A case of anti-laminin γ1 (p200) pemphigoid developed after dipeptidyl peptidase-4 inhibitor administration.

A 73-year-old man with diabetes mellitus was referred to our department for ultraviolet treatment for erythematous skin lesions with itching. On dipeptidyl peptidase-4 inhibitor (DPP-4i) sitagliptin (Januvia®) for diabetes mellitus, the erythematous skin lesions appeared and spread to the whole body. At the initial visit, erythema multiforme-like skin lesions with crusts were observed on the trunk and extremities, and the patient was suspected to have drug eruption. Histopathology demonstrated eosinophilic infiltration in the superficial dermis and inflammatory cell infiltration in the epidermis. Sitagliptin was discontinued, and erythematous lesions improved with oral prednisolone. Thereafter the patient was treated with phototherapy and  betamethasone sodium phosphate infusion for residual prurigo. However, blistering skin lesions appeared 5 months later. Histopathological findings were subepidermal blisters with eosinophilic abscess, and bullous pemphigoid was suspected. CLEIAs for autoantibodies to desmoglein 1 (Dsg1), Dsg3 and BP180 were negative. Direct immunofluorescence showed linear depositions of immunoglobulin G (IgG) and C3 at the epidermal basement membrane zone, and indirect immunofluorescence detected IgG anti-epidermal basement membrane zone antibodies, reacting with the dermal side of 1M NaCl-split normal human skin. IgG antibodies reacted with 200 kDa laminin γ1 (p200) by immunoblotting using dermal extracts. These results indicated that this patient was diagnosed with anti-laminin γ1 (p200) pemphigoid developed after DPP-4i administration. Although reports of DPP-4i-related bullous pemphigoid have accumulated, cases of anti-laminin γ1 (p200) pemphigoid developed after DPP-4i administration are rarely reported.

Drug-aggravated Bullous Pemphigoid in a 47-year-old Asian Woman - A Case Report.

INTRODUCTION: Bullous pemphigoid is the most common chronic recurrent autoimmune subepidermal blistering disorder most prevalent in the geriatric population. It varies widely in clinical presentation ranging from tense bullae to intense generalized pruritus. It is immunologic in origin with the presence of IgG antibodies. CASE REPORT: A 47-year-old female presented to the hospital with complaints of blisters in the lower limbs, which she self managed with neem oil, after which the blisters occurred over the body. The patient also experienced blisters over both upper and lower limbs, gluteal region, painful generalized ulcers, necrotic patches, multiple erythematous blisters, ulcer erosions over bilateral legs and upper limbs with few lesions, which were foul-smelling and oozing. On the second day of admission, the patient's CRP and ESR levels were tested and the levels were 33.5 and 35 mm/hr, respectively. The patient was treated with an injection of meropenem 1 g three times daily, dexamethasone 4 mg once daily, and ofloxacin 400 mg once daily. On the third day of admission, the patient complained of leg swelling, and subsequently, D-Dimer levels were checked, which showed a value of 5,740 and was treated with an injection of enoxaparin 40 mg for the same throughout the course of the hospital stay A skin biopsy confirmed the diagnosis of bullous pemphigoid. The culture test showed the growth of Klebsiella pneumonia and Acinetobacter baumani, which were resistant to most of the antibiotics. The patient was managed appropriately with modalities including antibiotics, anti-inflammatory agents, immunosuppressants, multivitamins, fluids, and albumin. The patient responded well to the treatment without new lesions or fever spikes. There was the presence of necrotic patches of old lesions alone at the time of discharge. CONCLUSION: This case report was done with the purpose of presenting an exemplary case of bullous pemphigoid aggravated by the application of neem oil and emphasizing the inappropriate use of folk medicine in an autoimmune disease like bullous pemphigoid.

Case Report: Pemphigoid Nodularis-Five Patients With Many Years of Follow-Up and Review of the Literature.

Pemphigoid nodularis is a rare form of pemphigoid that joins the clinical picture of prurigo nodularis and the immunological features of bullous pemphigoid, which is therapeutically challenging. Here, we analyze five female patients with a long-lasting course of nodular pemphigoid in terms of clinical and immunological characteristics and therapy. All the patients fulfilled clinical and immunological criteria of nodular pemphigoid. We applied numerous techniques allowing the proper diagnosis: direct and indirect immunofluorescence, salt split skin, ELISA, BIOCHIP, and fluorescence overlay antigen mapping using laser scanning confocal microscopy. Our study showed that 4 of 5 patients fulfilled the clinical and immunological criteria of nodular bullous pemphigoid. Two out of 4 patients presented exclusively nodular lesions; in the other two patients, blisters and erythematous lesions preceded prurigo-like lesions by a few years. The remaining patient had clinical and immunological criteria of nodular mucous membrane pemphigoid, presenting oral erosions, scarring conjunctivitis, and numerous disseminated nodules on the skin. All the patients were treated with multiple medicines; however, it was observed that the use of clobetasol propionate on the entire body plus antidepressants best controlled the disease. Pemphigoid nodularis mainly occurs in elderly women. In cases with coexisting psychological problems, antidepressants should be considered as an important complementary therapy to the basic one with clobetasol propionate.

A case report of steroid-refractory bullous pemphigoid induced by immune checkpoint inhibitor therapy.

The widespread use of immune checkpoint inhibitors in several malignancies has revealed new immune-related adverse events. Bullous pemphigoid (BP) is an antibody-driven autoimmune disease characterized by skin inflammation and fluid-filled bullae. Herein, a 69-year-old man with lung squamous cell carcinoma developed multiple vesicles and tense bullae 3 weeks after the initiation of a programmed death-1 (PD-1) inhibitor, pembrolizumab, and chemotherapy. Biopsy revealed a subepidermal bulla with lymphocytic and eosinophil infiltration, and immunohistochemical studies predominantly showed CD4+ cells, a few CD8+ cells, and the occasional CD20+ lymphocyte. The serum anti-BP180 antibody level, as well as the interleukin-6 and interleukin-10 levels, were elevated compared to the lower levels of tumor necrosis factor-α. Eosinophil levels were high and consistent with the development of blisters. A diagnosis of BP associated with PD-1 inhibitor therapy was made, and the Common Terminology Criteria for Adverse Events classification was grade 3. Immunotherapy was permanently discontinued, and the patient's bullous lesions failed to react to high-dose systemic corticosteroids combined with minocycline and niacinamide. Intermittent blister recurrence occurred in 2 months, eventually improving with the administration of two courses of intravenous immunoglobulin. At 5 weeks of follow-up, the patient's tumor was reduced on a computed tomographic scan. Despite stable BP treatment, however, he repeatedly developed complications due to the complexity of his underlying disease and could not be treated with anti-tumor therapy. Early recognition and management of serious immune-related bullous dermatologic toxicity are essential for patient safety.

Pemphigus Vulgaris and Bullous Pemphigoid of the Upper Aerodigestive Tract: A Review Article and Novel Approaches to Management.

BACKGROUND: Autoimmune bullous diseases are rare conditions characterized by blistering of the skin and mucous membranes. The 2 commonest forms are pemphigus vulgaris and bullous pemphigoid. The oral cavity or oropharynx may be the initial site of presentation or often the only site involved. SUMMARY: These conditions are often misdiagnosed or overlooked leading to poorer patient outcomes. Due to the chronic nature of these conditions and the systemic effects of treatment, there is a significant associated morbidity and mortality. As such, an understanding of the fundamentals of autoimmune bullous diseases is vital to those working in otolaryngology. The mainstay of management in both conditions is topical and systemic corticosteroids. There is also a role for immunomodulating and non-steroidal anti-inflammatory drugs as adjunct or alternative therapies. Surgical intervention may be required to protect the airway. Often multimodality treatment is required involving multidisciplinary input from otolaryngologists, oral surgeons, dermatologists, and rheumatologists. This review article will highlight the aetiology, pathology, clinical features, investigations, and management of both pemphigus vulgaris and bullous pemphigoid including recent advances in management.

Treatment options for autoimmune bullous dermatoses other than systemic steroids: A systematic review and network meta-analysis.

Autoimmune blistering diseases can eventually cause life-threatening complications if left untreated. Although there is no cure for these bullous diseases; their therapy is based on suppressing the immune system to cease the de novo formation of the generated antibodies. The current study aimed to assess the safety and efficacy of using standing alone alternative therapies beyond systemic steroids for management of autoimmune bullous diseases. We searched six literature databases for both randomized and quasi-randomized clinical trials that assessed the efficacy of drugs other than systemic steroids in autoimmune bullous diseases. Outcomes were calculated as odds ratios with 95% confidence-interval. We used the R software to perform conventional and network meta-analyses with a frequentist approach. The network ranking order for 629 bullous pemphigoid patients, from the best to the worst was, clobetasol propionate cream (40 mg; (P-score = .87), clobetasol propionate cream (10-30 mg; P-score = .77), nicotinamide plus tetracycline (P-score = .56), steroids (P-score = .29) and doxycycline (P-score = .01). Limitations of this study are the small sample of the included studies except for blister trial and lack of randomization in most trials. To conclude, Combined doxycycline and nicotinamides are safer and more effective option for extensive bullous pemphigoid patients than the usual use of systemic steroids. For limited disease, topical corticosteroid (40 mg/d) use provides a safer and better response modality than the other proposed treatments.

Treatment of bullous pemphigoid in Chinese patients with Tripterygium wilfordii Hook F.

Tripterygium wilfordii Hook F (TwHF) is a traditional Chinese herb used in many medicinal applications, but the treatment of bullous pemphigoid (BP) with TwHF has never been reported. The aim of this study was to evaluate the efficacy and safety of TwHF in BP patients. A retrospective study was performed from January 2015 to September 2019 in the Department of Dermatology, Peking Union Medical College Hospital. A total of 10 patients with mild to moderate BP and treated with TwHF were enrolled in the study with 10 mild or moderate BP patients treated with systemic glucocorticoid randomly selected as controls. In the TwHF group, a major response was seen in seven patients, a minor response in one and no response was seen in two patients. In the glucocorticoid group, a major response was seen in nine patients and a minor response in one patient. Two patients experienced treatment failure. The time to disease control in the TwHF group (34 ± 11 days) was longer as compared to the glucocorticoid group (18 ± 8 days, P < .05). Ten patients relapsed during the follow-up period. The adverse events in the TwHF group were lower than those in the glucocorticoid group (13 vs 19). Low-dose TwHF may be effective and safe for treating mild and moderate BP.

Blisters Induced by PUVA: A Report of 5 Cases. / Ampollas inducidas por PUVA. Presentación de 5 casos.

Blisters associated with PUVA treatments are an adverse effect of photochemotherapy that has been reported in the literature. Asymptomatic blisters appear spontaneously mainly on the lower limbs and resolve without treatment. The differential diagnoses to consider include a phototoxic reaction, pseudoporphyria, and PUVA-induced bullous pemphigoid. We describe the clinical and histologic features in 5 cases of blistering secondary to PUVA treatment. If this adverse effect is accurately diagnosed, photochemotherapy need not be interrupted, and unnecessary diagnostic procedures and additional treatments can be avoided.

Management of bullous pemphigoid: the European Dermatology Forum consensus in collaboration with the European Academy of Dermatology and Venereology.

Bullous pemphigoid is the most common autoimmune subepidermal blistering disease of the skin and mucous membranes. This disease typically affects the elderly and presents with itch and localized or generalized bullous lesions. In up to 20% of affected patients, bullae may be completely absent, and only excoriations, prurigo-like lesions, eczematous lesions, urticated lesions and/or infiltrated plaques are observed. The disease is significantly associated with neurological disorders. The morbidity of bullous pemphigoid and its impact on quality of life are significant. So far, a limited number of national treatment guidelines have been proposed, but no common European consensus has emerged. Our consensus for the treatment of bullous pemphigoid has been developed under the guidance of the European Dermatology Forum in collaboration with the European Academy of Dermatology and Venereology. It summarizes evidence-based and expert-based recommendations.

[Bullous pemphigoid: a review]. / Pemphigoïde bulleuse: revue de la littérature.

BACKGROUND: Bullous pemphigoid (BP) is the most common auto-immune bullous disorder. Its treatment is difficult due to high age and comorbidities of affected patients. OBJECTIVES: To assess the effects of treatments for BP. METHODS: Randomized therapeutic trials (RCTs) were identified using an automatic search on Pubmed et Embase until March 2009. Large retrospective series with homogeneous therapeutic management were also selected and analyzed. RESULTS: Forty-four articles were selected and analyzed, which included nine RCTs with a total of 1007 participants (653 patients were included in two trials). Two RCTs comparing different modalities of systemic corticosteroid therapy failed to show differences in measure of disease control. The addition of plasma exchanges (one RCT) or azathioprine (one RCT) allowed to halve the amount of prednisone required for disease control. A further 3-arms RCT compared plasma exchange or azathioprine plus prednisone, but failed to show significant differences for disease control or mortality of BP. One study compared tetracycline plus nicotinamide with prednisolone, no significant difference for disease response was evidenced. A large controlled clinical trial demonstrated that high doses of very potent topical corticosteroids increased initial disease control and 1-year survival of patients with extensive BP, as compared with oral prednisone. Another RCT compared two regimens of potent topical corticosteroids and a non-inferior rate of BP control was obtained with the mild regimen. Finally, a study comparing two immunosuppressant drugs (azathioprine, mycophenolate mofetil) in addition to prednisone failed to show any difference for disease control, recurrence rate or the cumulated doses of prednisone. CONCLUSIONS: Ultrapotent topical corticosteroids (clobetasol propionate; 20 to 40g/day) are effective treatments for BP with fewer systemic side-effects than oral high-dose corticosteroids. Systemic corticosteroids are effective but doses greater than 0.5mg/kg per day are associated with severe side-effects, including decreased survival. The effectiveness of the addition of plasma exchange or immunosuppressants (azathioprine, mycophenolate mofetil) to systemic corticosteroids has not been established. Combination treatment with tetracycline and nicotinamide needs further validation.

Efectividad del tratamiento tópico con esteroides en enfermedades vesículo-ampollares con signos de gingivitis descamativa: revisión de la literatura / The effectiveness of topical steroid treatment of vesiculo-bullous diseases with signs of desquamative gingivitis: a review of the literature

Existe una gran variedad de enfermedades que afectan las membranas mucosas las cuales incluyen la mucosa gingival. El signo de gingivitis descamativa constituye una condición que se caracteriza por la presencia de lesiones eritematosas, erosivas, atróficas y dolorosas en la encía marginal extendiéndose a otras localizaciones como la mucosa alveolar, palatina y yugal, entre otras. El manejo terapéutico de ésta alteración se basa principalmente en la administración de corticosteroides sistémicos y tópicos de alta potencia, al igual que el manejo dental apropiado. Es de importancia el control médico odontológico de éstos pacientes para garantizar la salud dental y sistémica del mismo. El propósito de ésta revisión es determinar, basándose en lo publicado en la literatura actual, hasta que punto es efectivo el tratamiento con corticosteroides tópicos lo que actualmente conocemos como signo de gingivitis descamativa

Penfigoide ampolloso relacionado con tratamiento con PUVA: aportación de dos nuevos casos / Bullous pemphigoid related to PUVA therapy: Two further cases

El penfigoide ampolloso es una enfermedad de etiología autoinmune caracterizada por el desarrollo de ampollas subepidérmicas, que afecta generalmente a personas de edad avanzada. A pesar de que el penfigoide ampolloso tiene un potencial carácter fotosensible, se ha descrito de forma excepcional el desarrollo de dicho proceso en el curso de tratamiento con PUVA, sobre todo en pacientes con psoriasis. La asociación de penfigoide ampolloso y psoriasis plantea dificultad a la hora de instaurar un tratamiento y consideramos una buena alternativa la utilización de metotrexate, con o sin corticoides asociados, en el manejo de dichos pacientes. Aportamos dos nuevos casos de penfigoide ampolloso relacionado con tratamiento con PUVA en pacientes con psoriasis

Bullous pemphigoid is an autoimmune disease that generally affects elderly people and is characterised by the development of subepidermal blistering. Although bullous pemphigoid is potentially photosensitive, its occurrence during the treatment course with PUVA, especially in patients with psoriasis, has exceptionally been described. The association of bullous pemphigoid and psoriasis gives rise to difficulties when initiating treatment and we consider that the use of methotrexate, with or without associated corticoids, is a good alternative in the management of such patients. We report two further cases of bullous pemphigoid related to PUVA therapy in patients with psoriasis

Actualización en penfigoides: análisis de 55 casos / Update in pemphigoid: analysis of 55 cases

El pengigoide (PMB o penfigoide de las membranas mucosas PMM) es una enfermedad de las mucosas, piel o de piel y mucosas, de naturaleza autoinmune que se caracteriza por la formación de ampollas. En esta ocasión se presenta una revisión de 55 casos, realizada en el IREPO (Instituto de Referencia de Patología Oral) y en el Servicio de diagnósticos de la Escuela Dental, entre los años 1978 y 1998, en todos los pacientes el diagnóstico fue confirmado con biopsia

A case of generalized pustular psoriasis followed by bullous disease: an atypical case of bullous pemphigoid or a novel bullous disease?

We describe a 31-year-old Japanese woman with generalized pustular psoriasis treated with PUVA who subsequently developed a bullous disease. Throughout the disease course, there was no phase of psoriasis vulgaris. Although several reports describe coexistence of psoriasis vulgaris and bullous disease such as bullous periphigoid, coexistence of generalized pustular psoriasis without any phase of psoriasis vulgaris and bullous disease is rare. As for the bullous disease, direct immunofluorescence study showed IgG and C3 deposition along the basement membrane zone. Indirect immunofluorescence disclosed IgG antibasement membrane zone antibodies. Indirect immunofluorescence on 1 mol/l sodium chloride-split skin demonstrated linear IgG staining almost exclusively on the dermal side of the split. Western immunoblot analysis revealed that the antibody was directed to neither epidermolysis bullosa acquisita antigen nor bullous pemphigoid antigens. Considering the unusual clinical course, we suspect the possibility of a novel autoimmune blistering disease.