Sarcoidosis
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Direct answer
Non-caseating epithelioid granulomas accumulating in affected organs — the lungs and intrathoracic nodes in over 90 per cent of patients — define sarcoidosis, a multisystem granulomatous disease of unknown cause. It presents with bilateral hilar lymphadenopathy, erythema nodosum, uveitis, hypercalcaemia or incidentally on radiography, supported by a lymphocyte-rich bronchoalveolar lavage with a raised CD4 to CD8 ratio. Corticosteroids are first-line for symptomatic disease, with methotrexate and other steroid-sparing agents behind them.
What you must remember
- Scadding chest radiograph stages: stage I bilateral hilar lymphadenopathy; stage II hilar nodes plus parenchymal infiltrates; stage III infiltrates alone; stage IV fibrosis with honeycombing and upward hilar retraction — stages describe involvement, not sequential progression.
- Two eponymous syndromes: Lofgren syndrome — fever, bilateral hilar lymphadenopathy, erythema nodosum and arthralgia — carries an excellent prognosis; Heerfordt syndrome (uveoparotid fever) — fever, parotid enlargement, uveitis and facial nerve palsy.
- Skin and systemic clues: lupus pernio (violaceous nasal and cheek plaques, chronic course), papules and scars; anterior uveitis and keratoconjunctivitis sicca; Bell palsy and hypothalamic involvement; splenic and hepatic granulomas; palpable lymph nodes.
- Calcium metabolism: granulomas express 1-alpha-hydroxylase and convert vitamin D, producing hypercalcaemia, hypercalciuria, renal stones and nephrocalcinosis — hypercalcaemia is a classic examination laboratory clue.
- Laboratory and lavage support: raised serum angiotensin-converting enzyme (nonspecific), hyperglobulinaemia, cutaneous anergy to tuberculin, and bronchoalveolar lavage lymphocytosis with a CD4 to CD8 ratio above about 3.5; fluorodeoxyglucose positron-emission tomography can reveal occult disease.
- Histology: non-caseating ("naked") granulomas — but tuberculosis and fungal infection must be excluded by stain and culture before the label is accepted, a critical step in India.
- Treatment: observe asymptomatic stage I and mild stage II disease; prednisolone (commonly 0.5 mg per kg, tapering over months) for symptomatic pulmonary, cardiac, neurological, ocular or hypercalcaemic disease; methotrexate, azathioprine or mycophenolate as steroid-sparing agents; hydroxychloroquine for skin and calcium disease; infliximab for refractory cases; cardiac sarcoidosis may need pacing and defibrillator therapy.
From an incidental radiograph to a treatment decision
A 32-year-old woman has a pre-employment chest radiograph showing bilateral hilar lymphadenopathy; she feels well, but on questioning reports a fortnight of shin nodules and ankle arthralgia — fever, bilateral hilar lymphadenopathy, erythema nodosum and arthralgia together are Lofgren syndrome, and that combination carries an excellent prognosis with observation alone. Her bloods show mild hypercalcaemia — the mechanism worth reciting: granuloma macrophages express 1-alpha-hydroxylase and convert vitamin D unregulated, also producing hypercalciuria, stones and nephrocalcinosis — and the serum angiotensin-converting enzyme is raised, nonspecifically. Confirmation runs through bronchoalveolar lavage lymphocytosis with a CD4 to CD8 ratio above about 3.5, and biopsy showing non-caseating "naked" granulomas — but only after stains and cultures exclude tuberculosis and fungal disease, the critical step in India. Staging is by Scadding: she is stage I (bilateral hilar lymphadenopathy); stage II adds parenchymal infiltrates, stage III is infiltrates alone, and stage IV is fibrosis with honeycombing and upward hilar retraction — stages describe involvement, not obligatory progression. Management now divides by organ and symptom: asymptomatic stage I and mild stage II disease are observed, and observation is the correct answer, not steroids; prednisolone at about 0.5 mg per kg tapering over months treats symptomatic pulmonary, cardiac, neurological, ocular or hypercalcaemic disease; methotrexate, azathioprine or mycophenolate spare the steroid; hydroxychloroquine serves skin and calcium disease; infliximab waits for refractory cases; Survey for the rest: anterior uveitis, Bell palsy, hepatic and splenic granulomas, lupus pernio — unlike erythema nodosum, a chronic-disease marker — and Heerfordt's uveoparotid fever.
Where students slip
In the Indian setting the decisive confusion is with tuberculosis, and the viva expects the full contrast: tuberculous granulomas caseate and stain or culture positive against sarcoid's non-caseating, microbe-negative, anergic picture. The second error is treating every stage — asymptomatic stage I resolves in the large majority, and "start steroids" is precisely the trap answer. The third is misreading lupus pernio as benign; it is the chronic-disease marker, the opposite of erythema nodosum. The one-liners recycle: CD4 to CD8 above 3.5, raised ACE, the 1-alpha-hydroxylase hypercalcaemia, tuberculin anergy, and Lofgren versus Heerfordt composition.
Frequently asked questions
What are the Scadding chest radiograph stages?
I bilateral hilar lymphadenopathy, II nodes with infiltrates, III infiltrates alone, IV fibrosis.
What is Lofgren syndrome?
The acute triad-plus of fever, bilateral hilar lymphadenopathy, erythema nodosum and arthralgia, indicating sarcoidosis with an excellent prognosis.
Why does sarcoidosis cause hypercalcaemia?
Granuloma macrophages express 1-alpha-hydroxylase, generating active vitamin D and unregulated intestinal calcium absorption.
What bronchoalveolar lavage pattern supports sarcoidosis?
Lymphocytosis with a CD4 to CD8 ratio above about 3.5.
Which features separate sarcoidosis from tuberculosis?
Non-caseating granulomas without demonstrable acid-fast bacilli, negative cultures, cutaneous anergy and, often, erythema nodosum with arthralgia.
When is treatment started?
For symptomatic pulmonary disease, hypercalcaemia, and cardiac, ocular or neurological involvement — not for asymptomatic stage I disease.