A 9 year old boy presented with progressive difficulty in walking for 2 months and weakness of upper limbs for 20 days. He had received 5 days of high dose methyl prednisolone 1 month into the illness which brought a temporary improvement for 10 days followed by progressive worsening. CSF was acellular with mildly elevated proteins. MRI spine showed enhancing lumbar nerve roots and the nerve conduction velocity demonstrated severe sensory motor demyelinating neuropathy.
We made a diagnosis of CIDP and he showed a gratifying response to a repeat dose of IV methyl prednisolone. We discharged him on oral steroids on which he continued to do well but started showing cushingoid features. We decided to add a steroid sparing agent and after mulling over the various options finally zeroed in on mycofenolate mofetil.
This was a good opportunity to review this important drug in autoimmune disorders. It is often overlooked and overshadowed by more glamorous drugs like rituximab and cyclosporine.
If was first discovered serendipitously by an Italian physician Gosio who was investigating the link between mouldy corn and pellagra. He isolated a crystalline substances which he found could inhibit the anthrax bacteria. Nobody bothered much about this interesting finding till several decades later, after many false starts it use as an immunosuppressant was established by people at Roche.
It inhibits the de novo production of purines. This reduces T and B cell proliferation and explains the immunosuppression.
Besides, it also has directly inhibits dendritic antigen presenting cells. This probably explains why it is a much more potent immunomodulator than other drugs like azathioprine.
Plus it is less nephrotoxic than cyclosporin because it also inhibits endothelin which mediates ischemic renal injury.
Its used orally in a dose of 20mg/kg twice a day or 600mg/me/dose BD.
Its use in transplant medicine ( renal, cardiac, intestinal) is well established. Rheumatologists are now comfortable using it in SLE ( especially renal disease) and myasthenia. Pediatric nephrologists use it for steroid dependant or frequently relapsing nephrotic syndrome.
Its use in paediatric neurology was reviewed by Dale et al in 2017. They found it was effective and safe in primary CNS vasculitis and NMOSD. Evidence was scantly but encouraging for MOG associated CNS disease. There was inadequate data for autoimmune encephalitis and multiple sclerosis. https://doi.org/10.1111/dmcn.14020
It was probably ineffective in Opsomyoclonus Ataxia syndrome.
It may take upto 6 months before its action kicks in and so needs some other support like oral steroids during this period. 3 monthly counts need to be monitored. Avoid using PPI's which interfere with its action. Abdominal cramps were the commonest side effect.
No comments:
Post a Comment