Non-bullous Lichen Planus Pemphigoides: A Case Report.

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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.

Nonbullous pemphigoid: Insights in clinical and diagnostic findings, treatment responses, and prognosis.

BACKGROUND: Nonbullous pemphigoid is an under-recognized phenotype of the autoimmune bullous disease pemphigoid, characterized by the absence of blisters. Several disease aspects have not been studied previously. OBJECTIVE: To describe the characteristics of nonbullous pemphigoid. METHODS: A retrospective review study of medical records. The diagnosis of pemphigoid was based on meeting 2 of the following 3 criteria: (1) pruritus, (2) positive direct immunofluorescence microscopy, or (3) positive indirect immunofluorescence microscopy on salt-split skin. RESULTS: The review included 69 patients. The mean delay in diagnosis was 29 months. Skin examination most often showed pruritic papules/nodules (37%) or pruritus without primary skin lesions (22%). Histopathologic findings were mainly nonspecific. Results of direct and indirect immunofluorescence microscopy were positive in 60% and 69%, respectively. During follow-up, blisters formed in 17%, which was associated with a positive indirect immunofluorescence microscopy (P = .014) and a positive BP180 immunoblot result (P = .032). The Kaplan-Meier estimates of mortality at 1, 2, and 3 years were 14%, 34%, and 46%, respectively, with an 8.6-fold increased all-cause mortality risk. LIMITATIONS: The retrospective study design. CONCLUSIONS: Nonbullous pemphigoid presented with heterogeneous pruritic skin lesions, resulting in delayed diagnosis. Direct and indirect immunofluorescence microscopy are essential to diagnose nonbullous pemphigoid, in contrast to histopathology, mainly showing nonspecific findings. An increased all-cause mortality risk was observed during follow-up.

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.

Nonbullous pemphigoid: A systematic review.

BACKGROUND: Bullous pemphigoid is an autoimmune disease that typically presents with tense bullae and severe pruritus. However, bullae can be lacking, a subtype termed nonbullous pemphigoid. OBJECTIVE: To summarize the reported characteristics of nonbullous pemphigoid. METHODS: The EMBASE and MEDLINE databases were searched using "nonbullous pemphigoid" and various synonyms. Case reports and series describing nonbullous pemphigoid were included. RESULTS: The search identified 133 articles. After selection, 39 articles were included, presenting 132 cases. Erythematous, urticarial plaques (52.3%) and papules/nodules (20.5%) were the most reported clinical features. The mean age at presentation was 74.9 years. Histopathology was commonly nonspecific. Linear depositions of IgG and/or C3 along the basement membrane zone were found by direct immunofluorescence microscopy in 93.2%. Indirect immunofluorescence on salt-split skin was positive in 90.2%. The mean diagnostic delay was 22.6 months. A minority of patients (9.8%) developed bullae during the reported follow-up. LIMITATIONS: Results are mainly based on case reports and small case series. CONCLUSION: Nonbullous pemphigoid is an underdiagnosed variant of pemphigoid that most often does not evolve to bullous lesions and mimics other pruritic skin diseases. Greater awareness among physicians is needed to avoid delay in diagnosis.

Determining the Incidence of Pneumocystis Pneumonia in Patients With Autoimmune Blistering Diseases Not Receiving Routine Prophylaxis.

Importance: Pneumocystis pneumonia (PCP) is a potentially lethal opportunistic infection that primary prophylaxis can help prevent. The risk of prophylactic therapy must be weighed against the incidence of PCP in the patient population. Prophylaxis most frequently involves trimethoprim-sulfamethoxazole, with second-line therapies, including atovaquone, dapsone, and pentamide. The indication for prophylaxis in immunocompromised patients without HIV is less well defined. Previously, an incidence of at least 3.5% has been proposed as a cutoff to justify prophylaxis. Objective: To assess the incidence of PCP in patients with autoimmune blistering diseases receiving no routine prophylaxis. Design, Setting, and Participants: This was a retrospective analysis of patient medical records to determine the incidence of PCP infections. The multicenter study was performed at tertiary care centers that provide care for patients with autoimmune blistering disease in Germany, Italy, Singapore, Israel, and the Netherlands. Patients had a confirmed diagnosis of pemphigus vulgaris/foliaceus, bullous pemphigoid, epidermolysis bullosa acquisita, mucous membrane pemphigoid/cicatricial pemphigoid, or anti-p200 pemphigoid. Main Outcomes and Measures: To determine the incidence of PCP defined as patients with the International Classification of Diseases, Ninth Revision (ICD-9), code 136.3, for PCP, or free text documentation of PCP occurring based on characteristic radiographic findings with elevated lactate dehydrogenase, or hospitalization for pneumonia with bronchioalveolar lavage demonstrating Pneumocystis jiroveci on confirmatory stains. Results: A total of 801 patients with autoimmune blistering diseases were included in this study; their mean (SD) age was 66.5 (17.6) years, and a total of 465 (58%) were female. Only 1 patient developed PCP, resulting in an incidence rate of 0.1%. This incidence significantly fell below the recommended threshold of 3.5% (0.1% vs 3.5%, χ21 = 27.0; P < .001). This incidence was significantly lower than the previously reported incidence of PCP in all immunosuppressed dermatologic patients (0.1% vs 1.3%; χ21 = 8.2; P = .004). Conclusions and Relevance: Routine Pneumocystis prophylaxis for patients with autoimmune blistering diseases does not seem to be warranted. Patients with autoimmune blistering disease seem to have a lower risk of PCP than the general population of immunosuppressed dermatology patients. Risks of routine prophylaxis include hyperkalemia, hypoglycemia, photosensitivity, thrombocytopenia, and more rare adverse reactions.

[A child with a S-shaped skin condition on his abdomen]. / Een kind met een S-vormige huidafwijking op zijn romp.

A 14-year-old boy with a pruritic erythematous plaque on his abdomen along the lines of Blaschko, visited the dermatology outpatient clinic. Histopathology of a skin biopsy confirmed the clinical diagnosis linear cutaneous lupus erythematosus. We treated the patient with potent topical corticosteroids.