Semaglutide induced bullous pemphigoid

Prevalence of SGLT2i and GLP1RA use among US adults with type 2 diabetes

Seborrheic pemphigoid

Tetracycline and niacinamide in the treatment of blistering skin diseases

Bullous pemphigoid (BP) is the most common autoimmune subepidermal blistering disease and predominantly affects older adults. In recent years, dipeptidyl peptidase-4 inhibitors (DPP-4i), widely prescribed for type 2 diabetes mellitus, have emerged as important pharmacologic triggers of BP. DPP-4 inhibitors as a class have been associated with BP, with the strongest evidence reported for vildagliptin, although cases involving linagliptin have also been documented. Linagliptin has also been increasingly recognized as a potential trigger of drug-associated disease. We report the case of an 81-year-old woman with long-standing type 2 diabetes mellitus treated with metformin and linagliptin who developed a generalized pruritic vesiculobullous eruption. Dermatologic examination demonstrated multiple tense bullae, erosions, crusted plaques, and post-inflammatory hyperpigmented lesions involving the trunk, extremities, and intertriginous regions. Histopathologic examination revealed a subepidermal blister with prominent eosinophilic infiltration. Direct immunofluorescence demonstrated linear C3 and IgG deposition along the basement membrane zone, while indirect immunofluorescence localized immunoreactants to the roof of the split, confirming the diagnosis of BP. The temporal association with linagliptin exposure and the absence of alternative triggers supported the diagnosis of DPP-4 inhibitor-associated BP. Linagliptin was discontinued, and treatment with prednisone was initiated, resulting in progressive improvement and complete cessation of new blister formation at follow-up. This case highlights the importance of recognizing medication-induced BP in older diabetic patients and reviews current evidence regarding the epidemiology, pathogenesis, clinical presentation, diagnosis, and management of DPP-4 inhibitor-associated BP.

Bullous pemphigoid (BP) is the most common autoimmune blistering skin disease worldwide. In the difficult-to-treat BP or if standard therapies are contraindicated, the use of biologics may be also considered although there is no strong evidence supporting their use. This study aimed to investigate clinical and diagnostic findings as well as treatment outcomes among patients diagnosed with BP and undergoing omalizumab or dupilumab in a real-world setting. Amulticenter retrospective cohort study was performed across 15 Italian tertiary referral hospital. Medical records of 2435 BP patients were screened, identifying 58 (2.3%) Caucasian patients who met the inclusion criteria. Within this study population, 39 (67.2%) were treated with dupilumab and 19 (32.8%) received omalizumab. Disease control was achieved in 90.6% of dupilumab-treated patients and complete remission on minimal therapy was observed in 71.0%. Omalizumab-treated patients achieved disease control in 77.8% of cases and 64.7% obtained complete remission on minimal therapy. Log-rank test comparing relapse rate between treatment groups was not significant (p = 0.58). Finally, parameter estimates associated with the fixed effect of time were consistently negative, indicating a generally significant (p = < 0.05) decrease in scores over time for patients treated with both biologics. This cohort of patients undergoing dupilumab or omalizumab adds to the existing evidence concerning the effectiveness of biologic agents in BP. Both biologics seem to be promising treatment adjuvants in the management of BP, with dupilumab showing a descriptive trend toward better outcomes.

A 72-year-old man with nonhealing facial erosions and bullae

Background: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are an innovative class of medications primarily used to manage type 2 diabetes and obesity. These agents not only improve glycemic control but also promote significant weight loss and reduce cardiovascular risk. Summary: GLP-1RAs are associated with various dermatologic effects, including injection-site reactions and immune-mediated responses such as hypersensitivity, urticaria, and bullous pemphigoid. “Ozempic face,” a term describing facial fat loss, has gained media attention due to its cosmetic implications. Additionally, hair loss, particularly in the form of telogen effluvium, has been observed, potentially linked to rapid weight loss from GLP-1RA use. Emerging evidence also highlights the therapeutic potential of GLP-1RAs in enhancing wound healing and treating inflammatory skin conditions like psoriasis. Key Messages: With the increasing use of GLP-1RAs for weight management, clinicians should remain alert to dermatologic side effects and consider appropriate dermatologic consultations when needed. Further research is essential to optimize the safe and effective use of GLP-1RAs, ensuring therapeutic benefits are maximized while minimizing adverse dermatologic outcomes.

Pembrolizumab, a programmed cell death protein 1 checkpoint inhibitor, is a novel drug used to treat a variety of advanced malignancies. However, it can also result in many immune-related adverse events, with cutaneous toxicities being the most frequent. Regarding pembrolizumab-induced skin adverse reactions, bullous pemphigoid (BP) has the worst effects on quality of life. Recently, there have been more and more reports of BP incidents resulting from pembrolizumab therapy in patients with cancer. This study aimed to define the clinical characteristics, diagnosis and management of pembrolizumab-induced BP and identify potential differences between classical BP and pembrolizumab-induced BP. Case reports, case series, and case analyses of pembrolizumab-induced BP up to 10 December 2022 were collected for retrospective analysis. Our study included 47 patients (33 males and 14 females) from 40 studies. The median age was 72 years (range 42-86 years). The median time to cutaneous toxicity was 4 months (range 0.7-28 months), and the median time to bullae formation was 7.35 months (range 0.7-32 months). The most common clinical features were tense bullae and blisters (85.11%), pruritus (72.34%), and erythema (63.83%) on the limbs and trunk. In 20 of the 22 cases tested, the serum anti-BP180 autoantibodies were positive. However, in 10 cases (91.90%, 10/11) the circulating autoantibodies of anti-BP230 were negative. 40 patients had skin biopsies and the skin biopsy revealed subepidermal bullae or blister eosinophil infiltration in 75.00% of patients with pembrolizumab-induced BP, 10.00% of patients with lymphocyte infiltration and 20.00% of patients with neutrophil infiltration. There were 20 patients (50%) with eosinophilic infiltration around the superficial dermis vessels, 8 patients (20.00%) with lymphocyte infiltration around the superficial dermis vessels, and 4 patients (10.00%) with neutrophil infiltration around the superficial dermis vessels. Direct immunofluorescence detected linear immunoglobulin G (IgG) IgG and/or complement C3 along the dermo-epidermal junction in 36 patients (94.74%) with BP. IgG positivity was detected by indirect immunofluorescence in 81.82% of patients with BP. All patients were in complete remission (95.65%,44/46) or partial remission (4.35%, 2/46) of BP, whereas 9/46 patients had a relapse or refractory. The majority of patients achieved BP remission after discontinuation of pembrolizumab with a combination of topically and systemically administered steroid treatments, or other medications. The median duration of BP remission was 2 months (range 0.3-15 months). A thorough diagnosis of pembrolizumab-induced BP should be made using clinical signs, biochemical markers, histopathological and immunopathological tests. Pembrolizumab-induced BP had similar clinical characteristics to classic BP. Temporary or permanent discontinuation of pembrolizumab therapy may be required in patients with perbolizumab-induced BP depending on the severity of BP and the response to medication. Pembrolizumab-induced BP may be effectively treated using topical and systemic steroid treatments in combination with other medications (e.g., doxycycline, niacinamide, dapsone, rituximab, intravenous immunoglobulins, dupilumab, cyclophosphamide, methotrexate, mycophenolate mofetil, and infliximab). Clinicians should provide better management to patients with BP receiving pembrolizumab to prevent progression and ensure continuous cancer treatment.

A case of bullous pemphigoid provoked by doxycycline-induced phototoxicity

Introduction Bullous pemphigoid (BP) is an autoimmune bullous disease characterized by subepidermal tense blisters, accompanied by urticarial or eczema-like lesions. Circulating autoantibodies in BP patients target BP180 and BP230 at the dermal-epidermal junction. There has been a growing interest in unraveling the intricate relationship between BP and diabetes mellitus (DM), but a comprehensive review is lacking. Areas covered A thorough search of PubMed was conducted to identify studies concerning the association between BP and DM (1978–2023). Our findings comprehensively summarize the intricate association between BP and DM, focusing on the characteristics, potential pathomechanisms, and the influence of various antidiabetic medications on BP development. Expert opinion DM emerges as a prevalent comorbidity and potential risk factor for BP. New-onset DM can manifest during BP treatment, primarily due to corticosteroid therapy. Among all antidiabetic medications, dipeptidyl peptidase-IV inhibitors (DPP-4i) have the most solid association with BP onset. Other antidiabetic medications have also been reportedly associated with BP, including meglitinides, glucagon-like peptide 1 (GLP-1)-receptor agonists, and sodium-dependent glucose transporters 2 inhibitors (SGLT-2i). We suggest prescribing DPP-4i in caution for elderly DM patients with a history of autoimmune diseases.

Introduction: Bullous pemphigoid (BP) is an autoimmune disease that typically presents with blisters, but sometimes early lesions may be eczematous, maculopapular, or urticarial. The aim of the present study was to highlight possible differences between typical bullous and non-bullous pemphigoid (NBP) and compare results with the literature. Material & methods: Patients receiving a diagnosis of BP between January 2000 and December 2019 were analyzed. Patients who developed a blister after 3 months from the onset of pruritus were considered as NBP. Demographic features, clinical findings at diagnosis and at 2-year follow-up, histological features, auto-antibodies titers, comorbidities and their treatment were retrieved. Categorical variables were evaluated for normal distribution using a histogram and a Q-Q plot. The χ² and Fisher’s exact tests were used to compare categorical variables between the groups. Continuous variables were compared between the groups using analysis of variance and the independent-samples t test. For multivariate analysis, logistic regression was performed. Results: A total of 532 patients received a diagnosis of BP. A total of 122 patients were enrolled in the study; 63 were females, and the mean age at the diagnosis was 77.2 years (±11.9 SD). 98 were affected by BP and 24 were categorized as NBP. Mean time to diagnosis was 2.9 months (±5.8 SD) for BP and 30.4 months (±59.8 SD) for NBP (p = 0.0001). Skin manifestations in NBP patients were, in order of frequency: urticarial, papular or nodular, eczematous, and excoriations. Pruritus intensity was high but similar in the two groups (Numerical Rating Scale – NRS, 9.3 vs. 8.9). Seven out of 24 NBP patients (29%) never developed blisters; the other patients developed blisters after a mean follow-up time of 24.9 months (±54.9 SD). NBP patients had a more frequent history of myocardial infarction than BP patients (37.5 vs. 10.2%; p < 0.003). More NBP patients were taking diuretics than BP patients (66.7 vs. 49%; p = 0.03). NBP patients had a worse response to pruritus compared to BP patients at 2 years (NRS 3.7 vs. 11; p 0.001). Conclusions: NBP patients have a delayed diagnosis and may be at an increased risk of cardiovascular disease, especially myocardial infarction. Severely and persistently itchy skin disorders in aged patients should be investigated for BP diagnosis.

Bullous pemphigoid (BP) is a chronic autoimmune blistering disease characterized by the presence of autoantibodies that target hemidesmosomal proteins, specifically BP180 and BP230. This immune response leads to the formation of subepidermal blisters and inflammation. The primary treatment for BP involves systemic corticosteroids; however, long-term use can result in significant adverse effects, and some patients may experience resistance to steroid therapy. We report the case of a 62-year-old male with multiple comorbidities who developed progressive, itchy blisters and extensive skin erosions affecting more than 50% of his body surface. Although he initially showed improvement with intravenous corticosteroids, new blister formation continued, and Staphylococcus aureus bacteremia prevented further use of immunosuppressive therapy. The patient was managed with targeted antibiotics, intravenous immunoglobulin (IVIG), and omalizumab. This treatment resulted in significant clinical improvement, the resolution of new blister formation, and a successful tapering of corticosteroids. Omalizumab has demonstrated promising efficacy in treating BP, especially in refractory cases. Given its favorable safety profile, further clinical trials are needed to determine its long-term role in the management of BP.

Bullous pemphigoid (BP) is the most common autoimmune blistering disease. It can be challenging to manage and is associated with an increased risk of mortality. Access to dermatologic care is essential for patients with BP. However, the influence of geographic residence and distance to specialty care on patient outcomes or treatment regimens is unknown. Assess whether the rural-dwelling or urban-dwelling geographic status of our patients impacts the treatment duration of systemic corticosteroids (CS) in the management of BP. Numerous secondary outcomes were evaluated including the cumulative systemic corticosteroid dose received, steroid-sparing agent utilized, and duration and number of follow-up appointments. Retrospective analysis of patient records from January 2013 to May 2019 seen at the university-associated clinic in Edmonton, Alberta. Patients were stratified based on their rural-dwelling or urban-dwelling status via their Forward Sortation Area. There were 59 patients with BP. Of these, 37 completed their systemic corticosteroid course. The time required for 51.0% of the urban group to complete their steroid course was 543 days, and for 51.5% of the rural group it was 507 days. Methotrexate and azathioprine were the most common steroid-sparing agents utilized in both groups. Rural patients were seen in follow-up significantly less often than urban patients. Our findings demonstrate that the location of a patient's geographic residence does not influence the systemic corticosteroid or steroid-sparing agent use at our center. Interestingly, rural patients are able to receive similar treatment to urban patients despite having significantly fewer follow-up appointments.

Introduction Bullous pemphigoid (BP) is the most common autoimmune subepidermal blistering disorder in older adults. There is increasing evidence that BP has connections with renal diseases, such as glomerulopathy and neoplasm; it is also linked to the receipt of renal replacement therapy. Areas covered In this review, we summarize the current evidence that BP is a comorbidity of common renal diseases. Furthermore, our exploration of the characteristics and possible mechanisms underlying these connections provides insights that may facilitate the prevention, diagnosis, and management of BP. Expert opinion There is mounting proof that BP is not just a skin immunological disorder but rather a systemic immune-mediated illness. Quantities of case reports focused on BP as a renal disease comorbidity and the coexistence of them is not accidental. However, the underlying mechanisms are still needed to be investigated. Clinicians should be alert to the comorbidities in order to facilitate effective treatment and improve patient prognosis.

Bullous pemphigoid (BP) is an autoimmune disease of the skin characterized by subepidermal blistering accompanied by severe itch, causing a profound decrease in quality of life and conferring significant mortality risk. Because age is a primary risk factor, this rare condition is becoming more common as our population ages. Consequently, there is a need for enhanced recognition and appropriate management of BP. The objective of this endeavour was to develop a series of practical recommendations to improve the diagnosis and management of BP based on available evidence and expert opinion where evidence was lacking, with a focus on disease management within the Canadian context. A panel of 9 Canadian dermatologists with interest and experience in BP identified key topics in its diagnosis and management. A broad literature review, along with clinical expertise and opinion, supported the development of manuscript sections on each identified topic. Where appropriate, the panel developed clinically relevant recommendations that were adopted by consensus following a modified Delphi process and prespecified agreement cut-off of 80%. Panel members reviewed draft consensus statements and rated their level of agreement with each using an anonymous online survey platform. Statements not achieving consensus were discussed and updated in a live virtual meeting, after which another round of anonymous voting was held. Through this process, 18 recommendations were approved by the panel. These statements can guide healthcare providers in the practical management of BP in Canada and beyond.