Sarcoidosis

Last updated: January 12, 2023

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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.

  • Average age of onset: 30–55 years [1][2]
  • Sex: : > (2:1)
  • Prevalence
    • Highest in African American and Scandinavian populations
    • 2–4 times higher in Black individuals than in non-Hispanic white individuals [3][4]

Epidemiological data refers to the US, unless otherwise specified.

The cause of sarcoidosis is unknown, but genetic predisposition (e.g., HLA-linked), exposure to substances associated with granuloma formation (e.g., beryllium and its salts), and infectious agents (e.g., mycobacteria) are believed to play a role. [5]

Sarcoidosis is a systemic disorder characterized by widespread, immune-mediated formation of noncaseating granulomas.

Overview

  • 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 [3]
    • Approx. one-third of patients develop progressive chronic disease.
  • Most common presenting signs and symptoms

Pulmonary sarcoidosis

Extrapulmonary sarcoidosis [7]

  • 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 [8]

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 [7]

Ocular sarcoidosis

Musculoskeletal findings

Neurosarcoidosis

Other findings [7]

Features of sarcoidosis are GRUELING: Granulomas, aRthritis, Uveitis, Erythema nodosum, Lymphadenopathy, Interstitial fibrosis, Negative TB test, and Gammaglobulinemia.

Lofgren syndrome

  • An acute clinical manifestation with fever and the following triad of symptoms:
  • Prognosis is good (spontaneous remission in ∼ 90% of affected individuals)

Heerfordt syndrome

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.

Chest x-ray

  • 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 [10]
Stages Chest x-ray findings
Stage 0
  • No pathological findings
Stage I
  • Bilateral hilar lymphadenopathy: bilateral enlargement of the lymph nodes of the pulmonary hila
Stage II
Stage III
Stage IV

Patients with pulmonary sarcoidosis may have moderate symptoms despite radiographic evidence of advanced disease.

High-resolution CT (HRCT) [11]

Laboratory tests

Bronchoscopy [14][15]

Pulmonary function tests

Pulmonary function tests (PFTs) show an early reduction of diffusion capacity and lung compliance.

Other tests

Differential diagnosis of granulomatous disease

Overview of granulomatous diseases [16][17]
Risk factors/prevalence Clinical features Lung biopsy Other laboratory findings
Sarcoidosis
  • Highest in African American and Scandinavian populations
  • 2–4 times higher in Black individuals than in non-Hispanic white individuals
Tuberculosis (TB)
Hodgkin lymphoma
Non-Hodgkin lymphoma
Pneumoconiosis
  • Exposure to mineral dust (e.g., silica)
Granulomatosis with polyangiitis
  • Prevalence in the US is highest among White individuals aged 65–74 years
Histoplasmosis [18]
  • AIDS
  • Exposure to bird or bat excrement

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. [9]

We list the most important complications. The selection is not exhaustive.

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  7. Ungprasert P, Ryu JH, Matteson EL. Clinical Manifestations, Diagnosis, and Treatment of Sarcoidosis. Mayo Clinic Proceedings: Innovations, Quality & Outcomes. 2019; 3 (3): p.358-375. doi: 10.1016/j.mayocpiqo.2019.04.006 . | Open in Read by QxMD
  8. Katta R. Cutaneous sarcoidosis: a dermatologic masquerader.. Am Fam Physician. 2002; 65 (8): p.1581-4.
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  10. Criado E, Sánchez M, Ramírez J, et al. Pulmonary Sarcoidosis: Typical and Atypical Manifestations at High-Resolution CT with Pathologic Correlation. RadioGraphics. 2010; 30 (6): p.1567-1586. doi: 10.1148/rg.306105512 . | Open in Read by QxMD
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  12. Tadros M, Forouhar F, Wu GY. Hepatic Sarcoidosis.. Journal of clinical and translational hepatology. 2013; 1 (2): p.87-93. doi: 10.14218/JCTH.2013.00016 . | Open in Read by QxMD
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