Sarcoidosis

DISEASE MANIFESTATIONS

Sarcoidosis comes in many forms. It primarily impacts the lung and lymphatic system, but can manifest in many parts of the body:¹

• Pulmonary system^1,4
• Lymphoid system⁴
• Cardiac system⁴
• Musculoskeletal sarcoidosis⁴
• Renal system⁴
• Hepatic system⁴
• Spleen and bone marrow^1,4
• Neurosarcoidosis (rare)⁴
• Gastrointestinal system⁴
• Cutaneous tissue⁴
• Parotid glands⁴
• Reproductive organs⁴
• Endocrine system⁴
• Ocular lesions⁴

MORTALITY

• From 1988-2007, 4.32 per 1,000,000 people (adjusted for average age and gender) suffered sarcoidosis-related mortality⁵
• Sarcoidosis is fatal in 1%-5% of patients⁴
  • Death is typically due to respiratory failure caused by pulmonary fibrosis⁴
  • Less often due to pulmonary hemorrhage caused by aspergilloma⁴

In patients with severe sarcoidosis contributing to death:

• 9% had pulmonary fibrosis⁵
• 25% had cardiac involvement⁵

PATHOGENESIS

Exposure of specific environmental antigens to genetically susceptible hosts leads to disease.^1,2

Sarcoidosis-Associated Granulomas

• Granuloma lesions form a characteristic discrete, compact, noncaseating epithelioid cell granuloma¹
• Lesion is composed of differentiated mononuclear phagocytes and lymphocytes¹
• Central portion of the granuloma consists of CD4+ lymphocytes with CD8+ lymphocytes present in periphery¹
• Fibrotic changes begin in the periphery and travel centrally¹

RISK FACTORS

Certain factors increase the risk an individual will develop sarcoidosis.^1,4,5,6,7

Age

• Typically found in young and middle aged adults¹ (20-40 y^1,4,6)
• Two peak ages of incidence: 25-29 and 65-69⁷

Race

• Increased risk for African Americans¹
• In the United States, the adjusted annual incidence of sarcoidosis is over 3 times greater in African Americans than caucasians⁸
  • 35.5 cases vs 10.9 cases per 100,000 population⁸

Genetics

• Pattern of familial clustering suggests there is a genetic predisposition^1,4
• Increased familial risk with mutations to antigen recognition proteins:¹
  • Human Leukocyte Antigen (HLA): HLA-A1¹
  • HLA-B8¹
  • HLA-DR3¹

Gender

• Risk is slightly increased for women⁷

Behavioral and Environmental Risk Factors

• Found more commonly in nonsmokers¹
• Increased incidence in winter and spring (unknown reason)⁴
• Potential causative agents:¹
  • Inorganic agents¹
    • Aluminum, zirconium, talc exposure¹
    • Often occupational exposure¹
  • Infectious agents¹ 
    • Mycobacterium tuberculosis and other mycobacteria¹
    • Mycoplasma¹
    • Viruses¹
    • Borrelia burgdorferi¹
    • Propionibacterium acnes¹
  • Organic agents¹
    • Pine tree pollen, clay¹