A 57-year-old woman presented to the rheumatology clinic with recurrent fever and painful ulcers on her legs since two months. Eight months prior to current presentation, she developed vertigo and decreased hearing in her left ear which she felt was "full of air" all the time. She was found to have sensorineural deafness in her left ear. Two weeks later, she developed fever with chills. A chest radiograph revealed infiltrates in her right lung and an elevated ESR. She was treated with oral antibiotics which relieved her symptoms. Then she developed gingival hypertrophy and a CT scan of the paranasal sinuses revealed subcutaneous soft tissue thickening of the right buccal area suggestive of an inflammatory process. She was treated with ibuprofen and felt better. Her past medical history was notable for hypothyroidism for 20 years and she as well was maintained on 50 mcg of thyroxin daily. She had undergone hysterectomy for uterine fibroids 15 years ago. She reported no recent travel history. Of note, she revealed contact with sick animals. She nursed her paralyzed pet dog and also had cats. She was treated with antibiotics yet continued to spike fever and came to our center for comprehensive evaluation. On examination, she appeared weak and ill. The temperature was 37.5 C, the blood pressure 139/69 mm Hg, the pulse 78 beats per minute, and the respiratory rate 16 breaths per minute, with 99% oxygen saturation at room air. Erythematous tender nodules were noticed on bilateral lower extremities (Figure 1).
The remainder of the examination was unremarkable. Her complete blood count revealed normocytic, normochromic anemia with normal white cell and platelet count. Her biochemistry showed normal kidney and liver function. No active sediment was present on urinalysis. Her three sets of blood cultures and one urine culture reported no growth. The test for latent tuberculosis by interferon gamma release assay (IGRA) was also negative. Serology for Brucella abortus and melitensis also came negative. Tests for chronic viral hepatitis B and C were also normal. Serological tests for connective tissue disease were negative as was the serum angiotensin converting enzyme level. Other relevant investigations are outlined in Table 1. An upper abdominal ultrasound showed hypoechoic, cystic lesions scattered across both lobes of the liver (Figure 2). A subsequent CT scan of the abdomen with contrast showed multiple oval hypoattenuating lesions in both lobes of the liver (Figure 3).
On liver biopsy there was evidence of cholestasis and multiple large irregular areas of necrosis, palisaded by epitheloid cells with associated granulomatous inflammation with a number of plasma cells (Figure 4).
Acid-fast bacilli culture of liver biopsy specimen after six weeks came out negative. Meanwhile, the patient continued to spike fever with maximum temperature of 101 F. Leg lesions were becoming worse with central necrosis and purulent discharge (Figures 5 and 6).
Pus cultures were negative for bacterial, fungal, and mycobacterial growth. A biopsy of the skin was performed. Pathological examination of frozen sections revealed surface ulceration with fibrinoid necrosis and vasculitis involving superficial and deep dermal vessels along with granuloma formation, neutrophilic infiltration, and debris (Figure 7).
Immunohistochemical testing was performed on biopsy specimen using immune-alkaline phosphatase technique which came negative for mycobacterial species. Real-time PCR for mycobacterial species also turned out to be negative. It was concluded from the skin biopsy that the patient had cutaneous granulomatous vasculitis. Treatment was commenced with prednisone 1 mg/kg/day and the patient was offered induction with cyclophosphamide which she refused due to associated toxicities. Meanwhile, azathioprine 2 mg/kg/day was added to prednisone. After seven weeks on prednisone and six weeks of azathioprine her lesions had healed almost completely (Figure 8). She was maintained on prednisone 5 mg bid and azathioprine 50 mg bid with healing lesions. A repeat CT scan of the abdomen revealed normal architecture of hepatic parenchyma.
Therefore, considering a chronic inflammatory process characterized by hearing loss, gingival hypertrophy, granulomatous hepatic lesions, and cutaneous ulcers with necrotizing granulomatous inflammation on skin biopsy, a unifying diagnosis of granulomatosis with polyangiitis (GPA) was made.