What is the significance of Anitschkow cells and Aschoff bodies in the diagnosis and management of rheumatic fever?

Anitschkow Cells vs. Aschoff Bodies: Histopathologic Markers of Rheumatic Heart Disease

Anitschkow cells are macrophage-derived stromal cells with characteristic "caterpillar" or "owl-eye" nuclei that are the primary cellular component of Aschoff bodies (nodules), which represent the pathognomonic histologic lesion of acute rheumatic fever and rheumatic carditis. 1

Cellular Characteristics and Origin

Anitschkow Cells

• Anitschkow cells are mononuclear cells with elongated nuclei displaying a distinctive chromatin pattern that appears as a central ribbon of chromatin resembling a caterpillar ("caterpillar cells") or an owl's eye when cut in cross-section 1
• Immunohistochemical studies demonstrate that Anitschkow cells stain prominently with macrophage markers, indicating their histiocytic/macrophage origin rather than myocyte derivation 1
• These cells demonstrate mitotic activity and stain positive for proliferation cell nuclear antigen (PCNA), suggesting active proliferation rather than simple cellular fusion 1
• The cells can be found individually scattered in inflamed myocardium or cardiac valves, or aggregated within Aschoff bodies 2

Aschoff Bodies (Aschoff Nodules)

• Aschoff bodies are granulomatous lesions composed of central fibrinoid necrosis surrounded by Anitschkow cells, multinucleated Aschoff giant cells, and lymphocytic infiltrates 1
• These nodules represent the pathognomonic histologic hallmark of acute rheumatic fever and are found in myocardium and cardiac valves 3, 1
• Three developmental stages have been identified: Stage 1 shows central fibrinoid necrosis without lymphocytes; Stage 2 contains occasional T lymphocytes (<10 cells); Stage 3 demonstrates lymphoid aggregates with both T- and B-lymphocytes admixed with macrophages 1

Clinical Significance in Diagnosis

Acute Rheumatic Fever

• The presence of Aschoff bodies with Anitschkow cells on histology confirms active acute rheumatic carditis, though biopsy is rarely performed clinically as diagnosis relies on the Jones Criteria 4, 3
• Histologic evidence of lymphocytic infiltration, Aschoff bodies, and fibrinoid necrosis definitively establishes acute rheumatic valvulitis 3
• The positive detection rate of active rheumatic lesions by endomyocardial biopsy is approximately 70%, though this invasive approach has limited clinical utility given the availability of echocardiography 5

Chronic Rheumatic Heart Disease

• Chronic rheumatic valvulitis shows neovascularization and dystrophic calcification rather than active Aschoff bodies 3
• The rare combination of both acute (Aschoff bodies, Anitschkow cells) and chronic features (calcification, fibrosis) indicates recrudescence of acute rheumatic fever superimposed on chronic disease 3
• This mixed histologic pattern should be considered in high-prevalence regions where patients may experience recurrent episodes despite chronic disease 3

Practical Clinical Implications

Why Histology Is Not Routinely Used

• Modern diagnosis of acute rheumatic fever relies on the revised 2015 Jones Criteria, which incorporate clinical findings and Doppler echocardiography rather than histologic confirmation 4, 6
• The Jones Criteria include carditis (clinical or subclinical by echo), polyarthritis, erythema marginatum, subcutaneous nodules, and chorea as major criteria 6
• Endomyocardial biopsy has limited value in assessing clinical activity because: (1) sampling error may miss focal lesions, (2) invasive risk outweighs diagnostic benefit, and (3) echocardiography provides adequate assessment of cardiac involvement 5

When Histologic Findings Matter

• Surgical valve specimens may incidentally reveal Aschoff bodies, confirming active disease that warrants intensified secondary prophylaxis 1
• Finding active histologic lesions in patients without clinical evidence of acute disease suggests subclinical ongoing inflammation requiring continued antibiotic prophylaxis 5
• In autopsy or forensic cases, Aschoff bodies provide definitive retrospective diagnosis of rheumatic fever 1

Key Distinctions and Pitfalls

Common Misconceptions

• Anitschkow cells are NOT specific to rheumatic fever—they can appear in other myocardial pathologies including viral myocarditis, ischemic injury, and even arteriosclerotic processes 2
• The Anitschkow chromatin pattern may represent a stress-related nuclear morphology rather than a specific cell type, as similar patterns occur in extracardiac tissues 2
• Aschoff bodies were historically thought to originate from damaged interstitial collagen, but evidence suggests they develop from injured myofibers 7

Diagnostic Caveats

• The absence of Aschoff bodies on biopsy does NOT exclude active rheumatic fever, as lesions may be focal and missed by sampling 5
• Chronic rheumatic heart disease can exist without detectable Aschoff bodies, as these acute inflammatory lesions resolve over time leaving only fibrosis and calcification 3
• Endocarditis can mimic rheumatic carditis histologically—clinical correlation with Jones Criteria and microbiologic studies is essential 6

Bottom Line for Clinical Practice

In contemporary practice, Anitschkow cells and Aschoff bodies serve as histopathologic confirmation rather than diagnostic tools, as the 2015 revised Jones Criteria with echocardiography provide superior diagnostic accuracy without invasive procedures. 4, 6 Their primary relevance is in surgical pathology specimens and understanding the pathophysiology of rheumatic heart disease rather than routine clinical diagnosis.