Læknablaðið : fylgirit - 01.07.1978, Page 94

collegues (1974) have suggested that
patients who develop granulocytopenia may
have abnormally gold-sensitive granulocyte
enzymes which catalyse the nove sjmthesis
of pyrimidine nucleotids.
D - Penicillamine
The rationale for using D-penicillamine
in rheumatoid arthritis was to dissociate
rheumatoid factor. This has amply been
confirmed in a number of studies, but in
addition the drug has been shown to cause
clinical improvement. The drug acts like
gold in that it takes at least three months
before its effect becomes apparent, and
it produces the same amount of clinical
benefit as gold. The major drawback is
the drug's toxicity. The list of potential
side effects is horrendous, but many can
be avoided by careful monitoring.
Proteinuria is common in patients
receiving D-penicillamine and need not be
a cause of withdrawal of the drug unless
it becomes very heavy, 2 g/day or more.
A nephrotic syndrome may occur with
D-penicillamine and biopsy of the kidney
shows both IgG and complement in the
glomerular basement membrane.
Recently Huskisson (1976) has published
an excellent review, which should be read
carefully before embarking on treating
patients with rheumatoid arthritis with the
drug.
Immunosuppressives
Cyclophosphamide and azathioprine have
both been used to treat severe and
progressive rheumatoid arthritis. Both
have been shown to be effective, but our
concern with their use is the potential
danger of late neoplasia. Removal of the
immunological surveillance mechanism by
these drugs is fraught with danger. We
would predict that tumours will start
being reported in patients with benign
disease treated with these compounds.
We do not use these drugs at the present
time.
Corticosteroid Therapy
It is now nearly three decades since
Hench introduced cortisone in the treatment
of rheumatoid arthritis, but the remarkable
fact is that we have so few really "hard"
facts about their use, for instance, it is
still not known just how toxic they are,
althcugh recent studies by ourselves have
shown that they may be associated with
high mortality (Brooks et al, 1975) as
well as morbidity (Lee et al, 1973).
Suppression of the cerebro-hypothalamo-
pituitary- adrenal axis (Nuki and Downie,
1971) is probably not as serious as
previously thought. Osteoporosis occurs
as a generalised phenomenon and is
associated with skin atrophy (McConkey
et al, 1965) and a low plasma zinc
concentration (Kennedy et al, 1975). The
other side effects need no comment as
they are well documented.
It is our practice to prescribe
prednisolone or prednisone in preference
to other oral preparatum but not to exceed
10 mg per day. We use corticotrophin to
tide patients over a severe exacerbation.
Levamis ole
Levamisole is a synthetic antihelmintic
and has been used extensively in veterinary
and human practice. The drug is rapidly
absorbed when taken by mouth and has a
plasma half-life of 4 hours in man. It is
extensively metabolised in the liver and
virtually eliminated from the body within
2 days. The metabolites are excreted
mostly in the urine.
Symoens and Rosenthal (1977) have
summarised in an extensive review the
evidence that levamisole is an immuno-
therapeutic and anti-anergic drug. The
evidence from studies on isolated cells,
experimental animals, healthy volunteers
and patients, indicated that the drug
restores to normal the functions of
phagocytes and T ljrmphocytes when these
are depressed. The evidence, however,
also indicates that these functions are not
increased above normal levels by therapeutic
doses. B cells do not seem to be
influenced by the drug. It appears that
levamisole restores a basic mechanism
common to all ceUs involved and acts by
altering intraceUular cycUc GMP / cycUc
AMP ratios.
Levamisole is effective in vitro and
i n v i v o . In animals the drug does not
suppress a primary invasion by virulent
bacteria, viruses or tumour ceUs. It
seems, however, to increase the protective
92