Crescentic Glomerulonephritis Requiring Hemodialysis and Elevated MPO-ANCA Level and Vasculitis Allergica Cutis in a 21-Year-Old Girl

Ismail H. Kara, MD; M. Emin Yilmaz, MD; Yasin Sari, MD; Ali Gür, MD; Hüseyin Büyükbayram, MD


May 01, 2002

Case Report

In March 1998, the patient was a 19-year-old girl with a 10-day history of emesis, myalgia, arthralgia, and weight loss, who was found on routine physical examination to have edema in her face and lower extremities. A year previously, she had developed a serous otitis attack, but without a history of allergy or asthma. Follow-up laboratory evaluation revealed: proteinuria (3+), 2-3 RBC/hpf in the urine, serum creatinine 3.6 mg/dL, creatinine clearance 67 mL/min, blood urea nitrogen (BUN) 33 mg/dL, and albumin 3.1 g/dL.

After 25 days, she was referred to a nephrologist for evaluation and treatment. Physical examination revealed high blood pressure (160/100 mm Hg) and 3+ pitting edema in the lower extremities. Laboratory data included 5.5 g/24 hour proteinuria, negative Bence-Jones proteinuria, 8-10 RBC/hpf in the urine, serum creatinine 12 mg/dL, BUN 77 mg/dL, calcium 9.5 mg/dL, phosphorus 4.3 mg/dL, total protein 5.8 mg/dL, albumin 2.5 g/dL, C-reactive protein (CRP) 3+, ASO 50 Todd units, Latex RF (-), erythrocyte sedimentation rate (ESR) 105 mm/hour, hematocrit (hct) 26%, normochromic normocytic red cells, leukocyte count of 13.400/mm3, normal levels of serum complement (C3c and C4), and negative findings in the following: cryoglobulin, immune-complex, ANA, anti-ds DNA, and anti-GBM antibody. However, 4+ positive MPO-ANCA, negative PR3-ANCA (enzyme-linked immunosorbent assay [ELISA] was used to determine the ANCA), and positive anti-hepatitis C virus (HCV) were found. HLAs were A11, A29, B14, BW4, BW6, CW7, DR1, and DQ1.

Renal biopsy showed RPGN with diffuse necrotizing and crescentic changes with 70% glomerules involved on light microscopy. Immunoglobulin (Ig) deposits or electron dense deposits were absent by immunofluorescence and electron microscopy, respectively. Pulse corticosteroid combined with cytotoxic agent (cyclophosphamide) treatment was initiated. However, the BUN and creatinine values steadily rose over days to weeks. A 10-times plasmapheresis was performed, but the patient was resistant to therapies. The combined cytotoxic treatment was stopped at 6 months. Finally, severe chronic renal failure developed. Arteriovenous fistula was placed and the patient was admitted into a chronic hemodialysis program in July 1998. During the course of dialysis, external otitis was diagnosed in right ear. Enterobacter cloacae was isolated (best clinical response for ciprofloxacin with MIC [≤ 0.5 mcg/mL]).

The patient was undergoing chronic hemodialysis with low-flux polysulphone dialyser and bicarbonate as dialysate (kT/V: 1.4). She developed arthralgia that was typically a migratory polyarthropathy characterized by sequential involvement of different joints in an asymmetrical pattern. She also developed various skin lesions, including erythematous maculopapular eruptions and subcutaneous nodules. Vasculitic ulcers erupted on her mouth and lips, elbows, wrists, ankles, fingers, and extremities (figure 1). First exacerbation of painful skin lesions occurred in August 1999, when she also had a sore throat and throat irritation, weakness, fever (38.2°C), weight loss (about 12 kg), and hematoma in bladder. Serum protein electrophoresis demonstrated a spike in the gamma region (21.8%, reference ranges: 10.7-19.2). Quantitative Ig assays revealed: IgA 140 mg/dL, IgG 128 md/dL, IgM 120 mg/dL, and total IgE 1055 IU/ml (0-87 IU/mL).

Case had a migratory polyarthropathy characterized by sequential involvement of different joints in an asymmetrical pattern and vasculitis allergica cutis on her mouth, lips, and hands.

The disease became worse in February 2000. The patient had a lower blood pressure (80/50 mm Hg), chronic headache (computed tomography was normal), and painful skin lesions. She also developed mononeuritis multiplex, especially in the peroneal, ulnar, and median nerves; abdominal pain; ascites; progressed dyspnea attacks (required intermittent O2); anemia; and eosinophilia. Laboratory examinations showed the following results: hct 21%, 6,800 white blood cells/mm3 (57% polymorphonuclear cells, 18% eosinophils, 17% lymphocytes, 7% monocytes, 1% basophils), platelets 303,000/mm3, BUN 128 mg/dL, creatinine 6.5 mg/dL, protein 7.5 g/dL, albumin 2.2 g/dL, Ig-lambda 435 mg/L (normal: 110-240 mg/L), Ig-kappa 456 mg/L (normal: 200-440 mg/L), kappa/lambda ratio 1.051, beta2-microglobulin 60 and later 86 mg/L (normal: 1-3 mg/L), ALT 17 IU/L, AST 15 IU/L, cholesterol 122 mg/dL, triglyceride 207 mg/dL, calcium 12.4 mg/dL, phosphorus 3.2 mg/dL, parathyroid hormone 3 pg/mL (normal:12-72, reference interval: 1-2500 pg/mL), serum ferritin > 2000 ng/mL (normal: 13-150 ng/mL), Protime mechanism 85% (N.W: 70-120), INR 1.118, aPTT 47.6 (N.W: 30-40), EPO 22.6 (N.W: 1.6-34) mIU/mL, negative ana, negative anti-ds dna, negative AMA assay, 1+ positive MPO-ANCA, positive anti-HCV but negative HCV RNA polymerase chain reaction (PCR), negative hepatitis B serology, and high levels of interleukin-6 20 pg/mL and soluble interleukin-2 receptor 3115 U/mL. Bacterial culture of skin lesion and blood were negative. Corticosteroid treatment was used, but no significant response was obtained.

Chest x-ray and thoracic magnetic resonance imaging (MRI) (with intravenous Gd-DTPA injection) revealed cardiomegaly and bibasilar minimal pleural effusion but no other specific findings such as cavitation. Electrocardiogram showed sinusal tachycardia, short PR and QTc interval, and left ventricular hypertrophy with repolarization abnormality (ST-T abnormality); abdominal ultrasonography showed small kidneys, minimal splenomegaly, and moderate ascites. Echocardiography revealed increases in left ventricle wall thickness, 60% left ventricular ejection fraction, and pericardial effusion (about 1.8 cm). Whole body scanning with intravenous injection of 15 mCi Tc-99m MDP revealed normal radiopharmaceutical biodistribution of bony structure.

According to laboratory, clinical, and histopathological features, it was suggested that the patient had an expression of mPA. After the last painful episode, the photomicrograph of skin biopsy from the left wrist showed severe necrotizing vasculitis with adjacent leukocyte infiltration and leukocytoclasia, especially round vessels by hematoxylin-eosin stain (Figure 2). Cytopathology of ascitic fluid revealed lymphocytes and macrophages in proteineous background. After 31 months of being followed, the patient died because of cardiopulmonary insufficiency while undergoing hemodialysis in September 2000.

Skin biopsy shows severe necrotizing vasculitis with adjacent leukocyte infiltration and leukocytoclasia, especially round vessels by hematoxylin-eosin stain (HE x 40).


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