Successful Treatment of Linear IgA Disease and Ulcerative Colitis With Sulfasalazine.

Linear IgA disease (LAD) is an uncommon autoimmune blistering disease that has been associated with medications, malignancy, and other autoimmune diseases, such as ulcerative colitis (UC). In this case report, a patient with a history of UC developed characteristic LAD lesions. While dapsone is considered first-line therapy for LAD, the treatment team opted for an underutilized, plausibly less toxic, and more simplified treatment regimen with sulfasalazine, successfully utilizing the two distinct actions of sulfasalazine's components - sulfapyridine and 5-aminosalicylate (5-ASA) - to concurrently treat both the LAD and UC symptoms. The authors discuss the pathophysiology of LAD and UC and expound on the mechanistic theory of their association. Additionally, the pharmacodynamics of sulfasalazine and considerations of its side effect profile are examined.

Refractory Bullous Systemic Lupus Erythematosus Successfully Treated with Rituximab: A Case Report and Literature Review.

Bullous systemic lupus erythematosus (BSLE) is a rare blistering skin manifestation of systemic lupus erythematosus (SLE). Dapsone is reported to be helpful in mild-to-moderate BSLE cases; however, its use may be limited or prohibited due to particular complications such as drug hypersensitivity, dose-dependent hemolytic anemia, and other significant hematologic abnormalities. Rituximab, an anti-CD20 monoclonal antibody, has been reported with off-label use in BSLE patients, but data are still limited. Hence, our objective is to explore the efficacy of rituximab among these patients. Herein, we report a 21-year-old Thai woman presented with blistering eruption on the oral cavity, scalp, trunk, and extremities for 1 month. The investigations revealed a positive direct Coomb's test, an elevated erythrocyte sedimentation rate (ESR), and a positive antinuclear antibody (ANA). Skin biopsy showed focal interface dermatitis. Direct immunofluorescence (DIF) illustrated mixed linear and granular deposition of immunoglobulin (Ig)G, IgM, IgA, and C3 along the dermo-epidermal junction (DEJ). Enzyme-linked immunosorbent assay (ELISA) showed circulating antibodies to type VII collagen. She was diagnosed with severe BSLE and autoimmune hemolytic anemia (AIHA) refractory to several oral immunosuppressants but was successfully treated with rituximab. The authors also performed a review of the literature on prior BSLE cases managed with rituximab.

Structural proteins of the dermal-epidermal junction targeted by autoantibodies in pemphigoid diseases.

The dermal-epidermal junction consists of a network of several interacting structural proteins that strengthen adhesion and mediate signalling events. This structural network consists of hemidesmosomal-anchoring filament complexes connecting the basal keratinocytes to the basement membrane. The anchoring filaments in turn interact with the anchoring fibrils to attach the basement membrane to the underlying dermis. Several of these structural proteins are recognized by autoantibodies in pemphigoid diseases, a heterogeneous group of clinically and immunopathologically diverse entities. Targeted proteins include the two intracellular plakins, plectin isoform 1a and BP230 (also called bullous pemphigoid antigen (BPAG) 1 isoform e (BPAG1e)). Plectin 1a and BP230 are connected to the intermediate filaments and to the cell surface receptor α6ß4 integrin, which in turn is connected to laminin 332, a component of the anchoring filaments. Further essential adhesion proteins are BP180, a transmembrane protein, laminin γ1 and type VII collagen. Latter protein is the major constituent of the anchoring fibrils. Mutations in the corresponding genes of these adhesion molecules lead to inherited epidermolysis bullosa emphasizing the importance of these proteins for the integrity of the dermal-epidermal junction. This review will provide an overview on the structure and function of the proteins situated in the dermal-epidermal junction targeted by autoantibodies.

[Generalized circumscribed scleroderma with blisters]. / Generalisierte zirkumskripte Sklerodermie mit Blasenbildung.

The patient suffered from a 20-year course of generalized circumscribed scleroderma and presented with blisters in circumscribed areas of the affected skin. The development of subepidermal blisters has been described in all clinical forms of circumscribed scleroderma. Aetiology and pathogenesis of blister formation have not yet been clarified. An obstruction of the lymphatic vessels due to the present sclerosis is favoured. Treatment of bullous circumscribed scleroderma is considered to be difficult. Oral steroids, methotrexate, hydroxychloroquine and PUVA methods have been used with varying success.

Autoantibodies Against Multiple Epitopes in Bp180 and Laminin Gamma-1 in Subepidermal Blistering Skin Disease Associated with Psoriatic Erythroderma.

We report a 79-year-old Japanese man who developed subepidermal blistering skin disease after an 8-year history of psoriasis. Histology of a bullous lesion revealed a subepidermal blister with a mixed inflammatory cell infiltrate and fibrin nets. Indirect immunofluorescence using normal human skin sections revealed IgG and IgA autoantibodies in the patient serum, which bound to the epidermal side of 1M NaCl-split skin sections. Immunoblot analysis revealed that both IgA and IgG antibodies reacted with the BP180 NC16a domain and the 120-kDa LAD-1 and that IgG antibodies also reacted with the BP180 C-terminal domain and laminin gamma-1. These findings indicated that autoantibodies to laminin gamma-1 and multiple epitopes in BP180 ectodomain played a role in the pathogenesis of this unique autoimmune subepidermal blistering skin disease associated with psoriasis.

Anti-p200 pemphigoid.

Anti-p200 pemphigoid is a rare subepidermal blistering skin disease. Patients' autoantibodies label the dermal side of 1 mol/L NaCl-split human skin by indirect immunofluorescence microscopy and recognize a 200-kd protein by immunoblotting of human dermal extract. Clinically, anti-p200 pemphigoid is characterized by tense blisters and vesicles, erosions, and urticarial plaques, closely resembling bullous pemphigoid and the inflammatory variant of epidermolysis bullosa acquisita. Recently, 90% of anti-p200 pemphigoid sera were shown to recognize laminin γ1. The C-terminus of laminin γ1 was identified as an immunodominant region and in its recombinant form was used by immunoblotting and enzyme-linked immunosorbent assay for the serologic diagnosis of this disease. Subsequent ex vivo and in vivo studies were, however, unable to show pathogenic activity of antilaminin γ1 antibodies. Both patients' sera and sera depleted from antilaminin γ1 antibodies induced subepidermal splitting in an ex vivo model of autoantibody-mediated leukocyte-dependent neutrophil activation. Antilaminin γ1 antibodies appear to be useful biomarkers that will further facilitate the diagnosis of anti-p200 pemphigoid. The true identity of the pathogenetically relevant autoantigen of this disease, which may either be a yet unknown isoform of laminin γ1 or even another 200-kd protein of the dermoepidermal junction, still needs to be elucidated.

Collagen IV in Normal Skin and in Pathological Processes.

CONTEXT: Type IV collagen is a type of collagen found primarily in the skin within the basement membrane zone. The type IV collagen C4 domain at the C-terminus is not removed in post-translational processing, and the fibers are thus link head-to-head, rather than in a parallel fashion. Also, type IV collagen lacks a glycine in every third amino-acid residue necessary for the tight collagen helix. Thus, the overall collagen-IV conformation is structurally more pliable and kinked, relative to other collagen subtypes. These structural features allow collagen IV to form sheets, which is the primary structural form found in the cutaneous basal lamina. There are six human genes associated with collagen IV, specifically COL4A1, COL4A2, COL4A3, COL4A4, COL4A5 and COL4A6. The aim of this review is to highlight the significance of this protein in normal skin, and in selected diseases. RESULTS: The alpha 3 protein constituent of type IV collagen is thought to be the antigen implicated in Goodpasture's syndrome, wherein the immune system attacks the basement membranes of the renal glomeruli and pulmonary alveoli. In addition, mutations to the genes coding for type IV collagen lead to the Alport syndrome. Furthermore, autoantibodies directed against denatured human type IV collagen have been described in rheumatoid arthritis, scleroderma, and SLE. Structural studies of collagen IV have been utilized to differentiate between subepidermal blistering diseases, including bullous pemphigoid, acquired epidermolysis bullosa, anti-epiligrin cicatricial pemphigoid, and bullous lupus erythematosus. Collagen IV is also of importance in wound healing and in embryogenesis. CONCLUSIONS: Pathological studies have demonstrated that minor structural differences in collagen IV can lead to distinct, clinically different diseases.