Sarcoidosis is a multisystem granulomatous (non-caseating) disease of unknown etiology. One of the great imitators.
Clinical Manifestations
Typically involves the lungs (90%) but 30% of patients present with extrapulmonary sarcoid involvement.
Sarcoid Pulmonary Disease
90% of patients have pulmonary involvement, often this is asymptomatic hilar adenopathy. Imaging defined by Scadding staging system which correlates to the chance of spontaneous remission (higher is worse). Although in general patients progress from one stage to the next, this system does not correlate particularly well with clinical severity. In fact, chest x-ray appearances are often more dramatic than functional impairment.
| Scadding stage | Findings | Frequency at presentation | Spontaneous resolution |
|---|---|---|---|
| 0 | Normal | 5-15% | |
| 1 | Bilateral adenopathy | 25-65% | 60-90% |
| 2 | Adenopathy with interstitial disease | 20-40% | 40-70% |
| 3 | Interstitial disease | 10-15% | 10-20% |
| 4 | Pulmonary fibrosis | 5% | 0% |
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| [Thoracic sarcoidosis (staging) | Radiology Reference Article | Radiopaedia.org](https://radiopaedia.org/articles/thoracic-sarcoidosis-staging) |
Symptoms can range from asymptomatic, dyspnea, cough, chest pain, wheeze. PFTs can be variable (normal, restrictive, obstructive, both). Co-existant asthma is common. Pulmonary hypertension is rare but possible.
Extrapulmonary Sarcoidosis
| Site | Manifestation |
|---|---|
| Cutaneous | lupus pernio, EN, etc. |
| Liver and spleen | 10% of patients. Liver enzyme elevation, cholestasis, liver failure, liver/spleen lesions. |
| Neurologic | CN palsy, HA, ataxia, weakness, aseptic lymphocytic meningoradiculitis |
| Ocular | Anterior uveitis |
| Cardiac | 5% of patients clinically. Cardiomyopathy, arrhythmia, heart block. Patients should be screened with ECG +/- echocardiogram. |
| Hypercalcemia | Common. Due to granulomatous activation of vitamin D. |
Sarcoid Syndromes
- Lofgren syndrome: bilateral hilar adenopathy, EN, migratory polyarthralgias, fever. Seen primarily in women, is pathognomic of sarcoidosis and does not need a biopsy. High likelihood of spontaneous remission.
- Heerfordt's syndrome a.k.a. uveoparotid fever: anterior uveitis, parotid enlargement, facial palsy, and fever
Sarcoidosis syndromes that do not require biopsy:
| Syndrome | Additional Findings/Symptoms |
|---|---|
| Asymptomatic bilateral hilar lymphadenopathy | No evidence of fevers, malaise, or night sweats to suggest a malignancy |
| Löfgren syndrome | Bilateral hilar lymphadenopathy, migratory polyarthralgia, erythema nodosum, and fever |
| Heerfordt syndrome | Anterior uveitis, parotitis, fever (uveoparotid fever), and facial nerve palsy |
| # Workup | |
| Consider the following investigations: |
| Class | Tests |
|---|---|
| Bloodwork | CBC (anemia, lymphopenia, thrombocytopenia), electrolytes (hypercalcemia), liver enzymes, renal function tests. CRP, ESR, RF (inflammation). |
| Cardiac | ECG +/- echo +/- holter, consider cardiac MR or PET |
| Infectious | HIV, TB |
| Hypercalcemia | 1,25 OHD. Consider 24 hour urinary calcium |
| Disease specific | Serum ACE not necessary, 70% sensitive and 90% specific with active disease but reflects any granulomatous disease |
| Pulmonary | CXR +/- CT, PFTs. Bronchial was low CD8, elevated CD4/CD8 ratio |
| Tissue | LN or transbronchial biopsy |
| Ophtho | referral to rule out ocular sarcoid |
Management
- who to treat?
- most patients don't require treatment, as those with stage 1/2 disease usually will have spontaneous remission, after which recurrence is rare (4-5%)
- steroids speed up remission, but with higher risk of recurrence (60-70%). Therefore, only are indicated if there are severe symptoms or end-organ damage:
- pulmonary: bothersome symptoms of SOB, cough. Deteriorating lung function with PFTs, and development of pulmonary hypertension.
- extrapulmonary disease: eye disease, CNS disease, cardiomyopathy or active cardiac involvement.
- typically also severe skin disease, hypercalcemia, symptomatic liver disease.
- Treatment options:
- Mild respiratory symptoms --> inhaled steroids
- Cutaneous sarcoidosis:
- Erythema nodosum --> NSAIDs alone
- Severe --> oral steroids +/- infliximab
- Neurosarcoid --> steroids +/- MTX +/- infliximab
- Otherwise --> oral prednisone, 20-40 mg daily for 1-3 months then slow taper if there is response. 2021 ERS guidelines suggest adding MTX if there is continued disease or cannot tolerate steroids. Otherwise can consider steroid-sparing agents (MTX, HCQ, LEF, TNFi) if relapse occurs.
- Sarcoidosis-associated fatigue should prompt consideration for pulmonary rehab, inspiratory muscle training, or trial of D-methylphenidate or modafinil for 8 weeks.
Prognosis and Outcomes
5% mortality risk. Most patients are asymptomatic. 2/3 will have remisson in a decade, after one year of spontaneous remission relapse is uncommon.
References
- IMR Slides 2021
- ERS clinical practice guidelines on treatment of sarcoidosis | European Respiratory Society