy measures for the fluconazole groups were significantly superior to placebo (p=0.0001); there were no significant differences between the fluconazole groups on these efficacy measures. The clinical relapse rate among cured patients over 6 months of follow-up was low at 4%. Fluconazole was well tolerated at all doses over the 12-month treatment period, with the incidence and severity of adverse events being similar between the fluconazole and placebo treatment groups. Mean time to clinical success in the fluconazole treatment groups was 6 to 7 months. This time frame may be used as a guideline for fluconazole treatment duration. CONCLUSION The results of this study support the use of fluconazole in the treatment of distal subungual onychomycosis of the toenail caused by dermatophytes. Doses between 150 to 450 mg weekly for 6 months were clinically and mycologically effective as well as safe and well tolerated.

Mycosis fungoides with onset before 20 years of age

BACKGROUND Recent identification of mycosis fungoides (MF) in a man in whom the diagnosis was established at age 22 months prompted us to evaluate our experience with early onset MF. OBJECTIVE Our purpose was to summarize the clinical characteristics and course of 24 patients in whom MF began by history before age 20 years and was confirmed by biopsy in 13 by that time. METHODS A retrospective study was conducted. RESULTS All 24 patients had patch/plaque disease and represented 4.3% of the 557 patients with cutaneous T-cell lymphoma seen by us since 1971. None progressed to a more advanced stage in up to 24 years (median, 12 years) after histologic diagnosis. Five patients (21%) presented with hypopigmentation. CONCLUSION Early onset MF is not more aggressive than that appearing in adult life. MF should be considered in the differential diagnosis of chronic dermatoses in young persons, particularly in those presenting with hypopigmentation.

Successful treatment of keratoacanthoma with intralesional fluorouracil

Forty-one keratoacanthomas (KA) occurring in thirty patients were treated with weekly intralesional injections of 5-fluorouracil (5-FU). Forty lesions cleared after an average of three injections in an average of 3.4 weeks (range, 2 to 6 weeks). This response suggests that intralesional injections of 5-FU are the treatment of choice for KAs.

Pathophysiology of dermatophyte infections

Dermatophyte infections are among the most common infections encountered in medicine. Often considered trivial, these infections are in fact frequently refractory and recurrent. This article presents an overview of the causes, symptoms, differential diagnosis, and clinical course of the most prevalent dermatophyte infections: tinea pedis, tinea cruris, tinea capitis, tinea corporis, and onychomycosis. Complicated situations such as follicular involvement, dermatophytoses in patients who are immunocompromised, and the exaggerated response to zoologically acquired fungal infections are also discussed.

Laugier-Hunziker syndrome

The Laugier-Hunziker syndrome represents a rare acquired pigmentary disorder of the lips, oral mucosa, and nails. We report the first case of this syndrome to be recognized in the United States and review other causes of hyperpigmentation in these locations.

A double-blind, randomized comparison of itraconazole capsules and placebo in the treatment of onychomycosis of the toenail

Onychomycosis accounts for up to 50% of all nail infections I and can be chronic and resistant to treatment. 2-4 Itraconazole has antifungal activity against a broad range of dermatophyte infections. 5 It has a high affinity for keratin and penetrates the nail plate by diffusion through the nail bed. It appears in the distal nail within 7 days of initiating therapy and persists in the nail at inhibitory levels for an extended period, 69 up to 9 months in one study. 6 In our study, 75 patients with cfinically and mycologically diagnosed onychomycosis of the toenail were enrolled for treatment with itraconazole, 200 mg, or placebo once daily for 12 weeks. Patients were reexamined at weeks 24, 36, and 48.

Common superficial fungal infections in immunosuppressed patients

HIV-positive patients and those persons immunosuppressed as a result of other diseases or chemotherapy are especially susceptible to mycotic infections. The superficial fungal infections seen most often in patients with HIV infection include seborrheic dermatitis, various dermatophyte infections, candidiasis, and onychomycosis. Uncommonly, systemic fungal infections, such as candidiasis, histoplasmosis, cryptococcosis, and coccidioidomycosis, may disseminate to the skin, producing a wide variety of cutaneous lesions. All cutaneous lesions in these patients should be biopsied and cultured if any question exists regarding the diagnosis. The diagnosis of superficial and deep mycotic infections in HIV-positive patients can be particularly difficult because the clinical presentation varies greatly and is often atypical.

Pharmacokinetics of three doses of once-weekly fluconazole (150, 300, and 450 mg) in distal subungual onychomycosis of the toenail

BACKGROUND Preliminary clinical data suggest that fluconazole is effective in the treatment of patients with onychomycosis. To design optimum dosage regimens, a better understanding of fluconazoles distribution into and elimination from nails is needed. OBJECTIVE The purpose of this study was to determine plasma and toenail concentrations of fluconazole. METHODS In this multicenter, randomized, double-blind investigation, fluconazole (150 mg, 300 mg, or 450 mg) or matching placebo was administered once a week for a maximum of 12 months to patients with onychomycosis of the toenail. A total of 151 subjects participated in the pharmacokinetic assessment. Blood samples and distal toenail clippings from both affected and healthy nails were obtained for fluconazole concentration determinations at baseline, at the 2-week visit, at each monthly visit until the end of treatment, and then at 2, 4, and 6 months (nail samples only at the latter two) after fluconazole was discontinued. RESULTS Fluconazole was detected in healthy and affected nails at the 2-week assessment in nearly all subjects. The median time to reach steady-state fluconazole concentrations in healthy nails was 4 to 5 months in the three fluconazole dose groups. In affected nails, steady-state fluconazole concentrations were achieved more slowly, with a median time of 6 to 7 months. At the 8-month assessment, affected toenail fluconazole concentrations were higher than corresponding plasma fluconazole concentrations, with ratios of 1.31 to 1.50 in the three active treatment groups. Toenail concentrations of fluconazole declined slowly after treatment was discontinued, with elimination half-lives of 2.5, 2.4, and 3.7 months for the 150, 300, and 450 mg doses, respectively. Measurable fluconazole concentrations were still present in toenails at 6 months after treatment in most subjects. CONCLUSION Fluconazole penetrates healthy and diseased nails rapidly, yielding detectable concentrations after two weekly doses. Once it penetrates nail, fluconazole persists for up to 6 months or longer after therapy is stopped. These favorable pharmacokinetic characteristics support a once-weekly fluconazole dosage regimen for the treatment of patients with onychomycosis.