Sarcoidosis as a multisystem inflammatory disorder

The rheumatology role is to integrate apparently unrelated inflammation. Ankle periarthritis, erythema nodosum, lupus pernio, uveitis, facial palsy, salivary enlargement, hypercalciuria and hilar nodes may belong to one granulomatous process, but infection, cancer and exposure must remain visible until diagnostic confidence is adequate. Record which organs are proven, probable, merely possible and already damaged.

Begin with chronology and exposure. Ask about cough and exertion, skin lesions, eye pain and vision, syncope and palpitations, hearing and cranial nerves, sensory or motor change, headache, thirst and stones, sicca or gland enlargement, arthritis, constitutional loss, travel, TB contact, mould, birds, metal and stone work, medicines and immune deficiency. Examine nodes, skin, joints, eyes grossly, pulse and rhythm, heart failure, cranial nerves, power and sensory level, liver and spleen.

Baseline tests are designed to find silent consequence, not to prove the label. Obtain FBC, creatinine and eGFR, adjusted calcium, liver profile, CRP or ESR, urinalysis, protein quantification when abnormal and an ECG. Chest radiograph and pulmonary physiology establish thoracic burden; thin-section CT clarifies an atypical or progressive pattern. Measure immunoglobulins and targeted autoimmune or infectious tests when the phenotype requires them.

Tissue strategy answers a clinical question. Biopsy an active accessible skin lesion or peripheral node when possible; EBUS-guided node sampling is often preferable for intrathoracic disease. Ask pathology to assess necrosis and alternative infiltrates and send separate material for mycobacterial and fungal tests. A steroid trial before securing tissue can temporarily shrink lymphoma and sterilise the most useful inflammatory signal.

Cardiac assessment starts with symptoms and a 12-lead ECG, but neither a normal ECG nor normal echocardiogram fully excludes patchy myocardial disease. Conduction change, ventricular ectopy, unexplained troponin or natriuretic peptide, cardiomyopathy or syncope prompts ambulatory monitoring, echocardiography and expert cardiac MRI. FDG-PET is useful for metabolically active inflammation and treatment response only after dietary preparation and specialist interpretation.

Neurological disease is anatomically diverse. Contrast MRI of brain, orbits and spine is directed by localisation; CSF can show lymphocytes, protein, low glucose or oligoclonal bands but is nonspecific and is principally useful for excluding infection and malignancy. Seek safer systemic tissue before neural biopsy. Facial palsy can be benign, while optic neuropathy, hydrocephalus, myelopathy and hypothalamic-pituitary disease demand rapid multidisciplinary treatment.

Renal assessment separates calcium load from granulomatous interstitial nephritis and unrelated glomerular disease. Measure serum calcium, creatinine, urine calcium where indicated, urinalysis and protein. A low 25-hydroxyvitamin D does not automatically justify replacement because calcitriol may be high; specialist measurement of both metabolites can guide difficult supplementation. Kidney biopsy is appropriate for unexplained impairment, active sediment or suspected interstitial disease when it changes therapy.

Ocular sarcoidosis includes anterior, intermediate and posterior uveitis, retinal vasculitis, lacrimal disease and optic neuropathy. Symptoms require same-day slit-lamp and dilated retinal assessment. Asymptomatic screening practice varies, but patients must receive a direct eye safety net. Local drops may control isolated anterior uveitis; posterior, optic or bilateral severe disease usually needs systemic coordination.

Observation is appropriate when organs are safe, symptoms acceptable and trajectory stable. Agree a timetable for symptoms, ECG or rhythm where indicated, calcium and organ profiles, lung function and imaging rather than discharging on a reassuring ACE. Löfgren syndrome often resolves and may need only a brief NSAID course if renal, gastrointestinal, cardiovascular and pregnancy risks permit.

For inflammatory disease threatening organ function or quality of life, prednisolone commonly starts at 20–40 mg each morning for four to six weeks, then tapers according to objective response toward 5–10 mg and eventual withdrawal over approximately six to twelve months. Cardiac, neurological, sight-threatening or severe renal disease may require IV methylprednisolone induction and earlier steroid-sparing therapy through the relevant organ team.

Methotrexate is the usual first steroid-sparing agent, often beginning at 10–15 mg once weekly with folic acid and increasing to 20–25 mg weekly if monitoring and response permit. Hydroxychloroquine can help selected skin, joint and calcium phenotypes. Azathioprine or mycophenolate is used when organ, pregnancy or toxicity considerations fit. Refractory disease may receive infliximab after TB, hepatitis and infection screening; all these uses require specialist commissioning and monitoring.

Treatment response is organ-specific. Falling FDG uptake or inflammation does not restore established myocardial scar, lung fibrosis, optic atrophy or axonal loss. Track the function that justified therapy—rhythm burden, ejection fraction, visual inflammation, neurological examination, calcium and eGFR, skin burden, FVC or gas transfer—and reduce glucocorticoid only when the whole pattern permits it.