Case Report: Localized bullous pemphigoid induced by local triggers: a case series and a proposal for diagnostic criteria based on a literature review.

Introduction: Localized bullous pemphigoid (LBP) is an infrequent bullous pemphigoid (BP) variant restricted to a body region. According to the most compelling evidence, LBP occurs in patients with pre-existent serum antibodies against the basement membrane zone, which occasionally acquire the capacity to induce disease after the influence of different local factors acting as triggers. Methods: We hereby present a multicenter cohort of 7 patients with LBP developed after local triggers: radiotherapy, thermal burns, surgery, rosacea, edema and a paretic leg. In addition, we conducted a review of the literature, and we propose a set of diagnostic criteria for LBP, also based on our case series and the 2022 BP guidelines from the European Academy of Dermatology and Venereology. Results: During follow-up, three of the patients from our series evolved to a generalized BP, with only one requiring hospitalization. Our literature search retrieved 47 articles including a total of 108 patients with LBP, with a 63% with a potential local precipitating factor previous to their diagnosis. LBP mostly affected older females, and a subsequent generalized progression occurred in 16.7% of the cases. The most frequently involved areas were the lower limbs. Radiation therapy and surgery were responsible for the inducement of nearly 2 in 3 cases of LBP. We observed a significantly higher risk of generalization in cases where the trigger led to the developing of LBP earlier (p=0.016). Our statistical analysis did not detect any other prognosis factor for generalization when assessing direct immunofluorescence, histological and serological results, or other patient related factors. Conclusion: LBP should be suspected in patients with recurrent localized bullous eruptions. The presence of a trauma history in the same anatomic area is reported in most cases.

Bullous pemphigoid associated with anti-programmed cell death protein 1 and anti-programmed cell death ligand 1 therapy: A case series of 13 patients.

We present a case series of 13 patients, the first Australian single-centre study of bullous pemphigoid (BP) associated with immune checkpoint inhibitors (ICI): cytotoxic T-lymphocyte antigen (CTLA4) and programmed cell death receptor (PD1) inhibitors. All our patients achieved adequate control of BP with a combination of treatments including oral prednisolone, intravenous immunoglobulin, rituximab and omalizumab. The majority of patients ceased or interrupted immunotherapy treatment upon diagnosis of BP and greater tumour progression was seen in the cohort who ceased immunotherapy.

Bullous Pemphigoid in X-linked Alport Syndrome.

Skin lesions in X-linked Alport syndrome (XLAS) are rarely observed. Bullous pemphigoid (BP) is caused by autoantibodies against BP180, also called α1 (XVII) chain, in the basement membrane zone (BMZ). A 48-year-old man with XLAS developed tense blisters. A skin biopsy showed a cleft between the basal cell layer and dermis, with the infiltration of neutrophils and eosinophils. α1 (XVII) staining was positive on the epidermal side of α2/5 (IV) staining. Oral prednisolone improved his symptoms gradually. Abundant tense blisters on the palms and soles might suggest an important role of the α5 (IV) chain in the integrity of BMZ.

Anti-laminin 332 antibodies in graft-versus-host disease-associated bullous pemphigoid after allogeneic peripheral blood stem cell transplantation.

We report a 48-year-old woman with bullous pemphigoid (BP) with antibodies against the B3 subunit of laminin 332 after the development of graft-versus-host disease (GVHD). She was diagnosed with recurrent acute lymphoblastic leukemia at 40 years of age and underwent two rounds of allogeneic peripheral blood stem cell transplantations (PBST). Two and a half years after the second PBST, multiple tense blisters appeared on her face, hands, and lower legs. The diagnosis of BP was based on hematoxylin eosin and immunofluorescence staining and immunoblotting analyses. A combination regimen of topical corticosteroids (clobetasol propionate) and tetracycline/niacinamide was administered. Complete clinical resolution was achieved after four weeks of therapy without the use of immunosuppressive drugs. To maintain the graft-versus-tumor effect, topical corticosteroids and immunomodulatory drugs are preferred for BP after hematopoietic stem cell transplantation considering the risk of recurrence of hematologic malignancies. To date, there have been no reports of successful treatment of GVHD-associated BP without immunosuppressive drugs. Chronic GVHD is characterized by the production of autoantibodies. Furthermore, this autoimmune subepidermal blistering disease, BP, may be a manifestation of chronic GVHD. However, the precise mechanism of autoantibody production in chronic GVHD is not yet fully elucidated.

[Bullous pemphigoid with unilateral sparing after axillary lymphadenectomy]. / Bullöses Pemphigoid mit Aussparung eines Armes nach axillärer Lymphadenektomie.

An 83-year-old woman presented to our outpatient clinic with bullous pemphigoid with a unilateral sparing of the left arm after axillary lymphadenectomy because of breast cancer. Cases of localized manifestations of bullous pemphigoid are mainly caused by lymphedema or radiation. The absence of blistering after lymphadenectomy is a rare and interesting manifestation. Pathophysiologically, blister formation may be attenuated or absent altogether due to decreased T­cell activation and thus reduced inflammatory infiltrate because of the absence of peripheral lymph nodes.

Development of bullous pemphigoid following radiation therapy combined with nivolumab for renal cell carcinoma: A case report of abscopal toxicities.

RATIONALE: Concern for immune-related adverse events from immunotherapy and radiation therapy are well-documented; however, side effects are mostly mild to moderate. However, high-grade, potentially life-threatening adverse events are increasing. While case reports regarding immunotherapy-related bullous pemphigoid (BP) have been rising, only 1 has described BP following concomitant use of both nivolumab and radiation therapy (RT). For that patient, nivolumab was used for 10 weeks prior to RT and development of PB followed 7 weeks later. This case presents a patient who tolerated nivolumab well for 38 months prior to developing BP less than 2 weeks after completing RT. PATIENT CONCERNS: We present the case of DH, a 67-year-old gentleman on nivolumab for metastatic renal cell carcinoma to the lung since May of 2017. Following progressing lung nodules, the patient had his nivolumab paused and completed a course of short-beam radiation therapy. After restarting nivolumab post-radiation, the patient presented with itchy rash and blisters on his arm, legs, and trunk. DIAGNOSIS: DH consulted dermatology following development of rash and was diagnosed with bullous dermatosis, likely bullous pemphigoid. Bullous pemphigoid following concomitant nivolumab (OPDIVO), despite prior tolerance and no history of autoimmune disease, was confirmed by biopsy a month later. INTERVENTIONS: Initial treatment was betamethasone 0.05% cream mixed 1:1 with powder to form paste applied twice daily. Given progressive symptoms and confirmatory biopsy of BP, nivolumab was held and 100 mg doxycycline and 80 mg prednisone daily was prescribed for a week, reduced to 60 mg during the second week. OUTCOMES: A week following discontinuation of nivolumab and beginning of doxycycline and prednisone, the blistering and rash was almost entirely resolved. Four months later, nivolumab was restarted and the patient continued low-dose tapering of prednisone until December. Since completing prednisone, the patient has shown no recurrence of bullous pemphigoid and has not developed any other immune-related adverse events to nivolumab upon rechallenge. Follow-up through October 2021 demonstrates the patient's sites of disease, both in- and out-field, have remained responsive to treatment. LESSONS: Treating physicians should be aware of off-target effects of radiotherapy for oligoprogressive disease, which may include abscopal toxicities and the development of new immune-related adverse effects.

[A rare presentation of kidney allograft intolerance syndrome: Bullous pemphigoid]. / Une présentation rare du syndrome d'intolérance au greffon renal : la pemphigoïde bulleuse.

Bullous pemphigoid is an autoimmune bullous cutaneous disease. We report the case of a 60 year-old male patient whose kidney allograft failed and was on hemodialysis for the previous 16 months. After tapering immunosuppressive medication, he presented simultaneous bullous eruption and kidney allograft intolerance syndrome. Investigation showed a positive BP180 anti-basement membrane zone antibody and skin biopsy was consistent with bullous pemphigoid. The patient was treated with corticotherapy and bullous pemphigoid resolved. The development of new onset diabetes and concerns over long term immunosuppression, halted the decision to continue corticotherapy and the patient underwent graft nephrectomy, with resolution of the kidney allograft intolerance syndrome without recurrence of the bullous disease. The occurrence of bullous pemphigoid in patients with failed renal allograft is rare, with only eleven cases reported in literature. This case illustrates how graft nephrectomy can provide a definitive cure to bullous pemphigoid in this setting.

Bullous pemphigoid-like rash revealing hypereosinophilic syndrome.

Hypereosinophilic syndrome (HES) is a rare haematologic disorder characterised by unexplained, persistent eosinophilia with organ involvement. We report the case of a 74-year-old patient who presented with a pemphigoid-like bullous rash as the only manifestation of an HES. This report highlights the importance of the dermatological manifestations of this potentially life-threating condition that may initially present as a skin-limited disease. Bullous pemphigoid (BP) is a very common autoimmune blistering dermatosis that may share common clinical and histological features or associate with an HES. HES should be considered when patients diagnosed with BP demonstrate atypical course under corticosteroids and/or recalcitrant blood eosinophilia.

Radiation-induced bullous pemphigoid after surgery for soft tissue sarcoma: About a rare case.

INTRODUCTION: Radiation therapy may cause a range of side effects of the skin within the irradiated area. Not of all the reactive effects of the skin induced by radiation therapy have to be related to some forms of radiodermatitis, and when non-standard clinical presentations overcome, it may be necessary to undertake appropriate diagnostic tools to not be in trap of wrong diagnosis. CLINICAL CASE DESCRIPTION: A 76 years-old man undertook resection surgery after a neoadjuvant radiation therapy for a soft tissue sarcoma of his groin region. After surgery, he developed an acute skin reaction comparable with a severe form of radiodermatitis. Despite cares, his clinical status got worse. Only skin biopsies guided us to the right diagnosis: it was a form of a bullous pemphigoid induced by radiation therapy. The consequent appropriate treatment was finally resolute. CONCLUSION: These forms have to be recognized in time, to undertake skin biopsies as soon as an evocative clinical presentation appears. The appropriate treatment, which consists in local or systemic corticotherapy, is resolute in most cases.

Localized bullous pemphigoid after knee replacement surgery.

Bullous pemphigoid (BP) most commonly presents as widespread, itchy, tense blisters in older patients. Localized bullous pemphigoid is a less common form of BP that can be more difficult to diagnose because of its similarity to more common conditions such as allergic contact dermatitis or bullous cellulitis. Prompt recognition of localized BP is important so that appropriate treatment can be started. We present a 57-year-old woman who presented with pruritic tense bullae overlying the surgical scar from a knee replacement 6 months prior on her anterior right knee. This case illustrates the potential for localized BP to be triggered by surgical procedures.

Diagnosis and treatment of bullous pemphigoid that developed twice after total knee replacement arthroplasty: a case report.

BACKGROUND: Total knee replacement arthroplasty (TKA) is frequently performed in South Korea. Simple swelling-associated blistering around the periphery of the operative wound is a well-known adverse effect. However, in rare cases, the blisters are bullous pemphigoid (BP). CASE PRESENTATION: A 75-year-old male presented with knee pain that had not improved despite 5 years of medication. We performed TKA of the left knee, placing a Stryker posteriorly stabilized prosthesis. Three days later, blisters developed near the buttocks and thighs and, on day 10 after surgery, around the operative site. A skin biopsy revealed BP. Commencing on day 14 after surgery, prednisolone 10 mg was administered twice daily. The symptoms improved by 3 weeks after surgery and were healed at 4 months. After 1 year, we performed TKA of the right knee. On day 2 after surgery, as formerly, blisters developed on the buttocks and an immediate biopsy revealed BP. Commencing on day 3 after surgery, prednisolone 10 mg was administered twice daily. On day 10 after surgery, the blisters on the buttocks had improved and no blisters were observed at the surgical site. All symptoms had resolved by 2.5 months after surgery. CONCLUSIONS: After TKA surgery, generalized BP may develop, diagnosed via skin biopsy. A quick diagnosis is important because early treatment can prevent symptom progression and shorten treatment.

A case of anti-BP230 antibody-positive bullous pemphigoid receiving DPP-4 inhibitor.

Bullous pemphigoid (BP) is a cutaneous autoimmune blistering disorder. Recently, it has been reported that dipeptidyl peptidase-4 inhibitors (DPP4i) is associated with the development of BP (DPP4i-BP). Patients with DPP4i-BP have autoantibodies (autoAbs) preferentially targeting full-length BP180, but not the BP180NC16a domain. In this report, we described a case of anti-BP230 antibody (Ab)-positive BP receiving DPP4i. A 78-year-old male with a medical history of type 2 diabetes receiving vildagliptin at 100 mg daily for 38 months was referred to our hospital with itching blisters on his body and extremities. Skin biopsy showed subepidermal bulla with eosinophil infiltration. Direct immunofluorescence staining revealed a linear staining pattern with complement C3 and IgG at the subepidermal basement membrane zone. By laboratory testing, autoAbs against BP180NC16a and full-length BP180 were negative by enzyme-linked immunosorbent assay (ELISA); however, anti-BP230 Abs were positive by ELISA (index: 123.91). His HLA genotype was DQB1*04:01 and 05:01. Based on these results, we diagnosed the patient with anti-BP230 Abs-positive BP associated with DPP4i. To the best of our knowledge, this is the first case of DPP4i-BP with only anti-BP230 Abs. Further accumulation of DPP4i-BP cases is needed to clarify the relationship between overall features of DPP4i-BP and anti-BP230 Abs.

Bullous Pemphigoid: Trigger and Predisposing Factors.

Bullous pemphigoid (BP) is the most frequent autoimmune subepidermal blistering disease provoked by autoantibodies directed against two hemidesmosomal proteins: BP180 and BP230. Its pathogenesis depends on the interaction between predisposing factors, such as human leukocyte antigen (HLA) genes, comorbidities, aging, and trigger factors. Several trigger factors, such as drugs, thermal or electrical burns, surgical procedures, trauma, ultraviolet irradiation, radiotherapy, chemical preparations, transplants, and infections may induce or exacerbate BP disease. Identification of predisposing and trigger factors can increase the understanding of BP pathogenesis. Furthermore, an accurate anamnesis focused on the recognition of a possible trigger factor can improve prognosis by promptly removing it.

[Bullous pemphigoid induced by cancer immunotherapy]. / Pemphigoïde bulleuse induite par l'immunothérapie antitumorale.

Bullous pemphigoid is the most frequent autoimmune bullous dermatosis. Cases induced by immune checkpoint inhibitors have been described. This antitumor immunotherapy changed the treatment of several malignant tumors, especially melanoma and non-small cell lung-cancer. Nevertheless, immune adverse events are common. We present a case of bullous pemphigoid induced by pembrolizumab to illustrate the link between this disease and the treatment with immune checkpoint inhibitors.

La pemphigoïde bulleuse (PB) est la dermatose bulleuse auto-immune la plus fréquente. De nombreux cas induits par les inhibiteurs des points de contrôle immunitaire (IPCI) ont été rapportés. L'immunothérapie antitumorale a révolutionné la prise en charge de certaines tumeurs malignes, notamment du mélanome et du carcinome pulmonaire non à petites cellules. Toutefois, les effets indésirables immunologiques sont fréquents. Nous présentons un cas de PB induite par le pembrolizumab pour illustrer le lien entre cette maladie bulleuse et le traitement par IPCI.