Definition

An inflammatory multisystem disease characterized by the presence of noncaseating granulomas of unknown etiology.

Pathophysiology

The cause of sarcoidosis is unknown, and current evidence suggests that the triggering of an inflammatory response by an unidentified antigen in a genetically susceptible host is involved. The granuloma is the pathologic hallmark of sarcoidosis. The initial inflammatory response is an influx of CD4+ (helper) T cells and an accumulation of activated monocytes. This leads to an increased release of cytokines and the formation of a granuloma. The granuloma may resolve or lead to chronic disease, including fibrosis.

Clinical Manifestations

Up to one-third of sarcoidosis pts are asymptomatic with 20-30% of pulmonary sarcoidosis being detected by CXR in asymptomatic individuals. Sarcoid manifests symptomatically in organs where it affects function or where it is readily observed. Löfgren's syndrome consists of hilar adenopathy, erythema nodosum, often with acute arthritis presenting in one or both ankles spreading to involve other joints.

Disease manifestations of sarcoid include:

• Lung: >90% of pts with sarcoidosis will have lung involvement. Features include hilar adenopathy, infiltrates, interstitial pneumonitis, and fibrosis; airways may be involved and cause obstruction to airflow; pulmonary hypertension from direct vascular involvement or lung fibrosis.
• Lymph nodes: intrathoracic nodes enlarged in 75-90% of pts. Extrathoracic lymph nodes affected in up to 20%.
• Skin: >33% will have skin involvement; lesions include erythema nodosum, maculopapular lesions, subcutaneous nodules, and lupus pernio (indurated blue-purple shiny lesions around nasal bridge, eyes, cheeks).
• Eye: uveitis 30% in the United States (higher in other countries); may progress to blindness.
• Bone marrow and spleen-lymphopenia, anemia 20%, splenomegaly 5-10%.
• Liver: involved on biopsy in >50%; 20-30% abnormal liver function studies.
• Kidney: parenchymal disease <5%, nephrolithiasis, acute renal failure due to hypercalcemia 1-2%.
• Nervous system: occurs in 5-10%; cranial/peripheral neuropathy, chronic meningitis, pituitary involvement, space-occupying lesions, seizures.
• Heart: disturbances of rhythm and/or contractility, pericarditis.
• Musculoskeletal: involvement of bone or muscle occurs in 10%, bone lesions consist of cysts in areas of expanded bone or lattice-like changes; joint involvement includes acute arthropathy often of the ankles and chronic mono- or oligoarthritis of knee, ankle, proximal interphalangeal (PIP) joints.
• Constitutional symptoms-fever, weight loss, anorexia, fatigue.
• Other organ systems-hypercalcemia 10%, endocrine/reproductive, exocrine glands, GI, upper respiratory tract.

Evaluation

• History and physical examination.
• CBC, Ca²⁺ , LFTs, ACE, tuberculosis screening.
• CXR and/or chest CT, ECG, PFTs.
• Biopsy of lung or other affected organ.
• Positron emission tomography (PET) has increasingly replaced gallium-67 scanning to identify areas of granulomatous disease. Both can be used to identify potential areas for biopsy.
• MRI can assess extrapulmonary sarcoidosis.

Diagnosis

Made on the basis of clinical, radiographic, and histologic findings. Biopsy of lung or other affected organs is helpful in supporting the diagnosis and ruling out other diseases. Pulmonary involvement can be approached by bronchoscopy with transbronchial lung biopsy. Differential diagnosis includes neoplasms, infections including HIV, and other granulomatous processes.

Outcome

Sarcoidosis is usually a self-limited, non-life-threatening disease. Remission occurs in >50% within 2-5 years of diagnosis with at least 20% developing chronic diseases. Death directly due to disease is low and usually related to lung, cardiac, neurologic, or liver involvement.