Therapeutic Approaches in CLIPPERS
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CLIPPERS for chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids, is a steroid-sensitive and steroid-dependent brainstem inflammatory disease of unknown origin. Since its first description in 2010, about 60 cases have been reported throughout the world. The mean age at onset is 50 years and men seem to be more frequently affected. In patients without chronic corticosteroid therapy or immunosuppressive agents, the disease had a relapsing remitting course, and the mean annualized relapse rate was 0.5. During attacks, although clinical and radiological improvement after high doses of corticosteroids was systematically observed, patients could display subsequent disability and hindbrain atrophy. Since no progressive course was observed, clinical and radiological sequelae were correlated with previous severe attacks. Therefore, maintaining the disease in remission may prevent the accumulation of disability. In the literature, no relapse occurred when chronic corticosteroid therapy was maintained above 20 mg per day. However, steroids side effects led to propose corticosteroid-sparing therapies. Unfortunately, no controlled therapy studies for CLIPPERS have been performed yet, and no therapeutic recommendations exist. Using the PubMed database, all articles having the following keywords “chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids” and “CLIPPERS” have been analysed. Considering that the mean annual relapse rate was 0.5, and that no relapse occurred when corticosteroid therapy was maintained above 20 mg per day, the therapeutic efficiency of corticosteroid-sparing agents was considered as “probable” when patients had a relapse-free period ≥24 months, in the absence of concomitant corticosteroid therapy. Corticosteroid-sparing agents whose efficiency is “probable” are methotrexate in two cases, cyclophosphamide in one case and hydroxychloroquine in one case. Considering the risk benefit ratio of corticosteroid-sparing agents, methotrexate seems to be the most suitable. Nevertheless, randomized controlled trials testing the different corticosteroid-sparing agents in CLIPPERS are necessary.
KeywordsClippers CLIPPERS mimics Immunosuppressive therapy Corticosteroid-sparing therapy Th17-mediated disease
Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids
Annualized relapse rate
Pontine perivascular enhancement responsive to steroids
Lymphocytic inflammation with pontine perivascular enhancement responsive to steroids
Chronic pontine perivascular enhancement responsive to steroids
The authors would like to thank all members of the International CLIPPERS Consortium Meeting.
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Conflict of Interest
The authors declare that they have no conflict of interest.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
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