A 47-year-old woman sought medical help for fatigue, fever, and dry cough. She had been healthy and no medical history of any disease. Ten days ago, she developed fatigue, and then was suffered by fever and a dry cough. She presented in a nearby hospital and was hospitalized for further examination. Laboratory data showed elevated white blood cell count of 15.14*10^9/L, severe anemia with hemoglobin of 58g/L, elevated serum C-reactive protein (CRP) level of 190.52 mg/L, and serum creatinine level of 272.9umol/L. Urine test showed mild proteinuria( +-) and hematuria ( +++). Urinary sedimentation revealed numerous red blood cells(RBC) per high power field (HPF). Chest CT showed no obvious infiltration lesions. Previously the patient was treated with transfusion, anti-infection(piperacillin)and other supporting treatment. However, her fever persisted and serum CRP remained in high level after receiving anti-infective treatment for 7 days. Moreover, her creatinine lever soared from 270umol/L to 595.7umol/L within 3 days. Her urine output was about ~ 1000ml per 24 hour on antiuretics with 100mg furosemide and had decreased rapidly. Besides, her serum anti-GBM antibody test was proved to be strong positive(+++), and therefore, she was highly suspicious of anti-GBM disease. Then she was transferred to our hospital for further treatment.
On hospitalization, her blood pressure was 133/80 mmHg, On physical examination, she had anemia appearance without anemia and negative neurological findings.
Laboratory tests showed the following: blood hemoglobin level 79g/L, leukocyte count 12.62*10^9/L with 84.5% neutrophils, serum albumin(Alb) 27.56 g/L, blood urea nitrogen (BUN) 12.25mmol/l, serum creatinine(Scr) 738.38umol/L, and CRP 180.62mg/L. The urinalysis was remarkable for the presence of 1 + proteinuria, 1 + WBC per HPF, and 3 + RBC per HPF. Serum immunological tests showed normal range of complements and immunoglobulins. Antinuclear antibody (ANA), serum double-stranded DNA (dsDNA), myeloperoxidase anti-nuclear cytoplasmic antibody (MPO-ANCA), and proteinase 3-ANCA (PR3-ANCA), phospholipase A 2 receptor (PLA2R) antibody, immunofixation electrophoresis of blood and urine were all negative. However, the anti-GBM antibody titers were higher than the upper limit of the kit (> 400 IU/mL) and semi-quantitive test showed 3+. Repeated blood culture tests were negative for bacteria or fungus. Other pathogens tests like fungus, bacteria, viruses including hepatitis B virus (HBV), hepatitis C virus (HCV), cytomegalovirus (CMV), Epstein-Barr virus (EBV), human immunodeficiency virus (HIV) were proved negative.
Chest CT scan showed no obvious infiltrates in the whole field. Ultrasonography of kidney revealed no obvious abnormal signs. Finally, the diagnosis of anti-GBM disease was established.
A percutaneous renal biopsy done under ultrasound guidance showed a severe crescentic glomerulonephritis (Fig. 1). No extraglomerular vasculitic changes were seen. Immunofluorescence microscopy revealed anti-glomerular basement membrane antibody deposition along the glomerular capillary wall in a typical linear pattern. Electron microscopic studies failed to disclose the presence of any electron-dense deposits within the mesangium or glomerular capillary wall.
She progressed to anuria, and hemodialysis was initiated for the progressively deterioration of renal function according to patient preference. Over a 2-week period, 6 serial plasmapheresis session were given three consecutive day a session with a subsequent decrease in the anti-glomerular basement membrane antibody titer to 184.31units. Pulse methylprednisolone (MP) therapy at a dosage of 0.5 g intravenously each day for 3 days at one cycle and then methylprednisolone 60 mg each day was given after the methylprednisolone pulse therapy.
On hospital day 10, the patient had a generalized seizure with consciousness disturbance, which was quickly controlled by diazepam followed by prophylactic use of levetiracetam, without any residual neurological sequelae. Blood pressure was within normal limits. The findings of electroencephalogram(EEG), echocardiogram(ECG), carotid Doppler studies, and CT scan of the brain were all normal. Magnetic resonance imaging (MRI) scan and angiography of the brain showed multiple ischemic lesions deep inside white matter of bilateral frontal and parietal lobe (Fig. 2A and 2B), accompanied with stenosis of anterior and posterior cerebral artery. In order to confirm cranial vasculitis, contrast MRI of vascular wall was performed and stenosis of cranial vessels was found, including right vertebral artery, left anterior and bilateral posterior cerebral artery (Fig. 2C). A diagnosis of cerebral vasculitis was supported by the clinical manifestation, imaging finding and rapid response to treatment, despite of negative CT and biopsy findings. Angiography was not performed in view of the potential risk and the limited guidance for treatment. The anti-GBM Ab level was 170 units then. ANCA levels were again negative. Pulse methylprednisolone and plasmapheresis were continued and cyclophosphamide was not added due to the extremely low level of lymphocytes counts.
The patient developed late-onset hemorrhage and formation of pseudoaneurysm (Fig. 3A-B) one week after renal puncture. Selective renal artery embolization under the guidance of digital subtraction angiography (DSA) was employed one week later, due to conservative therapy failed to address the condition. During the operation, angiography revealed the “beading” changes in small branches of renal artery (Fig. 3C). Therefore, renal vasculitis was highly considered. Combined with pre-existing neurological vasculitis, there were already two possible sites of vasculitis.
On 30th hospitalization day, she began to present with hemoptysis, manifested as a sudden newly-onset bilateral obvious pulmonary infiltrates on chest CT (Fig. 4), revealing alveolar hemorrhage associated with anti-GBM disease. Hemoptysis quickly resolved over the next 3 days after the second MP pulse therapy (500mg*3 days and followed by 60 mg/day and tapered by 40mg/day) and plasmapheresis were initiated. Two weeks later, titers of anti-GBM antibodies were found below the lower limit of the reference range (Fig. 5). The patient maintained a neurologically healthy condition on oral prednisone therapy. She was discharged on regular outpatient hemodialysis.