Sarcoidosis is a multisystem inflammatory disease characterised by the formation of non-caseating granulomas in affected organs. The cause remains unknown (likely abnormal immune response to an unidentified antigen in genetically susceptible individuals).
Hallmark: Non-caseating granulomas (no central caseous necrosis — distinguishing from tuberculosis which has CASEATING granulomas).
Lungs affected in ~90% of cases
Can affect virtually any organ: skin, eyes, lymph nodes, heart, nervous system, liver, bone marrow
Bimodal age distribution: 20–40 years and 50–65 years
More common and severe in Black African/Caribbean patients; also seen in Northern European, Asian populations
CXR Staging of Pulmonary Sarcoidosis
Stage
CXR Findings
Spontaneous Resolution Rate
Stage 0
Normal CXR (extrapulmonary disease only)
—
Stage I
Bilateral hilar lymphadenopathy (BHL) ONLY
55–90%
Stage II
BHL + pulmonary infiltrates
40–70%
Stage III
Pulmonary infiltrates WITHOUT BHL
10–20%
Stage IV
Pulmonary fibrosis
Irreversible
Löfgren Syndrome
Löfgren syndrome = BHL + erythema nodosum + polyarthritis + fever. It has an EXCELLENT prognosis — most cases resolve spontaneously within 1–2 years without treatment.
Acute presentation with bilateral hilar lymphadenopathy on CXR
Erythema nodosum — painful red nodules on shins (not specific to sarcoidosis — also seen in TB, streptococcal infection, IBD)
Polyarthritis — particularly ankle arthritis
Fever, fatigue, night sweats
Löfgren syndrome does NOT require biopsy confirmation in typical presentation
Extrapulmonary Manifestations
System
Manifestation
Clinical Note
Skin
Lupus pernio (violaceous facial skin plaques)
Specific to sarcoidosis; indicates chronic disease
Eyes
Anterior uveitis (most common — 25%)
URGENT ophthalmology referral — can cause blindness if untreated
Heart
Complete heart block, VT/VF
Can cause sudden cardiac death; requires cardiac monitoring ± pacemaker
Nervous system
Facial palsy (CN VII) — most common cranial nerve
Bilateral facial palsy = think sarcoidosis
Calcium
Hypercalcaemia, hypercalciuria
Granulomas produce 1,25(OH)₂ vitamin D (calcitriol) → renal stones, nephrocalcinosis
Liver/spleen
Hepatosplenomegaly, granulomatous hepatitis
Rarely causes significant liver failure
Investigations
Serum ACE (Angiotensin Converting Enzyme) — elevated in 60–70% of active sarcoidosis; NOT specific (also elevated in TB, Gaucher's disease); useful for monitoring disease activity
Calcium — hypercalcaemia (and hypercalciuria) from granuloma-derived calcitriol
BAL (Bronchoalveolar lavage) — CD4:CD8 ratio >3.5 suggests sarcoidosis
PFTs — restrictive pattern (FVC↓, TLC↓, DLCO↓) in pulmonary disease
ECG — heart block, arrhythmias
24-hour urinary calcium — renal stone risk assessment
Treatment Indications and Options
Stages I and II pulmonary sarcoidosis often resolve spontaneously — watchful waiting is appropriate for asymptomatic or mildly symptomatic patients. Treatment is required for organ-threatening or symptomatic disease.
Indication for Treatment
Examples
Symptomatic pulmonary disease
Progressive dyspnoea, deteriorating PFTs, hypoxia
Cardiac sarcoidosis
Heart block, VT — urgent treatment
Ocular sarcoidosis
Posterior uveitis, progressive visual loss
Neurological sarcoidosis
Cranial nerve palsies, CNS involvement
Hypercalcaemia
Symptomatic or renal impairment
First-line treatment: Prednisolone 0.5 mg/kg/day (20–40mg daily) for 4–6 weeks, then taper over months. Most patients require 12–24 months of treatment.
Second-Line and Steroid-Sparing Agents
Methotrexate — most commonly used steroid-sparing agent; monitor LFTs and FBC
Azathioprine — alternative steroid-sparing agent
Hydroxychloroquine — particularly useful for cutaneous and hypercalcaemia sarcoidosis
Infliximab (anti-TNF) — for refractory neurosarcoidosis and cardiac sarcoidosis
Long-term prednisolone side effects: osteoporosis, diabetes, hypertension, cataracts, adrenal suppression
Cardiac Sarcoidosis
Cardiac sarcoidosis can cause sudden cardiac death from complete heart block or ventricular arrhythmias. It may be clinically silent until a fatal event.
Corticosteroids are first-line (suppress granuloma activity and 1-alpha-hydroxylase)
Avoid vitamin D supplements and calcium supplements in sarcoidosis
Limit sunlight exposure — UV converts skin precursor to 25-OH vitamin D, further worsening hypercalcaemia
Hydration to prevent renal stones
Ocular Sarcoidosis
Anterior uveitis is the most common ocular manifestation of sarcoidosis. Symptoms: painful red eye, photophobia, blurred vision. URGENT ophthalmology referral — untreated uveitis causes synechiae, glaucoma, and permanent vision loss.
Annual ophthalmology screening for all sarcoidosis patients
Tuberculosis remains prevalent in the GCC expatriate workforce (particularly workers from South Asia, Southeast Asia, and Sub-Saharan Africa). Both TB and sarcoidosis can present with bilateral hilar lymphadenopathy, lung infiltrates, and constitutional symptoms. Distinguishing them is CRITICAL — corticosteroids are first-line for sarcoidosis but will worsen untreated TB.
Feature
Sarcoidosis
Tuberculosis
Granulomas
Non-caseating
Caseating (central necrosis)
AFB culture
Negative
Positive (Mycobacterium tuberculosis)
Mantoux/IGRA
Usually negative or weakly positive
Strongly positive (IGRA more specific)
ACE
Often elevated
May be elevated (less specific)
Response to steroids alone
Improves
May worsen (reactivation)
GCC TB Screening and Sarcoidosis Diagnosis
All expatriate workers in GCC require pre-employment chest X-ray — TB screening
BHL on CXR in an expatriate from high TB-prevalence country: TB must be excluded before diagnosing sarcoidosis
IGRA (QuantiFERON Gold) preferred over Mantoux in BCG-vaccinated populations (most South Asians)
Sputum AFB ×3 + culture if TB cannot be excluded clinically/radiologically
EBUS-guided biopsy with histology + cultures in ambiguous cases
Desert Dust and Environmental Triggers in GCC
Hypothesis: desert dust particles (beryllium, silica, organic antigens) may trigger sarcoid-like granulomatous reactions in susceptible individuals
Occupational exposure: construction workers, quarry workers exposed to silica dust may develop sarcoid-like pulmonary granulomatosis
Berylliosis (chronic beryllium disease) can be indistinguishable from sarcoidosis clinically — occupational history essential
Healthcare workers treating sarcoidosis patients should document occupational and environmental exposure history
First-line treatment = prednisolone; stages I and II often resolve spontaneously
Common Exam Traps
Serum ACE is NOT specific to sarcoidosis — elevated in TB, Gaucher's disease, histoplasmosis
Avoid vitamin D and calcium supplements in sarcoidosis — worsens hypercalcaemia
Corticosteroids are first-line for sarcoidosis — but EXCLUDE TB first (steroids alone will worsen TB)
Anterior uveitis = urgent referral — NOT watchful waiting; can cause blindness
GCC Clinical Practice Insights
TB vs Sarcoidosis: Diagnostic Pathway in GCC +
In GCC hospitals receiving expatriate workers from TB-endemic countries, BHL on CXR should trigger a structured TB exclusion protocol: IGRA + sputum AFB ×3 + cultures before proceeding to sarcoidosis biopsy. Starting prednisolone for presumed sarcoidosis without excluding TB can cause miliary TB and fatal dissemination. Respiratory physicians and infectious disease specialists should be involved in complex cases.
Cardiac Sarcoidosis Recognition in GCC Emergency Settings +
Cardiac sarcoidosis may present to GCC emergency departments with complete heart block, syncope, or VT. In a young patient with unexplained complete heart block or arrhythmia, sarcoidosis should be considered — particularly if there are pulmonary symptoms, BHL on CXR, or elevated ACE. Cardiac MRI with gadolinium is the investigation of choice. Emergency pacing may be required before immunosuppressive treatment is initiated.
Long-Term Corticosteroid Side Effects — Nursing Monitoring +
Patients on long-term prednisolone for sarcoidosis require monitoring for: blood glucose (steroid-induced diabetes — particularly in GCC where T2DM baseline rates are high), blood pressure, weight, bone density (DEXA scan annually; calcium + vitamin D supplementation but note sarcoidosis-specific hypercalcaemia risk — specialist guidance required), and eye pressure (steroid-induced glaucoma/cataracts). Proton pump inhibitor co-prescription should be considered for GI protection.
Hypercalcaemia Management in GCC Climate +
In the GCC's intense sunlight, UV radiation activates the skin's vitamin D synthesis pathway. For patients with sarcoidosis-associated hypercalcaemia, UV exposure worsens hypercalcaemia by increasing calcitriol production. Patients should be advised to limit sun exposure (particularly midday), use high-factor sunscreen, and avoid vitamin D supplements. Adequate hydration is also critical to prevent renal stone formation — challenging in GCC summer heat.
Practice MCQs
Q1. A 32-year-old woman presents with bilateral ankle swelling, painful red nodules on her shins, and a chest X-ray showing bilateral hilar lymphadenopathy. She is otherwise well. What is the most likely diagnosis and prognosis?
Correct answer: B — This is the classic presentation of Löfgren syndrome: BHL + erythema nodosum (painful red nodules on shins) + polyarthritis (ankle joints) with fever. It carries an excellent prognosis — majority resolve spontaneously without treatment. Biopsy is not required for a typical presentation. TB must be excluded but is less likely given the classic constellation and well appearance.
Q2. A patient with known sarcoidosis develops a painful red eye with photophobia. What is the most appropriate action?
Correct answer: C — Anterior uveitis (painful red eye, photophobia, blurred vision) in a patient with sarcoidosis requires URGENT ophthalmology referral. Untreated uveitis causes posterior synechiae, cataracts, glaucoma, and permanent visual impairment. Chloramphenicol treats bacterial conjunctivitis — not uveitis. Treatment requires topical steroids + mydriatics under specialist care.
Q3. Why does sarcoidosis cause hypercalcaemia?
Correct answer: C — This is a classic mechanism question. Activated macrophages within sarcoid granulomas produce 1-alpha-hydroxylase enzyme, which converts 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D (calcitriol — the active form). This causes increased intestinal calcium absorption and increased osteoclast activity → hypercalcaemia and hypercalciuria → renal stones. Corticosteroids treat this by suppressing granuloma activity.
Q4. How do non-caseating granulomas in sarcoidosis differ from the granulomas seen in tuberculosis?
Correct answer: C — The histological hallmark of sarcoidosis is non-caseating (non-necrotising) granulomas — epithelioid macrophages and giant cells without central caseous necrosis. TB granulomas have characteristic central caseous (cheese-like) necrosis and contain acid-fast bacilli (AFB). Both have giant cells (Langerhans type). This distinction is why biopsy plus AFB culture is essential in TB-endemic regions before diagnosing sarcoidosis.