Introduction

Sarcoidosis is a multisystem granulomatous disorder of unknown aetiology. It most commonly affects the lungs (>90% of cases) and lymphatic system, but can affect any organ. Many cases are asymptomatic, although some patients can have very severe disease. Treatment may involve NSAIDs and less often, steroids, but often none is required as many cases resolve spontaneously.
  • When it affects the lungs, we refer to it as an interstitial lung disease. The other main interstitial lung disease is idiopathic pulmonary fibrosis. Other types include occupational lung diseases (pneumoconiosis), and interstitial lung disease secondary to connective tissue diseases.

Sarcoidosis often produces non-caveating epithelioid granulomas, which can occur at any site in the body. Sometimes they give the appearance of TB on chest x-ray.

Epidemiology and Aetiology

  • Affects 10-20 per 100 000, and rates vary between races. Black Africans, followed by Scandinavians are at highest risk
  • Thought to have a genetic component. The most widely accepted hypothesis describes how in susceptible individuals, environmental factors (e.g. organic or inorganic agents) lead to a cell-mediated immune response, resulting in the formation of granulomas.
    • About 10% of cases show a familial pattern
  • The specific organs involved also vary between populations, with certain organs more common in certain populations.
  • Typical presentation is in patients aged 25-45
  • Lungs are most commonly affected, followed by eyes and skin.
    • The liver is also often affected, but this is rarely clinically significant
    • Rarely it an affect the heart and nervous system

Between 10-30% of patients will have a chronic or progressive disease course. The rest will typically resolve spontaneously, although this can take several years.

Signs and Symptoms

  • Many patients are asymptomatic
    • Up to 50%!
  • Dry cough
  • Chest pain
  • Fever
  • Dyspnoea (usually progressive)
  • Lymphadenopathy
  • Crackles on auscultation
  • Fatigue
  • Malaise
  • Weight loss
  • Weakness
  • Sarcoidosis is often a differential for a patient with lots of non-specific signs!
  • Symptom and disease progression occurs in 10-20% of patients – this usually involves a decline in lung function.
  • It can also cause a whole range of other non-pulmonary symptoms, making sarcoidosis a differential diagnosis for almost any unidentifiable disease! Examples include, Hepatomegaly, splenomegaly, lymphadenopathy, Bell’s palsy, uveitis, conjunctivitis and cataracts.
  • Skin signs and symptoms
    • Papules – often resembling Rosacea, or the malaria rash seen in SLE
    • Plaques that may mimic psoriasis
    • Erythema nodosum
  • Eye signs and symptoms
    • Occur in 20% of patients
    • Typically a uveitis
  • Neurological symptoms
    • Granulomas can form anywhere int he nervous system
    • Therefore – can cause any neurological sign
    • Sometimes cases Bell’s Palsy

Pathology

What is a granuloma?

  • A granuloma is a collection of WBC’s (mononuclear cells and macrophages) , surrounded by lymphocytes, plasma cells, mast cells, fibroblasts, and collagen. They can occur in any organ, but in sarcoidosis most commonly occur in the lung and lymphatics.
  • In the lung they tend to be distributed along the line of lymph nodes – Hence the association of sarcoidosis and hilar CXR changes

Investigations

Bloods

  • FBC – may cause anaemia or raised WCC
  • ESR – often raised
  • U+E
  • LFTs – may be derranged
  • Serum ACE (angiotensin converting enzyme)
    • Elevated in 60% of cases
    • Falls with treatment
    • Not routinely used for diagnosis or monitoring of treatment (lung function and CXR are better indicators)

Often discovered incidentally on CXR. The classical finding is hilar lymphadenopathy, where there are clear lung fields, with ‘fluffy’ opacities in the hilar region. Other changes may include lung infiltrates and fibrosis.
It can also cause non-specific CXR changes.

  • CXR is often used to stage the condition
  • Stage 0 – normal CXR
  • Stage 1 – BHL – bilateral hilar lymphadenopathy
  • Stage 2 – BHL + Infiltrates
  • Stage 3 – Peripheral pulmonary infiltrates alone
  • Stage 4 – Progressive pulmonary fibrosis ± bulla (honeycombing on CXR).

90% of patients with sarcoidosis will show CXR changes – thus an absence of CXR changes will all but exclude sarcoidosis from your differential diagnosis. Sarcoidosis should be suspected in patients with unilateral pain, but bilateral CXR signs

Pulmonary Function Tests may show a reduced lung volume and restrictive pattern

Diagnosis may be confirmed by tissue biopsy which will show the presence of a non-caseating granuloma.

  • Suitable biopsy sites include lung and liver tissue, lymph nodes and lacrimal glands

Hand X-ray – sometimes shows punched out lesions in the peripheral phalanges
Broncheoaleolar lavage – can show increased lymphocytes and neutrophils
CT/MRI – useful in some cases to assess the extent of pulmonary involvement

Differential diagnosis

Because of the wide range of presenting symptoms, the list of differentials is almost endless!

Most likely options include other illnesses that can cause progressive breathlessness, such as pulmonary fibrosis, lung cancer and TB.

It is also worth bearing in mind for any patient with vague symptoms of malaise, weight loss and fever. Neurological signs can mimic multiple sclerosis.

Sarcoidosis is a potential differential for almost any combination of symptoms.

Management

About 50% of patients will not require any specific treatment. The decision on when to treat is usually based on the severity and progressive nature of symptoms, and can be guided by the stage of the disease:

  • Stage 0 and 1 – usually resolve spontaneously
  • Stage 2+ and acute disease – may improve with NSAIDs and bed rest
  • Steroid Management – is in some circumstances (prednisolone 40mg for 4-6 wks, then gradually decline dose over 1yr depending on symptoms.  Indications for steroid use include:
    • Parenchymal lung disease – even if asymptomatic
    • Uveitis
    • Hypercalcaemia
    • Neurological involvement
    • Cardiac involvement
  • Very severe cases may require further intervention, including:
    • IV methyprednisolone
    • Immunosuprressants – e.g. cyclosporine, methotrxate, cyclophosphamide

In patients who do not respond to steroids, or who cannot take steroids, anti-TNF drugs and monoclonal antibody agents may be considered. The former carry a significant side-effect burden.

Patients should also have regular ophthalmology assessment for eye manifestations of the disease.

  • This may be treated with intra-ocular steroid injections (deeper than anterior chamber), or corticosteroid eye-drops (shallower disease)
  • Sarcoidosis can cause optic neuritis which can cause blindness if untreated. In these cases, IV corticosteroids are usually given

Neurological and joint disease is also usually treated with steroids.

Prognosis

  • <5% of patients with sarcoidosis will die as a result of complications of their disease
  • 20% of patients will have chronic or progressive disease – the rest will either resolve spontaneously or respond well to treatment
  • Those that do die of their complications typically develop severe pulmonary fibrosis, and may also develop pulmonary hypertension

References

Read more about our sources