ARTICLE
Auteur(s) : S. BLOK, W.H. VISSERS, M. Van DUIJNHOVEN,
P.C. van de KERKHOF
Department of Dermatology University Medical Centre St Radboud
P.O. Box 9101, 6500 HB Nijmegen Nijmegen, The Netherlands
Article accepted on 06/04/2004
Psoriasis is a polygenic disease and several triggering factors
may elicit or aggravate the expression of this disease [1].
Focal infections are a well-established triggering factor [2-5].
Provoking infections could be traced in 44% of a mixed series of
psoriatic patients [6]. In particular infections of the upper
respiratory tract may trigger psoriasis.
The mechanism of aggravation of psoriasis by focal infections has
been suggested to be mediated by bacterial superantigens [7]. In
particular, toxins from β-haemolytic streptococcus comprise
superantigens which may activate T-cells after presentation by
Langerhans cells to the β region of the T-cell receptor [8].
Staphylococcal superantigens were isolated from 17% of a group of
111 patients who showed a sudden onset or aggravation of
psoriasis [4]. The question arises to what extent “relapsing after
infections” is a constitutional trait restricted to a subpopulation
of genetically predisposed patients within the population of
patients with psoriasis?If such a subpopulation exists, what are
the major clinical characteristics of these patients?
A questionnaire was developed to find out to what extent patients
with psoriasis experienced aggravation of psoriasis as a consistent
feature and whether those patients with frequent relapse have other
clinical characteristics, different from patients who never relapse
following infections.
Materials and methods
A questionnaire was designed which comprised: (I) general
questions, (II) psoriasis related questions, (III) questions on the
relationship between focal infections and aggravation of
psoriasis.
(I) General questions comprised birthdate, sex and use of
medication
(II) Psoriasis related questions comprised age of onset and
clinical presentations at start, in particular whether psoriasis
followed an infection, whether aggravations of psoriasis following
infections were a consistent feature during the course of the
disease, family history of psoriasis, koebner phenomenon (the
appearance of new lesions following an injury of the skin),
pustulation and response to treatments. The infections were not
confirmed by a physician in all patients.
(III) Questions on details of the relationship between focal
infections, and aggravation of psoriasis were specified in greater
detail. The patients were asked (i) how often during last year and
during the years before the patient had an infection in general. In
particular the patients were asked to report tonsillitis,
pharyngitis, sinusitis, urocystitis, remaining infections. Further
we asked the patients (ii), how frequently he/she had relapsed
during the last year and the years before, (iii) whether a relapse
always, mostly (at least 5 out of 10 times), sometimes
(1-5 out of 10 times) and never followed an infection,
(iv) whether exacerbations were experienced as stressful and
whether stress did aggravate psoriasis.
The questionnaire was mailed to a group of 126 patients.
These patients had responded previously to an advertisement in the
newspaper that they were willing to fill in questionnaires, provide
blood and skin for research projects.
The questionnaire was mailed in the month of January 2003 and
answers were collected in the months of February and March. Out of
126 patients, 18 questionnaires were returned for reason
of unknown address and 45 questionnaires were answered and
returned, which corresponds to a response rate of 42%.
Statistical analysis comprised student T-test, chi square test and
multiple regression analysis.
Results
The average age of responders was 55 ± 13
(mean ± SD) years. In total 28 males and
17 females responded. The average age of onset of psoriasis
was 29.7 ± 12.8 (mean ± SD) years for males and
20.1 ± 15.4 (mean ± SD) years for females. The
age of onset for females was earlier as compared to males
(P = 0.04).
During the last year, 11 out of 45 patients (24%)
reported an exacerbation of psoriasis following an infection,
whereas 30 out of 45 patients (67%) indicated that a
relapse never followed an infection. Four patients out of
45 indicated that they had sometimes had a relapse following
an infection. Whilst 18 out of 45 (40%) of the patients did
not remember whether initiation of psoriasis followed an infection,
5 out of 45 (10%) indicated that such had been the case and
20 out of 45 (44%) indicated that such had not occurred at the
initiation of psoriasis. A positive correlation was shown between
failure of initiation of psoriasis following an infection during
the first year and failure of exacerbation on infection of
psoriasis during last year (X2 = 7.0,
P = 0.01). The relationship between psoriasis and
infections at initiation of psoriasis during the last year can be
seen in Table I. Patients who
indicated that recently their psoriasis was exacerbated by
infections consistently indicated that this held true during the
course of psoriasis.
Table I. Patients with
initiation of psoriasis following infections versus exacerbations
of psoriasis following infection during last year
| |
Initiation of psoriasis following
infection |
|
|
|
| Last year exacerbation after infection |
? |
Yes |
No |
Total |
| ? |
4 |
0 |
0 |
4 |
| Yes |
6 |
3 |
2 |
11 |
| No |
8 |
2 |
20 |
30 |
| Total |
18 |
5 |
22 |
45 |
The patients indicated whether a relapse “never”, “sometimes”
(1-5 out of 10 relapses) or “mostly (5-10 out of
10 relapses) followed an infection.The majority of patients
(n = 32) indicated that they never had a relapse
following an infection and 8 patients indicated that they
mostly experienced infection-induced aggravation of psoriasis,
whereas 5 patients indicated that they sometimes experienced
this association. The clinical characteristics of the patients
indicating mostly infection-induced aggravations were compared with
those who never experienced this association.
The age of onset in patients who mostly had infection-induced
aggravations of psoriasis was 17.6 ± 11.6 vs.
26.6 ± 14.2 in patients who never had this
association (P = 0.09). Six out of 7 patients who
mostly experienced psoriasis exacerbations following infections had
guttate psoriasis as first manifestations.
Patients who experienced mostly aggravation of psoriasis following
an infection had 4.6 ± 4.3 (mean ± 50) relapses
per year versus 1.1 ± 0.9 in patients who never
experienced this association. Multiple regression analysis between
the number of relapses of psoriasis during last year and the number
of infections during that year in patients who had mostly
aggravation of psoriasis following an infection revealed a
correlation coefficient r = 0.82. In this group of
patients the correlation of the number of relapses with pharyngitis
was 0.61, with sinusitis 0.43, with cystitis 0.057 and with
remaining infections -0.33.
Comparing patients who mostly experienced infection-induced
aggravation of psoriasis with those who never experienced such,
revealed that the occurrence of the Koebner phenomenon, the
appearance of new lesions following a trauma, was virtually
identical in both groups (Table II) and that pustulation occurred in
22% and 13% resp. of the patients (no statistically significant
difference). Table III indicates that
no statistically significant differences exist between both groups
with respect to experience of stress or relevance of stress to
induce a relapse. However 7 out of 8 patients (88%) who
experienced that aggravation mostly resulted from an infection also
experienced aggravations induced by stress.
Table II. Koebner phenomenon
in patients who mostly experienced exarcerbation after infection
vs. patients without this association
(X2 = 0.25, P = 0.88)
| ? |
| Never (0/10) |
8 (25%) |
23 (72%) |
1 (3%) |
| Mostly (5-10/10) |
2 (25%) |
6 (75%) |
0 (0%) |
Table III. Role of stress in
patients who mostly experienced exacerbation after infection vs.
patients without this association
| Aggravation following an
infection |
Exacerbation causes
stress |
Stress causes
exacerbation |
| Yes |
No |
Yes |
No |
| Never (0/10) |
17 (53%) |
15 (47%) |
19 (59%) |
13 (41%) |
| Mostly (5-10/10) |
5 (62%) |
3 (38%) |
7 (88%) |
1 (12%) |
| |
X2 = 0.23 |
p = 0.63 |
X2 = 2.23 |
p = 0.13 |
Discussion
The present questionnaire comprises a small group of patients.
Therefore, conclusions from this report only can be preliminary and
need to be confirmed by a study of a large patient populations.
However, the report suggests that aggravation of psoriasis by
infections is a consistent feature in a preselection of the
patients and not a general characteristic of the entire population
of patients with psoriasis.
Patients who show frequent aggravation of psoriasis following
infections differ in several respects from patients who
consistently do not show this association At the initiation of
psoriasis the majority of patients showing the association with
infections had guttate psoriasis (6 out of 8) and patients in
this group were 9 years younger as compared to patients who
did not experience this association. It is a well established fact
that guttate psoriasis is a frequent manifestation of childhood
psoriasis.
Patients who show exacerbations following infections usually have
guttate psoriasis at the start, however guttate psoriasis also may
occur in 50% of the patients who have psoriasis not dependent on
infections.
Relapses are 4 times as frequent in patients who experience
mostly infection-induced aggravations. The correlation coefficient
of r = 0.82 between aggravation of psoriasis and
infections in this group implies that infections are responsible
for the aggravation of psoriasis in 67% of the cases. A remarkable
observation is that a positive Koebner phenomenon occurred in 25%
of the patients irrespective whether they showed infection induced
aggravations or not. A positive Koebner phenomenon has been
reported in 25% of a large population of psoriatics [9].
Pharyngitis shows the highest correlation with relapses,
indicating that throat infections are most relevant to the
aggravation of psoriasis.
Although below the level of statistical significance, 7 out
of 8 patients who indicated having mostly exacerbations
following infections also indicated that stress induces aggravation
of the disease.
The present study indicates that aggravation of psoriasis by
infection is restricted to a subpopulation of 18% of psoriatics.
This subgroup is also characterized by guttate psoriasis at
initiation and an age of onset which is 9 years earlier as
compared to patients without this association. The course in the
first group is more severe with about 4 times as many
exacerbations and a tendency to be more prone to exacerbations by
other triggering factors such as stress.
Previously, a subtype of psoriatics has been defined as Type I:
early onset (< 40 years), a positive family history
and type II: absence of HLA Cw6, B13 and B57 [10]. Previously
it was shown that HLA-B13 may predispose to severe
streptococcal infections [11]. Recently microbial infection was
investigated by nasopharyngeal swabbing and standard methods of
bacterial isolation and assessment of titers of antibacterial
antibodies in patients with type I vs. type II psoriasis [12].
Patients with type I psoriasis had a significantly higher incidence
of laboratory indicators for streptococcal infections as opposed to
type II psoriasis, although healthy subjects expressing HLA-Cw6,
B13 and B57 had no indication for an increase of indicators
for streptococcal infections [12].
In conclusion, it is highly likely that a subgroup of psoriatics
exists who are prone to exacerbation following infections as a
genetic trait rather than a variable expression in the entire
population of psoriatics. n
References
1. Farber EM, Nall L. Epidemiology, natural history
and genetics. Psoriasis, third edition. Roenigk HH and
Maibach HI, eds. Marcel Dekker Inc, New York, Basel, Hong Kong,
1998; pp 107-57.
2. Farber EM, Nall L. Guttate psoriasis.
Cutis 1993; 51: 157-64.
3. Farber EM, Nall L. The natural history of
5.600 patients. Dermatologica 1974; 148: 1-18.
4. Yamamoto T, Katayama I, Nishioka K. Clinical
analysis of staphylococcal superantigen hyper-reactive patients
psoriasis vulgaris. Eur J Dermatol 1998; 8: 325-9.
5. Nyfors A, Lemholt K. Psoriasis in children. Br
J Dermatol 1975; 92: 437-42.
6. Nörholm-Pedersen A. Infections and psoriasis.
Acta Dermato-Venereologica 1952; 32: 159-67.
7. Leung DY, Travers JB, Norris DA. The role of
superantigens in skin disease. J Invest Dermatol 1995; 05:
37-42.
8. Vladimarsson H, Baker BS, Jonsdottir I, Powles A,
Fry L. Psoriasis: a T-cell mediated autoimmune disease induced by
streptococcal superantigens? Immunol Today 1995; 16:
145-9.
9. Eyre RW and Krueger GP. Response to injury of
skin involved and uninvolved with psoriasis, and its relation to
disease activity: Koebner reaction. Br J Dermatol 1982; 106:
153-9.
10. Henseler T, Christophers E. Psoriasis of early
and late onset: characterization of two types of psoriasis
vulgaris. J Am Acad Dermatol 1985; 13: 450-6.
11. Krain LS, Newcomer VD, Terasaki PI. HLA antigen
in psoriasis. N Engl J Med 1973; 288: 1245.
12. Weisenseel P, Laumbacker B, Besgen P,
Ludolph-Hauser D, Herzinger T, Roecken M, Wank P, Prinz JC.
Streptococcal infection distinguishes different types of psoriasis.
J Med Genet 2002; 39: 767-8.
| Aggravation
following an infection |
Last year
Koebner positive |
| Yes |
No
|
|
Version imprimable
Version PDF