Bullous pemphigoid (BP) is the most prevalent autoimmune blistering skin disorder, distinguished by a complex etiopathogenesis and a diverse clinical presentation [1]. Clinical professionals must acknowledge the extensive spectrum of clinical manifestations associated with BP and effectively tailor the diagnostic and therapeutic approaches to meet the individual needs of affected patients.

A 78-year-old female patient presented to the Clinic of Dermatology due to blistering lesions located on the right lower limb. According to the patient, the lesions first appeared over 6 months ago and were accompanied by severe itching. Notably, the patient had a history of right knee joint arthroplasty a year before. On admission, there were disseminated erosions and serous fluid-filled blisters present solely on the skin of the right knee and the right shin, with no involvement of mucous membranes (Figures 1 A, B). Following a physical examination, a thorough diagnostic evaluation was performed. Histopathological examination of a biopsy obtained from lesional skin revealed a subepidermal blister with an intact epidermal roof without signs of necrosis; the blister content included fibrin and isolated inflammatory cells. In the upper dermis, a diffuse inflammatory infiltrate with individual eosinophils was observed (Figures 1 C, D). Direct immunofluorescence (DIF) of perilesional skin using a short-arc mercury lamp-operated microscope (BX40, Olympus, Japan) was used to assess the intensity of deposits on the slides, which were graded using a semiquantitative 4-point scale (from “-” to “+++”) at the original objective magnification of ×40. The imaging revealed linear deposits of IgG4 (+++) (Figure 2) and C3 (++) along the dermo-epidermal junction. A six-parameter ELISA (Euroimmun, Lübeck, Germany) test showed a positive IgG antibody titre against BP180 (2.51 with a cut-off value 1.00). Considering the patient’s history of lower limb orthopaedic surgery and the immunopathological findings, a diagnosis of localized, trauma-induced bullous pemphigoid was established. During hospitalization, the patient was treated with intravenous methylprednisolone at a cumulative dose of 1250 mg and doxycycline 100 mg twice daily. In addition, oral nicotinic acid (vitamin PP) was administered. Discharge recommendations comprised oral treatment, specifically doxycycline 100 mg twice daily, methylprednisolone 24 mg daily with gradual tapering to 4 mg, and continued supplementation with vitamin PP, as well as topical treatment with clobetasol propionate ointment applied twice daily for 14 days, then once daily.

Figure 1

Clinical and histopathological features of a patient with localized surgery-induced bullous pemphigoid. The scar after knee surgery (A) and disseminated erosions and serous fluid-filled blisters on the skin of the right shin (B) were seen. Histopathological H + E staining revealed a subepidermal blister with an intact epidermal roof without signs of necrosis; the blister content included fibrin and isolated inflammatory cells (original magnification ×200) (C). A diffuse inflammatory infiltrate with individual eosinophils was observed in the upper dermis (original magnification ×400) (D)

Figure 2

Linear deposits of IgG4 (+++) along the dermo-epidermal junction visible in direct immunofluorescence (DIF) of perilesional skin (original objective magnification ×40)

BP exhibits a broad clinical spectrum and may be triggered by various external factors, including surgical trauma. The pathomechanism of trauma-induced BP remains incompletely understood. It is hypothesized that tissue injury initiates an inflammatory cascade, leading to autoreactivity against basement membrane components, particularly BP180 [2]. Isomorphic phenomenon (Köbner phenomenon) or similar cutaneous reactions are plausible in this clinical setting [3]. Alternatively, trauma may directly alter the structure of basement membrane proteins, thereby increasing their affinity for specific human leukocyte antigen (HLA) alleles [4]. Localized oedema, a common consequence of orthopaedic surgeries, likely triggers the pathogenesis of localized BP [5]. Notably, over 7% of individuals may have circulating BP180 and/or BP230 antibodies without any clinical manifestations of BP and with negative results of indirect immunofluorescence; however, these autoantibodies dose-dependently activate neutrophils in vitro [6, 7]. The oedema and vascular congestion resulting from the orthopaedic surgeries increased the local concentration of BP180 and BP230 antibodies, inflammatory mediators, and immune cells, ultimately leading to the localized formation of blisters [5]. Currently, no epidemiological studies evaluate surgery-induced BP, and the available data are derived solely from case reports. An analysis of reported cases revealed that out of 147 instances of pemphigoid diseases triggered by physical factors, 22 were induced by surgery [8]. The clinical-laboratory features of surgery-induced cases of localized pemphigoid diseases are presented in Table 1 [9–22]. In this context, the term “pemphigoid diseases” was used as the term “bullous pemphigoid, acronym BP” should be reserved only for patients in whom IgG antibodies to BP180 and/or BP230 were identified. The timing of onset can vary significantly, and several patterns emerge from case reports. Immediate-onset BP occurs within the first days or weeks after surgery and is likely a result of the aforementioned Köbner phenomenon. Interestingly, there are several cases of localized BP developing several months to even years after surgery. Such cases may arise from chronic subclinical inflammation or structural alterations at the dermal-epidermal junction following skin trauma, which predispose the affected area to subsequent immune-mediated attacks. In our patient, the lesions appeared 1 year after the knee joint arthroplasty. When suspecting autoimmune bullous dermatoses, DIF and molecular-biochemical serum studies to identify protein epitopes targeted by the autoimmune response represent the minimal and sufficient laboratory diagnostic examinations [1].