Diagnóstico genético de la epidermólisis bullosa: recomendaciones de un grupo español de expertos

Epidermolysis bullosa (EB) is a rare genetic disease that causes mucocutaneous fragility. It comprises a clinically and genetically heterogeneous group of disorder characterized by spontaneous or contact/friction–induced blistering. EB is classified into 4 types–simplex, junctional, dystrophic, and Kindler syndrome—and 30 subtypes. The disease is caused by defects in proteins implicated in dermal-epidermal adhesion. At least 19 genes have been characterized and more than 1000 mutations identified, thus rendering diagnosis complex. Molecular diagnosis of EB is the last stage of a laborious process that starts with a detailed clinical history compilation and careful procurement of a skin fresh biopsy that includes an area where the epidermis detaches from the dermis. The detachment area makes it possible to establish the cleavage plane by antigen mapping and, in the best scenario, to identify a single candidate gene to search for pathogenic mutations. The results of the molecular diagnosis enable the physician to provide appropriate genetic counseling (inheritance pattern, risk of recurrence, and options for prenatal and preimplantation diagnosis) and implement subsequent preventive programs, as well as to establish a reasonable clinical prognosis facilitating access to specific therapy and rehabilitation. Lastly, molecular diagnosis is essential for the participation of patients in clinical trials, a critical issue given the current incurable status of EB. The present guidelines aim to disseminate the procedure for diagnosing EB in our laboratory and thus avoid suboptimal or incomplete clinical diagnoses. The recommendations we provide are the result of more than 10 years’ experience in the molecular diagnosis of EB in Spain.     

Estudio retrospectivo de las características clínicas,histológicas e inmunológicas en una serie de 9 pacientes con epidermólisis ampollosa adquirida

IntroductionEpidermolysis bullosa acquisita (EBA) is an autoimmune subepidermal blistering disease caused by autoantibodies to type VII collagen. The clinical presentation is variable, with skin and mucosal lesions that can cause significant dysfunction. Different treatment options exist, but the results are often unsatisfactory.ObjectiveTo review all the cases of epidermolysis bullosa acquisita (EBA) diagnosed at our hospital over a 26-year period.Materials and methodsWe performed a retrospective review of the clinical, histologic, and immunologic features of EBA in 9 patients.ResultsMean age at presentation was 37 years and 66.67% of the patients were women. EBA occurred in association with malignant tumors, inflammatory bowel disease, and autoimmune disorders. The most common variant was inflammatory EBA (6 of the 9 cases). In all 9 patients, histology revealed a subepidermal blister and direct immunofluorescence showed linear deposits of immunoglobulin G and C3 in the basement membrane zone. Indirect immunofluorescence performed on salt-split skin substrate was positive in 6 patients and showed a dermal pattern in all cases. Five patients were tested for autoantibodies to type VII collagen using enzyme-linked immunosorbent assay, with positive results in 2 cases. Immunoblotting using recombinant noncollagenous domains (NC1) of type VII collagen was positive in all 6 cases in which it was performed. Response to treatment was variable.ConclusionsEBA is a rare disease with a variable clinical presentation that can be confused with that of other subepidermal blistering diseases. Correct diagnosis requires a high level of clinical suspicion and the use of all available diagnostic tests. Thorough evaluation of cutaneous and mucosal involvement and prompt initiation of appropriate treatment will ensure the detection and prevention of dysfunction and treatment-related complications.     

Motivos dermatológicos de consulta en atención primaria. Análisis de la demanda derivada

IntroductionSkin conditions are among the main reasons for seeking primary health care. Primary care physicians (PCPs) must diagnose skin conditions and determine their impact, and must therefore incorporate the relevant knowledge and skills into their education. The present study analyzes the reasons for primary care referral to dermatology (referral demand) as well as diagnostic agreement between PCPs and dermatologists informed by pathology where appropriate.Material and methodsData were collected for 755 patients and 882 initial dermatology appointments from February 1, 2012 through April 30, 2012 following primary care referral. Data obtained included age, sex, occupation, reason for referral, primary care diagnosis, and dermatologic diagnosis. Statistical analysis of the data for each diagnosed condition identified frequency, reasons for referral, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and the κ statistic for diagnostic agreement.ResultsThe most common diagnoses were seborrheic keratosis, melanocytic nevus, actinic keratosis, and acne. The main reason for referral was diagnostic assessment (52.5%). For skin tumors, sensitivity of primary care diagnosis was 22.4%, specificity 94.7%, PPV 40.7%, and NPV 88.3%, with a κ of 0.211. For the more common diagnoses, primary care sensitivity was generally low and specificity high.ConclusionsAccording to our results, primary care physicians are better qualified to rule out a given skin condition in a patient (high specificity) than to establish an accurate clinical diagnosis (poor sensitivity). This suggests that knowledge and skills training should be organized for primary care physicians to improve management of skin conditions—especially skin cancer, because of its impact. A more responsive system would ensue, with shorter waiting lists and better health care.     

Uso de probióticos para disminuir la gravedad de la dermatitis atópica en población pediátrica: revisión sistemática y metaanálisis

Background and objectiveProbiotics, defined as live microbial dietary supplements that provide health benefits for the host, have been suggested as a treatment for atopic dermatitis based on a variety of proposed mechanisms of action. We analyzed evidence for the efficacy of probiotics to attenuate the severity of atopic dermatitis in pediatric patients younger than the age of 18 years.Material and methodsSystematic review of trials of probiotics that included patients under the age of 18 years with a confirmed diagnosis of atopic dermatitis scored for severity using the Scoring Atopic Dermatitis SCORAD) tool. We performed a meta-analysis of the randomized placebo controlled trials. The following databases were searched: MEDLINE, Web of Science, Scopus, ClinicalTrials.gov, Epistemonikos, Trip Medical Database, and the Spanish Virtual Health Library.ResultsTwenty trials were retrieved and included in the systematic review. Sixteen supported the use of probiotics to attenuate SCORAD-evaluated severity. Meta-analysis found an overall mean difference in effect between probiotics and placebo of −0.38 (95% CI, −0.63 to −0.14) in favor of probiotics. However, trial heterogeneity was high (I² statistic, 76%) due to clinical and methodological variability.ConclusionsIn spite of clinical heterogeneity in trials attributable to different types of probiotic products and doses, and to the subjective variability of the SCORAD scale, we conclude that probiotics are beneficial for reducing the severity of atopic dermatitis as reflected by the SCORAD index.     

Carcinoma basocelular de la vulva. Descripción de dos casos y revisión de la literatura

—Although basal cell carcinoma is the most common malignant tumor of the skin, vulvar basal cell carcinoma accounts for less than 5% of all vulvar neoplasms.We are reporting the cases of basal cell carcinoma of two women aged 43 and 66, that showed vulvar ulcer, itching and bleeding. Both patients had excisional biopsy; one developed local recurrence and was treated by wide local reexcision.Basal cell carcinoma is a rare but important consideration in the differential diagnosis of cutaneous vulvar lesions. Accurate diagnosis depends upon a high index of suspicion, biopsy and histopathologic examination. Complete local excision is curative, although the recurrence rate is high, and metastases have been reported.     

Dermatosis ampollosa hemorrágica a distancia; dos nuevos casos por enoxaparina y revisión de la literatura

Enoxaparin is a low-molecular-weight heparin used in the prevention and treatment of pulmonary thromboembolism and other thrombotic disorders. The most common adverse reactions to enoxaparin are ecchymosis, skin necrosis, urticaria, angioedema, and eczema. The first 2 cases of bullous hemorrhagic dermatosis in areas distant from heparin injection sites were described in 2006.We present the cases of 2 men, aged 68 and 78 years, with progressive, advanced-stage lung cancer, who consulted with bullous hemorrhagic lesions without associated symptoms. Both patients reported that the lesions had appeared after initiation of heparin therapy at therapeutic doses.In our review of the literature, we found just 7 cases of heparin-induced bullous hemorrhagic dermatosis. We report a further 2 cases, caused by enoxaparin, in which treatment was continued and in which the lesions resolved in 2 to 3 weeks.     

Problemas de la CIE-10 para la codificación de diagnósticos dermatológicos. Estudio DIADERM

Background and objectives

The International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) has some shortcomings when it comes to coding certain dermatological disorders. To overcome these shortcomings, a compatible version of the ICD-10 specifically adapted to dermatology was produced in Spain in 1999. The recent DIADERM study recorded 10 999 dermatological diagnoses using a representative sample of dermatologists working at outpatient clinics in Spain. The aims of the current study were to identify diagnoses from the DIADERM study that could not be coded using the adapted ICD-10, determine why, and check if they could be coded using the draft ICD-11.