Sarcoidosis - clinical fact sheet and MCQ

Overview

Sarcoidosis is a chronic granulomatous disease of unknown aetiology, most commonly affecting the lungs and lymphatic systems, although any organ may be involved. It is characterised by non-caseating granulomas formed by an accumulation of T-helper lymphocytes and macrophages.

Epidemiology

Sarcoidosis affects all ages and ethnicities, with peak incidence in adults aged 20-39 years. In Australia, it is a relatively uncommon condition with prevalence estimated at 4.4-6.3 per 100 000 population. 

Aetiology and risk factors for sarcoidosis

It most likely results from a combination of genetic and environmental factors although the aetiology remains uncertain. Suggested triggers include:

• genetic susceptibility (family history)
• environmental and occupational exposures (eg organic and inorganic dust, combustion byproducts, industrial chemicals, metals like beryllium)
• infectious agents (eg Mycobacterium tuberculosis, Propionibacterium acnes)
• immunological dysregulation

Classification

Commonly used classification according to organ/system involvement:

• pulmonary sarcoidosis (>90% of patients)
• cutaneous sarcoidosis: eg erythema nodosum (image 1), lupus pernio (image 2)
• ocular sarcoidosis: uveitis is the most common subtype
• cardiac sarcoidosis: arrhythmias, heart block, congestive heart failure, cardiomyopathy
• neurosarcoidosis: can cause cranial nerve palsies, seizures, headache
• renal sarcoidosis: most commonly granulomatous interstitial nephritis 
• sarcoid arthropathy: arthralgia, inflammatory arthritis 
• other potential organ involvement including liver, GIT
  
  

Image 1: erythema nodosum (source: https://dermnetnz.org/topics/erythema-nodosum)

Image 2: lupus pernio (source: https://dermnetnz.org/topics/lupus-pernio) 

Clinical features

Initial presentation may be an incidental finding on chest X-ray, or due to symptoms, commonly cough or shortness of breath, or relating to other organ involvement.

Symptoms of sarcoidosis

• Respiratory symptoms such as dry cough, dyspnoea, and chest discomfort predominate
• Constitutional symptoms are common: fatigue, fever, weight loss
• Musculoskeletal symptoms, eg arthralgia, especially knees, ankles, elbows, wrists, are relatively common
• Ocular symptoms, eg red, painful eyes, photophobia, blurred vision

Other, less common presentations:

• skin lesions
• cardiac: palpitations, syncope
• neurological: headaches, seizures, cranial nerve abnormalities

Signs

Possible signs include:

• chest signs: eg wheezing and rhonchi
• non-tender lymphadenopathy (cervical, submandibular, rarely generalised)
• palpable hepatomegaly
• skin: papules/plaques and subcutaneous nodules
• eyes: ciliary injection, pupils can be normal or constricted, irregular and non-reactive; cells and flare in the anterior chamber (in anterior uveitis)

Red flags that suggest severe or organ-threatening disease:

• cardiac involvement (eg arrhythmias, heart block): may indicate infiltration of the myocardium and increased risk of sudden cardiac death
• ocular inflammation threatening vision
• neurological signs (facial palsy, seizures): may indicate cranial nerve, meninges, or brain parenchyma involvement, pituitary involvement, CNS vasculitis or space-occupying lesions
• severe hypercalcaemia, renal dysfunction
• progressive pulmonary fibrosis 
• pulmonary hypertension: may indicate advanced pulmonary sarcoidosis, chronic hypoxic vasoconstriction, and increased risk of right heart failure

Differential diagnoses for sarcoidosis

• Tuberculosis
• Histoplasmosis
• Lymphoma
• Lung cancer
• Hypersensitivity pneumonitis  
• Berylliosis

Investigations in primary practice

Initial workup

• Chest x-ray: typically shows bilateral hilar lymphadenopathy, may show bilateral pulmonary infiltrates 
• Blood tests: FBC, UECs, LFTs, serum calcium (hypercalcemia may be present)
• Abdominal ultrasound (may demonstrate abdominal adenopathy as well as splenic abnormalities)
• Pulmonary function tests (obstructive and restrictive abnormalities may occur)
• Baseline eye examination (screening for ocular involvement)
• ECG (screening for cardiac involvement)
• Interferon gamma release assay (to exclude tuberculosis)
• Serum ACE (marker of active disease, but has modest sensitivity and specificity and is not diagnostic)

Further testing (in most cases requested by respiratory physician or other medical specialist) 

• CT chest: for more detailed assessment of lung parenchyma, lymph nodes, and information about liver and spleen 
• Bronchoscopy with endobronchial ultrasound and transbronchial needle aspiration (gold standard for mediastinal sampling)
• Biopsy of affected organ (eg skin, lymph nodes): confirms non-caseating granulomas
• Nuclear imaging (PET) can be used to identify features of sarcoidosis and sites of disease 
• MRI to identify affected areas, including suspected cardiac or neurological involvement

Diagnosis

Sarcoidosis is a diagnosis of exclusion. It relies on:

• compatible clinical and radiological findings
• histological confirmation of non-caseating granulomas
• exclusion of other causes of granulomatous disease (eg TB, fungal infections, malignancy)

Management

Some specialised centres for management exist but most patients are managed according to the principal organ system involved (eg respiratory, rheumatology, ophthalmology, or neurology specialists). Multidisciplinary care is important as extrapulmonary disease is present in the majority of patients.

Not all patients require pharmacological treatment. Observation without pharmacotherapy may be an appropriate course of action (eg for asymptomatic or mild disease with a favourable pattern). The decision to treat is guided by the aim of improving symptoms and preventing organ damage, complications and disease progression.

Pharmacotherapy

• Corticosteroids are considered first-line treatment for sarcoidosis that requires therapy. Dosing and route of administration remain uncertain and vary depending on the clinical setting
• Criteria for initiating corticosteroids for sarcoidosis include:
  • progressive symptomatic pulmonary disease
  • asymptomatic pulmonary disease with persistent infiltrates or progressive loss of lung function
  • cardiac disease
  • neurological disease
  • ocular disease unresponsive to topical therapy
  • symptomatic hypercalcaemia
  • other symptomatic or progressive extrapulmonary disease
• Second line agents:
  • steroid-sparing agents for long-term management may include methotrexate, azathioprine, leflunomide, mycophenolate, hydroxychloroquine

• Subsequent lines of therapy include TNF-α inhibitors (e.g. infliximab, adalimumab), which may be considered in refractory cases

Other treatment considerations

• Pulmonary rehabilitation is recommended in patients with interstitial lung disease
• Observational studies have shown benefits from physical exercise in reducing sarcoidosis-associated fatigue and dyspnoea.
• Immunisation: consult the Australian Immunisation Handbook for recommendations on the administration of live and non-live vaccines in patients who are on immunosuppressive therapy
• Measures to prevent osteoporosis should be implemented in patients on corticosteroids. Calcium and Vitamin D supplements should be avoided unless clearly indicated, due to the risk of hypercalcemia (monitor calcium levels).
• Refractory and severe end-stage pulmonary sarcoidosis is an indication for consideration for lung transplantation 

Monitoring and follow-up

• Long term follow up with organ-specific monitoring is essential
• Regular (at least annual) ophthalmology reviews for patients with ocular involvement
• Monitor for cardiac sarcoidosis with ECG +/- imaging if any clinical suspicion arises

Prognosis

More than 60% of patients go into remission within 10 years after diagnosis, although residual changes may be seen on chest X-ray. In 10-40% of patients, sarcoidosis becomes chronic and progressive. 

Prevention and screening for sarcoidosis

No routine screening is recommended. For people with a family history, low threshold for investigation is advised if symptoms develop.

References

1. BMJ Best Practice. Sarcoidosis. Updated 1 April 2025. https://bestpractice.bmj.com
2. Bokhari SRA, Zulfiqar H, Mansur A. Sarcoidosis. [Updated 2023 Jun 25]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK430687/. (last accessed June 2025)
3. Ahmadzai H, Huang S, Steinfort C, et al. Sarcoidosis: a state of the art review from the Thoracic Society of Australia and New Zealand. MJA. 2018;208(11):499-504.
4. Thoracic Society of Australia and New Zealand. State of the art paper on sarcoidosis: an educational resource. 2018. Available at: https://thoracic.org.au/wp-content/uploads/2024/09/TSANZ-SarcoidosisPaper-2018-web-v3.pdf. (last accessed July 2025).
5. Moor CC, Kahlmann V, Culver DA, Wijsenbeek MS. Comprehensive Care for Patients with Sarcoidosis. J Clin Med. 2020;9(2):390.

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