A previously healthy 7-year-old boy was admitted to the hospital for evaluation of a 2-week history of intermittent fever to 40°C, abdominal pain with guaiac-positive stools, and migratory arthralgias involving major and minor joints. Several days before admission, he developed periorbital and peripheral edema, as well as pancytopenia. Admission blood pressure was normal. Physical examination showed an erythematous confluent macular rash on the left cheek, conjunctival injection, edema of the face and lower legs, upper abdominal tenderness, hepatomegaly, and scattered ecchymoses over the ankles. Abnormal admission laboratory study results included the following values: white blood cell count, 3.3 × 109 cells/L; hemoglobin, 9.0 g/dL (90 g/L); platelet count, 36 × 109 platelets/L (36 × 103/μL); reticulocyte count, 2.8%; erythrocyte sedimentation rate, 47 mm/h; C-reactive protein, 6.5 mg/dL; serum creatinine, 1.3 mg/dL (115 μmol/L); urine protein-creatinine ratio, 2.7; total protein, 4.9 mg/dL (49 g/L); serum albumin, 1.7 g/dL (17 g/L); lactate dehydrogenase, 214 U/L; C3, less than 40 mg/dL (<4 g/L); C4, less than 8 mg/dL (<0.8 g/L), and urinalysis with 3+ protein, 3+ blood, 12 to 16 dysmorphic red blood cells/high-power field, and hyaline casts. Transaminase levels were normal. Peripheral smear did not show schistocytes.
During the first week of hospitalization, our patient developed hypertension with blood pressure of 150/81 mm Hg, creatinine level increased to 2.8 mg/dL (248 μmol/L), and he had nephrotic-range proteinuria. Lactate dehydrogenase level increased to 2,495 U/L, and he continued to experience daily fever spikes. During his febrile period, while cultures and serological test results were pending, he was empirically treated with vancomycin, doxycycline, and ceftriaxone. He required 1 blood transfusion for anemia. Multiple imaging and diagnostic studies were negative for occult sites of infection, malignancy, or rheumatological disease (). Serum and urine protein electrophoresis showed distinct bands of restricted mobility, suggesting the presence of monoclonal proteins (). Serum immunofixation electrophoresis showed monoclonal components typed as immunoglobulin M (IgM) λ and IgG λ at 1 g/dL. Urine immunofixation electrophoresis showed a monoclonal IgG λ protein and monoclonal free λ and κ light chains. Analysis of cryoglobulins present in serum showed monoclonal IgG λ protein, monoclonal IgM λ protein, monoclonal free κ protein, and polyclonal IgM protein. Epstein-Barr virus viral load showed 200 copies/μg of DNA (IgG antibody positive, IgM antibody negative). The patient underwent bone marrow biopsy that showed a nonspecific hypocellular marrow.
Laboratory Studies Performed
Figure 1 Immunofixation electrophoresis of the patient’s (A) serum and (B) urine showed (A) monoclonal components typed as immunoglobulin M (IgM) λ and IgG λ and (B) a monoclonal IgG λ protein and monoclonal free λ and (more ...)
A percutaneous kidney biopsy was performed on hospital day 15. The biopsy specimen showed diffuse and global endocapillary hypercellularity with abundant mononuclear cells and basement membrane remodeling with duplication and cell interposition. Proteinaceous intracapillary thrombi were not seen. The interstitial compartment showed patchy minimal mononuclear inflammatory cell infiltrates. Tubules, arteries, and arterioles were without diagnostic abnormalities (). Immunofluorescence studies showed trace granular accumulation of IgG, IgM, C1q, and κ and λ light chains along the peripheral glomerular capillary walls. C3 staining was negative.
Figure 2 Light microscopy. Glomeruli show global hypercellularity with dilatation of capillaries. Crescents are not present. The interstitium shows only minimal patchy mononuclear inflammatory cell infiltrates. Tubules are without significant abnormalities. (Periodic (more ...)
Electron microscopy showed glomerular capillaries distended by mononuclear cells with areas of basement membrane remodeling and segmental accumulation of electron-dense deposits along the lamina rara interna (). Also present were unusual rhomboid intracytoplasmic inclusions with a crystalloid substructure (). A diagnosis of membranoproliferative glomerulonephritis type 1 was rendered.
Figure 3 Electron microscopy. (A) Low magnification shows a peripheral glomerular capillary tuft dilated by abundant mononuclear cell elements, some with large dense intralysosomal storage products that are also seen in podocytes. (Original magnification ×2,000.) (more ...)
During the next 14 days, the patient’s fever resolved and all key laboratory markers returned to normal. No immune suppression was administered. At 2 months after discharge, his blood pressure, creatinine, and complement levels were normal, and the child reported feeling well. Urine showed 1+ protein but otherwise was normal. At a 20-month follow-up, all serological test results continued to be negative. Creatinine clearance was normal, and urine protein was absent.