A 28-year-old male patient was admitted to the hospital after having oral pain for 1 month, skin ecchymosis with ulceration for 20 days, and abnormal renal function test results for 3 days. He had a medical history of chronic, untreated hepatitis-B for 18 years. One month prior to the admission, the patient began to experience oral pain. He was diagnosed with oral tuberculosis and received anti-tuberculosis treatment with rifampin and isoniazid, as well as appropriate analgesics when needed. He showed no improvement after 10 days of the treatment and developed ecchymosis and petechiae in both lower extremities. He was diagnosed with allergic purpura and received anti-allergic treatment with loratadine. Three days before coming to the hospital, he had shown no improvement with respect to oral pain or skin ecchymosis and had also developed foot ulcers. He returned to the hospital for further care.
After hospital admission, a physical examination revealed an anemic appearance, with no edema in the face or lower extremities. The patient had coarse breath sounds with wet rales on lung auscultation. There was a 5 cm x 5 cm grayish-white necrotic tissue bulging from the right side of the oral palate (Figure 1A). The lower extremities showed ecchymosis with skin ulceration and necrosis in the left toes (Figures 1B,C). Laboratory test results were as follows: Red blood cell count, 2.56 x 1012/L; hemoglobin, 67 g/L; eosinophils, 21.2%; serum albumin, 31.9 g/L; alanine aminotransferase, 81.3 U/L; aspartate aminotransferase, 106 U/L; serum creatinine, 538 mumol/L; uric acid, 584 mumol/L; cholesterol, 6.37 mmol/L; low-density lipoprotein, 4.06 mmol/L; C-reactive protein, 34.4 mg/L; hepatitis-B surface antigen HBsAg positive, hepatitis-B virus DNA <102, negative anti-nuclear antibody, and anti-double-stranded DNA antibody, normal serum immunoglobulin (Ig), IgA, IgM, and IgG, complement C3 and C4, and serum-free k- and lambda-levels; normal serum anti-myeloperoxidase antibody level; and anti-proteinase 3 (PR3) antibody > 400 RU/ml. Urinary analysis showed urine protein 4+, urine microalbumin/creatinine 2,654 mg/g Cr. A T-SPOT tuberculosis test and myocardial injury markers were negative. The oral ulcer smear was negative under acid-fast staining. Chest computerized tomography (CT) examination revealed bilateral multiple nodular shadows and pulmonary infection. Otolaryngoscopy suggested nasal mucosal erosion and necrosis. Sinus CT showed maxillary and ethmoid sinusitis. The Birmingham Vasculitis Activity Score was 27. Echocardiography showed mild mitral regurgitation. Electromyogram of extremities was unremarkable with normal sensory and motor functions.
Pathological examination of the renal biopsy specimen showed that 2 of 14 glomeruli had global sclerosis. Two glomeruli had segmental necrosis of the capillary loops, with no cellular or fibrous crescents. There were extensive detachments of renal tubular epithelial cells and exposure of the basement membrane, with infiltration of small focal individual nucleated cells and eosinophils in the renal interstitium. The electron microscopic findings were consistent with the light microscopy findings. Immunofluorescence examination showed linear depositions of IgG(+) along the glomerular basement membrane, with negative staining for IgG1, IgG2, IgG3, IgG4, IgA, IgM, C3, C4, k, lambda, and C1q. The final renal pathology diagnoses were acute tubulointerstitial kidney injury and antineutrophil cytoplasmic antibody (ANCA)-associated systemic vasculitis with kidney injury (nodular necrotic lesions) (Figures 2A,B).
Based on the 2016 treatment guidelines for vasculitis issued by the European League Against Rheumatism, we administered methylprednisolone 40 mg/day and cyclophosphamide 0.6 g intravenously for 10 days. The patient showed gradual improvement, including less oral pain, reduced size of skin ulcers, the disappearance of ecchymosis, and healing toe ulcers. His serum creatinine also decreased to 125 mumol/L.
We followed up with this patient every 1-2 months and performed CT scanning and laryngoscopy at the second follow-up. Results suggested that pulmonary nodules dissipated and ethmoid sinusitis improved. There had been a total of eight follow-up visits to date. His symptoms have significantly improved. Furthermore, the vasculitis score decreased to 4. Serum PR3 was normalized and anemia was corrected. Serum creatinine and estimated glomerular filtration rate returned to normal. Urine microalbumin/creatinine decreased to <1,000 mg/g Cr. Oral granuloma, foot ulcers, and nose and throat lesions were also healed (Figures 3A,B).