ARTICLE
Auteur(s) :, Ioannis Ketikoglou1,*,
Stelios Karatapanis1, Ioannis Elefsiniotis1,
Georgia Kafiri2, Antonios Moulakakis1
1Department of Internal Medicine, Hippocration
General Hospital, Athens GreeceFax: (+30) 210 7787807.
2Department of Pathology, Hippocration General Hospital,
Athens Greece
accepté le 6 Juillet 2004
Pegylated interferon alpha (Peg-IFN-a) is a conjugate of a
straight-chain polyethylenglycol with interferon alpha (IFN-a) [1].
Peg-IFN-a has the same characteristics and similar side effects as
IFN-a, but it differs because it has a more prolonged action,
better biologic activity and reduced immunogenicity [2].IFN-a is a
cytokine with pleiotropic activities. Its therapeutic role has been
proved in several malignant and chronic viral diseases. IFN-a can
cause many adverse reactions. Among them are the induction of
autoimmune phenomena or the exacerbation of autoimmune diseases. It
is well known that IFN-a can exacerbate psoriasis but de novo
development of this disease has very rarely been observed.We
describe a case of a patient with chronic hepatitis B treated with
Peg-IFN-a, who developed psoriasis for the first time.
Case report
A 32-year-old man was admitted in our hospital because of elevated
serum aminotransferases twice the upper normal limit and HbsAg
positive. His parents and two brothers are inactive HbsAg carriers.
There is no history of psoriasis in him or his family.
From the laboratory findings: serum HBV-DNA = 9.6 ×
105 copies/ml, HbsAg = positive, anti-HBc = positive.
HLA phenotype: A26(10), A30, B13, B38(16), Cw6, Cx, DR14(6),
DR7(DR52, DR53), DQ6(1), DQ2.
Liver biopsy showed mild chronic hepatitis B. Grading of
inflammatory lesions: 7 (0-18); staging: 6 (0-6), according to
Ishak’s grading and staging system [3]. The rest of the
hematological, biochemical and virological results were within
normal limits.
The patient was treated with pegylated interferon a2b
(Peg-IFN-a2b) [Peg-Intron, Schering-Plough]. He started with 200 μg
of Peg-IFN-a injected subcutaneously once a week and after 4 weeks
the dose was reduced to 100 μg weekly. One month after the
beginning of the treatment the patient complained about a psoriatic
type of eruption on the arms at the injection sites. Two months
later, the psoriatic eruption extended to the entire body surface (
(figure 1) ).
The patient also complained about mild pruritus. He underwent
dermatological consultation and a skin biopsy ( (figure 2) ) and the
results reaffirmed that this eruption was a plaque psoriasis. The
patient was not given special antipsoriatic treatment but he was
advised to stop therapy with PegIFN-a. After a month the eruption
progressively disappeared. The patient continued antiviral therapy
with lamivudine (a nucleoside analogue), 100 mg daily, showing
biochemical and virological response. No dermatological or other
adverse effects were observed during treatment with lamivudine in
the 18 months follow-up period.
Discussion
IFN-a is a cytokine with antiviral, antineoplastic and
immunomodulatory properties. Interferons, along with NK cells, are
considered the first line of defense against viral infections and
tumours. It has been suggested that IFN-a enhances humoral immunity
by increasing proliferation of B cells, which secrete antibodies
against invading pathogens. Moreover IFN-a enhances the CD8+
cytotoxic T cell (CTL) response by upregulating the expression of
MHC class I molecules on the cell surface. MHC I molecules are
responsible for presenting viral antigens to CTLs, thereby
triggering the destruction of the infected cell. MHC class II
molecules located on the surface of antigen presenting cells (APCs)
present viral antigens to helper T cells. Certain IFN-a subtypes
may increase the expression of MHC class II molecules by APCs [4].
IFN-a can induce autoimmune diseases such as autoimmune
thyroiditis, hemolytic anemia and thrombocytopenia, systemic
lupus-like syndromes, rheumatoid arthritis, sarcoidosis, etc. [5].
HLA haplotypes are correlated with autoimmunity: A1, A2, A3, DR3,
DR4, DR15, DR52, DQ2, DQ6 [6]. Moreover a great number of patients
who are under IFN-a treatment express autoantibodies (ANA, ASMA,
antithyroid, etc.) as an epiphenomenon without clinical
significance [7]. Interferon-related skin complications include a
variety of rashes and reversible mild hair loss [8].
Peg-IFN-a2b consists of IFN-a2b attached to a single 12 000
daltons polyethylene glycol chain molecule. This large molecule has
reduced renal clearance and a prolonged plasma half-life (4 days
instead of 4 hours) compared with IFN-a2b. Also Peg-IFN-a2b has
reduced immunogenicity of the IFN molecule. So the therapeutic
efficacy of PEG-IFN-a2b is greater than IFN-a2b [9]. Peg-IFN-a2b
usually causes local erythema at the site of injection. Some rare
cases of cutaneous necrosis have been reported [10].
The pathogenesis of psoriasis is unknown. Immunologic and
environmental factors have been implicated in its etiology. It is
hypothesized that the major histocompatibility complex contributes
to the susceptibility of psoriasis in many people. The major
genetic determinant for psoriasis is located in the PSORSI region
of the MHC on chromosome 6p21. The most likely candidate loci are
HLA-Cw*0602 [11-13] and corneodesmocin gene [11]. These genes are
in linkage disequilibrium with other genes. Other genes implicated
are SLC9A3R1 and NAT9 in PSORS2 locus in 17q24-q25 chromosome [11,
14]. With the impact probably, of some environmental factors, T
cells and dendritic APCs are activated and a “cytokine storm”
begins, composed of numerous cytokines, chemokines and growth
factors. A vicious circle occurs in which keratinocytes,
endothelial cells, neutrophils and macrophages are activated and
conspire in the creation of a psoriatic plaque [11]. Interferons
cause exacerbation and, rarely, induction of psoriasis in
susceptible persons.
In 1986 Quesada and Gutterman [15] reported three cases of
psoriasis aggravated by interferon a2b which was used for the
treatment of malignant diseases. Hartmann et al. [16] reported 3
more cases in 1989. In 1993 Garcia-Lora et al. reported the
induction of psoriasis after treatment of chronic hepatitis C with
IFN-a [17]. Since then, there have been some cases of psoriasis
reported that were exacerbated [18, 19] and a few induced by IFN-a
[20, 21]. In most of them the psoriasis appeared one to six weeks
after the initiation of treatment. After stopping treatment, the
psoriasis began to improve and later it disappeared.
Our patient, although without a family history of psoriasis, had
an HLA phenotype which is aggregative for autoimmune diseases
(DR52, DQ2, DQ6) and psoriasis (CW6), and presented this
complication four weeks after the initiation of the treatment. The
certainty of this relationship is confirmed by the amelioration of
psoriasis after stopping the treatment. The reduced immunogenicity
of PEG-IFN-a, possibly, was not a deterrent for the induction of
psoriasis.
This case report is the first in the literature, compared to
IFN-a, where Peg IFN-a induced de novo development of psoriasis in
a patient with chronic hepatitis B. Doctors should take into
account this possibility.
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