Sarcoidosis is a multisystem disorder characterized by noncaseating granulomatous inflammation and typically manifests with constitutional symptoms (e.g., fever, malaise), cough, dyspnea, anterior uveitis, erythema nodosum, and arthralgia. Sarcoidosis primarily affects the lungs, but systemic manifestations (e.g., erythema nodosum, uveitis, arthritis) are also possible. Chest x-ray is the preferred initial test in patients with suspected sarcoidosis; parenchymal disease with bilateral hilar lymphadenopathy is a characteristic sign, although results are often normal or inconclusive. A high-resolution CT is indicated in patients with an abnormal or inconclusive x-ray and in those with unexplained cough or dyspnea. Endobronchial and/or transbronchial biopsy is the gold standard; the most common histopathological finding being noncaseating granulomas with giant cells. Further laboratory tests (e.g., angiotensin-converting enzyme levels, serum calcium, and urinalysis) showing elevated angiotensin-converting enzyme (ACE) levels, hypercalcemia, and hypercalciuria may support the diagnosis. Glucocorticoid therapy is indicated with disease progression and/or to prevent organ damage (e.g., to the eyes, lungs, and heart). Spontaneous remission without complications is common during the early stages, but the risk of irreversible lung fibrosis increases with disease recurrence and progression.
Sarcoidosis is a systemic disorder characterized by widespread, immune-mediated formation of noncaseating granulomas.
- Inhalation of foreign antigen → monocyte differentiation → activation of interstitial dendritic cells and alveolar macrophages
- Interstitial dendritic cells migrate towards mediastinal lymph nodes and alveolar macrophages differentiate, serving as antigen-presenting cells to circulating T helper (Th) cells → differentiation and clonal expansion of T cells
- T cell recruitment and ↑ B-cell activity → local immune hyperactivity and inflammation → formation of in the lungs and the lymphatic system
- Granuloma formation: Mature granulomas are composed of epithelioid cells and macrophages surrounded by lymphocytes and fibroblasts.
- Fibrosis: Epithelioid cells secrete cytokines to recruit fibroblasts, leading to fibrosis → damage of organs and tissue
- Calcium dysregulation: : activated pulmonary alveolar macrophages → ↑ 1-alpha hydroxylase expression and activity → ↑ 1,25-dihydroxyvitamin D (calcitriol) → hypervitaminosis D → hyperphosphatemia, hypercalcemia, and, possibly, renal failure 
- Sarcoidosis is a disease with highly variable manifestations, ranging from asymptomatic to progressive, relapsing disease.
- Typically sudden onset with spontaneous remission in approximately two-thirds of patients 
- Approx. one-third of patients develop progressive chronic disease.
- Most common presenting signs and symptoms
- Lungs are the most commonly affected organ (90% of affected individuals).
- Often asymptomatic in the early stages
- Interstitial fibrosis
Extrapulmonary sarcoidosis 
- Occurs in approx. 30% of affected individuals
- Extrapulmonary findings usually involve the skin, eyes, heart, and/or the renal and central nervous systems.
Cutaneous sarcoidosis 
- Occurs in approx. 30% of affected individuals 
- : most common nonspecific cutaneous manifestation
- Lupus pernio
- Papular sarcoidosis
- Plaque-like lesions
- Scar sarcoidosis: papular lesions in preexisting scars (e.g., venipuncture sites) and/or elevation of scars or tattoos
Lymph node findings
- Most commonly affected extrapulmonary site
- Occurs in 70–90% of affected individuals
- Mediastinal lymph nodes: bilateral, hilar, and/or paratracheal mediastinal adenopathies (approx. 90% of affected individuals)
- Intraabdominal lymphadenopathy 
- Occurs in 10–25% of affected individuals 
- Can affect any part of the eye and associated structures
- Common manifestations include uveitis, conjunctival nodules, keratoconjunctivitis sicca
- Sarcoid uveitis
- Occurs in approx. 10% of affected individuals 
- Arthralgias and arthritis
- Initially asymptomatic with insidious course
- Clinical patterns
- Bone lesions
- Occurs in approx. 5% of affected individuals 
- Cranial nerve palsy (unilateral or bilateral facial nerve palsy is the most common)
- Diabetes insipidus
- Meningitis (e.g., acute aseptic meningitis, chronic meningitis)
- Peripheral neuropathy (e.g., mononeuropathy, mononeuritis multiplex, polyneuropathies)
- Myopathy (e.g., proximal myopathy, muscle atrophy)
Other findings 
- Heart: dilated or restrictive cardiomyopathy, myocarditis, pericardial effusion, arrhythmias (e.g., AV block), sudden cardiac death
- Kidneys: acute interstitial nephritis, nephrocalcinosis, nephrolithiasis
- Hepatic sarcoidosis
- Spleen: splenomegaly in ∼ 30% of affected individuals
- Exocrine glands: enlarged salivary and lacrimal glands
Subtypes and variants
- An acute clinical manifestation with fever and the following triad of symptoms:
- Prognosis is good (spontaneous remission in ∼ 90% of affected individuals)
Chest x-ray is the most appropriate initial test for suspected sarcoidosis and would likely reveal parenchymal disease with hilar lymphadenopathy. A high-resolution CT is indicated in patients with an abnormal or inconclusive x-ray and in those with unexplained cough or dyspnea. Endobronchial and/or transbronchial biopsy is the gold standard, with the most common histopathological finding being noncaseating granulomas with giant cells. Further laboratory tests (e.g., angiotensin-converting enzyme levels, serum calcium, and urinalysis) showing elevated angiotensin-converting enzyme (ACE) levels, hypercalcemia, and hypercalciuria may support the diagnosis.
- Preferred initial test
- Sarcoidosis is often an incidental finding detected on chest x-ray
- Findings: bilateral hilar lymphadenopathy with or without reticular opacities
- Radiographic findings are categorized into stages according to the affected lung structures.
|Stages of pulmonary sarcoidosis |
|Stages||Chest x-ray findings|
|Stage 0|| |
|Stage I|| |
|Stage II|| |
|Stage III|| |
Patients with pulmonary sarcoidosis may have moderate symptoms despite radiographic evidence of advanced disease.
High-resolution CT (HRCT) 
- Next diagnostic test if chest x-ray is abnormal or inconclusive and in patients with unexplained cough or dyspnea
- HRCT can detect parenchymal and mediastinal abnormalities such as:
- CBC and differential: leukocytopenia
- Inflammatory markers: ↑ ESR, CRP
- LFTs: ↑ alkaline phosphatase 
- BUN and creatinine
- Serum electrolytes and calcium: hypercalcemia (due to elevated levels of 1,25-dihydroxy-vitamin D)
- Urinalysis: hypercalciuria
- Serum markers
- Additional tests
- Biopsy: the gold standard for diagnosis
- Bronchoalveolar lavage (BAL): increased CD4:CD8 ratio
- Restrictive pattern (see “”)
- Obstructive and mixed patterns may also be seen (see “ ”).
Diffusing capacity of the lung for carbon monoxide (DLCO)
- Decreased diffusion capacity
- Sensitive parameter for disease activity
- Exclusion of differential diagnoses, particularly granulomatous diseases
- Suspicion of extrapulmonary manifestations
Differential diagnosis of granulomatous disease
|Overview of granulomatous diseases |
|Risk factors/prevalence||Clinical features||Lung biopsy||Other laboratory findings|
| || || |
The differential diagnoses listed here are not exhaustive.
Treatment is indicated for patients with symptomatic progressive disease, persistent pulmonary infiltration, and/or progressive decline of lung function. 
Isolated pulmonary sarcoidosis
- In most cases, no treatment is required.
- The disease is usually asymptomatic, nonprogressive, and has a high rate of spontaneous remission.
Symptomatic or extrapulmonary sarcoidosis
- First line: glucocorticoids
- Second line
- Third line: biological agents (e.g., ) for refractory disease
- Lung transplantation may be indicated in severe pulmonary disease that does not respond to other treatments.
- NSAIDs are always indicated for symptom relief.