Linear IgA Research Articles

Eosinophil-rich Linear IgA Bullous Dermatosis: A Case Report of a Rare Entity

Linear IgA bullous dermatosis (LABD) is an uncommon autoimmune bullous disease characterized by a subepidermal neutrophilic infiltrate. It classically presents as widespread tense vesicles in an annular pattern and is defined by the presence of linear deposition of IgA at the dermal-epidermal junction. Eosinophil-rich LABD has been rarely reported in the literature, including in association with COVID-19 booster vaccination, parvovirus B19 infection, hematologic malignancies, and drug-induced LABD. The varied clinical and histopathologic findings often make it difficult to differentiate LABD from other blistering diseases such as bullous pemphigoid and dermatitis herpetiformis. For this reason, immunofluorescence and serologic testing are critical for identifying the underlying diagnosis.

A Comparative Study of Direct Immunofluorescence Patterns in Linear IgA Bullous Dermatosis Versus Dermatitis Herpetiformis

Background: Dermatitis herpetiformis (DH) is typically characterized by granular IgA deposition in the papillary dermis on direct immunofluorescence (DIF), and linear IgA bullous dermatosis (LABD) is characterized by linear deposition of IgA along the basement membrane. Other DIF findings in both conditions may include IgG, IgM, and C3 deposition in various patterns. In cases where immunofluorescence findings are unclear, such as continuous but somewhat granular IgA deposition along the dermal–epidermal junction, additional DIF patterns may be helpful in the diagnostic process. Methods: Forty-five cases of digitized images of LABD and 48 digitized images of DH cases were analyzed. The data regarding the positivity and patterns of immunoglobulins were documented and analyzed. Results: None of the LABD cases had a picket fence pattern, while 47.9% (n = 23) of the DH cases had the pattern. Elevated levels of IgG and IgM were found in LABD compared with DH. In DH, higher IgM and kappa light chain levels were observed in the deposited particles compared with those in LABD. Conclusions: The “picket fence pattern” is highly specific for DH (Specificity 100%) but less sensitive (Sensitivity 47.9%). It may be helpful to differentiate between DH and LABD for a more accurate diagnosis.

Utility of Immunofluorescence in Immune-Mediated Vesiculobullous Lesions of Skin

Bullous lesions may be due to various causes, including bullous pemphigoid, pemphigus vulgaris, linear IgA disease, connective tissue disorders, and other rare vesico-bullous skin diseases. Though histopathology can help narrow down possible diagnoses, direct immunofluorescence is required for a definite diagnosis based on positivity patterns of different immunoglobulins. In this study, 47 cases of clinically suspected immune mediated vesiculo-bullous diseases (IMVBD) were confirmed with histopathology. Females were more commonly affected and the age range was from 10 to 93 years. Among these cases, 23 were diagnosed as pemphigus vulgaris, l6 as bullous pemphigoid, 3 each as pemphigus foliaceus and linear IgA disease. DIF, including testing for c1q, was instrumental for the diagnosis of the disease in order for the patient to get appropriate treatment.

Histopathologic Overlap Between Bullous Lupus Erythematosus and Linear IgA Bullous Dermatosis: A Comparative Study.

Bullous lupus erythematosus (BLE) and linear IgA disease (LAD) are rare autoimmune subepidermal blistering diseases, with overlapping features despite different pathogenetic mechanisms. Diagnosis is based on immunofluorescence and serology. This retrospective study was undertaken to compare the histopathologic features of BLE and LAD (11 cases each). The mean age was 36 years in both groups, and female preponderance was noted in BLE. Clinically, all cases presented as tense, itchy blisters distributed over the trunk, face, and extremities. Subepidermal neutrophil-rich blisters were seen in 60% BLE and 54.54% LAD cases. Eosinophils in the blisters were noted in 4 cases (36.4%) of linear IgA bullous dermatosis, but not in any of the BLE cases. The adjacent epidermal changes noted include spongiosis (33%; 40%), papillary microabscesses (22%; 20%), and basal tagging by neutrophils (77%; 70%). Superficial perivascular inflammation was seen in all cases while deep perivascular inflammation was observed in 54% BLE and 36% LAD cases. Lymphocytes were the predominant infiltrate. Increased dermal mucin was seen in 60% BLE and 45% LAD cases. None of the histopathologic features showed a statistically significant difference between the 2 groups. Hence, histopathology alone is of limited value in distinguishing the 2 groups. Diagnosis rests on immunofluorescence and serologic findings, which should be used even in cases that seem to be classic LAD or patients without history of systemic lupus erythematosus.

Histopathologic features in drug-induced, malignancy-associated, or idiopathic linear IgA bullous dermatosis: A retrospective comparative cohort study of 65 patients.

Histopathologic features in drug-induced, malignancy-associated, or idiopathic linear IgA bullous dermatosis: A retrospective comparative cohort study of 65 patients.

Targeted serum proteome profiling reveals nicotinamide adenine dinucleotide phosphate (NADPH)-related biomarkers to discriminate linear IgA bullous disorder from dermatitis herpetiformis

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.

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 β4 (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.

The "String of Pearls" Sign of Chronic Bullous Disease of Childhood (CBDC).

The "String of Pearls" Sign of Chronic Bullous Disease of Childhood (CBDC).

Exploring the Potential Advantages of Traditional Therapies in Autoimmune Blistering Illnesses: A Comprehensive Review and Analysis, Research

Autoimmune blistering diseases, such as Linear IgA Bullous Dermatosis (LABD) and Chronic Bullous Disease of Childhood (CBDC), provide considerable therapeutic treatment issues. Samana Aushadhis are regularly prescribed by Ayurvedic practitioners as part of therapy regimens for dermatological diseases including LABD and CBDC. Although anecdotal data and clinical observations point to the potential usefulness of traditional medicines in promoting long-term remission and alleviating symptoms, the precise mechanisms by which they exert their therapeutic benefits in LABD/CBD remain incompletely known in contemporary science. The potential advantages of traditional therapies in autoimmune blistering illnesses are being investigated through clinical trials, observational research, and mechanistic investigations. The therapeutic potential of these herbal remedies in LABD and CBDC is being investigated through clinical trials, observational research, and mechanistic investigations. Clinical trials, observational studies, and mechanistic investigations are being conducted in an effort to better understand the therapeutic potential of conventional medications in autoimmune blistering disorders. The effectiveness of these herbal treatments in causing remission and easing symptoms in LABD and CBDC is being closely examined. Overall, while traditional therapies hold promise in the management of autoimmune blistering diseases like LABD and CBDC, more research is necessary to fully understand their mechanisms of action and therapeutic potential. Through rigorous scientific inquiry, the integration of traditional and contemporary medicine may offer new avenues for managing these difficult conditions. Clinical trials, observational research, and mechanistic investigations are all contributing to the exploration of the therapeutic potential of these herbal remedies in LABD and CBDC.

Current Knowledge on Nail Involvement in Autoimmune Bullous Disorders.

There are few studies, mainly case reports, on the involvement of the nail unit in autoimmune bullous disorders. Nail involvement in autoimmune bullous disorders is a significant clinical phenomenon, marked by a range of manifestations, most often not presenting with blisters like on the skin but rather with alterations of the nail unit such as paronychia, onychomadesis, or onycholysis. This involvement is particularly notable due to the unique immunological features of the nail unit, including the expression of various antigens and the presence of Langerhans cells. Conditions like pemphigus vulgaris, bullous pemphigoid, epidermolysis bullosa acquisita, linear IgA disease, and bullous systemic lupus erythematosus can lead to nail abnormalities. The prevalence of nail manifestations varies according to the disorder, and diagnosis often relies on histopathological and immunofluorescence testing. Nail involvement correlates with disease severity and duration, sometimes serving as a herald sign. Further research is needed to guide therapeutic approaches for nail involvement in autoimmune bullous diseases. Nail involvement in autoimmune bullous nail disorders may be confusing as there are almost never bullae. One should keep the diagnosis in mind when facing an atypical paronychia.

Linear IgA bullous dermatoses in an Indian child with IgG predominance: a unique case report from a tertiary care hospital of Eastern India

Linear IgA bullous dermatoses in an Indian child with IgG predominance: a unique case report from a tertiary care hospital of Eastern India

Management of Linear IgA through Ayurveda -A Case study

Linear IgA bullous dermatosis (LABD)/ Chronic bullous disease of childhood (CBDC) is a rare autoimmune blistering disease characterized by the linear deposition of IgA at the dermoepidermal junction. The disease has an incidence of 0.2 to 2.3 per 1000000 million per year showing diverse clinical manifestations and etiologies1.In this case, a 6-year-old child presented with erythematous vesiculobullous lesions on her perianal region, groins, thighs and in both upper and lower limbs since 1 month.The symptoms were gradually progressive in nature.A biopsy was performed, which was consistent with linear immunoglobulin A bullous dermatosis and later confirmed by direct immunofluorescence studies.The child was advised to consume samana aushadhis (internal medicines)for 6 months, which led to remarkable changes in the lakshanas and the patient had no such symptoms till date.This case shows the significant role of ayurvedic intervention in the management of such diseases.

Diagnostic Utility of Direct Immunofluorescence on Paraffin-Embedded Skin Biopsy Samples for the Diagnosis of Autoimmune Vesiculobullous Lesions.

Background Autoimmune vesiculobullous diseases (AIBDs) are a group of diseases characterized by blisters of the skin/mucosa due to the presence of circulating autoantibodies against antigens in the epidermis or the dermo-epidermal junction. Direct immunofluorescence (DIF) for immunoglobulin (Ig)G, IgC3, and IgA on fresh-frozen tissue is the gold standard diagnostic test for AIBDs. However, DIF in the absence of frozen tissue is challenging for the diagnosis of AIBDs. This study aimed to analyze the practical utility of DIF using paraffin-embedded skin biopsy rather than fresh frozen tissue for the diagnosis of AIBDs. Methodology This cross-sectional comparative study included 30 cases of AIBDs. DIF for IgG and IgA was performed on paraffin-embedded tissue (PE-DIF) after proteinase digestion on histopathologically confirmed 15 pemphigus vulgaris (PV), three pemphigus foliaceous (PF), four bullous pemphigoid (BP), three dermatitis herpetiformis (DH), three subcorneal pustular dermatosis (SCPD), and one case each of linear IgA disease and pemphigoid gestationis (PG). PE-DIF staining pattern was compared with the DIF on fresh frozen tissue (FF-DIF). Results All cases of PV and PF showed an intercellular IgG chicken wire staining pattern similar to FF-DIF. However, background staining was more intense in PV cases while less intense in PF cases. Three BP cases showed linear IgG staining in PE-DIF. DH, SCPD, linear IgA disease, and PG cases did not show IgG positivity. Out of three DH cases, two cases showed granular IgA positivity while linear IgA positivity along the basement membrane was seen in a single case of linear IgA disease. Negative IgG staining was observed in SCPD. Immunofluorescence in PE-DIF was rapidly deteriorating than in FF-DIF. Conclusions DIF done on paraffin-embedded tissue can be used as a supplement and salvage technique with histopathology for the diagnosis of AIBDs,particularly when a cryostat facility for frozen tissue is not available and the patient is unable to undergo a second biopsy procedure.

S2k guidelines on diagnosis and treatment of linear IgA dermatosis initiated by the European Academy of Dermatology and Venereology.

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. 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. The guidelines summarizes evidence-based and expert opinion-based recommendations (S2 level) on the diagnosis and treatment of LAD. These guidelines will support dermatologists to improve their knowledge on the diagnosis and management of LAD.

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.

Linear IgA Bullous Dermatosis in Korea Using the Nationwide Health Insurance Database.

(1) Background: Linear immunoglobulin A bullous dermatosis (LABD) is a rare autoimmune, subepidermal blistering disease, characterized by linear IgA deposits along the epidermal basement membrane. LABD is idiopathic and is associated with medication and systemic autoimmune diseases. (2) Methods: We investigated the demographic characteristics, disease course, causative agents, and associated diseases in Korean patients with LABD. The Korean Health Insurance Review and Assessment Service database was used to obtain data. We identified 670 LABD cases between 2010 and 2022. (3) Results: The annual incidence of LABD was 1.3 per 100,000 persons, with a higher prevalence in individuals ≥60 years old. The patients were treated with dapsone for 30.7 ± 56.7 days, had 1.3 ± 0.7 hospital visits, and were hospitalized for 19.8 ± 19.7 days. Risk factors, including malignancy, commonly preceded LABD. Antibiotic use, specifically vancomycin and third-generation cephalosporins, was a risk factor. The mean age of LABD diagnosis was 55.9 ± 21.7 years. (4) Conclusion: This is the first published study to assess a nationwide cohort for LABD. The incidence of LABD was higher than that in other studies. Most case reports have linked LABD with the administration of specific antibiotics; however, this study shows there were more associations with other conditions.

Adult-onset linear IgA bullous dermatosis: a retrospective single-center cohort study of 81 patients and literature review.

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. 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. 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. 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.

Linear IgA dermatosis in 19 years old patient

Linear IgA dermatosis in 19 years old patient

Juvenile Bullous Pemphigoid with Similarity Clinical Features to Chronic Bullous Disease of Childhood

Introduction: Autoimmune bullous disease (ABD) is a specific autoimmune skin disease characterized by subepidermal vesicles and bullae. In pediatrics, there is an autoimmune bullous disease controversy with clinical clusters of jewel on Chronic bullous disease of childhood (CBDC) but dominant IgG autoantibodies. A similar clinical presentation challenges diagnosis; thus, supporting studies on direct immunofluorescence (DIF) as a specific autoantibody factor are necessary. Case: A 10-year-old boy with clinically tense-walled blisters with or without an erythematous base is itchy all over his body, with a predominance of palmoplantar, neck, inguinal, and axillary, presented by erosions, crusts, and a partial cluster of jewels lesion with mucosal involvement. A complete blood count shows leukocytosis and eosinophilia. Hematoxylin-eosin (HE) staining revealed a subepidermal cleft with eosinophil predominance, while direct immunofluorescence (DIF) revealed IgG deposits in the basal membrana and intercellular parts of the basal stratum. Discussion: Histopathology reveals subepidermal blisters of eosinophil dominance, and direct immunofluorescence (DIF) examination reveals IgG autoantibody deposit dominance, verifying the diagnosis of juvenile bullous pemphigoid. Given that BP180 (BPAG2) is one of the autoantigens involved, there may be similarities between the histology and clinical presentation of Bullous pemphigoid (BP) and CBDC. Conclusion: Autoimmune bullous diseases are difficult to differentiate clinically, histological studies and direct immunofluorescence are necessary to make a diagnosis.

Quantifying the clinical and economic burden of desquamating dermatological conditions: Implications for a supraregional burns centre

IntroductionThis study sought to identify the spectrum of desquamating skin diseases referred for tertiary burns care and quantify the care requirements and expense associated with caring for these patients within the burns service. MethodsPatient records were identified with non-burn induced skin loss between 2016 and 2022. Data was extracted from inpatient records, operative notes, dressing clinic records. A cost analysis was conducted using figures from the National Schedule of National Health Service Costs and our own unit-specific costs. Results20 patients were identified, with a median age of 46.5 and median TBSA of 30%. The mean length of stay was 21.2 days with 8/20 patients requiring intensive care. Overall mortality was 30%, rising to 50% if patients required ITU admission. Patients had a mean of 1.5 procedures under general anaesthesia and a mean operative time of 169minutes per patient. Post-operatively, a mean of 8.3 dressing changes were required per patient (range 1-21). 75% of patients were referred as suspected toxic epidermal necrolysis syndrome (TENS) yet, only 32% of patients histologically had TENS (32%), with linear IgA disease, pemphigus vulgaris, and bullous lupus comprising the other diagnoses. Cost analysis predicted a total cost to the unit of £1,422,106. ConclusionDesquamating dermatological diseases are life-threatening conditions with exhaustive care requirements. Our experiences highlight the importance of awareness of the range of desquamating skin conditions beyond TENS to enable optimum management, and the need to ensure adequate financial provisions to accommodate the care requirements mandated by these patients.