Sarcoidosis

Sarcoidosis is a multisystem granulomatous disease of unknown cause characterised by non caseating epithelioid granulomas, most commonly affecting the lungs and intrathoracic lymph nodes.

Incidence 5 to 40 per 100,000, highest in Black Americans and Scandinavians; onset 25 to 45 years, second peak in women over 50. Women more affected.

Immunopathogenesis: antigen driven Th1/Th17 response in genetically susceptible individuals (HLA DRB1*1101, BTNL2); triggers include mycobacterial antigens, inorganic dust.

Löfgren syndrome (acute): erythema nodosum, bilateral hilar lymphadenopathy, fever and arthritis; excellent prognosis (over 90% resolve).

Chronic: pulmonary fibrosis in 10 to 20%; mortality 1 to 5%, mainly from respiratory or cardiac disease.

Extrapulmonary: skin (lupus pernio, erythema nodosum, plaques), eye (anterior uveitis, 25%), heart, nervous system (facial palsy, aseptic meningitis, neuropathy), liver, kidney (hypercalcaemia, nephrocalcinosis), bone, parotid (Heerfordt syndrome), spleen.

Scadding chest radiograph stages 0 to IV (hilar adenopathy, parenchymal infiltrates, fibrosis).

• Many are asymptomatic with incidental hilar adenopathy.
• Cough, dyspnoea, chest tightness, fatigue, fever, weight loss, night sweats.
• Löfgren: tender red shin nodules, ankle periarticular swelling.
• Eye redness and photophobia, skin plaques, neurological deficits, palpitations, syncope, heart block, renal stones.

• Chest radiograph and HRCT: symmetric hilar and mediastinal adenopathy, perilymphatic nodules, fibrosis.
• Tissue confirmation (biopsy of accessible lesion, endobronchial ultrasound guided transbronchial needle aspiration of nodes, transbronchial biopsy) showing non caseating granulomas, excluding infection and malignancy.
• Bronchoalveolar lavage: lymphocytosis with CD4/CD8 ratio over 3.5.
• Laboratory: serum ACE (variable), calcium, 24 hour urinary calcium, 1,25 dihydroxyvitamin D, liver enzymes, creatinine, soluble IL 2 receptor, full blood count.
• Pulmonary function tests (restrictive, reduced DLCO).
• Organ assessment: ECG, Holter, echocardiogram, cardiac MRI or FDG PET for cardiac sarcoid; slit lamp ophthalmology; neuroimaging; FDG PET for activity.

• Observation for asymptomatic stage I or II disease with stable lung function; spontaneous remission in 60 to 80% of stage I.
• Löfgren syndrome: NSAIDs (naproxen 500 mg twice daily).
• Treatment indications: progressive or symptomatic pulmonary disease, and cardiac, neurological, ocular, renal, hypercalcaemic or severe skin involvement.
• Prednisolone 20 to 40 mg daily for 4 to 12 weeks (pulmonary), then taper to 5 to 10 mg over 6 to 12 months; treat for at least 12 months for relapse prevention. Higher doses (0.5 to 1 mg/kg) for neuro and cardiac disease.
• Steroid sparing agents: methotrexate 10 to 20 mg weekly (first line), azathioprine 2 mg/kg, mycophenolate 1 to 1.5 g twice daily, leflunomide 10 to 20 mg; infliximab 3 to 5 mg/kg (at 0, 2, 6 weeks then every 8 weeks) or adalimumab for refractory disease, neurosarcoid, lupus pernio.
• Ocular: topical corticosteroid drops (prednisolone acetate 1%) and cycloplegics for anterior uveitis; systemic therapy for posterior uveitis.
• Hypercalcaemia: avoid vitamin D and calcium, hydration, prednisolone 20 to 40 mg, hydroxychloroquine 200 to 400 mg.
• Skin: topical steroids, hydroxychloroquine 200 mg twice daily.
• Cardiac sarcoid: immunosuppression, pacemaker/ICD (see cardiac sarcoidosis).
• Monitoring: spirometry and imaging every 3 to 6 months; relapse in 15 to 30% after stopping therapy.
• Lung transplantation for end stage fibrotic disease; Pneumocystis prophylaxis and bone protection on prolonged immunosuppression.