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.

Bullous lesions in a young adolescent postrenal transplant.

Kidney transplant recipients frequently suffer from skin infections and malignancies. New dermatosis can appear after transplantation. Although children are maintained on varying degrees of chronic immunosuppression, there is still a possibility of autoimmune blistering skin conditions, which can pose a diagnostic challenge in terms of clinical presentation. Histopathology of skin lesions is very important which helps in correct diagnosis and prompt treatment. We report an extremely rare case of linear IgA dermatosis in a child who was postrenal transplant and treated successfully with dapsone and steroids.

Autoantibody Profile of a Cohort of 54 Italian Patients with Linear IgA Bullous Dermatosis: LAD-1 Denoted as a Major Auto-antigen of the Lamina Lucida Subtype.

Linear IgA bullous dermatosis (LABD) is characterized by presence of multiple IgA autoantibodies, and a comparatively lesser number of IgG antibodies, directed against different hemidesmosomal antigens. The main autoantigens are LAD-1, LABD-97, BP180 and BP230, type VII collagen and laminin 332. We retrospectively studied the serology of 54 Italian patients with LABD using enzyme-linked immunosorbent assay (ELISA), immunoblotting assay, and indirect immunofluorescence on monkey oesophagus and salt-split skin. Among these, indirect immunofluorescence of salt-split skin elicits the greatest sensitivity. Sixty-three percent of the sera were observed to be positive, with a lamina lucida pattern observed in 48%, a sub-lamina densa pattern in 2% and a mixed pattern in 13% of the cases. IgA reactivity to LAD-1 on immunoblotting was found in 52% of sera, to BP180-NC16A by ELISA in 32% and to BP230 in 26%. Only 17% of patients possessed circulating IgG autoantibodies. LAD-1 was determined to be a major autoantigen of the lamina lucida subtype. Combined serological assays demonstrated a high sensitivity (82%), suggesting that this approach could support diagnosis when a biopsy is not feasible or direct immunofluorescence results are negative.

A Case of Linear IgA Bullous Dermatosis Induced by Aspirin Therapy.

Linear IgA bullous dermatosis (LABD) is a rare autoimmune blistering disease that may be triggered by some diseases and medications. For the latter one, non-steroidal anti-inflammatory drugs (NSAIDs) have been identified as one of the potential causative agents to develop LABD. Here, a rare case of drug-induced LABD is introduced. A 13-month-old Iranian boy presented with a history of generalized blisters, displaying the classic "string of pearls" sign who was eventually diagnosed as a case of LABD. In his admission, he was diagnosed whit Mucocutaneous lymph node syndrome and treated with aspirin.  Some features like appearing the characteristic lesions one week following the administration of aspirin, rapid clearance of lesions after the withdrawal of the drug, and reappearance of new lesions after readministration of aspirin were highly suggestive of aspirin-induced LABD. To establish the diagnosis, we used the "Naranjo probability score" which determined the probable causative role of aspirin. The diagnosis was confirmed by showing the positive IgA deposition in the basement membrane zone in a direct immunofluorescence study of the skin biopsy. The child was treated with dapsone with dramatical response to the drug.

Linear IgA bullous dermatosis in adults and children: a clinical and immunopathological study of 38 patients.

BACKGROUND: Linear IgA bullous dermatosis (LABD) is a rare autoimmune subepithelial vesiculobullous disease due to IgA autoantibodies directed against different antigens of the basement membrane zone (BMZ) of the skin and/or mucosae. It affects mainly preschool-aged children and adults, with only few studies on large series. The aim of this study was to assess possible differences between adults and children regarding clinical presentation, immunopathologic features, management and course of the disease. METHODS: A retrospective review of 38 LABD patients, followed-up from November 2006 to September 2018, was performed. RESULTS: Of 38 patients, 27 were adults and 11 children. Mean age at diagnosis was 5.4 years and 60.6 years in the pediatric and adult group, respectively. Considering both groups, limbs were the most commonly involved site (73.7%), followed by trunk (55.3%), head (36.8%) and buttocks (13.2%). Interestingly, head (p = 0.008), particularly perioral (p = 0.001), involvement, as well as "string of pearls" arrangement (p = 0.03), were more prevalent in children. Mucosal involvement was seen in 9 (23.7%) patients and was more frequent in children than adults (45.5% vs 14.8%, respectively, p = 0.09). Linear IgA deposits along the BMZ were observed in 30 patients (78.9%), while linear/granular IgA deposits in 8 patients (21.1%). Dapsone was the most commonly used drug (78.9%) and complete remission was achieved in most cases (81.6%). CONCLUSIONS: Our epidemiological and clinicopathological findings relative to a large cohort of LABD patients are mostly consistent with the literature data. Interestingly, head, notably perioral, involvement and "string of pearls" arrangement occurred more frequently in the paediatric than adult group. The above clinical parameters may be regarded as diagnostic tools for LABD in children.

[Linear IgA bullous dermatosis]. / Lineare IgA-Dermatose.

Linear IgA bullous dermatosis is a rare autoimmune blistering disease that occurs in both children and adults. Strings of pearls, crowns of jewels, rosettes and urticarial plaques can occur on the whole integument with emphasis on the face (particularly perioral area) and genitalia. Pruritus is common and may be severe. The presence of IgA deposits along the basement membrane can usually be identified using direct immunofluorescence (DIF) microscopy. The histological and clinical features of this disorder may mimic those of dermatitis herpetiformis.

["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.

Clinical and Immunological Study of 30 Cases With Both IgG and IgA Anti-Keratinocyte Cell Surface Autoantibodies Toward the Definition of Intercellular IgG/IgA Dermatosis.

Several sporadic cases, in which direct and indirect immunofluorescence studies simultaneously detected IgG and IgA autoantibodies to keratinocyte cell surfaces, have been reported mainly under the name of IgG/IgA pemphigus. However, there have been no systematic studies for this condition. In this study, we collected 30 cases of this condition from our cohort of more than 5,000 autoimmune bullous disease cases, which were consulted for our diagnostic methods from other institutes, and summarized their clinical and immunological findings. Clinically, there was no male-female prevalence, mean age of disease onset was 55.6 years, and mean duration before this condition was suspected was 18 months. The patients showed clinically bullous and pustular skin lesions preferentially on the trunk and extremities, and histopathologically intraepidermal pustules and blisters with infiltration of neutrophils and eosinophils. Immunologically, ELISAs frequently detected IgG and IgA autoantibodies to both desmogleins and desmocollins. From the characteristic clinical, histopathological, and immunological features, which are considerably different from those in classical IgG types of pemphigus, we propose this disease as a new disease entity with preferential name of intercellular IgG/IgA dermatosis (IGAD). This was the largest study of IGAD to date.

Effectiveness and Safety of Rituximab in Recalcitrant Pemphigoid Diseases.

Introduction: Rituximab (RTX) is a monoclonal antibody targeting CD20, a transmembrane protein expressed on B cells, causing B cell depletion. RTX has shown great efficacy in studies of pemphigus vulgaris, but data of pemphigoid diseases are limited. Objective: To assess the effectiveness and safety of RTX in pemphigoid diseases. Methods: The medical records of 28 patients with pemphigoid diseases that were treated with RTX were reviewed retrospectively. Early and late endpoints, defined according to international consensus, were disease control (DC), partial remission (PR), complete remission (CR), and relapses. Safety was measured by reported adverse events. Results: Patients with bullous pemphigoid (n = 8), mucous membrane pemphigoid (n = 14), epidermolysis bullosa acquisita (n = 5), and linear IgA disease (n = 1) were included. Treatment with 500 mg RTX (n = 6) or 1,000 mg RTX (n = 22) was administered on days 1 and 15. Eight patients received additional 500 mg RTX at months 6 and 12. Overall, DC was achieved in 67.9%, PR in 57.1%, and CR in 21.4% of the cases. During follow-up, 66.7% patients relapsed. Repeated treatment with RTX led to remission (PR or CR) in 85.7% of the retreated cases. No significant difference in response between pemphigoid subtypes was found. IgA-dominant cases (n = 5) achieved less DC (20 vs. 81.3%; p = 0.007), less PR (20 vs. 62.5%; p = 0.149), and less CR (0 vs. 18.8%; p = 0.549) compared to IgG-dominant cases (n = 16). Five severe adverse events and three deaths were reported. One death was possibly related to RTX and one death was disease related. Conclusion: RTX can be effective in recalcitrant IgG-dominant pemphigoid diseases, however not in those where IgA is dominant.

Vancomycin Mediates IgA Autoreactivity in Drug-Induced Linear IgA Bullous Dermatosis.

Vancomycin (VCM) is known to induce linear IgA bullous dermatosis (LAD). However, in contrast to conventional LAD, in which circulating IgA autoantibodies against basement membrane proteins are commonly detected, patient sera from VCM-induced LAD yields negative results in indirect immunofluorescence microscopy, and the targeted autoantigen remains undetermined. By using sera from a typical patient with VCM-induced LAD, we identified that co-incubation of sera with VCM resulted in linear IgA deposition at the basement membrane zone by indirect immunofluorescence. Patient sera reacted with the dermal side of 1 mol/L NaCl-split skin and with the recombinant noncollagenous (i.e., NC1) domain of type VII collagen by both immunoblot and ELISA in the presence of VCM. The investigation of an additional 13 patients with VCM-induced LAD showed that 10 out of the 14 sera (71.4%) reacted with the NC1 domain of type VII collagen by ELISA when spiked with VCM, whereas only 4 (28.6%) tested positive without it. The enhancement of reactivity to NC1 by VCM, as determined by optical density via ELISA, was observed in 10 out of the 14 sera (71.4%). These findings indicate that type VII collagen is a target autoantigen in VCM-induced LAD and that VCM mediates IgA autoreactivity against type VII collagen, providing an insight into mechanisms involved in drug-induced autoimmune disease.

Skin and coeliac disease, a lot to think about: a case series.

Coeliac disease (CD) is an autoimmune disease, characterised by a permanent sensitivity to gluten. It is being progressively recognised as a multisystemic disease, with multiple extraintestinal manifestations. Skin conditions (eg, dermatitis herpetiformis) are an example of its manifestations; however, its underlying mechanisms are still not well understood. This article presents three cases of uncommon skin conditions in patients with a history of CD. Two of them concern linear IgA bullous dermatosis and erythema nodosum, which have been described in the literature as having potential associations with CD, though only a few cases were reported. The third case corresponds to pityriasis lichenoides-a rare lymphoproliferative disorder of unknown aetiology-, which has no correlation with CD in the literature reviewed. The authors aim to draw attention to the possibility of CD as a potential predisposing factor for the occurrence of these skin diseases.

C-Terminal Processing of Collagen XVII Induces Neoepitopes for Linear IgA Dermatosis Autoantibodies.

Transmembrane collagen XVII (COL17) is a hemidesmosomal component of basal keratinocytes that can be targeted by autoantibodies in autoimmune blistering disorders, including linear IgA dermatosis (LAD). COL17 can be physiologically cleaved within the juxtamembranous extracellular NC16A domain, and LAD autoantibodies preferentially react with the processed ectodomains, indicating that the processing induces neoepitopes. However, the details of how neoepitopes develop have not been elucidated. In this study, we show that C-terminal processing of COL17 also plays a role in inducing neoepitopes for LAD autoantibodies. First, the mAb hC17-ect15 targeting the 15th collagenous domain of COL17 was produced, which showed characteristics similar to LAD autoantibodies. The mAbs preferentially reacted with C-terminally deleted (up to 682 amino acids) recombinant COL17, suggesting that C-terminal processing shows neoepitopes on the 15th collagenous domain. The LAD autoantibodies also react with C-terminal deleted COL17. Therefore, neoepitopes for LAD autoantibodies also develop after C-terminal processing. Finally, the passive transfer of the mAb hC17-ect15 into human COL17-expressing transgenic mice failed to induce blistering disease, suggesting that neoepitope-targeting antibodies are not always pathogenic. In summary, this study shows that C-terminal processing induces dynamic structural changes and neoepitopes for LAD autoantibodies on COL17.

Linear immunoglobulin A dermatosis: A case report. / Dermatosis inmunoglobulina A lineal: a propósito de un caso.

We present the case of a sixty five year old woman with two months history of pruritus and hyperpigmented annular lesions on the trunk, buttocks and upper extremities. In addition, she presents vesicles with healthy skin on the basis, in the flexor aspect of wrists. No evidence of mucosal involvement. Histological study showed subepidermal vesicular dermatitis with inflammatory infiltrate of neutrophils and eosinophils. Direct immunofluorescence evidenced linear and continuous deposition of immunoglobulin A in basement membrane zone, compatible with linear immunoglobulin A disease.

En este texto se presenta el caso de una paciente de sesenta y cinco años con sintomatología de dos meses de evolución consistente en prurito y lesiones hiperpigmentadas anulares en tronco, glúteos y extremidades superiores. En el área flexora de las muñecas presenta vesículas sobre base eritematosa y piel sana, sin evidencia de compromiso mucoso. Al estudio histológico se constata dermatitis vesicular subepidérmica con infiltrado inflamatorio de neutrófilos y eosinófilos. La inmunofluorescencia directa muestra depósito lineal y continuo de inmunoglobulina A en zona de membrana basal, compatible con dermatosis por inmunoglobulina A lineal.