ARTICLE
Chrysotherapy is a classical treatment of cases of arthritis and arthrosis
of various origins which are resistant to conventional therapy [1].
Many clinicians from different countries have recently been using gold
in the treatment of pemphigus particularly in protracted forms or those
with mucosal involvement [2, 3].
Reported side effect of gold treatment vary from unspecific rashes to
severe conditions such as exfoliative dermatitis (Table
I) [4, 5]. We observed a patient with pemphigus, which developed
during treatment with gold. It provided us with some evidence to share
the opinion of those authors who have included gold in the list of agents
proven to induce pemphigus.
Case report
Mrs E.K.G. 64-year-old, suffering for many years from rheumatoid arthritis,
had been treated with gold sodium thiomalate.
The treatment, which lasted 18 months, started with a weekly administration
of 100 mg of gold sodium thiomalate (Solganal B oleosum®)
(i.m.) and continued with progressively increasing doses up to 22.0 g
per week.
Two months later, flaccid blisters appeared on the trunk and limbs.
Painful erosions developed in the mouth. The clinical examination showed
blisters and small vesicles of different sizes and stages of evolution
on the skin (Fig. 1).
There were numerous erosions and vesicles in the oral cavity predominantly
on the buccal mucosa and the palate.
The laboratory findings were within normal limits except for the elevated
WBC-11.6 g/l and ESR-62 mm. The Tzanck test yielded numerous acantholytic
cells. The histological examination revealed a subcorneal blister with
some acantholytic cells, lymphocytes, plasma cells and polymorphonuclears.
A mild, round-cell infiltrate was observed in the papillary dermis.
DIF yielded intercellular deposits of IgG in
the epidermis. Pemphigus antibodies at a titre of 1:40 were demonstrated
by IIF (rat-liver substrate).
Treatment with 6-methylprednisolone (Urbason®) was started
at an initial dose of 60 mg daily. Antiseptic lotions and flumethason
pivalate (Locacorten®) were applied locally. The diagnosis
of induced pemphigus in our cases was determined by the following features:
(1) history: there was a casual relationship between the gold therapy
and the blister eruption. During this time, the patient did not receive
any drugs apart from the gold sodium thoimalate and aspirin; (2) clinical
finding: besides the flaccid blisters typical of pemphigus vulgaris, small
vesicles grouped as in pemphigus herpetiformis were observed. It is well
known that induced pemphigus presents features of foliaceus, erythematosus
or herpetiformis variants [6]; (3) histology: the blister was situated
near the granular layer as in superficial pemphigus. The observed marked
acantholysis is compatible with drug-induced pemphigus [6, 7]; (4) immunofluorescence:
there were low titres for pemphigus antibodies which were not related
to the severity of the disease and are typical for drug-induced pemphigus
[6-8]; (5) evolution of the disease: the disease regressed shortly after
the inducing factor (gold sodium thiomalate) was eliminated and systemic
steroid therapy was started. Six months later the patient was clinically
healthy and the steroid therapy was stopped.
Discussion
Thiol drugs D-penicillamine, gold sodium thiomalate, pyritinol,
captopril, 5-thiopyridoxine, thiopronine, pyroxicam, mercaptopropionylglycine
are able to provoke acantholysis without antibody mediation, so called
biochemical thiolacantholysis [9].
The disruption of cell-cell adhesion provoked by thiol drugs may involve
biochemical interference with keratogenesis, a complicated epidermal function
in which cysteine sulfhydryl groups, cystine disulfide bonds, Ca2+
and thiol dependent-enzymes take part.
On the other hand, thiol drugs can provoke pemphigus via immune
mechanisms immunologic thiol acantholysis [9].
After eliminating the provoking agent e.g. gold therapy and administering
systemic steroid therapy the condition of our patient was well-controlled
and no new lesions were observed after the steroids were discontinued.
Six months later the patient was clinically healthy.
Miyamoto and Maeda [8] first reported an exacerbation
of pemphigus, due to gold therapy. Some authors include gold in the list
of drugs known to trigger pemphigus [7, 8, 10]. Moreover, it is well known
that thiol drugs capable of inducing pemphigus (gold sodium thiomalate,
thiopronine, captopril, D-penicillamine) may also induce other immune-mediated
eruptions (eczematous, erythema multiforme type, lichenoid, pityriasus
rosea-like, LE-like) [9].
To our knowledge, this is the first case of pemphigus induced by gold
sodium thiomalate. The pathomechanism of immunologic thiol acantholysis
may ensue from the direct interference of thiol drugs with the immune
system [9, 10].
It is surprising to have seen that a medication such as gold, which
is administered for some forms of pemphigus may exacerbate and even trigger
pemphigus. In fact, there are numerous examples in modern therapy of similar
effects highlighting the need for a unique approach to each, individual
patient.
REFERENCES
1. Thomas J. Gold therapy and its indications in dermatology. J Am
Acad Dermatol 1987; 16: 845-54.
2. Poulin Y, Perry HO, Muller SA. Pemphigus vulgaris: results of treatment
with gold as a steroid-sparing agent in a series of thirteen patients.
J Am Acad Dermatol 1984; 11: 851-7.
3. Solomon D, Saurat J-H. Oral gold therapy (Auranofin) in pemphigus
vulgaris. Dermatologica 1986; 172: 310-4.
4. Penney NS, Ackerman AB, Gottlieb NL. Gold dermatitis: a clinical
and histopathological study. Arch Dermatol 1974; 109: 372-6.
5. Cibbons RB. Complications of chrysotherapy: a review of recent studies.
Arch Intern Med 1979; 139: 343-6.
6. Ruocco V, Pisani M. Induced pemphigus. Arch Dermatol Res 1982;
274: 123-40.
7. Ruocco V, Sacerdoti C. Pemphigus and bullous pemphigoid due to drugs.
Intern J Dermatol 1991; 30: 307-12.
8. Miyamoto Y, Maeda M. Pemphigus induced by gold sodium thiomalate.
Arch Dermatol 1978; 114: 1855.
9. Ruocco V, De Angelis E, Lambardi ML. Drug pemphigus II. Pathomechanisms
and experimental investigations. Clin Dermatol 1993; 11: 507-13.
10. Brenner S, Wolf R, Ruocco V. Drug-induced pemphigus I. A Survey.
Clin Dermatol 1993; 11: 501
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