Treatment of refractory neurosarcoidosis with TNF‐inhibitors: what lies ahead?

Abstract

We read with interest the case series on the treatment of refractory neurosarcoidosis with infliximab. We were interested to know whether the serum and cerebrospinal fluid angiotensin converting enzyme or other makers of sarcoidosis might have been ascertained (such as increased cerebrospinal fluid CD4/CD8 lymphocyte ratios, lysozyme and b2-microglobulin), as these can have a role in monitoring disease activity, and in supporting a diagnosis if a patient (e.g. Case 1) declines biopsy. Likewise, a gallium or positron-emission tomography scan may indicate accessible disease worthy of biopsy, for example, salivary glands or lymph nodes. Sarcoidosis refractory to glucocorticosteroids is an important and difficult area, and although there have not been any randomised controlled treatment trials for isolated neurosarcoidosis, there is now a large body of evidence from placebo-controlled studies that anti-TNF-a agents have a relatively modest effect in modulating this disease, which is disappointing given the logical choice of TNF antagonists in sarcoidosis. Nonetheless, individual trials of therapy may be worthwhile as in the refractory cases reported, if monitored carefully, and the therapy discontinued quickly if ineffective, particularly with the awareness that tuberculosis might be unmasked as being the true diagnosis, rather than sarcoidosis. We also note that Pereira et al. tested azathioprine in two of their patients although did not assess anti-malarials. Azathioprine, as well as chloroquine and hydroxychloroquine have also been reported as being useful in a few small case series of neurosarcoidosis, but no clinical trial data exist. Hopefully, better agents that target CD4+ type 1 helper T-cell (TH1) immunity and associated sarcoid inflammatory pathways will become available as the immunology of this fascinating disease becomes apparent.