Key Differences Between Amyloidosis and Sarcoidosis
Amyloidosis and sarcoidosis are distinct systemic disorders with different pathophysiology, diagnostic features, and treatment approaches, with amyloidosis carrying a generally worse prognosis due to progressive organ dysfunction from protein deposition.
Pathophysiology
Amyloidosis
- Characterized by extracellular deposition of misfolded proteins (amyloid fibrils) in various organs 1
- Multiple types based on precursor protein:
- AL (light chain) amyloidosis: Most common type, caused by plasma cell dyscrasia with unstable immunoglobulin light chains 2
- ATTR (transthyretin) amyloidosis: Either hereditary (mutant) or wild-type (senile) 2
- AA (reactive) amyloidosis: Caused by serum amyloid A protein deposition during chronic inflammation 2
- Dialysis-related: Involves β-microglobulin 2 1
Sarcoidosis
- Characterized by non-caseating granulomatous inflammation 3
- Immune-mediated disorder with formation of epithelioid and giant cell granulomas 3
- Can affect multiple organs but primarily involves lungs, lymph nodes, and skin
Organ Involvement
Amyloidosis
- Typically affects multiple organs (median of 2 sites) 1
- Most commonly affects heart and kidneys 1
- Cardiac involvement is the main driver of prognosis and mortality 2
- Other affected organs include liver, GI tract, and nervous system 2
Sarcoidosis
- Primarily affects lungs and lymph nodes 3
- Can also involve liver, spleen, skin, eyes, and heart 3
- Rarely causes AA amyloidosis as a complication 3, 4
Clinical Presentation
Amyloidosis
- Heart failure with preserved ejection fraction 1
- Proteinuria (often nephrotic range) 1
- Peripheral and autonomic neuropathy 1
- Carpal tunnel syndrome (often precedes other symptoms) 1
- Macroglossia, periorbital purpura 1
- GI symptoms: early satiety, weight loss, alternating constipation/diarrhea 1
Sarcoidosis
- Respiratory symptoms: cough, dyspnea, chest pain
- Lymphadenopathy (often mediastinal)
- Skin lesions (erythema nodosum)
- Constitutional symptoms: fatigue, fever, weight loss
- Ocular manifestations: uveitis, conjunctivitis
Diagnostic Features
Amyloidosis
- Gold standard: Tissue biopsy with Congo red staining showing apple-green birefringence under polarized microscopy 2
- Biopsy sites: affected organs, abdominal fat pad, rectum, or bone marrow 1
- Cardiac imaging: echocardiography showing ventricular wall thickening with low QRS voltage on ECG 2
- Laboratory: Serum/urine monoclonal proteins, elevated BNP/NT-proBNP 2
- Nuclear imaging: Technetium Tc 99m dicarboxypropane diphosphonate to distinguish AL from ATTR 2
Sarcoidosis
- Tissue biopsy showing non-caseating granulomas 3
- Chest radiography/CT showing bilateral hilar lymphadenopathy and pulmonary infiltrates
- Elevated serum angiotensin-converting enzyme (ACE) levels
- Gallium-67 scintigraphy or FDG-PET showing characteristic uptake patterns 5
Treatment Approaches
Amyloidosis
- AL amyloidosis: Target the underlying plasma cell clone
- ATTR amyloidosis: Tafamidis for cardiac involvement to reduce mortality and hospitalization 6
- Supportive care for organ dysfunction 2
- Cautious use of diuretics
- Avoid β-blockers, calcium channel blockers, and digoxin in cardiac amyloidosis 2
Sarcoidosis
- Often self-limiting and may not require treatment
- Corticosteroids as first-line therapy for symptomatic disease 3, 4
- Steroid-sparing agents: methotrexate, azathioprine, hydroxychloroquine
- If AA amyloidosis complicates sarcoidosis, combination of corticosteroids and colchicine 3
Prognosis
Amyloidosis
- Varies by type and organ involvement:
Sarcoidosis
- Generally favorable outcome in most cases
- Chronic in 10-30% of patients
- Mortality rate 1-5%, usually due to pulmonary fibrosis or cardiac involvement
Relationship Between the Two Conditions
- AA amyloidosis can rarely complicate chronic sarcoidosis 3, 4
- When this occurs, both conditions should be treated simultaneously, typically with corticosteroids and colchicine 3
Key Clinical Pearls
- Consider amyloidosis in patients with unexplained heart failure with preserved ejection fraction, unexplained proteinuria, and peripheral neuropathy 1
- Early diagnosis of amyloidosis is crucial before irreversible organ damage occurs 2
- Sarcoidosis diagnosis requires exclusion of other causes of granulomatous inflammation
- Both conditions require multidisciplinary management due to multi-organ involvement