Sarcoidosis

Overview

Sarcoidosis is a chronic inflammatory disease characterised by non-caseating granulomas. Lungs are involved in >90% of cases but virtually every organ system can be affected.

Epidemiology

•Bimodal age distribution: primary peak 25-45 years, second peak in women >50
•More common and severe in Afro-Caribbean individuals; more common in women

Presentation

•~1/3 asymptomatic at diagnosis - found incidentally on CXR
•Systemic: fatigue, fever, night sweats, weight loss
Named syndromes in sarcoidosis
FeatureLöfgren's syndromeHeerfordt's syndrome (uveoparotid fever)
Key featuresErythema nodosum, bilateral hilar lymphadenopathy, polyarthralgia (especially ankles), feverUveitis, parotid swelling, facial nerve palsy (may be bilateral), fever
PrognosisGood - often resolves spontaneouslyVariable
•Pulmonary: dry cough, dyspnoea, fine crackles
•Skin: erythema nodosum (acute disease); lupus pernio - violaceous plaques on nose/cheeks/lips/ears (pathognomonic; marker of chronic, severe disease)
•Ocular: uveitis most common - anterior (red, painful, photophobic) or posterior (more persistent)
•Neurological: facial nerve palsy (CN VII, may be bilateral) - bilateral Bell's palsy should raise suspicion for sarcoidosis
•Cardiac: arrhythmias, heart block, restrictive cardiomyopathy, sudden cardiac death
•Renal: nephrolithiasis and nephrocalcinosis (hypercalcaemia-driven)
•Hepatic/splenic: hepatomegaly, splenomegaly; raised ALP most common LFT abnormality

Investigations

🥇 First-line

•CXR - bilateral hilar lymphadenopathy (BHL) is the hallmark finding
•serum calcium - hypercalcaemia supports diagnosis; identifies renal risk
•serum ACE - elevated in active disease (produced by granulomas); useful for monitoring activity, not for diagnosis alone
•FBC, LFTs, U&Es, ECG, PFTs - restrictive pattern (reduced FVC, reduced TLC, raised FEV1:FVC), reduced DLCO

🥈 Second-line

•HRCT chest - more sensitive than CXR for parenchymal changes
•bronchoalveolar lavage (BAL) - CD4:CD8 ratio >3.5:1 is characteristic

🏆 Gold standard

•tissue biopsy - non-caseating granulomas with epithelioid cells, absence of alternative cause (TB, fungal); via transbronchial biopsy, EBUS, or accessible lesion (skin, lymph node)
⚠️
Serum ACE is neither sensitive nor specific - also elevated in TB, lymphoma, hyperthyroidism, liver disease. Never use alone for diagnosis; main role is monitoring disease activity once sarcoidosis is established.

Differential diagnosis

•TB - most important; also causes BHL, chronic cough, night sweats; TB typically shows caseating granulomas; distinguish with ZN stain, cultures, IGRA/Mantoux
•Lymphoma - mediastinal lymphadenopathy, B symptoms; Reed-Sternberg cells on biopsy (Hodgkin's)
•Berylliosis - histologically indistinguishable from sarcoidosis; distinguished by occupational exposure history

Management

•Not all patients require treatment - many cases (especially Stage 1, Löfgren's syndrome) resolve spontaneously
•Symptomatic relief (arthralgia/fever): NSAIDs
•First-line systemic treatment: prednisolone (oral corticosteroids) - indicated for significant symptoms, progressive organ dysfunction, or cardiac/neurological involvement
•Cardiac and neurological involvement always warrants treatment
•Second-line (steroid-sparing): methotrexate, azathioprine
💡
Löfgren's syndrome is managed conservatively (NSAIDs, monitoring with serial CXR and PFTs); systemic corticosteroids are often not required given its self-limiting course.

Complications

•Pulmonary fibrosis (Stage 4) - irreversible; leading cause of sarcoidosis-related mortality
•Cardiac: complete heart block, ventricular tachycardia, sudden cardiac death
•Renal: nephrolithiasis, nephrocalcinosis, chronic kidney disease
•Blindness - from untreated posterior uveitis or glaucoma
•Long-term corticosteroid complications: osteoporosis, diabetes, adrenal suppression

Prognosis

•~2/3 achieve spontaneous remission; Stage 1 has best prognosis
•Poor prognosis markers: lupus pernio, cardiac/neurological involvement, Stage 3-4 CXR, Afro-Caribbean ethnicity
•Pulmonary fibrosis is the most common cause of death from sarcoidosis

Pathophysiology (high-yield mechanism)

•Exaggerated CD4+ Th1 response → macrophage activation → non-caseating granulomas (no central necrosis - distinguishes from TB)
•Granuloma macrophages overproduce 1-alpha-hydroxylase → excess calcitriol → hypercalcaemia and hypercalciuria → nephrolithiasis/nephrocalcinosis

CXR staging (pulmonary sarcoidosis)

Stage
CXR findings
Prognosis
0
Normal
Best
1
Bilateral hilar lymphadenopathy only
Often resolves spontaneously
2
BHL + pulmonary infiltrates
Variable
3
Pulmonary infiltrates only (BHL resolved)
Variable
4
Pulmonary fibrosis
Worst - irreversible