INTRODUCTION Granulomatous inflammation is a distinctive ...

Monthly tapering after 8 months over 4 months
Corticosteroid-sparing agents (second-line drugs) (Johns and Michele, 1999).
There is much less information known about alternative medications. Indications for their use
include the presence of contraindications to corticosteroids, serious steroid side effects, or lack of
response to treatment. The available alternative therapeutic agents include cyclosporine,
azathioprine, methotrexate, cyclophosphamide, chlorambucil, hydroxychloroquine, and radiation
therapy (Agbogu et al., 1995). There are no rigorous clinical trials of the different treatment
modalities.
Among the alternative therapies, cyclosporine is the best studied. Though there is evidence
suggesting that it is ineffective in pulmonary sarcoidosis because of poor penetration into lung
tissue (Wyser et al., 1997), it is effective in neurosarcoidosis. It is even beneficial in some patients
refractory to corticosteroids (Stern et al., 1992). It specifically inhibits CD4 cell immune responses.
It is ineffective as a single agent, but is a good adjunct to steroids. It can be started at 4 mg/kg /day
in two divided doses, given 12 hours apart. Trough levels should be monitored monthly to
maintain a therapeutic drug level. This will help to avoid side effects, which include hypertension,
renal dysfunction, hypomagnesemia, and toxic encephalopathy. There is no strict correlation
between blood levels and clinical response. Approximately 75% of patients may respond to
cyclosporine sufficiently to allow reduction of the steroid dose to one third to one sixth of the
stabilizing dose. The majority of patients will relapse on discontinuation of treatment (Agbogu et
al., 1995).
Chloroquine has been used for treatment of neurosarcoid, and is an antimalarial drug with Antiinflammatory
effects used as well in rheumatologic disorders, but the precise mechanism of action
is unknown Chloroquine was shown to be beneficial, but its major limiting factor was retinal
toxicity (Sharma , 1998).
Methotrexate has shown benefit in systemic sarcoidosis and in 61 % of a small series of
neurosarcoidosis patients. Its use has been recommended in neurosarcoidosis along with
corticosteroids and hydroxychloroquine. It is well tolerated, and there is less risk of
carcinogenicity when it is given at a dose of 5-15 mg/week. The effects may not be seen until 6
months after treatment. The risk of liver toxicity requires that liver enzymes be monitored every 6
to 9 weeks, and a liver biopsy should be done after a cumulative dose of 1 gram has been given.
Hypersensitivity pneumonitis develops in a small number of patients. Drug toxicity can be
minimized by the use of folinic acid (Sharma, 1998).
Azathioprine is an effective alternative. Its major advantage is moderate cost and tolerability.
Treatment is initiated with small doses that are gradually escalated to a target dose of 2-3
mg/kg/day. Blood counts and liver function tests should be monitored. Treatment should be
stopped if the white cell count drops below 3000 /MM3 or if liver enzymes rise to greater than five
times the upper limit of normal. Approximately 10% of patients develop an idiosyncratic reaction
to the drug, which manifests as a "flu-like" illness.
The major advantage of alternative medications is that they provide a "steroid sparing" effect and
make it possible to reduce the dose of the steroids to 15% to 30% of a stabilizing dose. These
immunosuppressants are best used as an adjunct to corticosteroids rather than as primary agents,
because complete withdrawal or tapering of steroids below 10 mg/day usually results in relapse.
No factors are known to predict response to a particular agent. Side effect profiles of most of the
alternative medications are few and reversible on withdrawal of the medication (Stern et al., 1992;
Agbugo et al., 1995).