Sarcoidosis
NICE CKS Sarcoidosis. Last revised: Jan 2024.
Background Information
Definition
Sarcoidosis is a multi-system disease characterised by the presence of non-caseating granulomas in the affected organs
Main cell types involved in a granuloma: macrophages and CD4+ Th1 cells
- Granuloma is composed of epithelioid cells and macrophages surrounded by lymphocytes and fibroblasts
Caseating vs non-caseating granulomas:
- Caseating granuloma
- Contains central necrosis (caseous necrosis)
- Commonly associated with infectious diseases, especially TB
- Non-caseating granuloma:
- Lacks central necrosis
- Commonly associated with non-infectious inflammatory conditions like sarcoidosis, Crohn's disease, hypersensitivity pneumonitis
Aetiology
The exact cause is unknown
Epideimology
Peak age of onset: 30-55 y/o
More common in females
More common in the following ethnicities:
- African-American
- Scandinavians and Northern Europeans
Clinical Features
Sarcoidosis most commonly affects the following organs:
- Lungs (~90%)
- Skin (~30%)
- Eye (~30%)
- But any organ may be involved
Clinical features by affected organ:
| Organ system | Clinical features |
|---|---|
| Lungs | Often asymptomatic initially
Becomes symptomatic when interstitial fibrosis develops:
|
| Skin |
|
| Eyes |
|
| Lymphatic |
|
| MSK |
|
| Neurological |
|
| Heart |
|
| Liver / spleen |
|
| Kidneys |
|
Syndromes that are highly specific for sarcoidosis:
- Lofgren syndrome (acute clinical manifestation)
- Triad of erythema nodosum + migrating polyarthritis + bilateral hilar adenopathy
- Heerfordt's syndrome (uveoparotid fever)
- Triad of uveitis + parotid swelling + facial nerve palsy
Diagnosis
1st line tests to order:
- Chest X-ray
- Lung function test (spirometry and DLCO)
- ECG (cardiac sarcoidosis can cause conduction abnormalities and sudden cardiac death)
- Routine bloods
If chest X-ray is suggestive of sarcoidosis → HRCT chest
Definitive diagnosis is by biopsy and subsequent histology demonstrating non-caseating granuloma
Lung Function Test
When fibrosis develops, a restrictive lung disease pattern is usually seen:
- ↑ FEV1:FVC ratio
- ↓ FVC and TLC
- ↓ DLCO
Biochemical Tests
The following are NOT diagnostic of sarcoidosis, but support the diagnosis (commonly featured in exams):
- Hypercalcaemia (pulmonary alveolar macrophages become activated → ↑ 1-alpha hydroxylase activity → ↑ vitamin D)
- Lymphopaenida
- Deranged LFT (most commonly ↑ ALP)
- ↑ Serum ACE level (not specific for sarcoidosis)
Imaging Findings
Typical chest X-ray findings:
| Stages | Chest X-ray findings |
|---|---|
| Stage I |
|
| Stage II |
|
| Stage III |
|
| Stage IV |
|
Top 3 differential diagnoses of hilar adenopathy on chest X-ray:
- Sarcoidosis
- TB
- Lymphoma
Biopsy
Recommended biopsy sites are the most accessible organ with clinical / radiographic involvement:
- Skin lesions / peripheral lymph nodes are easily accessible if present
- EBUS-TBNA is the preferred initial method for those with mediastinal / hilar lymphadenopathy (pulmonary sarcoidosis)
Management
Indication for Treatment
Treatment is indicated if any of the following:
- Risk of severe organ dysfunction (neurological / eye / heart involvement)
- Pulmonary sarcoidosis with
- Moderate to severe symptoms, or
- Stage II-IV disease (on CXR), or
- Progressive decline in lung function
Treatment Options
1st line: oral corticosteroids
- Isolated cutaneous / eye disease may be treated with topical steroids
2nd line:
- Methotrexate
- Azathioprine
- Lefunomide
- Myocophenolate mofetil
Monitoring sarcoidosis treatment generally relies on lung function test parameters (e.g. FVC and DLCO) as the primary objective markers of disease progression and response to therapy.