Medication Summary
Medications used in peripheral neuropathy in sarcoidosis are the same as those used for systemic sarcoidosis and neurosarcoidosis. Immunosuppressants are used to dampen or alter the inflammatory activity. Corticosteroids are preferred. Nonresponders may be tried on cyclosporine, azathioprine, and/or methotrexate. Preliminary evidence also suggests possible benefit from the use of tumor necrosis factor–α (TNF-α) antagonists in refractory cases.
Corticosteroids
Class Summary
These agents have anti-inflammatory properties and cause profound and varied metabolic effects. Corticosteroids modify the body's immune response to diverse stimuli and are the mainstay of treatment in neurosarcoidosis.
Oral prednisone is the corticosteroid most commonly used. When high-dose oral prednisone fails, patients may respond to methylprednisolone pulses (eg, 1 g/wk for 8 wk). Disagreement exists about the optimal dose, but doses listed here are typical. Often, high doses are required for 2-4 wk before tapering; taper may need to be continued for several months before discontinuing treatment altogether.
Prednisone
Prednisone, the most commonly used oral corticosteroid, works by altering the immune system and decreasing the inflammatory reaction that is responsible for granuloma formation in sarcoidosis. A negative tuberculin skin test is required prior to commencing high daily doses of steroids.
Prednisone may decrease inflammation by reversing increased capillary permeability and suppressing polymorphonuclear neutrophil (PMN) activity. It stabilizes lysosomal membranes and suppresses lymphocytes and antibody production. Use the lowest possible maintenance dose.
Immunosuppressants
Class Summary
These agents inhibit immune cell growth and proliferation, decreasing immune system activity.
Thalidomide (Thalomid)
Thalidomide is an immunomodulatory agent that acts to inhibit production of TNF-α, which is an important mediator of central nervous system inflammation. Thalidomide enhances TNF- α messenger RNA degradation. It inhibits the upregulation of interleukin-6 and downregulates nuclear factor-κβ activity. Both of these molecules are elevated during the CNS inflammatory process in neurosarcoidosis.
Cyclophosphamide
Cyclophosphamide is an antimitotic agent mainly used as steroid-sparing therapy.
Cyclosporine (Sandimmune, Neoral, Gengraf)
Cyclosporine is used extensively in patients who have undergone transplantation. In neurosarcoidosis, beneficial effects of cyclosporine as an adjunct to steroids have been reported, although mostly in CNS rather than peripheral nervous system involvement.
Azathioprine (Imuran, Azasan)
Cytostatic drug that has been used in numerous immune-mediated diseases. Active component, 6-mercaptopurine, thought to have immune-suppressing properties.
Methotrexate (Trexall, Rheumatrex)
Methotrexate is an antimetabolite used as an immunosuppressant, often in rheumatoid arthritis, severe psoriasis, and certain neoplastic diseases. Its use for neurosarcoidosis has not been tested sufficiently.
Antimalarials
Class Summary
The antimalarial agents chloroquine phosphate and hydroxychloroquine sulfate have been used in the treatment of patients with neurosarcoidosis who either do not respond to corticosteroid therapy or develop unacceptable side effects.
Chloroquine phosphate (Aralen)
Chloroquine produces an anti-inflammatory effect by suppressing lymphocyte transformation and may have a photoprotective effect.
Hydroxychloroquine (Plaquenil)
Hydroxychloroquine inhibits chemotaxis of eosinophils and locomotion of neutrophils and impairs complement-dependent antigen-antibody reactions. Hydroxychloroquine sulfate 200 mg is equivalent to 155 mg hydroxychloroquine base and 250 mg chloroquine phosphate.
Immunomodulators
Class Summary
These agents can change the immune system or block the effects of cytokines.
Infliximab (Remicade)
Infliximab inhibits the release of tumor necrosis factor-α (TNF- α), which is released in high concentrations by alveolar macrophages in active sarcoidosis. Agents that reduce TNF- α or block its effect have been shown to produce improvement in refractory cases.
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Atrophic right optic disc of a 37-year-old man with neurosarcoidosis and involvement of both optic nerves. Vision was lost. The disc is pale with sharp borders.
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Atrophic left optic disc of a 37-year-old patient with neurosarcoidosis and involvement of both optic nerves. The disc is pale with sharp borders. Vision was largely preserved.
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MRI of the brain in a 37-year-old man with neurosarcoidosis who had complete loss of vision in the right eye for 2 months and occasional blurry vision in the left. T1-weighted sagittal image shows intact optic nerves.
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MRI of the brain in a 37-year-old man with neurosarcoidosis who had complete loss of vision in the right eye and mild left eye blurriness. This fluid-attenuated inversion recovery (FLAIR) axial image shows a wedge-shaped area of infarction in the right temporo-occipital area. The optic nerves exhibit abnormal signal.
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MRI of the brain in a 37-year-old patient with sarcoidosis who had right eye blindness and mild blurry vision in the left eye. This postgadolinium, T1-weighted axial image shows right optic nerve enhancement along almost the entire intraorbital portion and a small amount in the prechiasmatic portion. The left optic nerve enhances from the level of the optic chiasm to the distal intraorbital portion. The right temporo-occipital infarct is seen as a faint hypodensity; it does not enhance after gadolinium administration.
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MRI of the brain in a 37-year-old man with sarcoidosis who had loss of vision in the right eye and blurry vision in the left eye. This scan was taken 6 months after the scan shown in Pictures 3, 4, and 5. Both the right and left optic nerves are enlarged and show abnormal signal on this T1-weighted axial image. The patient remained on oral prednisone from the time of the first scan and did not exhibit any further loss of vision in the left eye. Vision in the right eye never returned.
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MRI of the brain in a 37-year-old man with sarcoidosis who had loss of vision in the right eye and blurry vision in the left. This postgadolinium, T1-weighted axial image shows abnormal enhancement of both optic nerves, with the left optic nerve appearing worse on this study than in the study shown as Picture 5, which was done 6 months earlier. The right temporo-occipital hypodensity represents the old infarction.
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Early chest radiograph findings in sarcoidosis.
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Advanced chest radiograph findings in sarcoidosis.
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Noncaseating granuloma surrounded by epithelioid cells, from the medulla oblongata. Also shown are nodular inflammatory infiltrates consisting of multinucleated giant cells, macrophages, and lymphocytes (hematoxylin and eosin, 40x).
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Noncaseating granuloma in medulla oblongata showing the granuloma surrounded by epithelioid cells and nodular inflammatory infiltrates (hematoxylin and eosin, 20x).
