RESUMEN
BACKGROUND: Cytosolic phospholipase A2 (cPLA2α) is an enzyme suggested as a therapeutic target in inflammatory skin diseases. AVX001, a cPLA2α inhibitor, was investigated in a randomized, double-blind, placebo-controlled, split-design, first-in-man study in patients with mild to moderate psoriasis. OBJECTIVES: The primary objective was to evaluate cutaneous safety and tolerability of AVX001 in doses from 0.002% to 5.0%. Safety was assessed as local skin reaction adverse events (LSRAE) grades 3-4. The secondary objective was assessment of efficacy on modified PASI (mPASI) score compared with placebo. METHODS: Of 94 randomized men, 88 completed treatment with AVX001 and placebo. The treatment period was four weeks with two-week follow-up with assessment at screening, randomization and once weekly until study end. AVX001 and placebo were applied blinded at symmetrically affected areas once daily. RESULTS: AVX001 was safe with no grades 3-4 LSRAE. A 29% reduction in mPASI was seen at the 5% dose level at week four. Post hoc analysis of combined doses of 3% and 5% showed a clinical relevant effect with 31% reduction in mPASI (P = 0.058) and statically significant reduction of the infiltration (P = 0.036). The actively treated side showed improvement in mPASI score after one week of treatment, and the observed improvement continued throughout the four weeks of treatment. CONCLUSIONS: Treatment with AVX001 is well tolerated in doses up to 5%, and showed placebo-adjusted, clinical effects at a level of statistical significance. The improvement throughout the treatment period suggests that longer treatment could conceivably result in superior efficacy.
Asunto(s)
Ácidos Grasos Omega-3/uso terapéutico , Inhibidores de Fosfolipasa A2/uso terapéutico , Psoriasis/tratamiento farmacológico , Administración Tópica , Adulto , Anciano , Estudios de Cohortes , Citosol/enzimología , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Ácidos Grasos Omega-3/administración & dosificación , Ácidos Grasos Omega-3/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , Inhibidores de Fosfolipasa A2/administración & dosificación , Inhibidores de Fosfolipasa A2/efectos adversos , Placebos , Índice de Severidad de la EnfermedadRESUMEN
Organ transplant recipients (OTRs) are at high risk of developing cutaneous squamous cell carcinoma (SCC); prevention includes early treatment of premalignant actinic keratosis (AK). Photodynamic therapy (PDT) is a noninvasive field therapy that reduces new AKs in patients with existing AK and delays SCC development in mice. We investigated the effect of repeated PDT over 5 years for primary prophylaxis of skin dysplasia. These data represent an interim analysis of an on-going randomized controlled trial. During 2008-2011, 25 renal transplant recipients with clinically normal skin were randomized to split-side PDT of the face, forearm and hand, the contralateral side serving as untreated control. Patients received PDT on inclusion and at 6-monthly intervals for 5 years. Blinded evaluation was performed at each visit. We found that prophylactic PDT significantly delayed onset of AK compared with untreated skin, p = 0.020. At 3-year follow-up, we observed AK in 63% of patients in untreated skin areas compared with 28% of patients in PDT-treated skin, with a total number of cumulated AKs in untreated skin (n = 43) compared with PDT-treated skin (n = 8), p = 0.005. These preliminary data indicate a novel approach to early prevention of skin dysplasia that may reduce morbidity from multiple AKs and SCCs in OTR.
Asunto(s)
Queratosis Actínica/prevención & control , Trasplante de Riñón/métodos , Fotoquimioterapia/métodos , Lesiones Precancerosas/patología , Prevención Primaria/métodos , Adulto , Anciano , Femenino , Estudios de Seguimiento , Humanos , Estimación de Kaplan-Meier , Queratosis Actínica/tratamiento farmacológico , Queratosis Actínica/patología , Trasplante de Riñón/efectos adversos , Masculino , Persona de Mediana Edad , Lesiones Precancerosas/tratamiento farmacológico , Lesiones Precancerosas/prevención & control , Cuidados Preoperatorios/métodos , Valores de Referencia , Medición de Riesgo , Estadísticas no Paramétricas , Factores de Tiempo , Receptores de Trasplantes , Resultado del TratamientoRESUMEN
We present a case of pancreatic panniculitis in a patient with alcohol abuse where Corynebacterium tuberculostearicum was isolated from a pannicular nodule on the crus. The patient was started on linezolid treatment leading to regression of the patient's symptoms. Upon discontinuation of linezolid treatment progression of the skin symptoms progressed.