ARTICLE
Tolerance of the hepatitis B vaccination is usually good. The most frequent
skin complications are short-lived, local reactions. Severe general reactions
occur in less than 1/1,000 cases [1]. Since 1995, the generalization of
vaccination to the whole of the French population, with the aim of eradicating
hepatitis B, has increased the incidence of these side effects. Many cutaneous
side effects connected with hepatitis B vaccination have been reported
in the literature [2]. We report a case of generalized granuloma annulare
(GGA), occurring following hepatitis B vaccination with the recombinant
vaccine GenHevac B Pasteur®.
Observation
Mrs M-F.S, born in 1946, a hospital auxiliary, with no previous remarkable
medical history, received into the right deltoid area, at monthly intervals,
the three prescribed injections of the hepatitis B vaccination in 1986
and one year later the booster injection with the GenHevac B Pasteur®
vaccine. One month after the last booster, a disseminated, non-pruriginous
eruption with small, orange/flesh coloured, non-annular papules appeared
on the upper extremities then on the trunk and the lower extremities (Fig.
1 and 2).
The lesions persisted until June 1991. Two skin biopsies carried out respectively
in September 1988 and June 1991 led to a diagnosis of granuloma annulare
(GA). They showed, under a normal epidermis, areas of necrobiosis and
a dense infiltrate composed of histiocytes and many giant cells. A lymphocytic
infiltrate which was sometimes nodular surrounded the vessels, the walls
of which were not altered. These abnormalities involved all of the upper
and middle dermis (Fig. 3).
With fasting glycemia, the thyroid hormones were normal and there was
good immunity against hepatitis B (anti-Hbs antibodies > 10 I.U. Ag
HbS < 0. Ag HbC < 0). HIV serodiagnosis was negative. Treatment
with Dapsone at doses of 50 mg was started in June 91. This brought about
a complete regression of the lesions within 4 months and was continued
until April 1992 with no relapse when it was stopped. In April 1993, another
injection of Genhevac B Pasteur® was given (5 year booster).
Three weeks later an eruptive relapse of GA appeared on the central chest
and back and the upper limbs. Fifty mg of Dapsone per day for two months,
then 100 mg per day, was not effective. The lesions then regressed slowly
and had completely disappeared by December 1994.
Discussion
GGA has been studied by Dabski and Winkelmann [3]. It is distinguished
from the localized form by its extent and, its axial topography. GGA affects
older patients with a more chronic course which is resistant to treatment,
and an association with diabetes mellitus in 21% of cases. To our knowledge,
the association of GGA and hepatitis B vaccination, or even GA and hepatitis
B, has never been reported.
The pathogenesis and the etiology of GA are
still not well understood. Morhenn suggests that GA, like sarcoidosis,
is an autoimmune disease originating from a delayed hypersensitivity reaction,
mediated by T lymphocytes [4]. Considering the similarity of the histopathological
vessel changes in lesions of GA, the Arthus reaction and the presence
of circulating immune complexes, Dahl et al. think that GA could
be an immune-mediated type III reaction [5]. The activation of T lymphocytes
by a foreign antigen may, by means of its molecular similarity to an antigen
of the skin, lead to autoimmunization The antigenic stimulus which initiates
this immunological response in GA is not always identified or unique.
Isolated observations of GGA have been reported after insect bites, viral
infections (Epstein Barr virus, chickenpox-shingles, HIV), intradermal
reaction to tuberculin or in a context of immunodeficiency: AIDS, thyroiditis,
autologous bone marrow transplantation, malignant blood diseases, PUVA
therapy [6].
When a vaccination is carried out, the association of antigenic inoculation
and trauma linked to the injection could initiate an immunological response
leading to the appearance of cutaneous disorders such as GA in predisposed
subjects. In the literature, we have found two observations of GGA after
a BCG vaccination and in one of these observation, the GGA appeared one
month after the injection [7]. In our observation, the delay to relapse
of one month could be explained by an immune type III reaction which could
correspond to the delayed antibody response to vaccination. Given the
relapse after the 5 year booster injection, the hepatitis B vaccination
involvment in the appearance of this GGA is credible. The case that we
have reported may lead to other publications in order to better identify
the physiopathological mechanisms of GA. Other new side-effects, as a
consequence of hepatitis B vaccination, have yet to be reported but we
should not forget that this vaccination still has a very favourable benefit/risk
ratio. Worldwide, each year there are 2 million deaths from cirrhosis
or primary cancer of the liver in 250 million chronic carriers of the
hepatitis B virus [8, 9].
REFERENCES
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K. Frequency of adverse reactions to hepatitis B vaccine in 43,618 persons.
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2. Grézard P, Philippot V, Perrot H. Incidents et accidents de
la vaccination contre l'hépatite B. J Med Lyon 1995; 1502:
1133-6.
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and laboratory findings in 100 patients. J Am Acad Dermatol 1989;
20/1: 39-47.
4. Morhenn VB. Cell-mediated autoimmune diseases of the skin: some hypotheses.
Medical Hypotheses 1997; 49: 241-5.
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and direct immunofluorescence. Arch Dermatol 1977; 113: 463-7.
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disease in 84 patients with granuloma annulare: a retrospective study.
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généralisé après vaccination par le BCG. Ann
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8. Lilic D, Ghosh SK. Liver dysfunction and DNA antibodies after hepatitis
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