RESUMEN
BACKGROUND: Previously, a double-blind, randomized, multicentre study (LION study) compared the efficacy of continuous terbinafine 250 mg daily for 3 or 4 months with itraconazole pulse therapy 400 mg daily for 3 or 4 months. At the end of the study at week 72 terbinafine proved to be more effective. OBJECTIVES: To perform a 4-year follow-up of the Finnish participants in this study. METHODS: Patients were re-examined clinically and mycologically. RESULTS: Complete clinical and mycological cure with terbinafine for 4 months was 78% compared with 35% with terbinafine for 3 months, 24% with itraconazole for 4 months and 28% with itraconazole for 3 months. CONCLUSIONS: These results suggest that the initial treatment for onychomycosis should be a 4-month continuous course of terbinafine.
Asunto(s)
Antifúngicos/uso terapéutico , Itraconazol/uso terapéutico , Naftalenos/uso terapéutico , Onicomicosis/tratamiento farmacológico , Adolescente , Adulto , Anciano , Método Doble Ciego , Esquema de Medicación , Femenino , Estudios de Seguimiento , Dermatosis del Pie/tratamiento farmacológico , Dermatosis del Pie/microbiología , Humanos , Masculino , Persona de Mediana Edad , Onicomicosis/microbiología , Terbinafina , Resultado del TratamientoRESUMEN
We report a case of fixed drug eruption caused by fluconazole. A local provocation with 10% fluconazole test in petrolatum applied at the site of a previous lesion of fixed drug eruption reproduced the eruption clinically and histopathologically.
Asunto(s)
Antifúngicos/efectos adversos , Erupciones por Medicamentos/etiología , Fluconazol/efectos adversos , Adulto , Erupciones por Medicamentos/patología , Femenino , Humanos , Pruebas del ParcheRESUMEN
In a randomized, double-blind, double-placebo, multicentre study, terbinafine 250 mg daily for 12 weeks was compared with fluconazole 150 mg once weekly for 12 or 24 weeks in the treatment of onychomycosis. A total of 137 patients with culture-confirmed onychomycosis was divided into three groups: group A received terbinafine for 12 weeks, group B received fluconazole for 12 weeks, while group C received fluconazole for 24 weeks. At completion of the study (week 60), the mycological cure rate was higher in the terbinafine group than in the fluconazole groups: 89% vs. 51% and 49%, respectively (P < 0.001). The length of unaffected nail increased until week 24 in group B and until week 36 in group C, but was still increasing in group A at the final visit (week 60). Complete clinical cure of the target nail at week 60 was 67% in the terbinafine group, compared with 21% and 32% in the fluconazole groups, respectively. The incidence of adverse events was low for both study agents. We conclude that terbinafine 250 mg daily for 12 weeks is significantly more effective in the treatment of onychomycosis than fluconazole 150 mg once weekly for either 12 or 24 weeks.
Asunto(s)
Antifúngicos/administración & dosificación , Fluconazol/administración & dosificación , Naftalenos/administración & dosificación , Onicomicosis/tratamiento farmacológico , Adolescente , Adulto , Anciano , Antifúngicos/efectos adversos , Método Doble Ciego , Fluconazol/efectos adversos , Humanos , Persona de Mediana Edad , Naftalenos/efectos adversos , Terbinafina , Resultado del TratamientoRESUMEN
Cryptococcosis is an opportunistic infection caused by a fungus, Cryptococcus neoformans. It is usually seen in immunocompromised patients with AIDS, leukaemia, lymphoma, sarcoidosis or immunosuppressive treatments. We describe a patient who was treated with systemic glucocorticosteroids for 4 years because of lung sarcoidosis. During the last year of treatment, a papular eruption developed which later became ulcerative. In a histopathological examination of a skin biopsy, there was granulomatous inflammation, and the disease was treated as sarcoidosis without success. After 1 year's unsuccessful treatment, another skin biopsy and skin fungal culture revealed C. neoformans. Cryptococcal antigen was found in blood and cerebrospinal fluid, too. The patient was successfully treated first with an amphotericin-B-flucytosine combination and later with fluconazole.
Asunto(s)
Criptococosis/patología , Dermatomicosis/patología , Glucocorticoides/efectos adversos , Adulto , Biopsia , Criptococosis/complicaciones , Criptococosis/microbiología , Criptococosis/terapia , Dermatomicosis/complicaciones , Dermatomicosis/microbiología , Dermatomicosis/terapia , Humanos , Terapia de Inmunosupresión/efectos adversos , Masculino , Infecciones Oportunistas/complicaciones , Infecciones Oportunistas/microbiología , Infecciones Oportunistas/patología , Infecciones Oportunistas/terapia , Sarcoidosis/complicaciones , Sarcoidosis/tratamiento farmacológico , Sarcoidosis/patologíaRESUMEN
This multicentre, double-blind, randomized study compared the pharmacokinetics of itraconazole given at 200 mg once daily for 3 months and intermittently at 200 mg twice daily for 1 week per month followed by a 3-week drug-free period for 3 months in the treatment of onychomycosis. Patients were followed for 9 months after treatment. Itraconazole and hydroxy-itraconazole plasma concentrations and itraconazole nail tip concentrations were determined at regular intervals. With intermittent therapy (n = 64), increases of consistent magnitude were seen in the mean itraconazole and hydroxy-itraconazole plasma concentrations at the end of each 1-week treatment phase; values returned towards baseline during each subsequent 3-week drug-free period. The mean concentration of itraconazole in fingernail tips increased steadily from week 4, reached a maximum value at week 24 (213 ng/g), declined sharply between weeks 24 and 36 and returned to baseline by week 48; the mean concentration profile was similar for toenail tips (maximum value 305 ng/g at week 24) but decreased at a slower rate. With continuous therapy (n = 65), steady-state mean plasma concentrations of itraconazole and hydroxy-itraconazole were obtained within 4-5 weeks of the start of treatment and remained reasonably constant between weeks 4 and 12. The mean concentration of itraconazole in fingernail tips reached a maximum value at week 12 (524 ng/g) and returned towards baseline by week 48; in contrast, the maximum mean concentration of itraconazole in toenail tips was 698 ng/g at week 36 and did not return to baseline by week 48. No clear relationship was observed between response to treatment and concentration of itraconazole or hydroxy-itraconazole in plasma or itraconazole in nails, suggesting that concentrations exceeded therapeutic levels. In conclusion, intermittent therapy resulted in higher maximum itraconazole plasma concentrations but lower total drug exposure, and hence lower itraconazole nail concentrations, than continuous therapy. However, the intermittent schedule was not associated with a lower cure rate, which indicates that itraconazole nail concentrations remained within the therapeutic range.
Asunto(s)
Antifúngicos/administración & dosificación , Itraconazol/administración & dosificación , Onicomicosis/tratamiento farmacológico , Adolescente , Adulto , Antifúngicos/farmacocinética , Método Doble Ciego , Esquema de Medicación , Femenino , Humanos , Itraconazol/farmacocinética , Masculino , Persona de Mediana Edad , Onicomicosis/metabolismoAsunto(s)
Criptococosis/diagnóstico , Cryptococcus neoformans , Dermatomicosis/diagnóstico , Glucocorticoides/efectos adversos , Metilprednisolona/efectos adversos , Sarcoidosis Pulmonar/complicaciones , Adulto , Criptococosis/complicaciones , Criptococosis/microbiología , Dermatomicosis/complicaciones , Dermatomicosis/microbiología , Humanos , Masculino , Meningitis Criptocócica/complicaciones , Meningitis Criptocócica/diagnóstico , Meningitis Criptocócica/microbiología , Sarcoidosis Pulmonar/tratamiento farmacológicoAsunto(s)
Bloqueadores de los Canales de Calcio/efectos adversos , Felodipino/efectos adversos , Enfermedades de la Piel/inducido químicamente , Telangiectasia/inducido químicamente , Anciano , Dorso , Bloqueadores de los Canales de Calcio/administración & dosificación , Bloqueadores de los Canales de Calcio/uso terapéutico , Felodipino/administración & dosificación , Felodipino/uso terapéutico , Femenino , Humanos , Hipertensión/tratamiento farmacológicoAsunto(s)
Emigración e Inmigración , Tiña del Cuero Cabelludo/etnología , Niño , Preescolar , Recolección de Datos , Femenino , Finlandia/epidemiología , Humanos , Lactante , Masculino , Microsporum/aislamiento & purificación , Tiña del Cuero Cabelludo/tratamiento farmacológico , Tiña del Cuero Cabelludo/microbiología , Trichophyton/aislamiento & purificaciónRESUMEN
In this multicentre, double-blind, parallel group study, we evaluated the efficacy and safety of continuous treatment with itraconazole, 200 mg daily for 3 months, in comparison with itraconazole pulse therapy, 400 mg daily 1 week per month for 3 months, in the treatment of toe-nail onychomycosis. The study included 129 patients with distal subungual onychomycosis of the toe-nails, confirmed by microscopy and positive for dermatophyte culture; 65 received continuous treatment and 64 received pulse therapy. Patients were followed up for 9 months after treatment. After 12 months, there were 62 evaluable patients in the continuous group and 59 evaluable patients in the pulse group. The clinical response (i.e. the size of the affected area and the progress of the infection) and mycological cure (i.e. negative results on microscopy and culture) were the main outcome measures. A clinical response was defined as a cure or a marked improvement. Clinical response rates were 69%, in the continuous group, and 81% in the pulse group at month 12; the corresponding mycological cure rates were 66 and 69%. A better improvement in signs and symptoms was noted in the pulse group. Six patients were withdrawn from treatment because of adverse events, not all of which were thought to be drug-related. There were no clinically relevant laboratory abnormalities. We conclude that both regimens are effective, safe and well tolerated. The superiority of one treatment over the other was not established, but the results tended to favour pulse therapy. Equivalence testing confirmed that pulse therapy was at least equivalent to continuous treatment.
Asunto(s)
Antifúngicos/administración & dosificación , Itraconazol/administración & dosificación , Onicomicosis/tratamiento farmacológico , Adolescente , Adulto , Antifúngicos/uso terapéutico , Método Doble Ciego , Esquema de Medicación , Femenino , Estudios de Seguimiento , Dermatosis del Pie/tratamiento farmacológico , Dermatosis del Pie/microbiología , Dermatosis del Pie/patología , Humanos , Itraconazol/uso terapéutico , Masculino , Persona de Mediana Edad , Onicomicosis/microbiología , Onicomicosis/patología , Resultado del TratamientoRESUMEN
We studied the long-term results of 88 patients treated with itraconazole either with continuous or pulse therapy. No differences were noted in the treatment results between these two groups. Thirty-six weeks after cessation of a 12-week drug therapy total clinical cure was achieved in 35% of these patients with 93% negative culture. At a follow-up at week 104 the total clinical cure was 39%, with negative culture in 57%.
Asunto(s)
Antifúngicos/administración & dosificación , Itraconazol/administración & dosificación , Onicomicosis/tratamiento farmacológico , Esquema de Medicación , Estudios de Seguimiento , Humanos , Onicomicosis/microbiología , Dedos del Pie , Resultado del TratamientoRESUMEN
Over a 3 1/2 year period, from 1991 to 1994, we detected contact allergy to tioconazole in 72 patients by epicutaneous testing. During this period, tioconazole was included in the standard series of epicutaneous tests. Except for the first 6 months, the incidence of positive patch test reactions to tioconazole was over 1% of patients tested for contact allergy. As well as those tested with the standard series, 18 additional patients with tioconazole allergy were detected by direct testing with an imidazole patch test series. Of the various imidazole derivatives, tioconazole was the most important contact allergen. About half of patients with contact hypersensitivity to tioconazole, had additional contact allergies detected by the standard series. Men and women were equally affected. The present study suggests that tioconazole is an important contact allergen, which should be included into the patch test series in countries where it is used as a topical antifungal agent.
Asunto(s)
Antifúngicos/efectos adversos , Dermatitis Alérgica por Contacto/etiología , Erupciones por Medicamentos/etiología , Imidazoles/efectos adversos , Adulto , Anciano , Anciano de 80 o más Años , Antifúngicos/inmunología , Dermatitis Alérgica por Contacto/epidemiología , Erupciones por Medicamentos/epidemiología , Femenino , Finlandia/epidemiología , Humanos , Imidazoles/inmunología , Incidencia , Masculino , Persona de Mediana Edad , Pruebas del ParcheRESUMEN
Nail growth was studied over 20 weeks in five healthy volunteers by indenting eight nails in each subject with a dental burr. The indentations were drilled in the middle part of the lunula with the proximal edge of the indentation 1 mm from the cuticle. Their volume was measured by filling them with an elastic two-component material immediately after indentation and 4, 8, 12, 16 and 20 weeks thereafter. Nail growth as reflected by the volume changes of the indentations could be followed for 8-12 weeks in the thumb, the middle finger and the second toe and for 20 weeks in the big toe. The most rapid outgrowth, 8-12 weeks, occurred in the second toe and middle finger. The decrease in the volume of the indentations by approximately 30-35%, as they travelled from the lunula towards the distal end of the nail plate, also reflects nail growth from the nail bed. This study has shown that indentation of the nails and the measurement of their volume changes provides a reliable and simple method for the study of nail growth.
Asunto(s)
Dermatología/métodos , Uñas/crecimiento & desarrollo , Adulto , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Few studies have been made of the prevalence of onychomycosis among ordinary people. We therefore investigated 800 people aged between 6 and 80 years, in different age groups. We found 162 persons in whom onychomycosis was clinically suspected. However, only the 91, in whom the fungal culture was positive for dermatophytic fungi, were included in the final prevalence numbers. We found a prevalence of 13.0% in men, 4.3% in women, and 8.4% in the entire population including children. Onychomycosis was not found in any of the 200 people aged less than 20 years. The prevalences found in this study are much higher than those reported in the earlier studies made elsewhere in Europe.
Asunto(s)
Onicomicosis/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Femenino , Finlandia/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Distribución por SexoRESUMEN
We have studied drug eruptions at a single clinic since 1956. The last 5-year series comprises in-patients with drug eruptions during the period 1986-1990. The total number of cases in this series was 135, the most common types being fixed eruption, exanthematous eruption and urticaria. The causative agent was confirmed with a provocation test in 102 cases. The most common groups of causative drugs were antimicrobial agents, anti-pyretic/anti-inflammatory analgesics and drugs acting on the central nervous system. We also present a 35-year series of 1997 cases of drug eruptions, most of them proven with oral provocation. The types of drug eruption and the drug groups causing eruptions seem to be the same throughout the 35-year period. As there are no reliable laboratory methods of examining drug eruptions, oral provocation is the only reliable method in most cases.
Asunto(s)
Erupciones por Medicamentos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Erupciones por Medicamentos/diagnóstico , Erupciones por Medicamentos/etiología , Erupciones por Medicamentos/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios RetrospectivosAsunto(s)
Analgésicos/efectos adversos , Erupciones por Medicamentos/etiología , Trastornos de la Pigmentación/inducido químicamente , Enfermedades Cutáneas Vesiculoampollosas/inducido químicamente , ortoaminobenzoatos/efectos adversos , Analgésicos/uso terapéutico , Erupciones por Medicamentos/diagnóstico , Humanos , Masculino , Persona de Mediana Edad , Trastornos de la Pigmentación/diagnóstico , Enfermedades Cutáneas Vesiculoampollosas/diagnóstico , ortoaminobenzoatos/uso terapéuticoRESUMEN
In 15 months, we detected allergic patch test reactions to tioconazole in 14 patients. 9 of the 14 patients were allergic to additional imidazole derivatives used as antifungal agents. The positive patch test reactions to tioconazole may have been caused either by simultaneous sensitization or more probably by cross-reactivity between the various commercially used imidazole derivatives with a similar chemical structure. The abundant use of tioconazole in concentrated (up to 28%) topical formulations in Finland could be the major cause of the apparent increase in allergic reactions.
Asunto(s)
Antifúngicos/efectos adversos , Dermatitis por Contacto/etiología , Imidazoles/efectos adversos , Administración Cutánea , Adulto , Anciano , Antifúngicos/química , Femenino , Dermatosis de la Mano/diagnóstico , Dermatosis de la Mano/tratamiento farmacológico , Humanos , Imidazoles/química , Masculino , Persona de Mediana Edad , Onicomicosis/diagnóstico , Onicomicosis/tratamiento farmacológicoRESUMEN
The histamine concentration was measured from suction blister fluid obtained from normal and lesional skin of 8 patients with fixed drug eruption (FDE) caused by phenazone salicylate and from that of 2 healthy control subjects. In blister fluid samples obtained before peroral challenge with phenazone salicylate, the histamine concentrations were below 5 nmol/l both in uninvolved skin and in sites of previous FDE lesion (sample 0). After challenge, samples were taken from the incipient reaction that was visible after an average of 155 min. Histamine levels were significantly elevated in the blister fluid of 2 out of 8 FDE lesions (200 and 640 nmol/l) but in none of the uninvolved skin (sample 1). Two hours later (sample 2) the histamine levels were elevated in both uninvolved (mean 51.4 nmol/l) and lesional skin (mean 168 nmol/l). After 24 h (sample 3) the corresponding mean value was 25.4 nmol/l for uninvolved skin and 108 nmol/l for lesional skin. The histamine values in the blister fluid from FDE lesions in samples 2 and 3 were significantly higher (p less than 0.05) than those in the control blisters of uninvolved skin. An elevation of histamine levels comparable to that in the uninvolved skin of FDE patients was seen in the 2 healthy control subjects studied. The present study provides direct evidence of early release of histamine from mast cells or basophils in FDE and suggests that histamine is one of the mediators of clinical symptoms of FDE.