Pemphigoid diseases: Insights in the nonbullous variant and disease management

Bullous pemphigoid (BP) is a bullous skin disease, mainly occurring at old age. It is characterized by pruritus and blisters on the skin. The disease is caused by an autoimmune response against structural skin proteins BP180 and BP230, causing the epidermis and dermis to split, and thereby blisters to form. Nonbullous pemphigoid (NBP) is a variant of BP that presents with pruritus, but without typical skin blisters. It is unknown why blisters are absent in NBP. In this thesis, we aimed to learn more about the clinical and immunological features of NBP. We noticed that NBP can present with different skin lesions. Red papules and nodules were seen most common. On average, NBP patients were diagnosed after 23 months. The prevalence of pemphigoid in the nursing home population was 6%, and four elderly individuals with pruritus were newly diagnosed with NBP. Interestingly, a low dose of methotrexate was an effective treatment for NBP. Beside these clinical findings, we studied the underlying disease mechanism of NBP. In NBP, immunological reactivity against the BP230 protein was more common than to BP180, while in BP a response against BP180 was more often found. We also studied the presence of IgE antibodies against BP180 and BP230 in the serum and skin of BP and NBP patients, but found no differences. In conclusion, NBP can be a cause of pruritus at old age, and deserves more attention among physicians. Moreover, future research should focus on the underlying disease mechanism of NBP, to explain why blisters are absent

Pemphigoid diseases affecting the skin

Pemphigoid diseases are a heterogeneous group of subepidermal autoimmune blistering diseases (sAIBD) that are characterized by autoantibodies against different structural proteins of hemidesmosomes in the epidermal basement membrane zone (EBMZ). The group of pemphigoid diseases affecting the skin include various subtypes, such as bullous pemphigoid (BP), nonbullous pemphigoid (NBP), Brunsting-Perry cicatricial pemphigoid, lichen planus pemphigoides (LPP), pemphigoid gestationis (PG), and anti-p200 pemphigoid. Classification of sAIBD subtypes is mainly based on target antigens and/or clinical manifestations. Pathogenesis of pemphigoid diseases is mediated by predominantly IgG autoantibodies against different structural proteins in the EBMZ. Diagnosis is based on a combination of clinical features, an n-serrated linear pattern of immunodepositions along the EBMZ in direct immunofluorescence microscopy and immunoserology. BP is the most common subtype and most frequently affects elderly, the incidence of BP increased substantially in the past decades. The clinical manifestations of pemphigoid diseases are heterogeneous and represent a clinical spectrum. The typical presentation of BP is a severe pruritus with a predominantly cutaneous lesions consisting of tense blisters or vesicles, erythema and urticarial plaques. In NBP blistering is absent, while the pruritus is severe, and erythematous papules, plaques and excoriations may mimick other inflammatory dermatoses. Recommended therapies consists of whole-body application of superpotent topical corticosteroids, or systemic treatment with immunosuppressive or -modulating drugs.</p

Non-bullous Lichen Planus Pemphigoides:A Case Report

is missing (Short communication)

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

A lethal blistering autoimmune disease

Dermatomyositis is an autoimmune disease characterized by chronic inflammation of skin and muscle. Anti-melanoma differentiation-associated gene 5 (MDA5) associated dermatomyositis is a recently described variant that displays a unique dermatological phenotype consisting of punched-out cutaneous ulcers, palmar erythema, papules or blisters at typical sites of dermatomyositis. Moreover, anti-MDA5 associated dermatomyositis patients have an increased risk to develop a rapidly progressive interstitial lung disease with a potentially fatal course. Cutaneous ulcers are an important predictor for the development of interstitial lung disease. We report an illustrative case of anti-MDA5 associated dermatomyositis.</p

A lethal blistering autoimmune disease

Dermatomyositis is an autoimmune disease characterized by chronic inflammation of skin and muscle. Anti-melanoma differentiation-associated gene 5 (MDA5) associated dermatomyositis is a recently described variant that displays a unique dermatological phenotype consisting of punched-out cutaneous ulcers, palmar erythema, papules or blisters at typical sites of dermatomyositis. Moreover, anti-MDA5 associated dermatomyositis patients have an increased risk to develop a rapidly progressive interstitial lung disease with a potentially fatal course. Cutaneous ulcers are an important predictor for the development of interstitial lung disease. We report an illustrative case of anti-MDA5 associated dermatomyositis.</p

A lethal blistering autoimmune disease

Dermatomyositis is an autoimmune disease characterized by chronic inflammation of skin and muscle. Anti-melanoma differentiation-associated gene 5 (MDA5) associated dermatomyositis is a recently described variant that displays a unique dermatological phenotype consisting of punched-out cutaneous ulcers, palmar erythema, papules or blisters at typical sites of dermatomyositis. Moreover, anti-MDA5 associated dermatomyositis patients have an increased risk to develop a rapidly progressive interstitial lung disease with a potentially fatal course. Cutaneous ulcers are an important predictor for the development of interstitial lung disease. We report an illustrative case of anti-MDA5 associated dermatomyositis.</p

Oral Lesions in Autoimmune Bullous Diseases:An Overview of Clinical Characteristics and Diagnostic Algorithm

Autoimmune bullous diseases are a group of chronic inflammatory disorders caused by autoantibodies targeted against structural proteins of the desmosomal and hemidesmosomal plaques in the skin and mucosa, leading to intra-epithelial or subepithelial blistering. The oral mucosa is frequently affected in these diseases, in particular, in mucous membrane pemphigoid, pemphigus vulgaris, and paraneoplastic pemphigus. The clinical symptoms are heterogeneous and may present with erythema, blisters, erosions, and ulcers localized anywhere on the oral mucosa, and lead to severe complaints for the patients including pain, dysphagia, and foetor. Therefore, a quick and proper diagnosis with adequate treatment is needed. Clinical presentations of autoimmune bullous diseases often overlap and diagnosis cannot be made based on clinical features alone. Immunodiagnostic tests are of great importance in differentiating between the different diseases. Direct immunofluorescence microscopy shows depositions of autoantibodies along the epithelial basement membrane zone in mucous membrane pemphigoid subtypes, or depositions on the epithelial cell surface in pemphigus variants. Additional immunoserological tests are useful to discriminate between the different subtypes of pemphigoid, and are essential to differentiate between pemphigus and paraneoplastic pemphigus. This review gives an overview of the clinical characteristics of oral lesions and the diagnostic procedures in autoimmune blistering diseases, and provides a diagnostic algorithm for daily practice.</p

A lethal blistering autoimmune disease

Dermatomyositis is an autoimmune disease characterized by chronic inflammation of skin and muscle. Anti-melanoma differentiation-associated gene 5 (MDA5) associated dermatomyositis is a recently described variant that displays a unique dermatological phenotype consisting of punched-out cutaneous ulcers, palmar erythema, papules or blisters at typical sites of dermatomyositis. Moreover, anti-MDA5 associated dermatomyositis patients have an increased risk to develop a rapidly progressive interstitial lung disease with a potentially fatal course. Cutaneous ulcers are an important predictor for the development of interstitial lung disease. We report an illustrative case of anti-MDA5 associated dermatomyositis.</p