Sarcoidosis — Symptoms, Causes & Treatment | MyMedicPlus

Sarcoidosis is a multisystem granulomatous disease of unknown etiology, characterized by the formation of non-caseating granulomas in multiple organs. The lungs and mediastinal lymph nodes are affected in 90% of cases. It predominantly affects adults aged 20-40 years. Two-thirds of cases resolve spontaneously within 2-3 years. The condition disproportionately affects African Americans (incidence 35 per 100,000 versus 11 per 100,000 in white Americans) and Scandinavians. Extra-pulmonary involvement occurs in over 50% of patients — skin (25%), eyes (25%), liver (20%), heart (5–10%), and nervous system (5–10%). Löfgren syndrome (bilateral hilar adenopathy + erythema nodosum + acute arthritis) is an acute presentation with spontaneous remission in 85–90% of cases, rarely requiring immunosuppression. Annual incidence in the UK is approximately 5–6 per 100,000.

The exact cause is unknown. It is thought to result from an exaggerated immune response to environmental antigens (mycobacterial, propionibacterial, or organic dust antigens) in genetically susceptible individuals. HLA-DRB1 and HLA-DQB1 alleles confer susceptibility. Higher incidence among African Americans (10-17/100,000 vs. 5-6/100,000 in whites) and Scandinavians. Occupational exposures to metal dust, wood fires, insecticides, and inorganic particles are associated with increased risk. Clustering in healthcare workers, firefighters, and military personnel supports an environmental trigger. First-degree relatives of sarcoidosis patients have a 5-fold increased risk of the disease. HLA-DRB1*0301 (in white European populations) confers susceptibility to Löfgren syndrome, while HLA-DRB1*1501 is most strongly associated with African Americans. Sarcoidosis is not infectious, not contagious, and is not caused by autoimmunity in the conventional antibody-mediated sense.

Pulmonary symptoms (90%): dry cough, progressive dyspnea, and chest pain. Constitutional: fever, weight loss, fatigue. Cutaneous: erythema nodosum (painful red nodules on shins — acute, good prognosis), lupus pernio (indurated violaceous plaques — chronic, poor prognosis). Ocular: anterior uveitis (25%). Lofgren syndrome: fever + arthritis + erythema nodosum + bilateral hilar adenopathy — benign course. Cardiac sarcoidosis (5–10% of patients, detected more frequently on cardiac MRI and PET): palpitations, syncope, and sudden cardiac death from heart block or ventricular arrhythmias. Neurosarcoidosis (5%): cranial nerve palsies (VII — facial palsy most common), headache, seizures, and peripheral neuropathy. Hypercalcaemia (10–15%): macrophages in granulomas produce 1-alpha-hydroxylase converting vitamin D to active calcitriol — causes polyuria, polydipsia, constipation, and renal stones.

Chest X-ray Scadding staging: I (bilateral hilar lymphadenopathy), II (BHL + parenchymal infiltrates), III (parenchymal infiltrates only), IV (fibrosis). CT thorax provides better detail. Tissue biopsy showing non-caseating granulomas after excluding tuberculosis and other granulomatous diseases is required. Serum ACE elevated in 60%. Also: calcium, LFTs, ECG, 24-hour urine calcium, ophthalmology, and PFTs. Bronchoalveolar lavage (BAL): CD4/CD8 ratio above 3.5 strongly supports sarcoidosis — reflects characteristic CD4+ T-cell lymphocytosis. FDG-PET scan: useful for identifying active extrapulmonary disease sites and guiding biopsy; indispensable for cardiac sarcoidosis assessment. Cardiac MRI with late gadolinium enhancement (LGE) is the gold standard investigation for cardiac sarcoidosis — detects myocardial inflammation and fibrosis even before structural heart changes on echocardiography.

Many cases (especially Stage I-II) resolve spontaneously without treatment. Indications for therapy: progressive pulmonary impairment, cardiac sarcoidosis, neurosarcoidosis, hypercalcemia, ocular involvement, or disfiguring skin disease. Oral prednisone 20-40 mg/day (3-6 months) is first-line; typical maintenance 7.5-10 mg/day to minimise side effects. Steroid-sparing: methotrexate 10-15 mg weekly (most widely used, takes 3-6 months for benefit), azathioprine 1.5-2 mg/kg/day, hydroxychloroquine 200-400 mg/day (best for cutaneous and hypercalcaemia). Refractory: infliximab 3-5 mg/kg IV 8-weekly (anti-TNF) — most evidence for pulmonary and extrapulmonary disease (CRYSTAL trial). Cardiac sarcoidosis: corticosteroids combined with ICD (implantable cardioverter-defibrillator) for ventricular arrhythmias or complete heart block; permanent pacing for symptomatic high-grade block. Rituximab is emerging for highly refractory disease. Treatment is typically continued for 12–24 months for significant involvement, tapered gradually to avoid relapse.

Stage IV pulmonary fibrosis (irreversible, severe) — affects approximately 5% of patients and may progress to respiratory failure requiring lung transplantation; 5-year mortality in advanced pulmonary fibrosis exceeds 30%. Cardiac sarcoidosis: heart block, ventricular arrhythmias, and sudden cardiac death (SCD — requires ICD consideration); cardiac sarcoidosis accounts for 25–65% of sarcoidosis-related deaths in Japan and a significant proportion in the West. Neurosarcoidosis: cranial nerve palsies (CN VII most common — facial palsy), diabetes insipidus, meningitis, and hydrocephalus. Hypercalcaemia (nephrocalcinosis, renal failure): occurs in 10–15% of patients and can cause irreversible renal impairment. Chronic uveitis causing cataracts, glaucoma, and blindness if inadequately treated. Lupus pernio: disfiguring facial skin disease indicating systemic chronic sarcoidosis. Chronic fatigue affects up to 90% of patients and is a major but underrecognised long-term consequence.

No specific prevention. Regular monitoring: PFTs (every 3–6 months during active pulmonary disease), chest imaging, ECG and Holter monitoring (cardiac sarcoidosis screening — arrhythmia detection), ophthalmology (annual slit-lamp examination — uveitis is often asymptomatic), and serum calcium and renal function every 6 months. Avoid sun exposure if hypercalcaemic — UV light stimulates cutaneous vitamin D production which granuloma macrophages convert to active calcitriol, worsening hypercalcaemia. Vitamin D supplementation should be avoided unless serum calcium and levels are carefully monitored. Bisphosphonate prophylaxis (alendronic acid 70 mg weekly with calcium-free monitoring) for steroid-treated patients receiving prednisolone above 7.5 mg/day for more than 3 months. Pulmonary rehabilitation for stage III-IV disease.

Seek emergency care immediately for: acute respiratory failure (severe breathlessness at rest, SpO2 below 92%) — possible severe pulmonary sarcoidosis or cardiac arrhythmia from cardiac sarcoidosis; sudden loss of consciousness, palpitations, or syncope in a known sarcoidosis patient (cardiac sarcoidosis can cause life-threatening arrhythmias and requires urgent cardiac assessment); sudden vision loss or new neurological symptoms (cranial nerve palsy, weakness, confusion) in a patient with sarcoidosis — possible neurosarcoidosis or ocular sarcoidosis requiring urgent treatment. See a GP urgently for: unexplained persistent breathlessness, dry cough, or bilateral ankle swelling; erythema nodosum (tender red lumps on shins) with bilateral hilar lymphadenopathy on CXR (Lofgren's syndrome — a benign self-limiting form of sarcoidosis); or bilateral hilar lymphadenopathy found incidentally on chest imaging — urgent respiratory or thoracic medicine referral is required. Sarcoidosis frequently presents to A&E, dermatology, ophthalmology, or neurology — multidisciplinary awareness is key.