Sarcoidosis 

• Multisystem disorder of unknown etiology
• Affects young adults worldwide
• Presents with noncaseating granulomas in various organs
• Characterized by bilateral hilar lymphadenopathy and reticular opacities in the lungs
• Major sites: lungs, skin, eyes, joints
• Variable expression in musculoskeletal system, reticuloendothelial system, exocrine glands, heart, kidney, CNS

Etiology

• Inflammatory disease of unknown cause
• Associations:
  • Occupational/environmental exposures (beryllium, dust)
  • Microorganisms (mycobacteria, propionibacteria)
• Possible infective etiology post-transplantation
• Genetic components linked to MHC antigens (DR alleles)
• Cytokines involved: Th1, IL-2, IL-6, IL-8, IL-12, IL-18, IL-27, IFN-gamma, TNF-alpha

Epidemiology

• Incidence:
  • 11 cases per 100,000 in whites
  • 34 cases per 100,000 in African Americans
• Lifetime risk: 2.4% in the US
• Extrapulmonary sarcoid: 25-30% of patients
• Gender differences:
  • Cardiac involvement more common in males
  • Skin and eye features more common in females

Pathophysiology

• Poorly understood; genetic and environmental factors implicated
• Key role of T cells (inverted CD4/CD8 ratio)
• Noncaseating granuloma: macrophages, giant cells, epithelioid cells, lymphocytes, monocytes, mast cells, fibroblasts
• Increased TNF and TNF receptors
• B cell hyperreactivity with immunoglobulin production
• Elevated ACE levels and HLA class I antigens

Histopathology

• Noncaseating granulomas in biopsy of lymph nodes

History and Physical

• Symptoms: persistent dry cough, fatigue, shortness of breath
• Other symptoms: painful red skin lumps, uveitis, hoarseness, palpable lymph nodes, swollen joints, hearing loss, seizures, psychiatric disorders
• Cutaneous manifestations: papular, maculopapular, nodular, subcutaneous, hypopigmented, plaque sarcoidosis
• Common skin lesions: papular sarcoidosis on the face and neck, lupus pernio
• Ocular involvement: uveitis in 50% of patients
• Cardiac involvement: heart block, sudden death, ICD recommended
• CNS manifestations: diabetes insipidus, hyperprolactinemia
• Poor quality of life, psychiatric symptoms

Evaluation

• Lab Tests: FBC, LFTs, BUN, creatinine, glucose, electrolytes, serum calcium, ESR, CRP, serum ACE, adenosine deaminase, serum amyloid A, soluble IL-2 receptor
• Radiographic Tests: chest radiograph, CT, FDG-PET, gallium-67, thallium-201, MIBI-Tc, SPECT
• Pulmonary function tests: decreased DLCO, restrictive pattern, obstructive pattern in advanced cases
• Radiographic Stages:
  • Stage I: Bilateral hilar adenopathy
  • Stage II: Bilateral hilar adenopathy and reticular opacities
  • Stage III: Reticular opacities with shrinking hilar nodes
  • Stage IV: Reticular opacities with fibrosis
• Histopathology: noncaseating granulomas without mycobacteria and fungi

Treatment / Management

• Asymptomatic pulmonary sarcoidosis: no treatment, monitor symptoms, chest radiograph, pulmonary function
• Symptomatic pulmonary sarcoidosis: oral glucocorticoids, steroid tapering, steroid-sparing agents (methotrexate, azathioprine, infliximab, leflunomide, antimalarials)
• Lung transplant for end-stage lung disease

Differential Diagnosis

• Tuberculosis
• Cat scratch disease
• Lung cancer
• Lymphoma
• Occupational lung disease
• Fungal infection

Prognosis

• Asymptomatic patients: stable for years
• Symptomatic patients: guarded prognosis, common relapse, dyspnea, pulmonary hypertension
• Overall mortality rate: 5% for untreated patients
• Prolonged corticosteroid treatment: common adverse effects

Complications

• Pulmonary hypertension
• End-stage lung disease