Sarcoidosis
Aetiology and Pathophysiology
Aetiology: Unclear; thought to involve an exaggerated immune response to an unidentified antigen in a genetically predisposed individual.
Pathophysiology: Formation of non-caseating (non-necrotising) granulomas, primarily due to accumulation and activation of T-lymphocytes and macrophages.
Clinical Features
Sarcoidosis is heterogeneous. Many patients are asymptomatic and identified incidentally on imaging. Others present with systemic or organ-specific features.
General/Constitutional
Fever, malaise, fatigue, weight loss, night sweats.
Pulmonary
Present in up to 90% of cases.
Symptoms: Dyspnoea on exertion, dry cough, chest discomfort.
Signs: Often minimal; can include wheeze or reduced breath sounds if fibrotic changes occur.
Lymphatic
Dermatological
Specific lesions:
Yellowish-brown plaques or nodules (commonly on the face and extremities).
Infiltrative plaques over old scars.
Lupus pernio (violaceous lesions on the nose, cheeks, ears) is highly characteristic of chronic sarcoidosis.
Non-specific lesions:
Erythema nodosum (often with hilar lymphadenopathy and pulmonary involvement).
Erythema multiforme, alopecia, ichthyosis, and other presentations are less common.
Ocular
Uveitis (anterior or posterior), conjunctival lesions, reduced vision, photophobia, and possible risk of blindness if untreated.
Musculoskeletal
Arthralgia or arthritis (commonly ankles, knees, wrists).
Löfgren’s syndrome: Classic triad of erythema nodosum, bilateral hilar lymphadenopathy, and migratory polyarthritis (often affecting ankles). It is an acute presentation of sarcoidosis with a good prognosis.
Cardiac
Conduction abnormalities, arrhythmias, heart failure, or sudden cardiac death in rare but serious cases.
Neurological
Cranial nerve palsies (particularly facial nerve), peripheral neuropathy, meningitis, or intracranial lesions.
Other
Liver involvement (hepatomegaly, mild abnormal liver function tests).
Splenic involvement.
Renal involvement (hypercalcaemia, nephrolithiasis).
Investigations
Initial Work-up
Detailed history and clinical examination: Check for pulmonary, cutaneous, ocular, and other systemic signs.
Chest imaging:
Chest X-ray is the mainstay initial investigation. Commonly shows bilateral hilar lymphadenopathy, sometimes parenchymal changes.
High-resolution CT is more sensitive for pulmonary involvement.
Pulmonary function tests (PFTs): Assess the extent of pulmonary involvement (restrictive pattern +/- reduced diffusion capacity).
Additional/Confirmatory Tests
Biopsy:
Confirms diagnosis (non-caseating granulomas). May be obtained from accessible lymph nodes or skin lesions if present.
Transbronchial lung biopsy or endobronchial ultrasound (EBUS)-guided biopsy may be needed for intrathoracic lesions.
Serum angiotensin-converting enzyme (ACE):
Blood tests:
Full blood count, ESR/CRP (may be elevated).
Serum calcium (hypercalcaemia can occur due to increased vitamin D activation by granulomas).
Renal function tests (monitor for nephrolithiasis if hypercalcaemia is present).
Liver function tests (if hepatic involvement suspected).
Eye examination:
ECG and echocardiogram:
Differential Diagnosis
Tuberculosis or other granulomatous infections (e.g. fungal infections).
Malignancies causing lymphadenopathy (e.g. lymphoma).
Other causes of interstitial lung disease.
Autoimmune conditions presenting with arthralgias and erythema nodosum (e.g. inflammatory bowel disease–associated erythema nodosum).
Management Approach
General Principles
Treatment decisions are usually based on the presence of organ dysfunction, severity of symptoms, and risk of serious complications (e.g. cardiac or neurological involvement).
Some patients with mild, asymptomatic disease only require monitoring (watchful waiting), especially if there is no risk of permanent organ damage.
Pharmacological Treatment
Corticosteroids
First-line for moderate-to-severe disease (particularly with pulmonary, ocular, neurological, or cardiac involvement).
Oral prednisolone improves symptoms and prevents organ damage in active disease.
Dosage and duration vary according to severity and response. Taper gradually to the lowest effective dose.
Steroid-sparing agents
Cutaneous Lesions (Local Therapy)
Potent topical corticosteroids (with or without occlusion) for localised plaque lesions.
Intralesional corticosteroids for accessible lesions.
Referral to a dermatologist if lesions are extensive or resistant.
Biologic Therapy (e.g. Anti-TNF agents)
Non-pharmacological Support
Referral Considerations
Respiratory physician: Most patients with pulmonary sarcoidosis for definitive management.
Dermatologist: Significant or difficult-to-treat skin lesions.
Ophthalmologist: If ocular involvement is suspected or diagnosed.
Cardiologist / Neurologist: For cardiac or neurological involvement.
Other specialists: As per organ-specific complications.
Prognosis
Many patients have a self-limiting course, particularly those with acute presentations (e.g. Löfgren’s syndrome).
Chronic disease can lead to significant morbidity, particularly when there is chronic pulmonary fibrosis, cardiac, or neurological involvement.
Timely diagnosis, regular monitoring, and appropriate therapy are key to optimising outcomes.
