State-of-the-art diagnosis of autoimmune blistering diseases.

Autoimmune blistering disorders (AIBDs) are a heterogeneous group of approximately a dozen entities comprising pemphigus and pemphigoid disorders and dermatitis herpetiformis. The exact diagnosis of AIBDs is critical for both prognosis and treatment and is based on the clinical appearance combined with the detection of tissue-bound and circulating autoantibodies. While blisters and erosions on the skin and/or inspectable mucosal surfaces are typical, lesions may be highly variable with erythematous, urticarial, prurigo-like, or eczematous manifestations. While direct immunofluorescence microscopy (IFM) of a perilesional biopsy is still the diagnostic gold standard, the molecular identification of the major target antigens opened novel therapeutic avenues. At present, most AIBDs can be diagnosed by the detection of autoantigen-specific serum antibodies by enzyme-linked immunosorbent assay (ELISA) or indirect IFM when the clinical picture is known. This is achieved by easily available and highly specific and sensitive assays employing recombinant immunodominant fragments of the major target antigens, i.e., desmoglein 1 (for pemphigus foliaceus), desmoglein 3 (for pemphigus vulgaris), envoplakin (for paraneoplastic pemphigus), BP180/type XVII collagen (for bullous pemphigoid, pemphigoid gestationis, and mucous membrane pemphigoid), laminin 332 (for mucous membrane pemphigoid), laminin ß4 (for anti-p200 pemphigoid), type VII collagen (for epidermolysis bullosa acquisita and mucous membrane pemphigoid), and transglutaminase 3 (for dermatitis herpetiformis). Indirect IFM on tissue substrates and in-house ELISA and immunoblot tests are required to detect autoantibodies in some AIBD patients including those with linear IgA disease. Here, a straightforward modern approach to diagnosing AIBDs is presented including diagnostic criteria according to national and international guidelines supplemented by long-term in-house expertise.

Management Options for Linear Immunoglobulin A (IgA) Bullous Dermatosis: A Literature Review.

Linear immunoglobulin A (IgA) bullous dermatosis (LABD) is an autoimmune condition with various triggers. Because of the lack of randomized controlled trials on LABD treatment, management options are mostly anecdotal. This paper provides a comprehensive review of treatment options from a literature review of reported treatments to arm clinicians with a guideline for the management of LABD in both pediatric and adult patients as well as those recalcitrant to first-line therapy (dapsone and steroids). We additionally illustrate an algorithm to use for the management of LABD to aid clinicians when faced with unique patient circumstances.

Dermatosis por IgA lineal de la infancia inducida por cefalosporina

Introducción: La dermatosis por IgA lineal es un trastorno ampollar raro, que afecta sobre todo a niños menores de 5 años y se caracteriza por depósitos de IgA en la membrana basal dermoepidérmica. Se presenta con ampollas tensas que suelen localizarse en la zona peribucal y perineal. Objetivo: Describir una dermatosis por IgA lineal en la infancia inducida por cefalosporinas. Presentación de caso: Niño de 2 años de edad, fototipo III, que presentó una erupción vesículo-ampollar después de tratamiento con cefalosporinas por una infección en la piel. Por su presentación clínica característica y los hallazgos en la histopatología e inmunofluorescencia directa se diagnostica como dermatosis IgA lineal. Conclusiones: La dermatosis por IgA lineal es una enfermedad rara. Se conoce que en los últimos 20 años se han diagnosticado solo 4 casos en Cuba, por lo que es importante tener este hecho presente en el momento de plantear posibles causas de dermatosis ampollosas, para su intervención precoz. Es importante tener en cuenta que se puede manifestar por la exposición a fármacos como ocurrió en este caso.

Introduction: Linear IgA dermatosis is a rare blistering disorder, which mainly affects children under 5 years of age and is characterized by IgA deposits in the dermoepidermal basement membrane. It presents with tense blisters that are usually located in the perioral and perineal area. Objective: To describe linear IgA dermatosis in childhood induced by cephalosporins. Case Presentation: 2-year-old boy, phototype III, who developed a vesicle-blister rash after treatment with cephalosporins for a skin infection. Due to its characteristic clinical presentation and findings in histopathology and direct immunofluorescence it is diagnosed as linear IgA dermatosis. Conclusions: Linear IgA dermatosis is a rare disease. It is known that in the last 20 years only 4 cases have been diagnosed in Cuba, so it is important to have this fact present at the time of raising possible causes of bullous dermatoses, for early intervention. It is important to note that it can be manifested by exposure to drugs as happened in this case.

Morphological Spectrum of Vesiculobullous Skin Lesions: An Institutional Perspective.

Introduction A vesiculobullous lesion of the skin encompasses a group of dermatological disorders with protean clinicopathological features. They usually occur as a part of the spectrum of various infectious, inflammatory, drug-induced, genetic, and autoimmune disorders. Therefore, accurate diagnosis of these lesions is essential for appropriate management and to reduce the associated morbidity and mortality. The conventional skin punch biopsy is the mainstay in the diagnosis of dermatological diseases, especially when combined with confirmatory tests, such as direct immunofluorescence (DIF). Our study evaluated the clinicopathological spectrum of vesiculobullous lesions. Methods We studied 150 cases of vesiculobullous lesions at the Department of Histopathology, Liaquat National Hospital and Medical College Karachi, Pakistan. Written and informed consent was taken from the patients followed by skin punch procedure in which three biopsies were obtained, which included one biopsy from the lesion and two peri-lesional biopsies. One peri-lesional biopsy was sent in cryomatrix for DIF studies, whereas the other two were sent in formalin to follow the standard tissue-processing protocol. Results Our results showed that most patients belonged to the geriatric age group of more than 50 years (44.7%), and 54.7% of the patients were females. Total 74.7% of the patients had generalized lesions, followed by lower limbs (9.3%) and trunk (7.3%) involvement. Most patients were diagnosed with bullous pemphigoid (31.3%), followed by pemphigus vulgaris (27.3%), dermatitis herpetiformis (15.3%), Darier's disease (14.7%), pemphigus foliaceus (4.7%), epidermolysis bullosa (2%), linear immunoglobulin A dermatosis (2%), paraneoplastic pemphigus (0.7%), and drug reactions (0.7%). DIF studies were applied on 60 cases, out of which complement protein C3c was the most commonly deposited protein (53.3%). Conclusion Our study emphasized the diagnostic role of skin punch biopsy in the proper evaluation of vesiculobullous skin lesions. Histopathology is the cornerstone diagnostic tool in this regard, with DIF being a useful adjunct.

Diffuse cutaneous mastocytosis masquerading as linear IgA bullous dermatosis of childhood.

Diffuse cutaneous mastocytosis is a rare form of cutaneous mastocytosis that can appear in heterogeneous clinical presentations, including eruption of papules, erythematous plaques, blisters, and erythroderma. We report a 1.5- year-old boy who presented with itchy wheals and blisters spreading on his body. The patient was initially managed as a linear IgA bullous dermatosis of childhood (LABD) because of the similarity of clinical symptoms and the presenting of linear IgA deposits at the basement membrane. Due to the development of urticarial plaque after the resolution of the blisters, the diagnosis of diffuse cutaneous mastocytosis was made based on clinical, histopathological (hematoxylin-eosin, Giemsa, and toluidine blue staining), and direct immunofluorescent examinations (IgA, IgG, IgM, C3). The symptoms were improved following antihistamines and oral corticosteroid treatment.

Cephalosporin-induced linear IgA dermatosis in a child: Case report and literature review.

Linear IgA dermatosis (LAD) is a rare, subepidermal blistering disease with mucocutaneous involvement. It may be idiopathic or drug induced. We describe a 4-year-old girl who presented with a vesiculobullous eruption after she had been treated with cefixime for urinary tract infection. A diagnosis of drug-induced LAD was made based on clinical, histopathological, and immunofluorescence findings. Naranjo adverse drug reaction algorithm was used to assess imputability resulting with a "probable" association. In literature, cephalosporin antibiotics are rarely reported in association with LAD. To our knowledge, this is the first case of a cefixime-induced LAD among adults and children.

["Decoratively figured blisters" on the whole integument in initially diagnosed ulcerative colitis]. / "Schmuckvoll konfigurierte Blasen" am gesamten Integument bei erstdiagnostizierter Colitis ulcerosa.

The rare case of a 61-year-old patient suffering from linear IgA dermatosis is presented. The patient was previously hospitalized with chronic inflammatory bowel disease. The correct diagnosis of the disease was based on clinical and histological findings. Serological methods, such as indirect immunofluorescence, ELISA and immunoblotting are suitable for identification of the autoantibodies. In this case the detection of IgA antibodies along the basal membrane was achieved by direct immunofluorescence. Other bullous dermatoses with similar symptoms, such as an IgG-mediated bullous pemphigoid have to be excluded. The therapy of linear IgA dermatosis is ensured by steroid-containing topical agents, alongside antiseptic measures as well as systemic dapsone p.o.

[Humoral immune diseases: Cutaneous vasculitis and auto-immune bullous dermatoses]. / Immunité à médiation humorale : vascularites cutanées et maladies bulleuses auto-immunes.

Humoral immunity is the cause of multiple diseases related to antibodies (IgA, IgG, IgM) produced by the patient. Two groups of diseases are identified. The first group is related to circulating antigen-antibody complexes. The antigens are various. They are often unknown. These immune complexes cause a vascular inflammation due to the complement fixation. Consequently, this group is dominated by inflammatory vasculitis. In the second group, the pathology is due to the fixation in situ of antibodies to a target antigen of the skin that is no more recognized by the patient. This group is represented by the auto-immune bullous dermatoses.

[Topical corticosteroids as a therapeutic alternative in linear immunoglobulin A bullous dermatosis in childhood: case report]. / Corticoides tópicos como alternativa terapéutica en la dermatosis ampollosa por inmunoglobulina A lineal de la infancia: caso clínico.

Linear immunoglobulin A dermatosis of childhood is a rare autoimmune disorder. Its etiology remains unknown, although it has been linked to drugs, infections, immunological diseases and lymphoproliferative processes. We report the case of a 6 year old girl who consulted for perioral bullous lesions without other symptoms. Neither treatment with mupirocin nor methylprednisolone therapy achieved remission of cutaneous lesions. Skin biopsy showed a linear immunoglobulin A dermatosis. It was not possible to start treatment with dapsone because of a partial glucose-6-phosphate dehydrogenase deficiency, so topical treatment was maintained with good evolution of lesions. Linear immunoglobulin A dermatosis is a rare disease whose differential diagnosis includes other bullous diseases. Pathology is essential for diagnosis. When treatment with dapsone is not possible, topical corticosteroids may be an alternative, either alone or associated with other treatments.

La dermatosis por inmunoglobulina A lineal de la infancia es un trastorno autoinmunitario poco frecuente. Su etiología es desconocida, aunque se ha relacionado con fármacos, infecciones, enfermedades inmunológicas y procesos linfoproliferativos. Presentamos el caso de una niña de 6 años que consultaba por lesiones ampollosas periorales, sin otra sintomatología. Se pautó un tratamiento con mupirocina tópica primero y luego con metilprednisolona tópica, sin resolución del cuadro. Se realizó una biopsia cutánea, compatible con dermatosis por inmunoglobulina A lineal. No fue posible iniciar el tratamiento con dapsona por déficit parcial de glucosa-6-fosfato deshidrogenasa, por lo que se mantuvo el tratamiento tópico, con buena evolución de las lesiones. La dermatosis por inmunoglobulina A lineal es una enfermedad poco frecuente, cuyo diagnóstico diferencial incluye otras enfermedades ampollosas. La anatomía patológica es esencial para el diagnóstico. Si no es posible el tratamiento con dapsona, los corticoides tópicos pueden ser una alternativa, tanto en monoterapia como asociados a otros tratamientos.

Linear IgA dermatosis adult variant with oral manifestation: A rare case report.

Linear immunoglobulin A (IgA) dermatosis (LAD) is a rare autoimmune disorder that presents as a vesiculo-bullous lesion with cutaneous manifestations, but rare oral mucosal involvement. Here we discuss a case of a vesiculobullous lesion with severe oral and ocular mucosal involvement mimicking pemphigoid with histopathological evidence of subepithelial blisters. Direct immunofluorescence (DIF) confirmed the lesion as LAD of adult variant, although with atypical clinical features.

Unusual clinicopathological and immunological presentation of chronic bullous dermatosis of childhood (linear IgA dermatosis).

Linear IgA bullous dermatosis is a rare sulfone-responsive subepidermal blistering disorder of unknown etiology in which smooth linear deposits of IgA are found in the basement membrane zone. Chronic bullous dermatosis of childhood is equivalent to linear IgA disease of adulthood and is characterized by an abrupt onset of large, widespread and tense bullae on a normal or erythematous base. In this case, we describe an unusual presentation of chronic bullous dermatosis in a 14-month-old Saudi girl. Histopathological examination revealed subepidermal cell poor blisters with linear deposition of IgA, IgG, IgM, and C3 along the dermoepidermal junction. The unusual clinical, histopathological and immunofluorescence findings in this patient are discussed, with an account on the differential diagnosis in such cases along with a detailed review of the relevant literature.

Dermatosis IgA lineal: revisión y presentación de caso clínico / Linear IgA dermatosis: a case report and literature review

La Dermatosis IgA lineal es una enfermedad vesiculoampollar subepidérmica autoinmune caracterizada por anticuerpos IgA en la unión dermoepidérmica. Es una enfermedad poco frecuente, siendo la mayoría de los casos idiopáticos, pero con reporte de casos por medicamentos, infecciones virales, enfermedades autoinmunes y tumores malignos. Se presentará un caso clínico de Dermatosis IgA lineal causada por Diclofenaco.

Linear IgA dermatosis is an autoimmune subepidermal vesiculobullous disease characterized by IgA antibodies at the dermo-epidermal junction. It is an uncommon disease, with most cases idiopathic, but with case reports caused by drug, viral infections, autoimmune diseases and malignant tumors. A clinical case of Linear IgA dermatosis caused by diclofenac is presented.