RESUMEN
Linear IgA bullous dermatosis (LABD) and dermatitis herpetiformis (DH) represent the major subtypes of IgA mediated autoimmune bullous disorders. We sought to understand the disease etiology by using serum proteomics. We assessed 92 organ damage biomarkers in LABD, DH, and healthy controls using the Olink high-throughput proteomics. The positive proteomic serum biomarkers were used to correlate with clinical features and HLA type. Targeted proteomic analysis of IgA deposition bullous disorders vs. controls showed elevated biomarkers. Further clustering and enrichment analyses identified distinct clusters between LABD and DH, highlighting the involvement of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. Comparative analysis revealed biomarkers with distinction between LABD and DH and validated in the skin lesion. Finally, qualitative correlation analysis with DEPs suggested six biomarkers (NBN, NCF2, CAPG, FES, BID, and PXN) have better prognosis in DH patients. These findings provide potential biomarkers to differentiate the disease subtype of IgA deposition bullous disease.
Asunto(s)
Biomarcadores , Dermatitis Herpetiforme , Dermatosis Bullosa IgA Lineal , Proteoma , Humanos , Dermatitis Herpetiforme/sangre , Dermatitis Herpetiforme/diagnóstico , Dermatitis Herpetiforme/inmunología , Biomarcadores/sangre , Femenino , Masculino , Adulto , Dermatosis Bullosa IgA Lineal/sangre , Dermatosis Bullosa IgA Lineal/diagnóstico , Persona de Mediana Edad , Diagnóstico Diferencial , Proteómica/métodos , Inmunoglobulina A/sangre , Adolescente , Adulto Joven , Anciano , NiñoRESUMEN
INTRODUCTION: Linear IgA dermatosis (LAD) is a rare subepidermal autoimmune bullous disease (AIBD) defined by predominant or exclusive immune deposits of immunoglobulin A at the basement membrane zone of skin or mucous membranes. This disorder is a rare, clinically and immunologically heterogeneous disease occurring both in children and in adults. The aim of this project is to present the main clinical features of LAD, to propose a diagnostic algorithm and provide management guidelines based primarily on experts' opinion because of the lack of large methodologically sound clinical studies. METHODS: These guidelines were initiated by the European Academy of Dermatology and Venereology (EADV) Task Force Autoimmune Bullous Diseases (AIBD). To achieve a broad consensus for these S2k consensus-based guidelines, a total of 29 experts from different countries, both European and non-European, including dermatologists, paediatric dermatologists and paediatricians were invited. All members of the guidelines committee agreed to develop consensus-based (S2k) guidelines. Prior to a first virtual consensus meeting, each of the invited authors elaborated a section of the present guidelines focusing on a selected topic, based on the relevant literature. All drafts were circulated among members of the writing group, and recommendations were discussed and voted during two hybrid consensus meetings. RESULTS: The guidelines summarizes evidence-based and expert opinion-based recommendations (S2 level) on the diagnosis and treatment of LAD. CONCLUSION: These guidelines will support dermatologists to improve their knowledge on the diagnosis and management of LAD.
Asunto(s)
Dermatosis Bullosa IgA Lineal , Humanos , Dermatosis Bullosa IgA Lineal/diagnóstico , Dermatosis Bullosa IgA Lineal/tratamiento farmacológico , Europa (Continente) , Dermatología/normasRESUMEN
Linear IgA bullous dermatosis (LABD) is a rare autoimmune blistering disorder impacting children and adults. In this single-center retrospective chart review of pediatric patients with LABD at a large tertiary referral center, we report the unifying and unique clinical features of 10 pediatric patients. Patients typically presented with the "cluster of jewels" sign (n = 6; 60%), mucous membrane involvement (n = 5; 50%) and had a mean disease duration of 38 months; six patients (60%) required inpatient admission for management of their skin disease, including all five patients who had mucous membrane involvement. Our findings suggest that pediatric LABD may be a disease with high morbidity and may be associated with severe complications when mucous membranes are involved.
Asunto(s)
Dermatosis Bullosa IgA Lineal , Humanos , Estudios Retrospectivos , Dermatosis Bullosa IgA Lineal/tratamiento farmacológico , Dermatosis Bullosa IgA Lineal/diagnóstico , Dermatosis Bullosa IgA Lineal/patología , Masculino , Femenino , Niño , Preescolar , Adolescente , LactanteRESUMEN
BACKGROUND: Linear IgA bullous dermatosis (LABD) is a rare autoimmune blistering disorder that may be drug-induced or paraneoplastic. We aim to characterize features of LABD and determine differentiating factors among idiopathic, drug-induced, or malignancy-associated diseases. METHODS: We conducted a single-center retrospective chart review of adult patients with linear IgA bullous dermatosis at a large tertiary referral center and a literature review of adult linear IgA bullous dermatosis. RESULTS: Eighty-one patients were included in the study. Ten patients (12.3%) had comorbid malignancy and nine (11.1%) had inflammatory bowel disease. Median disease duration was significantly shorter in both drug-induced (1.2 vs. 48.8 months; P < 0.001) and malignancy-associated (1.7 vs. 48.8 months; P < 0.001) LABD compared with idiopathic LABD. Recurrent episodes occurred significantly more often in idiopathic LABD compared to those with drug-induced (76.1 vs. 11.5%; P < 0.001) or malignancy-associated disease (76.1 vs. 33.3%; P = 0.019). Time to diagnosis was significantly shorter in the drug-induced (0.2 vs. 5.4 months; P < 0.001) and malignancy-associated groups (0.7 vs. 5.4 months; P = 0.049) compared with idiopathic; similarly, time to improvement was significantly shorter in both drug-induced (0.4 vs. 3.0 months; P < 0.001) and malignancy-associated disease (1.1 vs. 3.0 months; P = 0.016). Clinical morphology was indistinguishable between groups. Limitations included retrospective data collection, data from tertiary referral centers, and limited racial and ethnic diversity. CONCLUSION: Screening for underlying malignancy, as well as for a predisposing medication or possibly inflammatory bowel disease, may be advisable in patients with LABD, particularly when it is newly diagnosed.
Asunto(s)
Dermatosis Bullosa IgA Lineal , Adulto , Femenino , Humanos , Masculino , Edad de Inicio , Erupciones por Medicamentos/etiología , Erupciones por Medicamentos/diagnóstico , Erupciones por Medicamentos/epidemiología , Enfermedades Inflamatorias del Intestino/complicaciones , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Dermatosis Bullosa IgA Lineal/diagnóstico , Dermatosis Bullosa IgA Lineal/tratamiento farmacológico , Dermatosis Bullosa IgA Lineal/epidemiología , Neoplasias/complicaciones , Síndromes Paraneoplásicos/inmunología , Síndromes Paraneoplásicos/diagnóstico , Síndromes Paraneoplásicos/etiología , Recurrencia , Estudios RetrospectivosAsunto(s)
Dermatosis Bullosa IgA Lineal , Psoriasis , Anomalías Cutáneas , Enfermedades de la Piel , Humanos , Dermatosis Bullosa IgA Lineal/inducido químicamente , Dermatosis Bullosa IgA Lineal/diagnóstico , Pemetrexed/efectos adversos , Nivolumab/efectos adversos , Vesícula/inducido químicamente , Psoriasis/tratamiento farmacológico , Inmunoglobulina ARESUMEN
Linear IgA/IgG bullous dermatosis (LAGBD) is a relatively rare autoimmune bullous disease characterized by both IgA and IgG antibodies to basement membrane zone. The heterogeneity and pathogenesis of antibodies and the relationship between IgA and IgG in LAGBD have not been fully elucidated. We observed clinical, histological and immunological features of three LAGBD cases at different time points in the disease course. In our cohort, two cases showed IgA antibodies to epidermal antigens vanished when their lesions cleared after 3 months of treatment. One refractory case showed increasing antigens targeted by IgA antibodies with the progression of the disease. Collectively, the results suggest that IgA antibodies may play a major role in LAGBD. In addition, epitope spreading may be related to disease relapse and treatment refractory.
Asunto(s)
Enfermedades Autoinmunes , Dermatosis Bullosa IgA Lineal , Humanos , Dermatosis Bullosa IgA Lineal/diagnóstico , Dermatosis Bullosa IgA Lineal/tratamiento farmacológico , Autoanticuerpos , Enfermedades Autoinmunes/diagnóstico , Inmunoglobulina G , Inmunoglobulina ARESUMEN
Linear IgA/IgG bullous dermatosis (LAGBD) is a rare autoimmune subepidermal bullous disorder characterized by linear deposition of concurrent IgA and IgG autoantibodies along the basement membrane zone (BMZ). The clinical features of LAGBD can be diverse, including tense blisters, erosions, erythema, crusting and mucosa involvement, while papules or nodules are generally absent. In this study, we present a unique case of LAGBD, which showed prurigo nodularis-like clinical appearance on physical examination, linear deposition of IgG and C3 along the basement membrane zone (BMZ) in direct immunofluorescence (DIF), IgA autoantibodies against the 97-kDa and 120-kDa of BP180 and IgG autoantibodies against the 97-kDa of BP180 by immunoblotting (IB), while BP180 NC16a domain, BP230, and laminin 332 were negative by enzyme-linked immunosorbent assay (ELISA). After administration of minocycline, the skin lesions improved. We performed a literature review of LAGBD cases with heterogeneous autoantibodies and found clinical presentations of most cases resemble bullous pemphigoid (BP) and linear IgA bullous disease (LABD), which is consistent with previous reported findings. We aim to increase our understanding of this disorder and to enhance the importance of applying immunoblot analyses and other serological detection tools in clinic for precise diagnosis as well as accurate treatment strategy of various autoimmune bullous dermatoses.
Asunto(s)
Dermatosis Bullosa IgA Lineal , Prurigo , Enfermedades Cutáneas Vesiculoampollosas , Humanos , Prurigo/diagnóstico , Prurigo/tratamiento farmacológico , Dermatosis Bullosa IgA Lineal/diagnóstico , Dermatosis Bullosa IgA Lineal/tratamiento farmacológico , Enfermedades Cutáneas Vesiculoampollosas/diagnóstico , Enfermedades Cutáneas Vesiculoampollosas/tratamiento farmacológico , Autoanticuerpos , Inmunoglobulina A , Inmunoglobulina GRESUMEN
La enfermedad IgA lineal se trata de un trastorno autoinmune poco frecuente. En la infancia aparece sobre todo en edad preescolar, y en adultos es necesario realizar un buen diagnóstico diferencial con otras enfermedades ampollosas como la dermatitis herpetiforme o el penfigoide ampollar. Hasta un cuarto de los casos se relacionan con infecciones o con la toma de medicamentos entre los que destacan antibióticos y antiinflamatorios no esteroideos. El diagnóstico se basa en la clínica, biopsia cutánea e inmunofluorescencia. Típicamente se presenta como ampollas anulares tensas de morfología anular con imagen característica en collar de perlas. Al realizar el estudio de inmunofluorescencia directa se evidencia una banda lineal de IgA en la unión dermoepidérmica. Suele responder de forma completa a la retirada del fármaco causante y al tratamiento con Dapsona oral y glucocorticoides tópicos. (AU)
Asunto(s)
Humanos , Femenino , Lactante , Dermatosis Bullosa IgA Lineal/diagnóstico , Dermatosis Bullosa IgA Lineal/tratamiento farmacológico , Dermatosis Bullosa IgA Lineal/patología , Vesícula , Enfermedades Cutáneas VesiculoampollosasAsunto(s)
Dermatosis Bullosa IgA Lineal , Síndrome de Stevens-Johnson , Humanos , Dermatosis Bullosa IgA Lineal/inducido químicamente , Dermatosis Bullosa IgA Lineal/diagnóstico , Síndrome de Stevens-Johnson/diagnóstico , Síndrome de Stevens-Johnson/etiología , Etanercept/efectos adversos , Antibacterianos/efectos adversos , Vancomicina/efectos adversos , Inmunoglobulina AAsunto(s)
COVID-19 , Dermatosis Bullosa IgA Lineal , Humanos , Dermatosis Bullosa IgA Lineal/inducido químicamente , Dermatosis Bullosa IgA Lineal/diagnóstico , Dermatosis Bullosa IgA Lineal/tratamiento farmacológico , Vacunas contra la COVID-19/efectos adversos , COVID-19/prevención & control , Vacunación/efectos adversos , Inmunoglobulina ARESUMEN
Linear IgA bullous disease (LABD) is a rare, acquired, autoimmune, pruritic, and blistering skin condition. Dapsone is a first line treatment option, however, there are limited options if this fails, or if contraindicated. We present a case of successful management of LABD with sulfasalazine. A 46-year-old Caucasian female with LABD was commenced on high dose corticosteroids. She failed to wean, and dapsone was contraindicated due to a history of primary sclerosing cholangitis and risk of hepatitis. Following the failure of mycophenolate mofetil, sulfasalazine was trialed and successfully controlled both this patient’s LABD and ulcerative colitis. There is little literature on the use of sulfasalazine in dermatological conditions. We present sulfasalazine as an option for patients who are unable to use classically used treatments for LABD, or in those who have a dual diagnosis, as in this case, allowing for one agent to manage both conditions. Furthermore, The National Institute for Health and Care Excellence guidance mentions sulfasalazine as one of the few drugs that can be continued during the COVID-19 pandemic, and its use spared this patient from the significant immunosuppression associated with other treatment modalities.J Drugs Dermatol. 2022;21(12): doi:10.36849/JDD.6717.
Asunto(s)
Tratamiento Farmacológico de COVID-19 , Dermatosis Bullosa IgA Lineal , Adulto , Humanos , Femenino , Persona de Mediana Edad , Sulfasalazina/uso terapéutico , Pandemias , Dermatosis Bullosa IgA Lineal/complicaciones , Dermatosis Bullosa IgA Lineal/diagnóstico , Dermatosis Bullosa IgA Lineal/tratamiento farmacológico , Dapsona/uso terapéutico , Inmunoglobulina A/uso terapéuticoRESUMEN
Linear IgA bullous dermatosis (LABD) is an auto-immune disease affecting young children and adults, characterized by the linear deposition of IgA at the basement membrane zone with resultant complement activation and a cascade of immune reactions. There is a loss of adhesion at the dermo-epidermal junction and subsequent blister formation. It is a rare disease that has a good prognosis with adequate therapy. However, the underlying depressed immunity associated with the disease may expose them to such infections as tuberculosis. We report the case of an 11-years-old Nigerian female adolescent with LABD, diagnosed at the age of four years but defaulted on follow-up, who developed disseminated tuberculosis (pulmonary, lymph nodes, abdominal and pericardial effusion) seven years after the appearance of the initial blistering skin lesions. She commenced anti-tuberculosis drugs, steroids, and a tube pericardiostomy for the pericardial effusion. Dapsone was initiated for the LABD during the continuation phase of anti-tuberculosis therapy, with subsequent disappearance of the skin rash within two weeks.
La dermatose bulleuse linéaire à IgA (DBL) est une maladie auto-immune affectant les jeunes enfants et les adultes, caractérisée par le dépôt linéaire d'IgA dans la zone de la membrane basale, avec l'activation du complément qui en résulte et une cascade de réactions immunitaires. Il y a une perte d'adhérence à la jonction dermo-épidermique et une formation ultérieure de vésicules. C'est une maladie rare qui a un bon pronostic avec un traitement adéquat. Cependant, l'immunité déprimée sous-jacente associée à la maladie peut les exposer à des infections telles que la tuberculose. Nous rapportons le cas d'une adolescente nigériane de 11 ans atteinte de la LABD, diagnostiquée à l'âge de quatre ans mais en défaut de suivi, qui a développé une tuberculose disséminée (pulmonaire, ganglions lymphatiques, épanchement abdominal et péricardique) sept ans après l'apparition des lésions cutanées vésiculeuses initiales. Elle a commencé à recevoir des médicaments antituberculeux, des stéroïdes et une péricardiostomie par sonde pour l'épanchement péricardique. La dapsone a été initiée pour la DLB pendant la phase de continuation du traitement antituberculeux, avec une disparition de l'éruption cutanée en deux semaines. Mots clés: IgA linéaire, dermatose bulleuse, tuberculose disséminée, adolescent.
Asunto(s)
Dermatosis Bullosa IgA Lineal , Derrame Pericárdico , Adolescente , Adulto , Niño , Preescolar , Femenino , Humanos , Inmunoglobulina A/uso terapéutico , Dermatosis Bullosa IgA Lineal/diagnóstico , Dermatosis Bullosa IgA Lineal/tratamiento farmacológico , Dermatosis Bullosa IgA Lineal/patología , NigeriaRESUMEN
Linear immunoglobulin A (IgA) bullous dermatosis (LABD) is a rare disorder involving subepidermal blistering characterised by IgA deposition along the basement membrane. The clinical features of LABD are variable but can include bullae, vesicles and erythematous lesions. Histopathology reveals formation of subepidermal bullae and linearly deposition of IgA in the basement membrane of the epidermis. LABD has been reported as a rare complication of ulcerative colitis (UC). We report the case of a young woman with UC complicated by LABD. The latter manifested as vesicles with erythema on almost the entire body. A biopsy of the skin lesions revealed linear IgA deposits in the basement membrane according to a direct immunofluorescence assay. Prednisolone administration resulted in clinical remission of UC but poor improvement of skin lesions. Oral administration of diaminodiphenyl sulfone led to improvement of blisters. Thereafter, abdominal and skin symptoms did not recur and she was discharged from hospital.