A 12-year-old Caucasian girl presented at her general practitioner because of swollen legs and spotted skin macular rash over her face, on her arms and on her chest. She was also complaining about headaches, abdominal pain, arthralgia and macroscopic haematuria. In the last few weeks she had gained 4 kg body weight. At admission to the children’s hospital she presented in a poor general state with hypertension of 143/99 mmHg, considerable oedema of the legs and facial rash. Laboratory results showed anemia (hemoglobin 9.2 g/dl), leukopenia (2.650/μl), normal thrombocyte counts, acute renal failure (creatinine 5.8 mg/dl, urea 166 mg/dl) with hyperkalemia (6.4 mmol/l) and metabolic acidosis. Furthermore, macroscopic haematuria with dysmorphic erythrocytes, proteinuria of 6.6 g/m2 body surface area per day, serum albumin of 19.6 g/l and oliguria were observed. Abdominal ultrasound demonstrated ascites but no pleural or pericardial effusion, enlarged kidneys with increased echogenicity and lacking corticomedullary differentiation.
Further diagnostic tests showed extremely low complement levels (C3 and C4 below detection level), markedly elevated anti-nuclear-antibodies (ANA 1:320; normal value <1:100) and a particularily strong increase of anti-double-stranded nuclear antibodies (anti-dsDNA, 1500 U/ml; normal value <7 U/ml). Other autoimmune phenomena were carefully excluded: tests for ANCA, anti-GBM, anti-phospholipid antibodies, and anti-extractable nuclear antigen all yielded negative results. Neither the patient nor her relatives had any other immune abnormality at present or in the past history. The patient did not show any signs of hemolysis or abnormal coagulation.
Renal biopsy performed immediately in the next morning confirmed the diagnosis of renal involvement in lupus erythematosus showing diffuse proliferative glomerulonephritis (GN) with cellular crescents in 15 of 18 glomeruli, severe interstitial oedema, acute inflammation and acute tubular necrosis (Figure 1a-c). On immunofluorescence, IgA, IgG, IgM as well as C1q and C3c depositions, i.e. a so-called fullhouse pattern, were detected in a mesangiocapillary pattern (Figure 2). This pattern of immune complex deposition was also confirmed on electron microscopy. Of note, tubuloreticular or fingerprint like structures were not present. Therefore, a very active diffuse global proliferative lupus nephritis (WHO IV B, ISN/RPS IV-G (A)) was diagnosed. Of note, no chronic changes, i.e. tubular atrophy or interstitial fibrosis, were seen in the kidney. Due to mild depressive mental state an additional EEG was performed. The result showed dysrhythmic oscillations that led us to hypothesize cerebral vasculitis. MRI angiography, however, was normal.
After the diagnosis of severe proliferative lupus nephritis was confrmed by renal biopsy we intensively discussed the therapeutic options and decided to immediately initiate the standard immunosuppressive treatment schedule according to the Euro Lupus Trial [3] with methylprednisolone pulse therapy (4 pulses with 400/200/200/100 mg/m² BSA respectively) followed by oral prednisone administration tapered from 60 to 10 mg/m²/48 h over an 48 week period, intravenous cyclophosphamide pulse (in total 6 pulses in 4 weeks interval) and additionally 10 courses of immunoadsorption over a period of 2 weeks. The general clinical condition rapidly improved, but the patient still needed intermittent hemodialysis due to oligoanuria and antihypertensive treatment with amlodipine, atenolol and enalapril. She received pneumocyctis carinii prophylaxis and standard therapy for end stage renal disease. As no substantial improvement of renal function could be achieved after the 2nd CPH pulse and immunoadsorption, the patient received a Cimino fistula for intermittent hemodialysis. Unexpectedly, in the further follow-up diuresis increased and subsequently also serum creatinine levels substantially improved so that hemodialysis could be discontinued about 12 weeks after initial admission. Maintenance immunosuppressive therapy with mycophenolate mofetil (MMF) was started 3 months after admission (Figure 3). Of course at this stage a re-biopsy would have been very helpful to adjust the therapy and indeed this was discussed with the patient and her parents who refused in view of the positive clinical course and the well-known, albeit low risk of a kidney biopsy.
At further follow-up creatinine levels, proteinuria and complement C3 values improved and returned to normal range. ANA and dsDNA antibodies were only intermittently detectable. The patient had 2 short episodes of clinical relapse with leukopenia, proteinuria and increase in dsDNA that were successfully treated for 4 weeks with an increased dosage of oral steroids. Today, six years after the initial presentation the patient is in complete remission under permanent immunosuppression with MMF (2x750mg) in combination with prednisone (5 mg/48 h) and enalapril (40 mg). She has normal renal function with creatinine levels continuously in the normal range, no proteinuria and no other signs of SLE.
