Fever, nephrotic syndrome, and rapidly progressive renal failure

A 52-year-old African woman, living in France since 5 years, presented with dyspnea and pyrexia. She had a 1-month history of sore throat treated with amoxicillin, migratory polyarthralgia, drenching night sweats, and an evanescent, maculo-papular, non-pruritic rash mainly on her limbs lasting less than 1 week at a time. She denied smoking, alcohol abuse, and illicit drugs use. She had no risk factors for HIV. Examination on admission revealed a temperature of 39.51 degrees C, tachycardia, a blood pressure of 120/70mm Hg, pallor, jaundice, splenomegaly, and bilateral inflammation of knee and ankle joints with synovitis, and severe tenderness of the wrist with signs of fluid overload. There was no sign of meningeal irritation, no focal neurological deficit and normal fundus examination. There were fine crepitations involving the left lung base. Heart sounds were normal on auscultation with no murmur. She was admitted for analgesia and antibiotics pending the results of infective screens and blood tests. Peripheral smear showed no malarial parasite. Her coagulation profile was normal and there was no biochemical evidence of hemolysis. Biochemistry values are summarized in Table 1. Human Immunodeficiency Virus serology, plasma HIV viral load, and p24 determination were negative. Serologies for, hepatitis B and C, Parvovirus B19, cytomegalovirus, Epstein-Barr virus, leptospira, bartonella, rickettsia, chlamydia, mycoplasma pneumoniae, legionella, Widal test, rapid malaria test, toxoplasma, and syphilis were all negative. Brucella agglutination test and leishmania leukococentration were also negative. Hemoglobin electrophoresis ruled out sickle cell disease. Laboratory evaluation for systemic or malignant diseases, including rheumatoid factor, antibodies to double-stranded deoxyribonucleic acid, smooth muscle cell, liver/kidney microsomal, mitochondrial, anti-cardiolipin, anti-Scl, antineutrophilic cytoplasmic antibody, anti-Ro, anti-La, anti-SM, anti-ribonucleoprotein, anti-Jo-1, and anti-glomerular basement membrane antibodies were all negative. Immunological parameters were noncontributory with polyclonal hypergammaglobulinemia, normal immunoglobulin (Ig) A, IgM, complement levels, and negative cryoglobulinemia. Chest X-ray was normal. Renal ultrasound showed enlarged, swollen kidneys measuring 12.6cm in length each. Total body computed tomography revealed splenomegaly, with the rest of the scan being unremarkable. This association between a nephrotic syndrome, fever, cutaneous lesions, pharyngitis and arthralgias suggested the diagnoses of either postinfectious or membranoproliferative glomerulonephritis. A first trans-jugular kidney biopsy was then performed (Figure 1). Trans-thoracic echocardiography suspected the presence of mitral valve endocarditis. Despite empirical treatment with Cefotaxim and gentamicin, she did not improve. The maculo-papular rash on her limbs persisted alongside with high fevers. Bone marrow biopsy and aspiration revealed moderately hyper-cellular marrow with trilineage maturation, and increased number of macrophages, however, without hemophagocytosis. Repeated serologies and cultures were negative. A second trans-oesophageal echocardiography revealed that the systolic function and chamber sizes were normal; there was no valvular dysfunction, evidence of vegetations, nor pericardial effusion. Her renal function worsened (creatinine peaking at 600 mu mol/l 1 week later) and hemodialysis became necessary. Suspecting a rapidly progressive glomerulonephritis, of postinfectious or vasculitic nature, a second trans-jugular kidney biopsy was performed (Figures 2 and 3). At this stage we were faced with a severely ill 52-year-old African woman presenting with pyrexia of unknown origin, migratory polyarthopathy, fleeting maculopapular rash, pancytopenia, and rapidly progressive glomerulonephritis with renal failure requiring renal support.