Linear IgA bullous dermatosis of childhood: Retrospective single-center cohort.

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.

Eosinophil-rich linear IgA bullous dermatosis induced by mRNA COVID-19 booster vaccine.

We present a case of eosinophil-rich linear IgA bullous disease (LABD) following the administration of a messenger RNA COVID-19 booster vaccine. A 66-year-old man presented to the emergency department with a 3-week history of a pruritic blistering rash characterized by fluid-filled bullae and multiple annular and polycyclic plaques. He was initially diagnosed with bullous pemphigoid based on a biopsy showing a subepidermal blister with numerous eosinophils. However, direct immunofluorescence studies showed linear IgA and IgM deposition along the basement membrane zone with no immunoreactivity for C3 or IgG. Additionally, indirect immunofluorescence was positive for IgA basement membrane zone antibody. The patient was subsequently diagnosed with LABD and initiated on dapsone therapy with resolution of his lesions at 3-month follow-up. This case illustrates the growing number of autoimmune blistering adverse cutaneous reactions from vaccination. Dermatopathologists should be aware that features of autoimmune blistering diseases can overlap and may not be distinguishable based on these histopathological findings alone. Confirmation with direct immunofluorescence and/or serological studies may be necessary for accurate diagnosis.

Linear IgA bullous dermatosis associated with immunotherapy.

Linear IgA bullous dermatosis (LABD) is a rare mucocutaneus blistering autoimmune disease caused by IgA autoantibodies. Its clinical manifestation can be indistinguishable from bullous pemphigoid (BP), a similar autoimmune bullous disease caused by IgG and IgE autoantibodies. Although BP has been reported as an adverse cutaneous effect of immunotherapy, LABD has rarely been associated with immunotherapy in the literature. We present the case of a 67-year-old woman with metastatic ovarian cancer receiving anti-PD1 and anti-CTLA4 with new onset pruritic tense bullae to the trunk, hands, elbows (in annular distribution) that occurred after immunotherapy. Skin biopsy showed subepidermal blister with abundant neutrophils on H&E histology, and linear IgA staining at the basement membrane on direct immunofluorescence consistent with the diagnosis of LABD. The condition did not improve on initial prednisone taper, but blisters rapidly resolved a few days after initiation of dapsone therapy. We favor that our patient's LABD is secondary to her immunotherapy. Our case highlights the importance of both H&E histology and direct immunofluorescence in diagnosis of blistering disorders in patients on immunotherapy to help in choosing the most effective treatment option in an attempt to avoid discontinuation of immunotherapy.

Linear IgA bullous dermatosis of childhood.

A 4-year-old boy presented with blistering on his face and distal upper and lower extremities. Subepidermal blisters containing neutrophils and eosinophils visualized on histology supported the diagnosis of linear IgA bullous dermatosis of childhood (LABDC). The dermatosis presents with vesicles and tense blisters in an annular distribution, erythematous papules, and/or excoriated plaques. Histopathology shows subepidermal blisters with a neutrophilic infiltrate in the dermis, mainly concentrated at the tips of dermal papillae in the early stage of the disease, which can be mistaken for the pattern of neutrophilic infiltration as seen in dermatitis herpetiformis. Dapsone is the treatment of choice, which is started at a dosage of 0.5mg/kg/day. Linear IgA bullous dermatosis of childhood is a rare autoimmune disease that can be mistaken for other conditions with similar presentations but should always be considered in the differential diagnosis of children with blistering.

Disseminated Tuberculosis in a Nigerian Adolescent with Linear IgA Bullous Dermatosis: A Case Report and Review of Literature.

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.

Flame Figures in Linear Immunoglobulin A Bullous Dermatosis Secondary to Parvovirus B19 Infection.

ABSTRACT: Flame figures represent a characteristic but nondiagnostic histological finding in eosinophilic dermatoses. Some bullous autoimmune diseases with a predominant eosinophilic infiltrate, such as bullous pemphigoid, pemphigoid gestationis, and pemphigus vegetans, may show them. However, it is rare to find them in predominant neutrophilic bullous dermatoses such as linear immunoglobulin A. We present a 60-year-old man with a history of chronic urticaria, which presented a bullous disease after an acute parvovirus B19 infection. The histological findings showed an exceptional linear immunoglobulin A bullous dermatosis with an eosinophilic infiltrate in the dermis forming "flame figures." The clinical and histopathological findings for this entity may be identical to those of other dermatoses. For this reason, combining these findings with direct immunofluorescence analysis is essential for correct diagnosis of this bullous disease.

Linear IgA dermatosis in association with angioimmunoblastic T-cell lymphoma infiltrating the skin: A case report with literature review.

Angioimmunoblastic T-cell lymphoma (AITL) is an aggressive form of peripheral T-cell lymphoma, characterized by systemic symptoms, diffuse lymphadenopathy, hepatosplenomegaly and immunodysregulation. Half of AITL is associated with cutaneous symptoms, but only few cases with bullous eruption have been described. Association with a linear IgA dermatosis is extremely rare. Linear IgA dermatosis can be idiopathic, or linked with drug intake or neoplastic disorders. Some cases of linear IgA dermatosis presenting as toxic epidermal necrolysis (TEN) have been described, most of them being drug induced. We here present the case of a 72-year-old man recently diagnosed with AITL who developed a bullous eruption, presenting as TEN. Histopathology showed deep cutaneous involvement of the lymphoma with a sub-epidermal blistering and direct immunofluorescence revealed a heavy IgA linear deposit on the dermal-epidermal junction. A diagnosis of linear IgA dermatosis associated with cutaneous involvement of an angioimmunoblastic T-cell lymphoma was made. Chemotherapy and corticosteroids allowed cutaneous improvement but the patient died of his lymphoma shortly after.

Linear IgA dermatosis of the childhood-Report of an amoxicillin-induced case.

Linear IgA dermatosis (LAD) is a rare autoimmune disorder in children. A 9-year-old boy was presented with blisters on the intact skin (face, body, arms, hands, soles, perigenital and perianal area) after amoxicillin treatment. Systemic corticosteroids and dapsone treatment for 6 weeks was successful. Clinical and immunofluorescence examinations are most important for differentiation of LAD and other drug-induced bullous dermatoses. They enable an early introduction of proper therapy.

Linear IgA bullous dermatosis associated with ulcerative colitis: A case report and literature review.

We report the case of a 59-year-old Japanese woman who developed linear IgA bullous dermatosis during treatment for ulcerative colitis that manifested as pruritic vesicles with erythema on the trunk and scalp. Histopathological examination revealed subepidermal bulla with neutrophil and eosinophil infiltration in the upper dermis. Direct immunofluorescence revealed linear IgA deposits at the basement membrane zone, and indirect immunofluorescence using split skin revealed IgA reaction to the epidermal side (lamina lucida type). We reviewed 33 reported cases of linear IgA bullous dermatosis associated with ulcerative colitis and found that ulcerative colitis preceded the onset of linear IgA bullous dermatosis in 94% of the patients and that IgA-positive patients in split skin indirect immunofluorescence all showed the lamina lucida type, indicating that target antigens for serum IgA antibodies may reside in the lamina lucida. Regarding the pathogenetic association of ulcerative colitis and linear IgA bullous dermatosis, intestinal inflammation may induce the exposure and presentation of intestinal antigens that are cross-reactive to cutaneous antigens, stimulating autoimmune response to antigens of cutaneous basement membrane zones.

Drug-induced Linear IgA Bullous Dermatosis: A Case Report and Review of the Literature.

Linear IgA bullous dermatosis (LABD) is a rare subepidermal autoimmune blistering disease characterized by linear deposition of IgA along the basement membrane zone. Although most reported cases are idiopathic, there is a subset of patients with drug-induced LABD. Various drugs have been associated with the drug-induced form of the disease. This paper reviews the literature on drugs reported to elicit linear IgA dermatosis and its specific clinical presentation. In addition, a case report of a 77-year-old male patient with linear IgA dermatosis induced by vancomycin is described. The aim of this paper is to emphasize the need to include this differential diagnosis in cases of suspected adverse drug reactions, as well as to highlight the role of drugs in LABD.

Non-infectious diffuse vesiculobullous rash in a pancreas and renal transplant recipient.

Solid organ transplant patients are well established to be at risk of herpes simplex virus and varicella zoster virus infection and reactivation. We present a case of a 41-year-old woman with a history of pancreas and renal transplant who presented with what appeared to be disseminated herpes simplex virus or varicella zoster virus induced rash, but who was ultimately diagnosed and treated as linear IgA bullous dermatosis. This case alerts physicians to other non-infectious dermatoses as a cause of vesiculobullous rash in solid organ transplant patients.

Diagnostic patterns and delays in autoimmune blistering diseases of the mouth: A cross-sectional study.

OBJECTIVES: To describe the natural history and factors influencing diagnostic delays among patients with autoimmune blistering diseases of the mouth. MATERIALS AND METHODS: In this cross-sectional study, 27 newly diagnosed patients were interviewed, and professional and patient delays were calculated. Disease extent and severity scores were determined using Saraswat scoring system. RESULTS: Twenty-seven patients were interviewed and examined. Patient delay was significantly longer in patients who had desquamative gingivitis as initial presentation, in those who tried to use home remedies and over the counter medications, and in patients with less severe disease. Most patients (n = 21 [77.7%]) made more than one consultation, and the mean time needed to reach a definitive diagnosis (i.e. professional delay) was 83.2 ± 21.4 days (range from 21 to 130 days). Professional delay was significantly correlated with the number of previous consultations (r = .78) and was significantly longer in patients who had desquamative gingivitis as initial presentation. CONCLUSION: Diagnosis of oral blistering diseases is often delayed. Diagnostic delay is more common in patients presenting with desquamative gingivitis and those with less severe disease. Improving patients and healthcare professionals' awareness about oral blistering diseases might help reduce diagnostic delay.

Idiopathic linear IgA bullous dermatosis: prognostic factors based on a case series of 72 adults.

BACKGROUND: Linear IgA bullous dermatosis (LABD) is a clinically and immunologically heterogeneous, subepidermal, autoimmune bullous disease (AIBD), for which the long-term evolution is poorly described. OBJECTIVES: To investigate the clinical and immunological characteristics, follow-up and prognostic factors of adult idiopathic LABD. METHODS: This retrospective study, conducted in our AIBD referral centre, included adults, diagnosed between 1995 and 2012, with idiopathic LABD, defined as pure or predominant IgA deposits by direct immunofluorescence. Clinical, histological and immunological findings were collected from charts. Standard histology was systematically reviewed, and indirect immunofluorescence (IIF) on salt-split skin (SSS) and immunoblots (IBs) on amniotic membrane extracts using anti-IgA secondary antibodies were performed, when biopsies and sera obtained at diagnosis were available. Prognostic factors for complete remission (CR) were identified using univariate and multivariate analyses. RESULTS: Of the 72 patients included (median age 54 years), 60% had mucous membrane (MM) involvement. IgA IIF on SSS was positive for 21 of 35 patients tested; 15 had epidermal and dermal labellings. Immunoelectron microscopy performed on the biopsies of 31 patients labelled lamina lucida (LL) (26%), lamina densa (23%), anchoring-fibril zone (AFz) (19%) and LL+AFz (23%). Of the 34 IgA IBs, 22 were positive, mostly for LAD-1/LABD97 (44%) and full-length BP180 (33%). The median follow-up was 39 months. Overall, 24 patients (36%) achieved sustained CR, 19 (29%) relapsed and 35% had chronic disease. CR was significantly associated with age > 70 years or no MM involvement. No prognostic immunological factor was identified. CONCLUSIONS: Patients with LABD who are < 70 years old and have MM involvement are at risk for chronic evolution.

Sublamina densa-type linear IgA bullous dermatosis with IgA autoantibodies specific for type VII collagen: a case report and clinicopathological review of 32 cases.

Linear IgA bullous dermatosis (LABD) is a rare autoimmune bullous disorder characterized by linear deposits of IgA at the basement membrane zone(BMZ) and/or by circulating IgA anti-BMZ antibodies. Comparing with other immuno-bullous diseases, LABD represents a heterogeneous disease entitywith diversity of pathogenic IgA autoantibodies to different hemidesmosomal antigens and an association with malignancies and occasional drug use. We herein present an 82-year-old Japanese man with LABD, whose indirect immunofluorescence using 1M NaCl-split skin showed positive staining for IgA at the dermal side alone. Fluorescence overlay antigen mapping using laser scanning confocal microscopy (FOAM-LSCM) was employed to examine the in vivo bound patient's IgA, which was specific for type VII collagen (COL7), a prominent antigen of the sublamina densa. One year later, he developed malignant lymphoma, suggesting the diagnosis of paraneoplastic LABD. We reviewed 32 cases of sublamina-densa type LABD with anti-COL7 IgA antibodies thus far reported in the literature to compare the clinicopathological characteristics of this rare disease variant and emphasize that COL7 is the main autoantigen in sublamina densa disease.

Flame figures in linear IgA bullous dermatosis: a novel histopathologic finding.

BACKGROUND: Linear IgA bullous dermatosis (LABD) is an autoimmune subepidermal blistering disease usually with a neutrophil rich inflammatory infiltrate, and characterized by linear IgA deposition at the basement membrane zone (BMZ), and neutrophil predominant dermal inflammation. We report a case of LABD with numerous eosinophils and flame figure formation, a unique histopathologic finding not previously reported. A 69-year-old woman presented with a rapidly progressive, intensely pruritic rash over forearms, breasts, axillae, hips, and thighs. Thelesions were comprised of annular vesicles and bullae with hemorrhagic crusts and erosions. The clinical differential diagnosis included bullous pemphigoid(BP), LABD, and epidermolysis bullosa aquisita (EBA). RESULTS: A biopsy from a bullous plaque on the wrist revealed a subepidermal blister with neutrophils and numerous eosinophils with flame figure formation.Direct immunofluorescent (DIF) microscopy revealed linear deposition of IgA at the BMZ. CONCLUSIONS: Although unusual, the combined findings supported a diagnosis of LABD. Increased eosinophils may be associated with drug-induced LABD and may explain the numerous eosinophils in our case. It is important to be aware of this finding as the pathology may easily be misdiagnosed as BP, or possibly bullousWells syndrome. This case emphasizes that combined clinical, pathologic, and DIF findings are essential in the diagnosis of bullous dermatoses.

A toxic epidermal necrolysis-like presentation of linear IgA bullous dermatosis treated with dapsone.

Linear IgA bullous dermatosis is a rare autoimmune vesiculobullous disease characterized by linear deposition of IgA along the basement membrane zone. It is classically idiopathic, but may also arise secondary to drug exposure. A heterogeneous spectrum of clinical features has been described, including a rare, morbid variant mimicking toxic epidermal necrolysis. Herein, we present a case of vancomycin-induced linear IgA bullous dermatosis that manifested clinically as toxic epidermal necrolysis and resolved with dapsone therapy.

Trimethoprim-sulfamethoxazole-induced linear IgA bullous disease presenting as toxic epidermal necrolysis.

BACKGROUND: Linear IgA bullous dermatosis (LABD) is an autoimmune blistering skin disorder characterized by linear IgA deposits along the dermoepidermal junction. Usually idiopathic, LABD can be drug-induced. OBJECTIVE: To report the atypical characteristics of a case of trimethoprim-sulfamethoxazole-induced LABD presenting as toxic epidermal necrolysis (TEN). METHODS: A 63-year-old woman treated with trimethoprim-sulfamethoxazole for Pneumocystis jirovecii infection developed a generalized maculopapular rash with herpetiform lesions, rosette-like lesions, and tense bullae with Nikolsky sign. RESULTS: Anti-basement membrane zone antibodies were negative, but immunoblot revealed a 160 kDa band corresponding to subepidermal class IgA desmoglein 1. Skin biopsy specimens revealed a subepidermal bulla and direct immunofluorescence showed linear IgA deposition along the basement membrane zone. A diagnosis of toxic epidermal necrolysis was excluded and replaced by trimethoprim-sulfamethoxazole-induced LABD. CONCLUSION: We report a case of trimethoprim-sulfamethoxazole-induced LABD with a 160 kDa IgA desmoglein 1 found by immunoblotting analysis, probably by epitope spreading.