Unusual Presentation of Bullous Pemphigoid as Erythroderma in an Elderly Male
Year: 2025
Type: article
Abstract: Dear Editor, Bullous pemphigoid (BP), a sub-epidermal blistering disorder, is known to manifest in several rare clinical variants, including dyshidrosiform, prurigo-nodularis-like, prurigo-like, ecthyma gangrenosum-like, intertrigo-like, papular, eczematous, vegetating, vesicular, toxic epidermal necrolysis-like, and erythrodermic forms.[1] Despite their clinical distinctions, all these variants share the same immunopathological findings, aiding in the diagnosis of BP. We present a unique case of BP manifesting as erythroderma in a 72-year-old male with multiple comorbidities, including diabetes mellitus, hypertension, and triple coronary artery disease. The patient presented with a 2-year history of recurrent, tense, fluid-filled blisters and had been diagnosed with BP and received various treatments, including oral prednisolone, azathioprine, rituximab (administered following the rheumatoid arthritis protocol), and monthly omalizumab for nine doses. Initial improvement was seen with omalizumab, but the patient did not respond to the last three doses. The patient had a history of multiple medications, including metformin, insulin, clopidogrel, cilnidipine, atorvastatin, trimetazidine, ivabradine, dutasteride, and famotidine for the past 1 year, with a prior history of telmisartan, which was later discontinued. Prior to the onset of lesions, the patient was on metformin, gliclazide, amlodipine, and vildagliptin. Vildagliptin was continued during the BP disease phase and discontinued eight months prior to the patient’s presentation to our department. Among these, vildagliptin, known for its strong association with BP, was identified as the most likely trigger and subsequently stopped. The patient experienced intense pruritus and persistent formation of tense blisters, which progressively worsened over the last eight months, eventually leading to the development of erythroderma. The patient exhibited erythroderma with prominent lichenification, multiple tense, fluid-filled blisters on the arms, trunk, and thighs, along with areas of erosion, but without oral, genital, or scalp involvement, or lymphadenopathy [Figures 1 and 2]. There was no family history of similar lesions. Tzanck smear and Gram stain revealed an absence of acantholytic cells along with the presence of a few eosinophils and neutrophils. Laboratory investigations revealed anemia (Hemoglobin: 9.8 g/dL), leukocytosis (Total leukocyte count: 19,000/μL) with significant eosinophilia (60%), normal renal and liver function, and glycosuria, indicating poor glycemic control. Direct immunofluorescence (DIF) revealed IgG and C3 deposits at the dermo-epidermal junction, and a skin biopsy from an abdominal blister revealed a split at the dermo-epidermal junction with many eosinophils [Figure 3]. Serum IgE was markedly elevated at 2598 IU/mL. Ultrasound of the abdomen and computed tomography of the chest revealed no significant abnormalities; however, the dual-energy X-ray absorptiometry (DEXA) scan indicated the presence of osteoporosis.Figure 1: Tense blisters on the left leg against a background of lichenificationFigure 2: Interspersed erosions on a background of severe lichenificationFigure 3: Direct immunofluorescence showing linear IgG and C3 deposits at the dermo-epidermal junctionGiven the patient’s multiple comorbidities and limited treatment options, we re-initiated omalizumab at 300 mg subcutaneously every two weeks, along with potent topical corticosteroids. This resulted in a dramatic improvement, with eosinophil counts decreasing to 8% after a single dose and sustained reduction in itching and blisters over 3 months of biweekly injections, with no adverse effects. We report this case as bullous pemphigoid presenting as erythroderma is rare. The diagnosis was supported by intractable pruritus due to the disease activity, presence of interspersed erosions, eosinophilia, raised serum IgE, and direct immunofluorescence showing C3 deposits from non-bullous skin. The absence of mucosal involvement, along with histopathology and DIF findings, argued against a diagnosis of paraneoplastic pemphigus. Common drug triggers for BP include gliptins, programmed death-ligand 1 (PD-L1) /programmed cell death protein 1 (PD-1) inhibitors, angiotensin-converting enzyme inhibitors, nonsteroidal anti-inflammatory drugs, and penicillin derivatives. In our patient, we suspect vildagliptin played a role in disease persistence, as it was continued during the active BP phase. The recalcitrance observed may have been influenced by its ongoing use, which aligns with previous reports linking gliptins to BP exacerbation. Erythroderma, or exfoliative dermatitis, is defined as the presence of erythematous and desquamative confluent lesions covering more than 90% of the body surface area. This condition can arise from various etiologies, including eczema, psoriasis, drug reactions, malignancies, and autoimmune blistering diseases. Pemphigus foliaceus is most frequently associated with erythroderma, while the association with BP is rare, first reported in 1982.[2] Similar to our patient, previous reports have documented BP presenting with blisters preceding erythroderma; however, some cases began with erythroderma alone, with all diagnoses confirmed by histopathology or detection of IgG and C3 at the basement membrane zone [Table 1]. There are also reports of erythroderma in bullous pemphigoid associated with psoriatic erythroderma.[11] The erythrodermic variant of bullous pemphigoid can be difficult to distinguish in psoriatic patients, as it is well known that psoriasis and bullous pemphigoid may coexist, and various factors (including BP) can cause psoriasis to become erythrodermic. However, the absence of a previous history of skin lesions and the lack of histopathological features of psoriasis in our patient suggest otherwise. Erythroderma in BP may stem from a Th2-driven immune response with elevated IL-4, IL-5, IL-6, and IgE, or from chronic pruritus leading to extensive lichenification.Table 1: A brief review of previously reported cases of erythrodermic bullous pemphigoidBP is managed with potent topical corticosteroids along with dapsone or tetracyclines, and severe BP requires oral steroids and conventional immunosuppressants. This patient had high levels of IgE, which are usually correlated with BP pathogenesis and activity. Omalizumab, a recombinant anti-IgE monoclonal antibody, binds to FcϵRI and FcϵRII on the surface of mast cells, basophils, and dendritic cells, thereby reducing inflammatory cell activation and the inflammatory cascade, and helping to control the disease.[12] This case highlights the rare presentation of BP as erythroderma in an elderly patient, with limited treatment options, and also demonstrates the potential efficacy of omalizumab in managing severe, treatment-recalcitrant BP. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest. Use of artificial intelligence (AI) The preparation of this manuscript was carried out entirely by the authors without the use of artificial intelligence technologies.
Authors: Anish Thind, Stephen, Ashwajit Singh, Sukhjot Kaur
Institution: Dayanand Medical College & Hospital
Language: English
Subfield: Pathology and Forensic Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W4415697204