Table 5.
Therapeutic Management of Sarcoidosis Depending on Organ Involvement
| Organ Involvement | When to Treat | First-Line Treatment | When to Use Second-Line Treatment | Second-Line Treatment | Third Line | Fourth Line | References |
|---|---|---|---|---|---|---|---|
| Lung sarcoidosis | Stage II or III with worsening respiratory symptoms, worsening of functional impairment (FVC < 65%, DLCO < 60%), progression of parenchymal abnormalities on CT (honeycombing, excavations, … ), endobronchial stenosis, active stage IV | Corticosteroids 20–40 mg/d for at least 4 weeks then tapering to 5–10 mg/d (maintenance regimen) on 1–6 months. Maintain 5–10 mg/d for 1–3 months then slow tapering depending on clinical benefit | Increasing symptoms despite CS, or issues with CS tapering (if CS cannot be lowered under 10 mg/d). The clinician needs to be sure that parenchymal lesions are due to active disease (using PET-CT) | MTX 15 mg/d or more, AZA 1–2 mg/kg/d, LFN 20 mg/d | TNFi: IFN 3–5 mg/kg (IV) week 0, 2, 6 then each 4–8 weeks/ADA 40 mg (SC) each 14d, or each 7d if severe | Consider CYC, MMF, RTX, TCZ, JAKi, clinical trials | 18,161,162 |
| Sarcoidosis arthritis | impaired quality of life, proven arthritis | Corticosteroids 20–40 mg/d for at least 4 weeks then tapering to 5–10 mg/d (maintenance regimen) on 1–6 months. Maintain 5–10 mg/d for 1–3 months then slow tapering depending on clinical benefit | Increasing symptoms despite CS, or issues with CS tapering (if CS cannot be lowered under 10 mg/d). | HCQ, MTX, AZA, LFN | TNFi | Switch biologic (TCZ, RTX) or JAKi or clinical trial | 163 |
| Heart sarcoidosis | Proven cardiac sarcoidosis (PET CT, MRI + extracardiac granuloma or cardiac granuloma alone) | Corticosteroids max 30 mg/d and consider association with MTX in first line | Progression on MRI or PET-CT | MTX | TNFi (prefer IFX) | CYC, IVMP | 82,164,165 |
| Eye involvement | Anterior uveitis | Topical steroids + cycloplegics | Persistent uveitis or recurrent flares | Consider peri or intraocular CS | ND | ND | |
| Unilateral intermediate or posterior uveitis without complications | Consider peri or intra ocular CS | Persistent uveitis | (± IVMP) + systemic CS 1 mg/kg/d for 3 to 6 weeks | If CS > 7 mg/d or unacceptable CS side effects, consider MTX or AZA | TNFi, MMF or LFN. If failure, consider RTX, TCZ or clinical trial | 49,62,166,167 | |
| Severe intermediate or posterior uveitis with ON or ME or ORV or both eye involvement | (± IVMP) + systemic CS 1 mg/kg/d for 3 to 6 weeks | CS > 7 mg/d or unacceptable side effects of CS | MTX or AZA | TNFi, MMF or LFN | If failure, consider TCZ or JAKi | ||
| Skin involvement | Lupus pernio | Localized cutaneous sarcoidosis | Extended cutaneous disease or esthetic/functional threatening skin sarcoidosis | ||||
| Intralesional triamcinolone, DXC, HCQ, TNFi, TLD | Non-severe lesions | Severe lesions (thick, major extension, inflammatory) | First line | Second line | Third line | 48,129,130,145,150,168,169 | |
| Topical CS can be used. If systemic treatment needed, prefer HCQ, DXC, MTX, TLD. If refractory, TNFi or JAKi may be used | Topical treatments (dermocorticoids, topical tacrolimus, topical retinoids) | Intralesional triamcinolone (thick plaques), laser, dynamic phototherapy | Consider systemic therapy (prefer HCQ, DXC, MTX, TDM) | Consider other drugs before IS: systemic CS, pentoxifylline, apremilast, acitretin | Consider TNFi. JAKi may be considered | ||
| Naso pharyngeal involvement | Disturbing symptoms, cartilage perforation, … | Local CS can be used but systemic CS are often needed | Refractory disease or unacceptable side effects or contra indication to CS | Consider HCQ, MTX, AZA | Consider TNFi | Other IS (CYC), clinical trials, … | 170 |
| Neurosarcoidosis | Almost always warranted | CS (1 mg/kg) ± IVMP (short regimen for facial palsies) | Refractory disease or unacceptable side effects or contra indication to high dose CS | MTX, AZA, LFN, MMF | Consider TNFi (IFX) | Switch TNFi (ADA) or CYC, RTX, RCI, radiation therapy, clinical trials … | 52,71,171 |
| Renal sarcoidosis | Hypercalcemia and hypercalciuria | CS 0.3–0,5 mg/kg then tapering to 5–10 mg/d (12 months) | Persistent hypercalcemia | HCQ, CQ | Ketoconazole (600–800 mg/d) | ND | |
| Renal failure | CS 0.5–1 mg/kg/d (IVMP is useless) with slow tapering over 18–24 months | Refractory disease or unacceptable side effects or contra indication to high dose CS | AZA, MMF (avoid MTX in acute kidney injury) | ND | ND | 45,56,172 | |
Abbreviations: ADA, adalimumab; AZA, azathioprine; CS, corticosteroids; CT, computed tomography; CYC, cyclophosphamide; DLCO, diffusing capacity of the lung for carbon monoxide; DXC, doxycycline; FVC, forced vital capacity; HCQ, hydroxychloroquine; IFX, infliximab; IS, immunosuppressants; IV, intravenous; IVMP, intravenous methylprednisolone pulse; JAKi, Janus kinase inhibitor; LFN, leflunomide; MMF, mycophenolate mofetil; MRI, magnetic resonance imaging; MTX, methotrexate; PET, positron emission tomography; RTX, rituximab; SC, subcutaneous; TCZ, tocilizumab; TLD, thalidomide; TNFi, tumor necrosis factor alpha inhibitor.