Bullous Pemphigoid Associated with Acquired Hemophilia A

KARGER
22 May, 2019 ,

This is a case of a  68-year-old Thai woman diagnosed and treated for bullous pemphigoid (BP) for 11 months who recently presented with a 3-day history of extensive hemorrhagic bullae and large intra-oral buccal hematoma. Laboratory investigations confirmed a prolonged activated partial thromboplastin time, a low factor VIII level, a high factor VIII inhibitor level, and elevated anti-BPAG180 and anti-BPAG230 titers, confirming the diagnosis of BP associated with acquired hemophilia A (AHA). Immunosuppressive therapy with systemic corticosteroids and cyclophosphamide combined with bypassing agents for bleeding control resulted in significant clinical improvement and subsequent negative antibody levels. 

 

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A 68-year-old Thai female presented with tense bullae on the extremities. Initial investigations, including histology and direct immunofluorescence, were performed in another hospital prior to this admission. Histopathology showed subepidermal vesicles, well-preserved dermal papillae, and a dense inflammatory cell infiltrate, predominantly eosinophils. Direct immunofluorescence demonstrated linear IgG and C3 deposition along the dermoepidermal junction. The patient was diagnosed with BP. For treatment of BP, she was prescribed oral prednisolone 20 mg/day, nicotinic acid 150 mg/day, and topical 0.05% clobetasol propionate cream, which resulted in clinical improvement. Her skin lesions have been stable for 10 months with a maintenance dose of oral prednisolone 5 mg/day and nicotinic acid 200 mg/day.
 

Her past medical history included hypertension, dyslipidemia, and type 2 diabetes mellitus. Her medications included hydrochlorothiazide 25 mg/day, losartan 50 mg/day, and neutral protamine hagedorn/regular insulin (70/30) 36 U/day for 10 years. She has not received any new medications. She denied a previous bleeding tendency in her personal and family history.

One month prior to presentation at our hospital, she developed new tense bullae on the trunk and extremities. She was treated at another hospital, where her oral prednisolone dose was increased to 15 mg/day without clinical improvement.

Three days before she was seen at the otorhinolaryngology outpatient department of our hospital, she developed a large hematoma on the right buccal mucosa with extensive new tense bullae that became hemorrhagic on her trunk and extremities. The patient was admitted to our hospital in the otorhinolaryngology department for close monitoring of upper airway obstruction. She had no signs of gastrointestinal bleeding, such as hematemesis, melena, hemoptysis, and hematuria.

Dermatological examination revealed multiple hemorrhagic and few clear tense bullae on the trunk and extremities involving approximately 20% of the body surface area. Complete blood count showed moderate anemia (hemoglobin level of 7.9 g/dL) and normal white blood cell and platelet count. International normalized ratio was normal, but activated partial thromboplastin time (aPTT) was prolonged at 75.1 s (normal range: 22–33 s). The mixing test showed failure to correct aPTT, indicating that this patient had a factor inhibitor in the intrinsic pathway. Factor VIII level was 0% (normal: 50–150%), and factor VIII inhibitor level was 28 BU/mL (normal: negative), which thus confirmed the diagnosis of AHA. Enzyme-linked immunosorbent assays (ELISAs) for anti-BPAG180 and anti-BPAG230 were both more than 200 RU/mL, correlating to high activity of BP.

After consultation with hematology, anemia from blood loss was corrected with blood transfusion, and bleeding was controlled with activated prothrombin complex concentrate APCC (factor eight bypassing activity [FEIBA VH, Baxter BioScience, Westlake Village, CA, USA]) and tranexamic acid. To suppress antibody production, she received intravenous dexamethasone 20 mg daily for 1 week. The aPTT gradually decreased from 75.1 to 52.6 s. Factor VIII inhibitor level also decreased from 28 to 5.68 BU/mL. Her cutaneous eruptions and intraoral hematoma resolved in 3 weeks. Oral prednisolone 30 mg/day (0.5 mg/kg/day) in combination with cyclophosphamide 50 mg/day were prescribed as maintenance therapy.

At 1-month follow-up, aPTT and factor VIII level returned to normal. Factor VIII inhibitor level was also undetectable. The patient did not develop any further bleeding event. She still continues on a tapering dose of oral prednisolone 5 mg/day and cyclophosphamide 50 mg/day to control BP and AHA up to 7 months after the onset of AHA.