A 44-year-old woman visited the department of ophthalmology in our hospital because of hyperemia in both eyes, which had rapidly worsened two months prior. She was diagnosed with bilateral necrotizing scleritis (Figure 1(a)) and was referred to our department to assess the involvement of an autoimmune disease. Her medical history revealed that she had been experiencing pus-like discharge from bilateral nipples for the past three months and had thus visited a dermatologist; she was treated with antibiotics, but there was no improvement. More recently, she had suffered from nasal congestion and discharge. She was afebrile, and auscultation revealed no rales in her lung fields and no abnormal heart sounds. Subcutaneous induration was observed in both breasts, along with discharge from the nipples (Figure 1(b)). Pale erythema and a skin ulcer were found on the right breast (Figure 1(c)). No lymph node enlargement was observed from the neck to the axilla. Laboratory test results showed an elevated white blood cell count (10,730/muL) with high polymorphonuclear neutrophil level (70.1%), normal liver and renal function, C-reactive protein (CRP) in almost normal range (1.2 mg/L), and a slightly elevated erythrocyte sedimentation rate (ESR) (48 mm/h). Immunological tests were negative for rheumatoid factor, antinuclear antibodies, and myeloperoxidase- (MPO-) ANCA; however, PR3-ANCA was slightly elevated (5.9 U/mL; normal value <2.0 U/mL). The patient tested negative for tuberculosis (TB) in an interferon-gamma releasing assay. Urinalysis showed no abnormalities, including hematuria and proteinuria. Computed tomography (CT) of the thorax indicated no abnormalities in the lung fields; however, tumor-like lesions were found in her breasts (Figure 2(a)). CT of the paranasal sinuses showed sinusitis in the right maxillary sinus, and nasopharyngolaryngoscopy demonstrated purulent discharge from the middle meatus. Mammography demonstrated a round, microlobulated, and high-density mass lesion in the right breast, which was classified as category 4, and a 7.5 cm circumscribed, round, and high-density mass lesion in the left breast, which was classified as category 3 (Figure 3). Ultrasonography demonstrated a well-defined, rough-margined, heterogeneous, low-echoic, and unmeasurable giant mass lesion in the left breast and an irregular-shaped, ill-defined, heterogeneous mass lesion in the right breast. Breast cancer, fibroadenoma, sclerosing adenosis, mastitis, and abscess formation were differential diagnoses.
A bacterial culture test and cytological examination of the exudate from the nipples were performed to differentiate between infection and neoplastic lesions. Although a small amount of Serratia marcescens, Corynebacterium species, Anaerococcus species, Finegoldia magna, and Peptoniphilus species were present in the bacterial culture, infectious mastitis was ruled out considering her clinical course. Cytology revealed infiltration of inflammatory cells, which were mainly lymphocytes and agglomeration of epithelioid cells containing multinucleated giant cells, without malignant cells. Core needle biopsy of her left breast (from the location of the arrow in Figure 2(a)) showed inflammatory cell infiltration consisting of lymphocytes with surrounding fibrotic lesions without vasculitis. A biopsy of a skin ulcer on the right chest wall (from the location of the arrow in Figure 1(c)) showed granuloma formation, including lymphocytes and plasma cells outside the blood vessels without vasculitis. These lesions were suspected as granulomatous mastitis considering breast imaging, nonsignificant bacterial culture, and cytological and pathological examination. Based on the presence of bilateral scleritis, cutaneous granuloma formation, inflammatory breast masses, right maxillary sinusitis, and PR3-ANCA positivity, the patient was diagnosed with a probable case of localized GPA according to the diagnostic criteria of the Ministry of Health, Labor and Welfare of Japan. She was treated with methylprednisolone pulse therapy, followed by a daily dose of 40 mg of prednisolone (PSL) and trimethoprim/sulfamethoxazole. Her symptoms improved, and the titers of CRP, ESR, and PR3-ANCA were normalized. Fifteen months later, when PSL was tapered to 5 mg/day, she complained of cough and nasal discharge. The titer of CRP and ESR had increased to 95.8 mg/L and 80 mm/h. The PR3-ANCA titer had increased to 26.5 U/mL, and whole-body CT revealed pulmonary consolidation in the right lower lobe (Figure 2(b)) and a small nodule in the right breast (Figure 2(c)) as new lesions with recurrence of maxillary sinusitis (Figure 2(d)). A biopsy of the small nodule in the right breast (from the location of the arrow in Figure 2(c)) showed lymphocyte-dominant inflammatory cell infiltration and granulomas with polynuclear giant cells around the blood vessels in the subcutaneous fat layer, which can be interpreted as necrotizing granulomatous vasculitis (Figures 4(a) and 4(b)). Granulomatous lesions were found in the nasal cavity, and a biopsy of this site showed necrotizing granulomatous inflammation with giant cells. These lesions did not contain caseous necrosis. Thus, the diagnosis was conclusively confirmed as a case of localized GPA; daily PSL was increased to 10 mg, and remission induction therapy for GPA, consisting of four once-weekly doses of 375 mg/m2 rituximab (RTX), was introduced. After treatment, all symptoms gradually resolved, and the titers of CRP, ESR, and PR3-ANCA normalized.