A 7-year-old girl presented with a 6-week history of persistent fever, fleeting pruritic rash, arthralgia, and gross hematuria. Two weeks preceding this, she and her family had experienced severe upper respiratory symptoms, and streptococcal pharyngitis was diagnosed in her mother. On examination, the patient had normal vital signs, mild peripheral edema, and a 2 to 3/6 systolic murmur localized over the cardiac apex. The rash was migratory, primarily involving trunk and limbs (Fig 1). Hemoglobin level was 12.7 g/dL (127 g/L), white blood cell count was 15 × 103/μL (14.5 × 109/L), and C-reactive protein level was 14.5 g/dL (145 mg/L). Serum electrolyte, blood urea nitrogen, and creatinine levels were normal. Urinalysis was 4+ for protein and showed greater than 100 red blood cells/high-power field with red blood cell casts. Her complement 3 (C3) level was low at 68 mg/mL (0.68 g/L), but C4 level was normal at 24 mg/mL (0.24 g/L). Results for all cultures, including throat swab, were negative. Initial antistreptolysin O titer was increased at 250 IU/L and a titer repeated in a week was 325 IU/L. Echocardiography showed a small pericardial effusion and mild mitral regurgitation. Significant proteinuria and persistent hematuria in this unusual setting led to a renal biopsy (Figure 2, Figure 3).
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The rash is erythematous with well-defined, but irregular, borders and central clearing. In the presence of the associated clinical manifestations, the likely diagnosis is erythema marginatum.
What do you see under the light microscope in Fig 2?
Segmental endocapillary and extracapillary proliferation with a fibrocellular crescent and a patchy cellular infiltrate in the interstitium. Immunofluorescence microscopy showed mesangial and capillary staining for C3, but was negative for immunoglobulin G, immunoglobulin M, immunoglobulin A, and C1q.
What is the characteristic lesion indicated by the arrow seen on EM in Fig 3 and what is its significance?
The arrow indicates a subepithelial electron-dense hump characteristic of poststreptococcal glomerulonephritis. Electron-dense deposits represent localization of immune complexes. It is postulated that upregulation of adhesion molecules on the endothelium and activation of complement in the more proximal layers of the glomerular capillary wall result in chemoattractant generation, leukocyte recruitment, and release of a variety of proteolytic enzymes, resulting in hematuria and proteinuria. Approximate correlation between degree of proteinuria and number of subepithelial deposits was shown.1
What is your diagnosis?
Acute rheumatic fever with concomitant poststreptococcal glomerulonephritis. The case satisfied revised Ducket-Jones criteria with 1 major (erythema marginatum) and 2 or more minor criteria (fever, arthralgia, leukocytosis, and increased C-reactive protein level).
The increasing antistreptolysin O titer confirmed recent streptococcal infection and echocardiography was consistent with World Health Organization criteria for organic subclinical carditis.2 The presence of hematuria with red blood cell casts suggested concomitant glomerulonephritis, and the low C3 level with characteristic findings in the renal biopsy specimen was consistent with poststreptococcal glomerulonephritis. Antistreptolysin O titer at 1-month follow-up, although decreasing, was still significantly increased at 265 IU/L.
Although the association of renal disease and acute rheumatic fever has been well described since Rayer’s report in 1840, its frequency and nature remain debatable. Retrospective autopsy reviews reported glomerular involvement in 3% to 38.6%, but were not substantiated with EM findings.3 In the only prospective study examining the relationship between acute rheumatic fever and poststreptococcal glomerulonephritis, none of the EM findings were classic for this kidney disease, although 6 of 22 had light microscopy features of glomerulonephritis.4 Although there are a number of rheumatogenic strains of streptococcus, there are fewer nephritogenic strains and only 3 (M1, 3, and 12) were associated with both sequelae.5 This might explain the infrequent coincidence of the 2 diseases.
Final Diagnosis
Acute rheumatic fever with concomitant poststreptococcal glomerulonephritis.
References
1. 1Sorger K, Gessler M, Hubner FK, et al.Follow-up studies of three subtypes of acute postinfectious glomerulonephritis ascertained by renal biopsy. Clin Nephrol. 1987;27:111–124. MEDLINE
2. 2Rheumatic fever and heart disease: Report of a WHO Expert Consultation. Geneva, 29 October–1 November 2001. [No Authors Listed]World Health Organ Tech Rep Ser. 2004;923:1–122. MEDLINE
3. 3Gibney R, Reineck J, Bannayan GA, Stein JH. Renal lesions in acute rheumatic fever. Ann Intern Med. 1981;94:322–326. MEDLINE
4. 4Grisham E, Chen S, Salmon MI, Churg J. Renal lesions in acute rheumatic fever. Am J Pathol. 1967;51:1045–1061. MEDLINE
5. 5Lin WJ, Lo WT, Ou TY, Wang CC. Haematuria, transient proteinuria, serpinginous-border skin rash and cardiomegaly in a 10-year-old girl. Eur J Pediatr. 2003;162:655–657. MEDLINE |
CrossRef
Case provided by Rajiv Sinha, MD,1 Khalid Al-AlSheikh, MD,1 Julie Prendiville, MB,2 Alex Magil, MD,3 and Douglas Matsell, MDCM,1 Divisions of 1Nephrology and 2Dermatology, Department of Pediatrics, British Columbia Children’s Hospital; and 3Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada.
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