Sarcoidosis: Comprehensive Guide To Causes, Symptoms, Treatment
Multisystem granulomatous disease with non-caseating granulomas affecting skin, lungs, eyes, and more.
Sarcoidosis is a multisystem inflammatory disease characterised by the formation of
non-caseating granulomas
in various organs, most commonly the lungs, lymph nodes, skin, eyes, and heart. These granulomas represent clusters of immune cells responding to an unknown trigger, leading to diverse clinical manifestations.What is sarcoidosis?
Sarcoidosis involves the development of discrete, compact, non-caseating epithelioid granulomas in affected tissues. Unlike tuberculosis, these granulomas lack central necrosis (caseation). The disease can be asymptomatic or present with systemic symptoms such as fatigue, weight loss, fever, and arthralgias. Cutaneous involvement occurs in 25-30% of cases and serves as an important diagnostic clue due to its accessibility for biopsy.
Granulomas consist of epithelioid histiocytes, multinucleated giant cells (Langhans-type), and a sparse lymphocytic rim, often termed ‘naked granulomas’ due to minimal surrounding inflammation.
Who gets sarcoidosis?
Sarcoidosis affects individuals worldwide across all races, ages, and sexes, with peak incidence between 20-40 years. It is more common in women and shows higher prevalence in people of African or Scandinavian descent. In the US, incidence is 10/100,000 in Caucasians versus 35/100,000 in African Americans.
- Family history increases risk; monozygotic twins have an 80-fold higher concordance.
- Associated with autoimmune conditions like vitiligo, Sjögren syndrome, and thyroid disease.
Causes
The aetiology of sarcoidosis remains unknown, but it is widely regarded as a dysregulated immune response to environmental antigens in genetically susceptible individuals. Key factors include:
- Genetic predisposition: Associations with HLA-DRB1*0301/DQB1*0201, TNF-α, TGF-β, and TLR-4 genes.
- Environmental exposures: Inorganic dusts (silica, beryllium), organic antigens (tree pollen, pesticides), and occupational hazards like firefighting or bird breeding.
- Infectious triggers: Possible roles for Mycoplasma, Propionibacterium acnes, Borrelia burgdorferi, and herpesviruses, though not proven causative.
- Drug-induced: Reactions mimicking sarcoidosis reported with checkpoint inhibitors, anti-TNF agents, and interferon.
No single pathogen has been consistently isolated, supporting an exaggerated host response rather than direct infection.
Signs and symptoms
Patients may be asymptomatic (discovered incidentally on chest X-ray) or present with constitutional symptoms: fever, night sweats, anorexia, and weight loss. Specific organ involvement dictates the clinical picture.
Skin findings
Cutaneous sarcoidosis manifests in two forms:
- Non-specific (9%): Erythema nodosum (painful red nodules on shins), pruritus.
- Specific (4-30%): Maculopapular eruptions, plaques, lupus pernio (violaceous plaques on nose/ears), subcutaneous nodules (Darier-Roussy), ichthyosiform changes, ulcerations.
Lupus pernio is pathognomonic and associated with chronic disease.
Symptoms and signs of specific organ involvement
| Organ | Frequency | Key Features |
|---|---|---|
| Pulmonary | 90% | Dyspnoea, dry cough, hilar lymphadenopathy (stage I), interstitial infiltrates (stage II/III) |
| Lymph nodes | 75% | Painless peripheral adenopathy in 20-30% |
| Eye | 25% | Anterior uveitis (most common), posterior involvement, keratoconjunctivitis sicca |
| Cardiac | 5-25% | Arrhythmias, heart block, cardiomyopathy |
| Neurologic | 5-10% | Cranial nerve palsies (VII most common), aseptic meningitis, hypothalamic lesions |
| Hepatic/Splenic | 15% | Granulomas on biopsy, mild LFT elevation |
| Musculoskeletal | 10-40% | Arthralgias, Löfgren syndrome (acute triad: EN + arthritis + hilar adenopathy) |
Hypercalcemia/hypercalciuria occurs in 10-20% due to granulomatous 1α-hydroxylase activity producing active vitamin D.
Diagnosis
Diagnosis relies on compatible clinical/radiologic findings, histologic confirmation of non-caseating granulomas, and exclusion of alternative causes (e.g., mycobacterial/fungal infections, hypersensitivity pneumonitis).
- Biopsy: Skin, lung, lymph node; shows ‘naked’ epithelioid granulomas without organisms on special stains.
- Imaging: Chest X-ray (bilateral hilar lymphadenopathy in 85%), HRCT for parenchymal disease.
- Laboratory: Elevated ACE (60%), hypercalcemia, anaemia, hypergammaglobulinaemia, elevated CD4/CD8 ratio in BAL fluid.
- Pulmonary function: Restrictive pattern, reduced DLCO.
- Ophthalmology review: Slit-lamp exam essential.
Differential diagnoses
- Infectious granulomas: TB, atypical mycobacteria, histoplasmosis, coccidioidomycosis.
- Foreign body reaction: Berylliosis, talc granulomatosis.
- Other: Langerhans cell histiocytosis, granuloma annulare, necrobiosis lipoidica.
- Skin-specific: Discoid lupus, granulomatous rosacea, cutaneous lymphoma.
Treatment
Many cases remit spontaneously; treat only symptomatic or organ-threatening disease. Surveillance for 2-3 years recommended.
- First-line: Oral glucocorticoids (prednisone 20-40 mg/day) for pulmonary, ocular, neurologic involvement.
- Steroid-sparing: Methotrexate (10-25 mg/week), azathioprine.
- Refractory: Infliximab (anti-TNF), rituximab.
Treatment of cutaneous sarcoidosis
Mild cases observed; treat for cosmesis or progression:
- Topical: High-potency steroids, calcineurin inhibitors (tacrolimus).
- Intralesional: Triamcinolone (5-20 mg/mL) for plaques/nodules.
- Systemic: Hydroxychloroquine (200-400 mg/day, good for lupus pernio), methotrexate.
- Other: Allopurinol, tetracyclines, laser therapy, excision for disfiguring lesions.
Erythema nodosum: NSAIDs, short-course prednisone.
Prognosis
Two-thirds remit within 2-3 years; 10-30% chronic requiring long-term therapy. Five-year mortality 1-7%, mainly from pulmonary fibrosis, cardiac sarcoid.
- Good prognosis: Löfgren syndrome, age <40, Caucasian, stage I chest X-ray.
- Poor prognosis: African descent, lupus pernio, cardiac/CNS/ocular involvement, hypercalcemia, stage III/IV lung disease.
Cutaneous lesions may persist years; subcutaneous nodules resolve in 1-2 years but can recur.
Frequently Asked Questions (FAQs)
Q: Is sarcoidosis contagious?
A: No, sarcoidosis is not infectious and cannot be transmitted person-to-person.
Q: Can sarcoidosis be cured?
A: Most cases resolve spontaneously without treatment; chronic cases managed long-term.
Q: Does sarcoidosis always affect the lungs?
A: Lungs involved in 90%, but isolated extrapulmonary disease occurs.
Q: What is the best treatment for skin sarcoidosis?
A: Depends on type; topical/intralesional steroids first-line, systemic for severe cases.
Q: How is sarcoidosis diagnosed?
A: Clinical features + non-caseating granulomas on biopsy + exclusion of mimics.
References
- Sarcoidosis — DermNet NZ. 2023. https://dermnetnz.org/topics/sarcoidosis
- Sarcoidosis: a comprehensive review and update for the dermatologist — PubMed (J Am Acad Dermatol). 2012-05-01. https://pubmed.ncbi.nlm.nih.gov/22507585/
- Darier-Roussy subcutaneous sarcoidosis — DermNet NZ. 2023. https://dermnetnz.org/topics/darier-roussy-subcutaneous-sarcoidosis
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