Sarcoidosis is a multisystem inflammatory disorder characterized by noncaseating granuloma formation, most commonly in the lungs and hilar lymph nodes. Many patients are asymptomatic, especially in the early stages of disease. Symptomatic patients typically present with , cough, and dyspnea. The cause of sarcoidosis is unknown but is thought to be related to an environmental exposure in a genetically predisposed individual. Chest x-ray is the preferred initial test for individuals with suspected sarcoidosis since bilateral hilar lymphadenopathy and/or pulmonary involvement is present in ∼ 90% of affected patients. Sarcoidosis is a diagnosis of exclusion that typically requires characteristic clinical features and/or findings on chest imaging, noncaseating granulomas on biopsy, and exclusion of more common causes of granulomatous disease or lymphadenopathy. While most patients with pulmonary sarcoidosis do not require immunosuppressive therapy, patients with symptomatic or progressive disease are typically treated with glucocorticoids. Spontaneous remission without complications is common in patients with early-stage pulmonary disease, 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 
- Cardiac sarcoidosis: 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
Lofgren syndrome 
- An acute clinical manifestation with fever and the following triad of symptoms:
- Prognosis is good (spontaneous remission occurs in 70–80% of affected individuals). 
General principles 
- Sarcoidosis is a diagnosis of exclusion supported by:
- Obtain initial studies to:
- Rule out differential diagnoses (e.g., other granulomatous diseases).
- Assess pulmonary and extrapulmonary disease (including ophthalmological evaluation).
- Consider additional studies (e.g., biopsy) under specialist guidance based on suspected organ involvement.
Pulmonary involvement and/or hilar lymphadenopathy are present in ∼ 90% of patients. Obtain chest imaging in all patients. 
Initial studies 
- CBC and differential: leukocytopenia
- Inflammatory markers: ↑ ESR, CRP
- Urinalysis: hypercalciuria
- 1,25-OH and 25-OH vitamin D levels in patients with hypercalcemia
- ↑ IgG
- 12-lead ECG: concerning findings include heart block, frequent PVCs, tachyarrhythmias
Increased ACE levels may be seen. However, they are not specific for sarcoidosis and should not be used in isolation for diagnosis or monitoring. 
- Chest x-ray 
|Radiographic stages of pulmonary sarcoidosis |
|Stages||Chest x-ray findings|
|Stage 0|| |
|Stage I|| |
|Stage II|| |
|Stage III|| |
|Stage IV|| |
Stage I pulmonary sarcoidosis is often an incidental finding detected on chest imaging. 
- High-resolution CT (HRCT) 
Patients with pulmonary sarcoidosis may have minimal to no symptoms despite significant radiographic abnormalities.
Pulmonary function testing (PFTs) 
- Typically shows a restrictive pattern
- Obstructive and mixed patterns may also be seen. (See “ .”)
- Diffusing capacity of the lung for carbon monoxide (DLCO) is decreased.
Additional studies 
Consider the following studies under specialist guidance based on suspected organ involvement:
- Bronchoalveolar lavage (BAL):↑ CD4:CD8 ratio 
- TTE for pulmonary hypertension screening if ↓ DLCO or if enlarged pulmonary artery is present on HRCT
- Cardiac MRI and/or cardiac FDG-PET if there are concerning findings on 12-lead ECG or suspected cardiac sarcoidosis
- CBC demonstrates cytopenias (abdomen) to assess for splenic involvement if
- Gold standard for the diagnosis
- Tissue should be obtained from the most easily accessible lesions (e.g., cutaneous lesions, superficial lymph nodes).
- Request fungal and mycobacterial staining and culture to rule out differential diagnoses. 
- Noncaseating granulomas with giant cells
Histopathological confirmation is not required in patients with pathognomonic presentations, i.e., , , and . 
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.
General principles 
- Consult a pulmonologist and/or other specialists as required.
- Most patients with pulmonary sarcoidosis do not require immunosuppressive therapy.
Glucocorticoids with/without DMARDs are indicated for patients with any of the following:
- Symptomatic progressive disease
- Persistent pulmonary infiltration
- Progressive decline of lung function
- Organ transplantation (e.g., lung, heart, liver) may be indicated in patients with severe, refractory disease.
Immunosuppressive therapy 
- First-line: glucocorticoids, e.g., prednisone 
- If no response or adverse effects to glucocorticoids: DMARDs may be added.