Linear IgA Research Articles

Association between the subepidermal autoimmune blistering diseases linear IgA disease and the pemphigoid group and inflammatory bowel disease: two case reports and literature review

We report two patients with subepidermal autoimmune blistering diseases and inflammatory bowel disease (IBD) [one with linear IgA disease (LAD) and ulcerative colitis (UC), and the other with mucous membrane pemphigoid (MMP) and Crohn disease (CD)], and present a review of all previously reported cases. We reviewed the literature, and found 48 cases of patients with autoimmune blistering diseases and IBD. The blistering diseases were LAD (25 patients), bullous pemphigoid (BP) (21), MMP (1) and pemphigoid gestationis (1), while the IBD types comprised UC (40) and CD (8). We describe the clinical and immunopathological features and demographic characteristics of the patients. In all but one case, the diagnosis of IBD predated the development of the skin condition. The association was more common with LAD than BP. The immunopathogenesis of IBD and autoimmune blistering diseases is discussed and a link between them hypothesized, namely, that the presentation of multiple antigens to the immune system during the unregulated inflammation in the bowel wall results in excitation of the immune system and recognition of autologous antigens.

Development of a method to detect anti-BP180NC16A IgG subclasses and the significance of anti-BP180NC16A IgG in bullous pemphigoid

Objective To develop an assay to quantitatively detect anti-BP180NC16A IgG subclasses and to assess the significance of anti-BP180NC16A lgG in bullous pemphigoid (BP).Methods The Glutathione S-transferase (GST)-BPI80NC16A fusion protein was expressed in E.coli system and purified by affinity chromatography.An improved enzyme-linked immunoabsorbent assay (ELISA) was developed and used to detect anti-BP180NCI6A IgG subclasses in serum samples from 10 patients with BP,5 patients with pemphigoid gestationis (PG),1 patient with linear IgA bullous dermatosis (LIBD) and 2 patients with pemphigus.Results The optimal condition for the ELISA was determined by cross assay as follows:the concentration of GSTBP180NC16A fusion protein for coating,500 μg/L; the condition for coating,4 ℃ for 12 hours; the dilution ratio of sera and secondary antibody,1∶ 100 and 1 ∶ 2000 respectively; the condition for incubation,37 ℃ for 1 hour;,the condition for the enzyme-substrate reaction,37 ℃ for 20 minutes.Of the 10 patients with BP,all were positive for anti-BP180NC16A IgG1,9 for IgG2,5 for IgG3,and 9 for IgG4.Anti-BP180NC16A IgG was undetected in any of the serum samples from 2 patients with pemphigus vulgaris or 1 patient with adult LIBD.All the 5 sera from patients with PG; were positive for all the anti-BP180NC16A IgG subclasses,which were predominated by IgGl and IgG3.Conclusion The developed ELISA is a highly specific and reproducible semiquantitative method for the detection of anti-BP180NCI6A IgG subclasses in patients with BP and PG. Key words: Pemphigoid,bullous; Immunoglobulin G; Enzyme-linked immunosorbent assay; AntiBP180NC16A

Linear Arrangement of Neutrophils Along the Basal Layer in Bullous Pemphigoid

Bullous pemphigoid is an inflammatory autoimmune subepidermal bullous disease with distinct immunohistological features. We report an unusual case of a 59-year-old woman with a bullous eruption whose lesional skin biopsy showed a subepidermal blister with a linear arrangement of neutrophils, mimicking linear IgA bullous dermatosis. However, direct immunofluorescence studies demonstrated IgG and C3 linear deposition along the basement membrane zone, compatible with bullous pemphigoid. We suggest that bullous pemphigoid should therefore be considered in the differential diagnosis of neutrophil-rich subepidermal bullous diseases along with dermatitis herpetiformis and linear IgA.

IgA vasculitis versus linear IgA bullous dermatosis, or is this a distinct immunologic disease characterized by IgA autoantibody directed against a shared antigen in the basement membrane zone and the vascular endothelium?

IgA vasculitis versus linear IgA bullous dermatosis, or is this a distinct immunologic disease characterized by IgA autoantibody directed against a shared antigen in the basement membrane zone and the vascular endothelium?

Amlodipine-induced linear IgA disease

A 58-year-old woman presented with a 3-week history of a pruritic rash, which had started a week after commencing treatment with amlodipine. On physical examination, large, well-demarcated erythematous plaques, surrounded by small clusters of clear vesicles, were seen on the patient's torso. Subepidermal blisters with neutrophils and eosinophils were seen in a skin biopsy, and direct immunofluorescence showed deposition of IgA along the basement membrane, in keeping with a diagnosis of linear IgA dermatosis (LAD). Amlodipine was discontinued, and the patient was started on prednisolone 30 mg, supplemented shortly afterwards by dapsone, which resulted in prompt resolution of the rash. Only a few cases of drug-induced LAD have been reported, mostly in association with vancomycin. To our knowledge, this is the first reported case precipitated by amlodipine.

Is “Drug-Induced” Linear IgA Bullous Dermatosis a Separate Entity?

In the 1970s, linear IgA bullous dermatosis (LABD) was first described and differentiated from bullous pemphigoid and dermatitis herpetiformis, which have some overlapping features. In the 1980s, the drug vancomycin was pointed to as a causative agent. Most vancomycin recipients also take many other agents, which calls into question its role in LABD. Fortuna and colleagues reviewed the English-language literature on drug-induced LABD published …

Chronic bullous disease of childhood with IgG predominance: What is the locus standi?

Linear IgA disease (LAD) is an acquired, autoimmune, subepidermal, blistering disease, characterized by linear deposition of IgA along the dermoepidermal junction on immunofluorescence. Some cases known as ‘mixed immunobullous disease’ show weak staining with other immune reactants like IgG, IgM or C3. We report a rare case of a child having typical manifestations of LAD (chronic bullous disease of childhood), but with IgG predominance rather than IgA. Obviously it is improper to term this as linear IgA disease. Such cases are reported in literature as variants of LAD, with a multitude of terms like mixed immune bullous disease, linear IgG / IgA disease, linear IgA / IgG disease, and so on. In view of the tremendous confusion that these multiple terms cause in the absence of any practical benefit, we propose that the broad term ‘chronic bullous disease of childhood’ be applied to all childhood cases, irrespective of the nature of the immune deposits.

Possible Dual Immunoreactivity for Laminin-332 and Type VII Collagen in a Case with Vancomycin-Induced Linear Iga Bullous Dermatosis Manifesting as Erythroderma

We report a unique case of vancomycin-induced linear IgA bullous dermatosis (LABD) presenting as erythroderma. Direct immunofluorescence showed a linear IgA deposition at the dermal side of the basement membrane zone (BMZ), and double immunostaining using patients’ skin as a substrate revealed that the in vivo IgA signal co-localized with laminin-332 and type VII collagen. Our case is the first documentation of vancomycin-induced LABD, in which the pathogenic IgA deposit would concomitantly recognize the two distinct antigens at the dermal BMZ.

Chronic Bullous Disease Of Childhood with IgG Predominance: What is the locus standi?

Chronic Bullous Disease Of Childhood with IgG Predominance: What is the locus standi?

Clinical Relevance of Autoantibodies in Patients with Autoimmune Bullous Dermatosis

The authors present their experience related to the diagnosis, treatment, and followup of 431 patients with bullous pemphigoid, 14 patients with juvenile bullous pemphigoid, and 273 patients with pemphigus. The detection of autoantibodies plays an outstanding role in the diagnosis and differential diagnosis. Paraneoplastic pemphigoid is suggested to be a distinct entity from the group of bullous pemphigoid in view of the linear C3 deposits along the basement membrane of the perilesional skin and the “ladder” configuration of autoantibodies demonstrated by western blot analysis. It is proposed that IgA pemphigoid should be differentiated from the linear IgA dermatoses. Immunosuppressive therapy is recommended in which the maintenance dose of corticosteroid is administered every second day, thereby reducing the side effects of the corticosteroids. Following the detection of IgA antibodies (IgA pemphigoid, linear IgA bullous dermatosis, and IgA pemphigus), diamino diphenyl sulfone (dapsone) therapy is preferred alone or in combination. The clinical relevance of autoantibodies in patients with autoimmune bullous dermatosis is stressed.

Linear IgA bullous dermatosis induced by ampicillin/sulbactam

Linear IgA bullous dermatosis induced by ampicillin/sulbactam

Evaluation of clinical and histopathologic/direct immunofluorescence diagnosis in autoimmune vesiculobullous dermatitis: utility of direct immunofluorescence

Autoimmune bullous diseases are heterogeneous diseases and the differentiation between the various bullous disease is important for treatment and prognosis. Direct immunofluorescence microscopy is still the gold standard in differentiating these diseases. Our aim was to determine the diagnostic accordance between clinical and histopathological/direct immunofluorescence diagnosis of patients with autoimmune vesicolulobullous skin diseases. A total of 197 cases with clinical diagnosis of vesiculobullous dermatitis was included in the study. The slides stained with H&E were retrospectively re-evaluated for histopathological diagnosis, and had already been evaluated with direct immunofluorescence microscopy. Data were analyzed using the Scientific Package for Social Sciences software. Results were evaluated using Kappa statistics. The clinical and histopathological/direct immunofluorescence accordance for cases ranged from 0% to 100% (Kappa value=0.29). The accordance was 58.8% in pemphigus vulgaris, 53.8% in pemphigus foliaceus, 37.9% in bullous pemphigoid and, 5.2% in dermatitis herpetiformis. Cases of limited numbers in our study were linear IgA bullous dermatitis in 2 cases, Grover's disease in 1 case, epidermolysis bullosa acquisata in 5 cases and, Hailey-Hailey disease in 1 case. The percentages of accordance in these cases were 50%, 100%, 40% and, 0%, respectively. The accordance was good in pemphigus vulgaris, pemphigus foliaceus and bullous pemphigoid, but low in dermatitis herpetiformis. Based on our results, we recommend direct immunofluorescence microscopy to be added to light microscopy for the definitive diagnosis of autoimmune blistering disease. Only light microscopic findings are not sufficient and direct immunofluorescence microscopy is the gold standard.

Immunofluorescence in Oral Pathology—Part II: Pathology and Immunofluorescent Patterns in Subepidermal Immunobullous Disorders

ABSTRACT The immunobullous disorders are a group of autoimmune diseases in which components of the epidermis and basement membrane zone are targeted, resulting in the formation of cutaneous and mucosal blisters. Based on the level of blistering, the autoimmune blistering diseases may be subdivided into intraepidermal and subepidermal. An exhaustive list of immunobullous disorders is beyond the scope of this review, but those involving oral mucosa are taken into consideration. One major group namely the subepidermal immunobullous diseases which includes bullous pemphigoid (BP), mucosal pemphigoid [cicatricial pemphigoid (CP) or (MMP)], epidermolysis bullosa acquisita (EBA) linear IgA bullous disease (LABD) are discussed in this section. The diagnosis of these diseases requires clinicopathological correlation; immunofluorescence methods provide a useful adjunct to light microscopy. These methods entail the use of fluorescein-linked antibodies to immunoglobulins, complement components, or other proteins either in the skin biopsy or sera. In continuation with part I, the immunofluorescence patterns in the above listed immunobullous disorders are reviewed in detail with a summary of pathogenesis and characteristic histopathological findings. How to cite this article Rao RS, Premalatha BR, Mysorekar V. Immunofluorescence in Oral Pathology—Part II: Pathology and Immunofluorescent Patterns in Subepidermal Immunobullous Disorders. World J Dent 2012;3(1):68-73.

A critical reappraisal of the current data on drug-induced linear immunoglobulin A bullous dermatosis: A real and separate nosological entity?

Linear IgA disease (LAD) has been associated with a variety of drugs over the past 30 years. To review current literature on all available cases of drug-induced LAD, in order to ascertain whether a close relationship is justified, so that it constitutes a real and separate nosological entity. The PubMed database was searched for all articles written in English related to drug-induced LAD published between January 1980 and December 2010. The literature review shows that at least 84 articles were published, describing a total of 103 patients. Of these articles, only 46, from 13 countries, were included in this analysis, with a total of 52 patients: 24 (46.2%) were believed to be induced by vancomycin and 28 (53.8%) by drugs other than vancomycin. Challenge-dechallenge-rechallenge testing protocol was performed on only 6 (11.5%) of 52 patients, of which only 5 showed a positive result, while the Naranjo algorithm was performed on only 2 of them (0.3%). The evidence of this review analysis is based only on case reports. No study on large samples of drug-induced LAD is currently available. The literature analysis reveals no strong scientific evidence to support the notion that some drugs have induced LAD; therefore in many reviewed cases, we must question whether drug-induced LAD is really the underlying entity. Further and thorough investigations using one of the available algorithms for adverse drug reaction are warranted.

Treatment of subepidermal immunobullous diseases

The subepidermal immunobullous diseases are a group of autoimmune blistering disorders of the skin and mucous membranes that share the common features of autoantibody deposition and blister formation at the dermal-epidermal junction or basement membrane. This group includes bullous pemphigoid, linear IgA disease, dermatitis herpetiformis, and epidermolysis bullosa acquisita, among others. Although these disorders share some common features, each disease is unique in its clinical presentation, histopathology, and immunofluorescence patterns, which allows for accurate diagnosis and disease-specific treatment strategy. Treatment of these disorders is complex and requires expert knowledge of disease pathogenesis. We review common treatment approaches for each of these disorders.

IgA Anti-p200 Pemphigoid

Anti-p200 pemphigoid is a rare autoimmune subepidermal blistering disorder. Clinically, it may resemble bullous pemphigoid, linear IgA bullous dermatosis, or dermatitis herpetiformis. Immunologically, anti-p200 pemphigoid is characterized by the development of IgG antibodies directed against a basement membrane zone protein with a molecular weight of 200 kDa. We report the first case, to our knowledge, of anti-p200 pemphigoid associated with IgA antibodies and having clinical features resembling pemphigus herpetiformis or dermatitis herpetiformis localized on traumatized areas. Histopathological examination of lesional skin showed dermal-epidermal separation and microabscesses composed of neutrophils in the dermal papillae. Direct immunofluorescence disclosed the presence exclusively of linear in vivo-bound IgA along the basement membrane zone. With the use of laser scanning confocal microscopy, in vivo-bound IgA was localized above collagen type IV and colocalized with laminin 332. Indirect immunofluorescence showed circulating IgA antibodies against basement membrane zone at a titer of 1:160 that reacted with the floor of an artificial blister of salt-split skin. Western immunoblot analysis using dermal extract confirmed the reactivity of circulating IgA antibodies with the 200-kDa antigen corresponding to laminin γ1; however, immunoblotting using recombinant protein of 107 amino acid C-terminus of laminin γ1 was negative for circulating IgA antibodies. Immunoelectron microscopy disclosed the reactivity of circulating IgA autoantibodies within the lower lamina lucida. To the best of our knowledge, this is the first case fulfilling the immunopathological criteria for anti-p200 pemphigoid associated with IgA antibodies and having unusual clinical features.

Treatment of Chronic Bullous Disease of Childhood

Chronic bullous disease of childhood (CBDC) is generally a self-limited disease of prepubescent children that resolves within months to years. However, as discussed in the previous issue of Dermatologic Clinics, the disease is associated with significant morbidity and usually requires systemic therapy. Treatment is aimed at controlling blistering while avoiding adverse reactions. There are several anecdotal reports of treatment options, but controlled or comparative studies are lacking. This article discusses the management options of CBDC in more detail.

Management of Linear IgA Disease

Linear immunoglobulin A (IgA) disease is an acquired autoimmune blistering disease of the skin and mucous membranes that runs a chronic course over 3 to 6 years before remitting. It typically presents with papulovesicles and blisters configured in an arcuate pattern on an urticated base, with 2 peaks of onset. The first peak is in young prepubescent children, called chronic bullous disease of childhood, and the second peak affects patients older than 60 years of age. In this article, the management of linear IgA in adults is considered.

Autoimmune bullous skin diseases. Part 1: Clinical manifestations

Autoimmune bullous skin diseases are characterized by autoantibodies against adhesion molecules of the skin. Pemphigus is a disorder with an intraepidermal loss of adhesion and is characterized by fragile blisters and erosions. Pemphigus vulgaris often shows extensive lesions of the oral mucosa, while pemphigus foliaceus is commonly restricted to cutaneous involvement with puff pastry-like scale formation. Paraneoplastic pemphigus is obligatorily associated with malignancies and often presents as hemorrhagic stomatitis with multiforme-like exanthems. IgA pemphigus typically presents with pustules and annular plaques but not with mucosal involvement. The clinical spectrum of the pemphigoids includes tense blisters, urticarial plaques, and prurigo- like eczematous lesions. Pemphigoid gestationis mostly occurs during the last trimester of pregnancy and mucous membrane pemphigoid primarily involves the oral mucosa and conjunctivae and leads to scarring. Linear IgA bullous dermatosis manifests with tense blisters in a "cluster of jewels"-like pattern in childhood and is more heterogeneous in adulthood. Classical epidermolysis bullosa acquisita shows extensive skin fragility. Dermatitis herpetiformis is associated with gluten-sensitive enteropathy and manifests clinically with severe itching and papulovesicles on the extensor surfaces of the extremities and the lumbosacral area. The intention of the review is to demonstrate the heterogeneous clinical spectrum of autoimmune bullous disorders.

Pemphigoid diseases: Pathogenesis, diagnosis, and treatment

Pemphigoid diseases (including bullous pemphigoid, mucous membrane pemphigoid, pemphigoid gestationis, linear IgA dermatosis, lichen planus pemphigoides, and anti-p200 pemphigoid) are a subgroup of autoimmune bullous skin diseases characterized by an autoantibody response toward structural components of the hemidesmosome resulting in subepidermal blistering. By the use of different in vitro systems and experimental animal models, the pathogenic relevance of these autoantibodies has been demonstrated. Recent advances in the understanding of autoantibody responses have led to novel diagnostic tools and a more differentiated therapeutic approach for these disorders. This review covers the most recent understanding of the pathophysiology, diagnosis, and treatment of this group of autoimmune diseases.