What is the role of immunosuppressants in the treatment of neurosarcoidosis?

Updated: Nov 13, 2018
  • Author: Gabriel Bucurescu, MD, MS; Chief Editor: Tarakad S Ramachandran, MBBS, MBA, MPH, FAAN, FACP, FAHA, FRCP, FRCPC, FRS, LRCP, MRCP, MRCS  more...
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Answer

Immunosuppressants such as cyclosporine, methotrexate, and cyclophosphamide have been used with varying results. Almost all of the studies completed to date have involved treatment of CNS sarcoidosis as opposed to peripheral neuropathy.

A retrospective report of 26 patients with refractory neurosarcoidosis monitored for a mean of 81.2 months demonstrated steroid sparing in 10 of 26 patients and clinical improvement in 15 of 26 patients treated with alternative medications or irradiation. Medications and results were as follows:

  • Azathioprine : positive response in 8 of 14 patients

  • Cyclophosphamide: positive response in 11 of 14 patients

  • Cyclosporine: positive response in 2 of 3 patients

  • Chloroquine: positive response in 1 of 1 patient

  • Methotrexate: positive response in 1 of 3 patients

On the basis of this experience, the authors recommend azathioprine and cyclophosphamide as the alternative agents of choice in corticosteroid-resistant neurosarcoidosis, with methotrexate reserved for patients who either do not respond to those alternative agents or are intolerant of them. Azathioprine has been used as an alternative to corticosteroids when the adverse effects are intolerable, but reports in the literature are sparse.

Cyclosporine has been reported to lead to improvement in some patients. It has been successful in controlling the disease in patients undergoing transplantation. In one series, the response rate was 75%, but the patients had relapses once the therapy was stopped.

Methotrexate can be used as a steroid-sparing agent. It is generally well tolerated, with minimal adverse effects except for potential liver toxicity. Thus, patients on long-term dosing need to have careful monitoring of liver function, including liver biopsies. In one study, the remission rate for patients on methotrexate was 61%.

Cyclophosphamide use has been more limited. Short-term therapy has not been associated with good response. Therapy lasting at least several months is needed to determine efficacy. In one study, intermittent intravenous cyclophosphamide was associated with better compliance and lower risk of malignancy, especially bladder malignancy; however, bladder toxic effects did occur. Patients showed improvement in the course of the disease.

Chloroquine and hydroxychloroquine also have been used. In a study by Sharma, chloroquine and hydroxychloroquine were effective in controlling neurologic sarcoidosis in patients who did not respond to corticosteroids or developed severe adverse effects. These agents stabilized or controlled symptoms in 10 of 12 patients.

Several recent reports have shown successful treatment with infliximab, [36, 37, 38] rituximab, [39] mycophenolate mofetil. [38, 40] Mycophenolate was not effective in treating sarcoid myopathy, however. [40] Combination treatment with infliximab and mycophenolate mofetil also appears promising. [38]

Tumor necrosis factor–α (TNF-α) is believed to be a key cytokine in the pathogenesis of sarcoidosis, and TNF-α inhibitors are being increasingly used to treat refractory sarcoidosis. Several cases of refractory neurosarcoidosis treated with thalidomide have been reported. Treatment ranged from 4 weeks to 6 months. [41] Similarly, preliminary evidence suggests a possible benefit from infliximab in the treatment of neurosarcoidosis. [42, 43, 44]


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