Linear IgA Research Articles

Epidermolysis bullosa acquisita: A comprehensive review

Epidermolysis bullosa acquisita is a rare autoimmune blistering disease which results in vesicle and bullae formation on the skin and erosions on the mucous membranes. EBA is mediated by autoantibodies to collagen VII. Clinically, it can present with numerous phenotypes, though the most common are the mechanobullous and inflammatory variants. Patients with mechanobullous EBA develop non-inflammatory bullae and erosions at sites of trauma while patients with the non-mechanobullous type develop inflammatory lesions which often mimic other blistering conditions including bullous pemphigoid, linear IgA bullous disease, and mucous membrane pemphigoid. Diagnosis is established by having a consistent clinical presentation, DIF, and autoantibodies against collagen VII. In apparent "seronegative" patients, the diagnosis is challenging due to the need for confirmatory tests which are often not routinely accessible outside of the specialized center. In light of EBA's rarity, and lack of any randomized controlled trials, treatment guidelines rely on the small case series presented in the literature. There has been variable success utilizing the arsenal of immunosuppressants and biologics. Development of experimental murine models has facilitated a deeper understanding of EBA's pathogenesis and allows for preclinical testing of numerous novel drug targets predominantly targeting inhibition of neutrophil activation. We herein review the presentation, diagnosis, treatments, and future avenues of research in EBA.

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

BackgroundLinear 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.MethodsA retrospective review of 38 LABD patients, followed-up from November 2006 to September 2018, was performed.ResultsOf 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%).ConclusionsOur 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.

Mucous membrane pemphigoid and oral blistering diseases.

The autoimmune blistering disorders present with variable frequency in the oral cavity. Recognition of their key clinical features at presentation is important, as there are many causes of oral ulceration. Careful history-taking, clinical examination, an understanding of pathogenesis and appropriate investigations are essential. With the exception of the rare genodermatoses that may lead to blistering and oral ulceration, the majority of patients have an acquired disorder. These include the rare autoimmune blistering diseases mucous membrane pemphigoid (MMP), pemphigus vulgaris (PV), linear IgA disease, epidermolysis bullosa acquisita and paraneoplastic pemphigus. Important clinical differential diagnoses include erythema multiforme, which may be mistaken for PV in appearance, while oral lichen planus may be indistinguishable from MMP. Angina bullosa haemorrhagica may also present with tense haemorrhagic bullae, and in the absence of diagnostic tests, requires an astute clinical diagnosis based upon the history. Newer laboratory techniques have facilitated identification of target antigens and epitopes in the autoimmune blistering diseases, particularly in MMP. Current interest is in whether these relate to clinical presentation and outcomes. There have also been recent investigations into the use of saliva as an alternative medium to serum for the diagnosis of oral vesiculobullous lesions. Assessment of disease severity and measurement of quality of life at presentation and subsequent follow-up is paramount to interpreting therapeutic response. Furthermore, combining these scores with serological and/or salivary biomarkers is valuable in the assessment of clinical response. In this paper, we discuss MMP and its important differential diagnoses.

Oral autoimmune vesicobullous diseases: Classification, clinical presentations, molecular mechanisms, diagnostic algorithms, and management.

Mucocutaneous blistering autoimmune diseases are a group of systemic, rare, chronic disorders characterized by humoral-mediated immunologic mechanisms against epithelial, basement membrane, and subepithelial tissues. Morbidity and mortality can be completely different among these diseases, with outcome being dependent on an early and accurate diagnosis, systemic comorbidities, and the patient's response to treatment. Definitive diagnosis is based on clinical and histopathologic findings. Because clinical presentations among these diseases are often similar, different immunofluorescence tests and ELISAs are used to confirm the specific diagnosis. Oral mucosa may often be the first site of clinical manifestation from which the disease spreads to other mucosal surfaces and skin. Thus, often dentists and oral medicine specialists may be the first to encounter patients with such diseases. In this review we discuss the most frequent autoimmune vesicobullous disorders, namely pemphigus vulgaris, mucous membrane pemphigoid, bullous pemphigoid, and linear IgA disease.

Linear IgA bullous dermatosis

Linear IgA bullous dermatosis is arare 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.

Bullous Systemic Lupus Erythematosus and Membranous Lupus Nephritis in a Filipino Child

Bullous eruptions are rare cutaneous manifestations of systemic lupus erythematosus. We report a case of an 8-year old Filipino girl with vesiculobullous systemic lupus erythematosus (SLE) and membranous lupus nephritis on kidney biopsy who presented with clinical nephrotic features of generalized edema, proteinuria, hypoalbuminemia and hyperlipidemia. The 2012 Systemic Lupus International Collaborating Clinics (SLICC) classification criteria for SLE were met. Immunohistopathologic examination of the skin lesion revealed a sub-epidermal split with neutrophilic infiltrates along the dermo-epidermal junction, moderate perivascular, periadnexal and interstitial infiltrates composed of predominantly neutrophils with neutrophilic dusts, lymphocytes, plasma cells, rare eosinophils and increased dermal mucin. Direct immunofluorescence showed strong continuous linear IgG deposits along the basement membrane and weak linear IgM and IgA deposition along the basement membrane zone (BMZ). To our knowledge, this is the first report of vesiculobullous SLE in a Filipino child. This case is a rare form of cutaneous lupus in children. Bullous SLE (BSLE) should be considered in the differential diagnosis of children presenting with generalized bullous eruptions.

Evaluation of the value of indirect immunofluorescence on different substrates in the diagnosis of autoimmune subepidermal bullous diseases

Objective To evaluate the value of indirect immunofluorescence (IIF) on three different substrates including normal human skin (NS) , monkey esophagus (ME) and salt-split human skin (SS) in the diagnosis of autoimmune subepidermal bullous diseases. Methods A total of 56 patients with autoimmune subepidermal bullous diseases, including 47 with bullous pemphigoid (BP) , 6 with epidermolysis bullosa acquisita (EBA) , 2 with linear IgA bullous dermatosis, and 1 with anti-P200 pemphigoid, were diagnosed in and enrolled from Department of Dermatology, Institute of Dermatology, Chinese Academy of Medical Sciences between January 2015 and December 2016. Seventy patients with pemphigus, 15 patients with chronic eczema and 15 healthy adults served as controls. Blood samples collected from these patients and controls were subjected to IIF on three different substrates including NS, ME and SS, and the fluorescence deposition was observed. The sensitivities and specificities of IIF in the diagnosis of different subepidermal bullous diseases were compared. Statistical analysis was carried out with SPSS 13.0 software by using chi-square test for the comparison of enumeration data. Results IIF on NS or ME in the serum of patients with BP showed linear deposition of fluorescent material along the basement membrane zone. IIF on SS showed linear deposition of fluorescent material in the epidermis in the patients with BP, but in the dermis in the patients with EBA and anti-P200 pemphigoid. The sensitivities of IIF on NS, ME or SS in the diagnosis of subepidermal bullous diseases were 73.2%, 60.7% and 94.6% respectively, and the specificities were 98.0%, 100% and 97.1% respectively. There were significant differences among the sensitivities (χ2 = 18.2, P 0.05) . The diagnostic sensitivity of IIF on SS was significantly higher than that of IIF on NS or ME (χ2 = 8.0, 16.7, both P < 0.05) . Conclusion In the diagnosis of autoimmune subepidermal bullous diseases, IIF on SS is superior to IIF on ME or NS. Key words: Fluorescent antibody technique, indirect; Pemphigoid, bullous; Autoimmune subepidermal bullous disease; Diagnosis; Sensitivity; Specificity

BP180-related autoimmune blistering diseases

BP180-related autoimmune blistering diseases include bullous pemphigoid, lichen planus pemphigoides, linear IgA bullous dermatosis, pemphigoid gestationis and cicatricial pemphigoid. There are multiple autoantibody-reactive sites on the extracellular region of BP180. Current studies show that there is heterogeneity in the autoimmune blistering disease-related target sites on BP180, and different clinical manifestations of the same disease are related to the heterogeneity of target sites. However, further studies and analysis are still needed for the mechanism of the heterogeneity. Key words: Pemphigoid, bullous; Pemphigoid gestationis; Pemphigoid, benign mucous membrane; Linear IgA bullous dermatosis; BP180

Consensus on the treatment of autoimmune bullous dermatoses: dermatitis herpetiformis and linear IgA bullous dermatosis - Brazilian Society of Dermatology.

Dermatitis herpetiformis and linear IgA bullous dermatosis are autoimmune diseases that present with pruritic urticarial papules and plaques, with formation of vesicles and blisters of subepidermal location, mediated by IgA antibodies. Mucosal lesions are present only in linear IgA bullous dermatosis. The elaboration of this consensus consisted of a brief presentation of the different aspects of these dermatoses and, above all, of an updated literature review on the various therapeutic options that were discussed and compared with the authors’ experience, aiming at the treatment orientation of these diseases in Brazil. Dermatitis herpetiformis is a cutaneous manifestation of celiac disease, and can be controlled with a gluten-free diet and dapsone. On the other hand, linear IgA bullous dermatosis arises spontaneously or is triggered by drugs, and can be controlled with dapsone, but often requires the association of systemic corticosteroids and eventually immunosuppressants.

Linear IgA bullous dermatosis: case report

Linear IgA bullous dermatosis: case report

Unilateral vancomycin-induced linear IgA bullous dermatosis

Unilateral vancomycin-induced linear IgA bullous dermatosis

Childhood sclerosing cholangitis associations in a Tunisian tertiary care hospital: a many-faceted disease.

Tfifha M, Kamoun T, Mama N, Mestiri S, Hassayoun S, Zouari N, Jemni H, Abroug S. Childhood sclerosing cholangitis associations in a Tunisian tertiary care hospital: a many-faceted disease. Turk J Pediatr 2019; 61: 905-914. Sclerosing cholangitis (SC) is a liver disorder affecting children and adults, causing chronic cholestasis and secondary biliary cirrhosis. The purpose of this study was to present different associated diseases to SC in a Tunisian tertiary care hospital. Six patients were identified with SC associated with other diseases, four males and two females. The first symptom was liver enlargement in all cases with abnormal liver biochemistry. A moderate increase in AST and ALT levels was registered in all cases with moderate cholestasis in 4 patients. Three of them presented an auto-immune condition. Two patients were diagnosed with auto-immune hepatitis prior to SC and Crohn disease in only one patient. One developed linear IgA bullous dermatosis. Three patients were diagnosed with Multisystemic Langerhans Cell Histiocytosis (LCH). The primary site of LCH was the liver associated secondary to insipidus diabetes (one case), mastoiditis (two cases) and chest localization (one case). The outcome of those patients was variable with poor prognosis especially for SC secondary to LCH. No patient underwent liver transplantation. SC is a rare disorder with variable clinical presentations. To our knowledge, this is the first report of this condition in Tunisian and North African children. Diagnosis and treatment of SC and its associations remains a challenge, especially because there is still no effective medical therapy aimed at preventing disease progression. Pediatric liver transplantation is the only life-extending therapeutic alternative for patients with end-stage liver failure. Liver transplantation has not been performed on young children in our country.

A Case of Linear IgA Bullous Dermatosis Developed after Administration of Vancomycin Hydrochloride

A Case of Linear IgA Bullous Dermatosis Developed after Administration of Vancomycin Hydrochloride

Linear IgA bullous dermatosis

Aim: to present a clinical case of linear IgA bullous dermatosis.Materials and methods. A 44 years old patient complaining of skin rashes on the trunk and extremities, accompanied by severe itching was examined. We carried out a morphological investigation of biopsy samples derived from the lesion and apparently unaffected skin areas using the method of indirect immunofluorescence.Results. The patient having rashes in the form of multiple vesicles and small bubbles with a tight cover, which had been grouped into figures resembling pearl necklaces, demonstrated the presence of focal subepidermal cracks (subepidermal bubble in one location), as well as a linear deposition of IgA along the epidermal basement membrane. According to the clinical picture and following the histological and immunofluorescent investigation of skin biopsies, the patient was diagnosed with linear IgA bullous dermatosis. Lesion regression was achieved as a result of systemic therapy with prednisolone at a dose of 50 mg per day.Conclusion. The diagnosis of linear IgA bullous dermatosis should be made on the basis of skin biopsy investigation by the method of indirect immunofluorescence. Systemic glucocorticosteroids are seen as an effective approach to the treatment of such patients.

Linear IgA bullous dermatosis in a child successfully responding to oral antibiotics

Linear IgA bullous dermatosis in a child successfully responding to oral antibiotics

Rash induced by enteral vancomycin therapy in an older patient in a long-term care ventilator unit: case report and review of the literature

BackgroundOral vancomycin is a first-line treatment for severe Clostridium difficile colitis. Oral vancomycin is perceived to lack systemic absorption or systemic adverse effects; however, a few cases of hypersensitivity to oral vancomycin have been reported, all in hospitalized patients.Case presentationIn the present case, a 66-year-old woman with end-stage neurodegenerative disease residing in a long-term care facility developed a maculopapular rash following treatment with enteral vancomycin for recurrent C. difficile colitis. The rash resolved after withdrawal of the drug.ConclusionRashes associated with oral vancomycin treatment include maculopapular rash, urticaria, red man syndrome, and linear IgA bullous dermatitis. Risk factors for systemic vancomycin absorption include renal insufficiency, severe intestinal inflammation, and high vancomycin dose and duration. Routine serum testing of vancomycin levels, even in these high risk cases, is not recommended. Clinicians should be aware that enteral vancomycin can cause hypersensitivity reactions which may be serious.

Linear IgA Disease and Celiac Disease: Are They Mutually Exclusive?

Adult Linear IgA disease or linear IgA bullous dermatoses(LABD) is a idiopathic or drug-induced autoimmune blistering disease characterized by the linear deposition of IgA at the dermoepidermal junction. Only 0.5 to 2.3 cases of Linear IgA are estimated to be reported each year. Although the clinical features of this disorder can be difficult to distinguish from dermatitis herpetiformis, the distinct immunopathologic findings in LABD and the absence of an associated gluten-sensitive enteropathy has historically confirmed the status of LABD as a distinct disease. We present a case of a patient with LABD with a concomitant high-gluten sensitivity. A 42 year-old women with a history of recurrent gastric ulcers presented with skin blisters. The patient stated she also has noticed that she is very sensitive to wheat containing products including cleaning supplies and shampoos. Upon examination, a clinical diagnosis of dermatitis herpetiformis was made. An upper endoscopy was performed which was positive for gastric ulcers. On duodenal biopsies, histology showed increased intraepithelial lymphocytes with villous blunting. On biochemical testing the patient was found to have an iron deficient anemia with no elevated levels of IgA in her serum. Transglutaminase Antibody IgA Titers were > 250.0, gliadin deamidated Ab, IgG and IgA were both elevated. A skin biopsy was performed which showed linear deposits of IgA seen at the dermo-epidermal junction. Treatment was initiated with dapsone therapy in which the patient was responsive over the course of treatment. This case illustrates a rare condition of LABD in a patient with concomitant celiac disease. This shows the importance of recognizing that a patient can present with linear IgA disease and continue to display strong gluten sensitivity. A high index of suspicion must be mainitained in patients with presumed celiac disease and dermatological manifestations who are not responding adequately to gluten free therapy.

Mucous Membrane Pemphigoid: A Rare Cause of Dysphagia

A 74 year old female with a history of presumed bullous pemphigoid (BP), presented with a few cutaneous blisters, multiple oral blisters, odynophagia, dysphagia to solids and liquids and 2 days of spitting blood. An upper endoscopy (EGD) showed severe inflammation, denuded and blistering esophageal mucosa that easily bled on contact that involved the entire esophagus. Biopsies were not performed but there was high suspicion that this was esophageal involvement with BP. The patient was started on pantoprazole twice daily, liquid carafate, viscous lidocaine and later was started on prednisone and mycophenolate. Two months later the patient reported resolution of her odynophagia but continued to have dysphagia and poor oral intake. Repeat EGD showed marked improvement of the esophagus but she continued to have friable esophageal tissue that bled on contact and scar formation. Biopsies revealed benign squamous mucosa, no evidence of infectious organisms, dysplasia or malignancy. Due to the scar formation in the esophagus and the extensive mucosal involvement we concluded the patient had mucous membrane pemphigoid (MMP) rather than bullous pemphigoid. Due to worsening nutritional status a dobhoff tube was placed for nutrition. The patient unfortunately died from cardiac arrest.MMP is a rare, 2 cases per million, auto-immune relapsing and remitting inflammation of the mucosa that leads to chronic subepithelial blistering, mucosal fibrosis and scarring of healed lesions which distinguishes it from BP which usually heals without scar formation. MMP is characterized by inflamed and eroded mucosa but can also have blistering lesions of the skin while BP is characteristic lesion are tense bullae and rarely effects mucous membranes. In a study of 457 cases of MMP only 4% affected the esophageal mucosa. MMP is diagnosed by the gold standard of direct immunofluorescence with linear IgG or IgA or C3 staining along the basement membrane. Goal of treatment is to decrease blister formation and promote healing which is accomplished with glucorticoids, immune-suppressants, like mycophenolate and acid suppression. As mucosal lesions heal and scar formation takes place strictures often form and require esophageal dilation. Disease progression can be chronic and life threatening if it effects mucous membranes of the airways. MMP is associated with an increased risk for malignancy-associated laminin 332 lymphoma.1712_A Figure 1. Esophageal Denuding and Blistering due to Mucous Membrane Pemphigoid.1712_B Figure 2. Esophageal Scarring after Mucous Membrane Pemphigoid.

Linear IgA dermatosis in a 7 year old child

Linear IgA dermatosis in a 7 year old child

Chronic bullous disease of childhood: A rare case report

Chronic bullous disease of childhood: A rare case report