SN7 SHORT NOTE 5M

Describe sarcoidosis with its morphology, clinical features and diagnosis.

Pathology · 2nd Professional — Para-Clinical

Definition

Sarcoidosis is a multisystem disease of unknown cause, characterised by non-caseating epithelioid granulomas in many organs, most often the lung and hilar lymph nodes.

A diagnosis of exclusion — tuberculosis, fungal infection, berylliosis and lymphoma must all be ruled out first
Commonest in young adults, with a female preponderance; incidence varies greatly between populations

Pathogenesis

An exaggerated CD4 TH1 response to an unidentified antigen in a genetically susceptible person
Interferon-gamma and IL-2 drive macrophage activation and granuloma formation
The paradox of sarcoidosis — intense local T cell activity in the lung with peripheral anergy, so the Mantoux test is typically negative despite a vigorous granulomatous response

Morphology

Non-caseating granulomas — compact collections of epithelioid cells with giant cells, surrounded by a rim of lymphocytes and fibroblasts; "naked" granulomas with a sparse lymphocytic cuff
Asteroid bodies — stellate eosinophilic inclusions within giant cells
Schaumann bodies — laminated concretions of calcium and protein
Neither inclusion is specific, and both occur in other granulomatous disease — a point frequently examined
Distribution in the lung is along lymphatics — peribronchial, perivascular and subpleural, which is why transbronchial biopsy has a high yield
Healing by fibrosis may produce upper-zone pulmonary fibrosis and honeycombing

CLINICAL PEARL

"Non-caseating" is the whole point, and in India it is never enough on its own. Tuberculous granulomas caseate and sarcoid granulomas do not — but early or treated tuberculosis may show little caseation, and sarcoid granulomas may show minor central necrosis. Ziehl–Neelsen staining and culture are mandatory before immunosuppressing anybody, because steroids given for misdiagnosed tuberculosis are catastrophic.

Clinical Features

System	Features
Lung (over 90%)	Bilateral hilar lymphadenopathy, often asymptomatic and found incidentally; reticulonodular infiltrates; restrictive defect and reduced transfer factor
Skin	Erythema nodosum, lupus pernio (violaceous nodules on the nose and cheeks), plaques, scar infiltration
Eye	Anterior uveitis (may cause blindness), keratoconjunctivitis sicca
Lymph nodes, liver and spleen	Painless enlargement
Metabolic	Hypercalcaemia and hypercalciuria — activated macrophages produce 1-alpha-hydroxylase and so excess calcitriol
Heart and nervous system	Arrhythmias, heart block, cardiomyopathy; cranial nerve palsies (especially facial), diabetes insipidus — uncommon but serious
Named syndromes	Lofgren syndrome — erythema nodosum + bilateral hilar lymphadenopathy + arthralgia + fever; carries an excellent prognosis. Heerfordt syndrome — uveitis + parotid enlargement + facial palsy + fever

Investigation and Applied Aspects

Chest radiograph staging — 0 normal; I hilar adenopathy alone; II adenopathy with infiltrates; III infiltrates alone; IV fibrosis
Serum ACE is raised in about 60% but is neither sensitive nor specific; it is used for monitoring rather than diagnosis
Biopsy showing non-caseating granulomas with negative stains and culture is required; transbronchial or endobronchial ultrasound-guided nodal biopsy
Most cases remit spontaneously, particularly stage I, so treatment is reserved for progressive lung disease, or involvement of the eye, heart, nervous system or kidney, or hypercalcaemia
Corticosteroids are the mainstay when treatment is needed, with methotrexate or other agents as steroid-sparing alternatives
Bilateral hilar lymphadenopathy in India has a wide differential — tuberculosis, lymphoma and sarcoidosis — and tissue diagnosis matters greatly before treatment is chosen

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