Læknablaðið : fylgirit - 01.07.1978, Síða 93

Chloroquine particularly accumulates in
the pigmented tissue of the eye. Bernstein
et al (1963) have shown, that the drug
does not concentrate in iris, choroid or
pigment epithelium in albino rats. In
vitro studies have shown that the drug
avidly binds to melanin (Perez et al, 1964),
and there is considerable evidence that
retinal toxicity is due to accumulation of
the drug in the pigmented layers of the
eye (Bernstein and Ginsberg, 1964). Why
blanching of the hair and eyebrows (Dall
and Keane, 1959) often accompanies retinal
toxicity remains obscure. Retinal damage
is a dosage phenomenon. On average
550 g are required before damage occurs,
although patients have been reported who
developed chloroquine retinopathy after
much smaller doses (Scherbel et al, 1965).
The incidence of the complication is
difficult to assess from the literature,
but varies from 0.1 to 15 per cent (von
Sallman and Bernstein, 1963, Henkin and
Rothfield, 1963). Presumably this wide
divergence in incidence reflects different
diagnostic criteria. Nevertheless, the
complication is very serious since with
few exceptions (Crews 1964) progressive
blindness developes despite discontinuing
therapy (Hobbs, Sorsby and Freedman,
1959).
It is our belief that anti-malarials should
be prescribed with the greatest caution,
and probably not for longer than a year.
Chrys otherapy
There seems little doubt that gold salts
exert a beneficial effect in rheumatoid
arthritis (Fraser, 1945), Empire
Rheumatism Council 1960 and 1961,
Cooperative Clinics of the American
Rheumatism Association, 1973, Sigler et
al 1974 and Luukkainen et al, 1977). The
study of Luukkainen et al (1977) is of
particular interest since it suggests that
progression of erosive changes may be
delayed, but not, it should be noted,
arrested completely. Jessop and Currey
(1968) noted no benefit of gold in adjuvant
arthritis in rats, although others have
observed its benefit in mycoplasma
arthritis in mice (Sabin and Warren, 1940).
The main indication for gold therapy is
failure of the patient to respond to non-
steroidal anti-inflammatory drugs. The
gold preparation used in the United
Kingdom is sodium aurothiomalete
(myocrisin). After weekly injections of
small doses of 10 mg and 25 mg to avoid
allergic reactions the patient is given
weekly injections of 50 mg until a total of
500 mg has been given. After this
injections can be given every 2 weeks
until 1 g has been given. Thereafter
monthly injections are given. The problem
to-day is when to discontinue therapy,
since relapse tends to occur.
Toxic reactions are the most worrying
aspect of gold therapy and require
discontinuing therapy in about one third of
patients. Gold is probably the most toxic
preparation in the British Pharmacopoeia
(Gerwood, 1973) and causes more deaths
per prescription than any other drug.
The highest incidence of toxicity occurs
after 200 to 400 mg, and appears lower
after 1 g (Jessop, 1972). Toxicity can
be avoided by excluding patients with
dermatitis, hepatic and renal disease.
Gold dermatitis is often preceeded by
pruritus and eosinophilia (Davis et al,
1973). In practice it is difficult often to
know whether a rash is due to gold or
not, but it is wise to err on the safe side
and discontinue therapy if a rash, however
mild, occurs. Gold is excreted in the
urine and may give rise to renal damage
(Strunk and Ziff 1970). Gold inclusions
lying between the epithelial cells and the
glomerular capillary wall basement
membrane are often seen, but their role
in causing proteinuria remains uncertain
(Strunk and Ziff, 1970). What is certain,
however, is that acute tubular necrosis
may occur and is invariably fatal. A
nephrotic syndrome may occur due to
membranous glomerulonephritis (Vaamonde
and Hunt, 1970), and surprisingly carries
a good prognosis. A trace of proteinuria
is not a contraindication for continuing
treatment with gold, but a proteinuria of
30 mg per 100 ml or more certainly is
(Jessop, 1972).
Haematological complications often occur
without warning. Eosinophilia if marked
and persistent is a definite contraindication
to continuing gold therapy. Persistent
thrombocytopenia is often fatal, and
pancytopenia and neutropenia also carry a
high mortality despite D-penicillamine or
dimercaptol therapy. Westwick and his
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