Dear Editors, Bullous pemphigoid (BP) is the most common autoimmune subepidermal blistering disease, predominantly affecting elderly patients around the age of 80 years.1 The incidence is rising, attributed to demographic changes and improved diagnostic capabilities, particularly through the detection of specific autoantibodies.1, 2 Clinically, BP presents with tense, fluid-filled blisters and erythema, often accompanied by urticarial plaques and intense pruritus. The typical blistering lesions may be preceded by an eczematous stage or prurigo-like lesions. Mild oral involvement occurs in 10-20% of patients.3, 4 Standard treatment involves high-potency topical corticosteroids. In moderate, severe, or refractory cases, systemic corticosteroids are used. Alternative immunomodulating agents include doxycycline, dapsone, mycophenolate mofetil, azathioprine, and methotrexate. Recent studies suggest potential benefits of biologics such as omalizumab and dupilumab.5-8 A 73-year-old Caucasian female patient presented in 2020 with disseminated, crusted-erosive, and intensely pruritic plaques to our dermatology department. Clinical examination revealed multiple excoriations, postinflammatory hypopigmentation, and erythematous plaques on the upper and lower extremities. The trunk and mucous membranes were uninvolved, with no standing blisters present. Between 2011 and 2014, the patient had been treated for prurigo nodularis using cyclosporine, without therapeutic success. Despite persistent skin changes with pruritus, no systemic therapy was administered during the interim period. Histopathological examination revealed impetiginized parakeratosis with serum inclusions, irregular psoriasiform acanthosis, focal spongiosis, and Langerhans cell clusters. The dermis showed partial fibrosis with increased vasculature, vessel ectasia, and perivascular lymphocytic and eosinophilic infiltration. Direct immunofluorescence initially showed no evidence of autoimmune bullous dermatosis. However, indirect immunofluorescence revealed IgG autoantibodies against the epidermal basal lamina. Subsequent direct immunofluorescence after salt-splitting demonstrated IgG at the blister roof. Laboratory findings included hypochromic, microcytic anemia (hemoglobin 8.2 g/dl; normal 12–16 g/dl), elevated gamma-GT (186 U/l; normal <40 U/l) with normal transaminases, despite known hepatic parenchymal damage due to former alcohol abuse. Serological tests for hepatitis, HIV, and Treponema pallidum, as well as an Interferon-γ release assay, were negative. Total serum IgE was markedly elevated (2569 kU/l; normal <100 kU/l). Indirect immunofluorescence was negative for BP180 antibodies but showed elevated BP230 antibodies (1:2560). Based on the clinical presentation, histopathological findings, and serological results, a diagnosis of a moderate non-bullous pemphigoid was established. A comprehensive diagnostic work-up did not reveal any evidence of malignancy, and the premedication did not include any drugs known to trigger bullous pemphigoid. Initial treatment consisted of topical corticosteroids (clobetasol propionate), oral prednisolone, and doxycycline. Due to pre-existing hepatic damage and anemia, methotrexate and dapsone were contraindicated. In 2021, clinical exacerbation occurred. Off-label treatment with omalizumab for three months, based on elevated total serum IgE, showed no clinical benefit. Subsequently, immunosuppressive therapy with mycophenolate mofetil (maximum 3 g/day) and prednisolone was initiated (April 2021–May 2022). Following further deterioration, treatment was switched to dupilumab combined with prednisolone and doxycycline. While the skin condition improved, complete prednisolone withdrawal was not achievable. In March 2024, further exacerbation occurred with severe pruritus (NRS 8/10), extensive erosions, and first-time appearance of plantar blisters (Figures 1, 2) despite ongoing dupilumab, doxycycline, and low-dose prednisolone (5 mg/day). Due to limited therapeutic alternatives, treatment was switched to lebrikizumab in April 2024 using the approved dosing regimen for atopic dermatitis (500 mg on days 0 and 14, followed by 250 mg every two weeks). Lebrikizumab is a high-affinity monoclonal IgG4 antibody that selectively binds to soluble IL-13, blocking IL-13 signaling without affecting IL-4 signaling.9 This mechanism modulates Th2-mediated inflammatory processes that may be relevant in BP pathogenesis. After initial corticosteroid pulse therapy, significant improvement was observed compared to dupilumab treatment, with marked pruritus reduction (NRS 1/10). Prednisolone was successfully discontinued in September 2024. Lebrikizumab monotherapy has been continued every four weeks since January 2025, with a stable skin condition maintained through July 2025. The patient achieved sustained clinical remission (Figures 3, 4) with complete pruritus resolution and successful corticosteroid withdrawal. No adverse events related to lebrikizumab were observed during the treatment period. Laboratory findings showed a decrease in BP230 antibody titers to 1:640 under dupilumab, but a further reduction to 1:20 under IL-13 blockade alone. This case represents, to our knowledge, the first reported successful treatment of adult BP with lebrikizumab. The patient's complex medical history, including hepatic impairment and previous treatment failures, highlights the need for alternative therapeutic approaches in refractory BP cases. Case reports like ours indicate that not only the combined blockade of IL-4 and IL-13 but also the inhibition of IL-13 alone may play an important role in the treatment of BP, highlighting the relevance of the selective inhibition of IL-13 in the disease's Th2-mediated pathogenesis. The successful corticosteroid withdrawal and sustained clinical improvement suggest that lebrikizumab may provide effective long-term disease control in BP patients who have failed conventional therapies. This is particularly valuable in elderly, multimorbid patients where traditional immunosuppressive agents may be contraindicated. Further studies are warranted to evaluate the efficacy and safety of lebrikizumab in BP management. The authors would like to thank the patient for providing consent for this case report. None.
Grentner et al. (2026) studied this question.