Invasive pulmonary aspergillosis associated with bullous pemphigoid

Abstract

The incidence of invasive pulmonary aspergillosis (IPA) has increased over the past few decades due to widespread use of immunosuppressants. Most cases have been reported in patients with hematological malignancy, especially those undergoing hematopoietic stem cell transplantation (HSCT), and in patients with chronic granulomatous diseases, chronic obstructive pulmonary disease, or those undergoing solid organ transplantation. Thus far, there is only one report of IPA in a patient with bullous pemphigoid (BP) [1, 2], the most common autoimmune blistering skin disorder [3, 4]. Here we report a case of IPA associated with BP that was treated with a moderate dose of oral prednisolone for just three weeks. A 70-year-old Japanese man was referred to our hospital for diabetic renal failure with tense blisters and erythema on his trunk and extremities. He reported skin involvement for eight months and was diagnosed with BP based on a positive chemiluminescence enzyme immunoassay (CLEIA) for BP180, which was performed at another hospital. He was taking minocycline and nicotinamide for BP and linagliptin for type 2 diabetes. Physical examination revealed tense blisters on his trunk and extremities with mild oral involvement that was not tested for a herpes virus (Figure 1). A biopsy specimen revealed subepidermal blisters with prominent eosinophilic infiltration. Direct immunofluorescence on the perilesional skin revealed linear IgG and C3 deposits at the epidermal basement membrane zone. CLEIA for BP180 (MBL, Nagoya, Japan) was 85.8 U/mL (cut-off 9 U/mL). The patient was treated with 0.5 mg/kg/day (30 mg/day) prednisolone, 200 mg/ day minocycline, and 1.5 g/day nicotinamide; linagliptin was discontinued (day 1). The BP disease area index decreased in three weeks, although mucosal involvement persisted (skin erosions/blisters, 32 to 15; skin urticaria/erythema, 21 to 0; and mucosa, 2 to 2), which resulted in tapering the prednisolone to 25 mg/day. Dialysis for renal failure was initiated on day 16, and the patient complained of general fatigue. He developed fever on day 21. Laboratory test results revealed elevated C-reactive protein and β-D glucan levels. Computed tomography of the chest revealed ground-glass opacity in the upper lobe of the right lung. Pulmonary findings worsened on day 26 (Figure 2) despite micafungin administration, and on day 27 Aspergillus fumigatus was identified with bronchoalveolar lavage. An enzyme-linked immunosorbent assay for Aspergillus was positive. Invasive pulmonary aspergillosis was diagnosed and micafungin was replaced with amphotericin B, as voriconazole could not be administered owing to the patient’s renal failure. On day 29, the patient developed disseminated intravascular coagulation and died. Autopsy findings revealed fungal invasion of the lung, heart, esophagus, liver, pancreas, and thyroid (Figure 3). To the best of our knowledge, there is one report of IPA associated with BP; in this case, the patient had received DOI: 10.1111/ddg.13947 Invasive pulmonary aspergillosis associated with bullous pemphigoid Clinical Letter