Sarcoidosis is a systemic granulomatous disease of unknown aetiology, mainly affecting the lungs and lymphatics. It affects people worldwide (incidence, 4.7-64/100000; prevalence, 1-36/100000/year). Although it is most often a benign acute or subacute condition, sarcoidosis may progress to a disabling chronic disease in 25% of the cases, with severe complications in about 5%, such as lung fibrosis, cardiac or neurosarcoidosis, defacing lupus pernio or blindness due to uveitis.

When indicated, corticosteroids (CS) are the mainstay of treatment. Due to the kinetics of granuloma resolution, the usual and quite 'dogmatic' duration of treatment is said to be one year, following four classical steps. The long-term use of CS is hindered by cumulative toxicity and efforts have to be made to taper them, as quickly as possible, to the lowest effective dose. A recent report mentioned 39% of the CS-treated patients requiring a steroid-sparing agent. Chloroquine (CQ) and hydroxychloroquine (HCQ) are anti-malarial drugs that have been used since the 1960's as steroidsparing agents on the basis of a landmark study by Siltzbach reporting their efficacy in 43 patients with skin and intrathoracic sarcoidosis. Subsequently, two small randomized controlled trials have shown significant and prolonged improvement on pulmonary symptoms. Only small case series/reports have shown CQ/HCQ efficacy on extra-pulmonary sarcoidosis with response rates ranging from 67 to 100%. Nevertheless, CQ/HCQ are daily used for skin, bone, and joint sarcoidosis, as well as hypercalcemia. Nowadays, HCQ is preferred over CQ because of a lower incidence of gastrointestinal and ocular adverse reactions, which can be minimized by close attention to the dosage and regular retinal examination. Its profile of safety is well-known since it has long been employed to treat systemic lupus erythematous or rheumatoid arthritis. Its action is thought to rely on its ability to accumulate in lysosomes of phagocytic cells, to affect antigen presentation and reduce pro-inflammatory cytokines. The investigator hypothesize that HCQ may be an efficacious add-on therapy for extra-pulmonary sarcoidosis leading to a significant steroid-sparing effect.

• Inclusion Criteria :

  • at least 18 years of age

  • pathologically proven sarcoidosis as defined by the American Thoracic Society (ATS)/European Respiratory Society (ERS)/World Association of Sarcoidosis and Other Granulomatous Disorders (WASOG) criteria

  • non severe ocular sarcoidosis requiring systemic treatment

  • non severe skin sarcoidosis requiring systemic treatment

  • non severe osseous sarcoidosis requiring systemic treatment

  • non severe sarcoidosis with joint involvement requiring systemic treatment

  • non severe sarcoidosis-related hypercalcemia requiring systemic treatment

  • non severe peripheral nervous system sarcoidosis requiring systemic treatment

  • non severe sarcoidosis-related non-severe Ear, Nose and Throat (ENT) involvement requiring systemic treatment

  • symptomatic hypercalciuria >200 mg/24h (24 h urine) OR

    • - > 20 mg/mmol creatinine on urine sample
    • - > 180 mg/g creatinine on urine sample

  • signed informed consent

  • affiliated to National French social security system

• Exclusion Criteria :

  • severe sarcoidosis involvement requiring another immunosuppressant or anti-TNF antibody or methylprednisolone i.v. pulses
  • previous (<3 months before screening) or concurrent treatment with immunosuppressants
  • previous treatment with corticoid (patient weaned for 3 months before inclusion)
  • previous treatment with antimalarial drugs (HCQ/CQ) (patient must have been off plaquenil for at least 12 months)
  • treatment with citalopram, escitalopram, hydroxyzin, domperidone and piperaquine
  • known hypersensitivity or intolerance to HCQ/CQ or 4-aminoquinoline derivatives and prednisone
  • heart rhythm disorders on EKG (QT prolongation) (except atrial fibrillations)
  • severe ophthalmological impairment or ophthalmological impairment that does not allow ophthalmic monitoring; previous history of maculopathy or retinopathy
  • end-stage lung, liver, cardiac, or renal disease
  • sarcoidosis with central nervous system involvement
  • cardiac sarcoidosis
  • clinical evidence of active infection (including infection with herpes virus and varicella-zoster virus) or severe/unstabilized comorbidity (e.g. moderate to severe heart failure) or unstabilized psychosis
  • chronic viral (HIV or HBV) infection
  • untreated latent/active tuberculosis
  • pregnancy or lactation (βHCG will be test by blood analysis at inclusion)
  • concurrent vaccination with live vaccines during therapy
  • inability to understand information about the protocol and to sign informed consent or not suitable candidate to comply with the requirements of this study
  • patient participating in other interventional research
  • persons under court protection
  • Use of effective contraception for the duration of the study . (Contraception is considered effective when it consists of one of the following: use of a male condom during all sexual activity and/or efficient oral hormonal contraception (better considered combined contraception) and/or an intrauterine device (IUD) and/or hormone-releasing intrauterine system (IUS) and/or history of bilateral tubal ligation and/or history of vasectomy, provided the male partner is the trial participant's only sexual partner and/or sexual abstinence)