ARTICLE
Auteur(s) : VN
Saxena1, J Dogra2
1Unit of dermatology. SMS Medical College, Jaipur
India
2CGHS, Jaipur India
accepté le 20 Avril 2005
Psoriasis is a relapsing scaly and hyperproliferative disorder that
affects 1-3% of the world’s population. The most characteristic
lesion is a chronic, sharply demarcated, dull red scaly plaque
present on extensors of the body and scalp. The basic cell
pathology in psoriasis is inflammatory cell infiltration, increased
cytokine production and hyperproliferation of keratinocytes. The
hyperproliferation is preceded by infiltration of activated T cells
[1, 2], which play a critical role in triggering psoriasis [3].
Baker et al. [4] suggested that among T cells, CD 8 + T cells
predominate in lesional epidermis of psoriasis, thus indicating a
pathogenetic role of this type of T cell in the development of the
skin lesion. The influx of these T-cells may indicate the presence
of streptococcal antigens in the skin of these patients, possibly
as a result of inadequate elimination by the immune system
[5].Group A streptococcal infection in the throat and occasionally
in the perianal region may be responsible for causing initial and
recurrent attacks of acute guttate psoriasis [5-9]. Of these acute
guttate psoriasis cases about 68% go on to develop typical plaque
psoriasis [10]. Patients with chronic plaque psoriasis may
experience guttate flares of their disease [10], and exacerbation
of chronic plaque psoriatic lesions following streptococcal
tonsillitis has been reported a long time ago. Induction of
psoriatic lesions following inoculation of killed streptococcal
material has been observed and such infections have also provoked
exacerbation of psoriasis at distant sites [11].The strongest
evidence linking T cell activation to psoriasis [5, 8, 12] is from
the clinical observation that immuno-suppressive drugs such as
corticosteroids and cyclosporin A, by inhibiting T-cell activation
and cytokine release, are effective in the treatment of psoriasis
[13]. It is suggested that molecular mimicry between keratin and
the M- protein of streptococci lead to T-cell influx into the skin
and the development of psoriatic plaques [14].Valdimarsson [15],
suggested the existence of a specific cellular immune response in
guttate psoriasis to super-antigen, perhaps related to Group A
streptococci and Leung et al. [16, 17] suggested that super
antigens have an important role in the development of chronic
plaque psoriasis.Cohen Terveart and Esseveld [18] quoted that
Lancefield’s group A type 12 streptococci produce an antigen that
is responsible for acute diffuse haemorrhagic glomerulonephritis.
This syndrome includes a capillaropathy which results from an
antigen-antibody reaction. Acute glomerulonephritis occurs a few
weeks after an acute tonsillitis. Similarly, the dermal capillary
changes in chronic psoriasis could be a late manifestation of
streptococcal infection.The above observations suggest that
streptococcal antigen is an integral part of this disease and/or
the continuing sub clinical streptococcal infection might be
responsible for refractory chronic plaque psoriasis [6, 19]. Our
open study is based on the hypothesis that Group A streptococci, is
somehow solely responsible for chronic plaque psoriasis, as in
rheumatic heart disease and post streptococcal nephritis.
Material and methods
Thirty histopathologically confirmed patients with chronic plaque
psoriasis were included in this study (twenty males and ten
females). Age ranged from 10 years to 67 years. Patients either had
a history of no previous therapy or had taken various treatment
regimens (mentioned in textbooks), but with minimal response and
had a history of frequent relapses. Histories of exacerbating
factors like trauma, drugs, alcohol, smoking, metabolic, endocrine,
sunlight and AIDS were taken. History of psoriasis in other family
members, if any, was recorded. Criteria for exclusion included
pustular psoriasis, history of spontaneous remission of the
disease, pregnancy and other associated systemic disease and
allergy to penicillin.
Patients taking any prior treatment were advised to discontinue
the same for four weeks, before they were enrolled for this trial.
Informed consent was obtained from all the patients.
In all the patients, routine blood counts, liver function tests,
renal function tests, ASLO titre, C-reactive protein and throat
swab cultures were done. Based on PASI score, a clinical assessment
of the site, size, number, erythema scaling and induration of
previous and any fresh lesions were carried out in all the patients
(at 12 weeks interval up to 1 year). Response to treatment based on
% improvement was graded as nil (< 10%), mild (11-30%),
moderate (31-60%), good (61-90%) and excellent (91-100%).
The total duration of study was two years. Initially, the
patients were examined fortnightly for six months and then every
month.
1.2 million units of injection benazthine penicillin were given
intramuscularly, after a sensitivity test, fortnightly for 24
weeks. Therapy with benzathine penicillin was maintained at 1.2
million units once a month, after 6 months of initial therapy, for
the rest of the study period, as the average duration of
demonstrable anti microbial activity in the plasma was about 26
days. For statistical analysis of data the paired t-test was
applied.
Results
Thirty patients completed the study period of 2-years.The duration
of the disease ranged from a few months to 26 years. The majority
of the patients had the illness for 5 years or more (21 out of the
total 30). Exacerbating factors such as drug history, smoking,
alcohol, trauma, endocrine factors, metabolic factors, sunlight and
AIDS were not present in any of the cases. Fifteen patients (50%)
had ASLO titer more than 200 IU/ml (positive) (table 1)( Table 1 ). The ASLO titer in these patients
became less than 200 IU/ml (negative) after 24 weeks of
therapy. 7 patients had C-reactive protein positive, of which five
were negative after 24 weeks.
On throat swab culture group A streptococcus was reported in two
cases while in six cases the reported organism was streptococcus
viridians and in three cases enterobacteriacae species.
After the initial 4 weeks of therapy the majority of patients
showed no clinical improvement in erythema, in duration and
scaling. A significant improvement in the PASI score was evident
from 12 weeks in the majority of patients (p-value < 0.001)
(table 2)( Table 2 ). All patients
tolerated the therapy well and no side effects were reported in any
case.
At twenty-four weeks of therapy an excellent response was seen
in 14 patients (46.6% and p-value < 0.001), good response was
observed in 12 patients (40%) and mild response in 4 patients
(13.4%).
At thirty-six weeks of treatment 20 patients (66.66%) showed
excellent improvement in lesions (p-value < 0.001) and 9 cases
(30%) had good improvement. One patient reported moderate
improvement. These results improved still further at 48 weeks
(table 1). None of the patients during the study period of 2 years
had a relapse, except for the development of few small new lesions
in 6 patients during the winter season which were markedly less as
compared to previous years and cleared on continuing the same
treatment.
Table 1 Showing clinical data and PASI-score (before
and after therapy) of psoriasis patients
|
S. No
|
Code of patient
|
Age
|
Duration of illness
|
ASLO
|
C-reactive-Protein
|
PASI-SCORE
|
|
Before initiation of therapy
|
After 12 weeks
|
After 24 weeks
|
|
After 48 weeks
|
|
1.
|
MK
|
30 yrs
|
20 yrs
|
+
|
-
|
53.8
|
27.6
|
5.0*
|
2.7*
|
1.2
|
|
2.
|
ML S
|
49 yrs
|
26 yrs
|
-
|
-
|
4.8
|
3.2
|
1.4
|
0.6**
|
0.0
|
|
3.
|
K B
|
48 yrs
|
3 yrs
|
-
|
-
|
42.0
|
14.0
|
11.4
|
5.5**
|
1.0
|
|
4.
|
N A
|
30 yrs
|
4 yrs
|
+
|
-
|
68.5
|
30.0
|
6.8*
|
4.3*
|
0.7
|
|
5.
|
B
|
45 yrs
|
6 yrs
|
-
|
-
|
10.8
|
8.2
|
2.8
|
1.2**
|
0.0
|
|
6.
|
M
|
21 yrs
|
8 yrs
|
+
|
+
|
6.4
|
4.0
|
1.6*
|
0.0*
|
0.0
|
|
7.
|
M
|
14 yrs
|
2 yrs
|
+
|
-
|
53.8
|
21.2
|
5.0*
|
3.1*
|
0.0
|
|
8.
|
K
|
46 yrs
|
6 yrs
|
+
|
-
|
54.0
|
41.2
|
21.5
|
4.6*
|
1.6
|
|
9.
|
R K
|
22 yrs
|
8 yrs
|
-
|
+
|
19.2
|
15.5
|
7.2
|
2.0**
|
0.9
|
|
10.
|
S
|
14 yrs
|
5 yrs
|
+
|
-
|
41.0
|
25.0
|
12.7
|
2.7*
|
0.8
|
|
11.
|
S
|
28 yrs
|
10 yrs
|
+
|
+
|
38.4
|
15.8
|
3.7*
|
0.4*
|
0.0
|
|
12.
|
C K
|
14yrs
|
6 months
|
-
|
-
|
39.6
|
37.4
|
17.5
|
5.0**
|
1.2
|
|
13.
|
S.
|
26 yrs
|
7 yrs
|
+
|
-
|
15.8
|
6.8
|
1.4*
|
0.0*
|
0.0
|
|
14.
|
K. S.
|
48 yrs
|
6 yrs
|
-
|
-
|
42.7
|
34.3
|
19.0
|
9.3**
|
9.3
|
|
15.
|
R V
|
33 yrs
|
13 yrs
|
-
|
-
|
36.8
|
25.1
|
11.8
|
5.6**
|
1.0
|
|
16.
|
G D
|
25 yrs
|
4 yrs
|
-
|
+
|
12.0
|
8.8
|
5.4
|
1.8**
|
0.0
|
|
17.
|
R R
|
38 yrs
|
12 yrs
|
+
|
-
|
25.0
|
8.3
|
2.1*
|
0.6*
|
0.0
|
|
18.
|
K L
|
67 yrs
|
4 yrs
|
-
|
-
|
20.0
|
3.7
|
2.0*
|
0.8*
|
0.0
|
|
19.
|
U S
|
30 yrs
|
12 yrs
|
-
|
-
|
56.0
|
53.8
|
51.7
|
40.3***
|
26.1
|
|
20.
|
S R
|
53 yrs
|
18 yrs
|
-
|
-
|
40.6
|
19.1
|
2.6*
|
1.2*
|
0.0
|
|
21.
|
R
|
20 yrs
|
10 yrs
|
+
|
+
|
34.3
|
26.1
|
11.4
|
2.7*
|
0.7
|
|
22.
|
S
|
27 yrs
|
10 yrs
|
+
|
-
|
41.6
|
20.0
|
14.0
|
3.7*
|
1.0
|
|
23.
|
M L
|
30 yrs
|
9 months
|
+
|
+
|
37.4
|
29.1
|
12.7
|
2.5*
|
0.9
|
|
24.
|
R S
|
25 yrs
|
10 yrs
|
+
|
-
|
19.0
|
11.4
|
1.6*
|
0.8*
|
0.0
|
|
25.
|
G
|
32 yrs
|
1 yr
|
-
|
-
|
14.0
|
11.4
|
4.6
|
1.4**
|
0.0
|
|
26.
|
MA
|
10 yrs
|
3 yrs
|
+
|
+
|
46.8
|
19.8
|
4.3*
|
0.8*
|
0.0
|
|
27.
|
R
|
38 yrs
|
12 yrs
|
-
|
-
|
21.5
|
10.3
|
2.0*
|
0.7*
|
0.0
|
|
28.
|
S
|
23 yrs
|
9 yrs
|
+
|
-
|
15.5
|
12.7
|
1.4*
|
0.0*
|
0.0
|
|
29.
|
R K
|
35 yrs
|
20 yrs
|
-
|
-
|
37.4
|
19.0
|
14.0
|
0.3*
|
0.0
|
|
30.
|
M
|
42 yrs
|
5 yrs
|
-
|
-
|
34.3
|
11.4
|
2.5*
|
0.7*
|
0.0
|
Table 2 Mean ± SD of PASI-score of psoriasis patients
|
Period
|
Mean ± SD
|
Mean change ± SD
|
p-value
|
Statistical significance
|
|
Before initiation of therapy
|
32 .7 32.76 ± 16.26
|
|
|
|
|
After 12 weeks
|
19.14 ± 11.88
|
↓13.62 ± 10.18
|
< .001
|
Highly significant
|
|
After 24 weeks
|
8.70 ± 9.86
|
↓24.06 ± 14.03
|
< .001
|
,,
|
|
After 36 weeks
|
3.51 ± 7.15
|
↓29.25 ± 14.84
|
< .001
|
,,
|
|
After 48 weeks
|
1.54 ± 4.86
|
↓31.22 ± 15.29
|
< .001
|
,,
|
Discussion
Streptococcus pyogenes (group A β haemolytic streptococcus) may
initiate several non-suppurative diseases: rheumatic fever,
glomerulonephritis, and erythema nodosum are widely known but acute
guttate psoriasis is familiar to few other than dermatologists.
Acute guttate psoriasis is strongly associated with preceding or
concurrent streptococcal infection, particularly of the throat [8].
The majority of these cases transform into refractory plaque
psoriasis [10]. As guttate psoriasis is an initial response to
streptococcal infection we presume that chronic plaque psoriasis is
a delayed manifestation.
Two pathways by which streptococcal infection lead to psoriasis
have been proposed [20]. One is tonsillar or pharyngeal infection
with group A streptococcus [7] and the other is cutaneous
colonization of bacteria. In both of these pathways, superantigenic
exotoxins that these bacteria produce stimulate pathogenetic
T-cells, thereby triggering or aggravating the skin eruption [20].
Apart from the polysaccharide antigen on which Lancefield grouping
is based, S. pyogenes possesses both T- and M-protein antigens
associated with the bacterial cell wall. Of these, M- antigens are
important in determining the virulence of the streptococci and
recently a close structural similarity has been reported between
human skin keratin and one of these antigens, namely M-6 protein
[8, 21].
Sigmundsdottir et al. [14] stated that human CD4 + T lymphocytes
(Th cells) can be functionally distinguished according to their
cytokine secretion pattern. It has been shown that Th 1 cells,
characterized by interferon gamma (IFN-γ) production, are
responsible for cell mediated immunity and inflammatory responses,
while Th 2 cells, characterized by interleukin 4 (IL-4) are
involved in the switching of Ig M to Ig E and are associated with
allergic diseases. In psoriatic lesions, the Th 1 type of cytokine
pattern has been demonstrated and accumulation of various
cytokine-releasing T cells sub-sets in psoriatic epidermis may
regulate the inflammatory process and keratinocyte hyperplasia [14,
22]. They also observed that in the majority of patients with
active psoriasis, Th 1 type responses to one or more of the M-6
peptides 145, 146, 149 and 150, which share 5-6 a.a. with human
epidermal keratins, were demonstrated and these T-cells disappeared
from the blood during clinical remission, while responses of
healthy controls and atopic dermatitis patients were low or
absent.
We suggest that psoriasis is analogous to rheumatic heart
disease with a single etiology but varied manifestations in
genetically predisposed individuals. Similarly, we propose the
pathogenesis of psoriasis be grouped into three major categories as
in rheumatic fever [23]:
- 1) Direct infection by the group A streptococcus [5-8,
10, 19];
- 2) A toxic effect of streptococcal extra-cellular
products on the host tissues [10];
- 3) An abnormal or dysfunctional immune response to one
or more as yet unidentified somatic or extra-cellular antigens
(probably super antigen) produced by all or by some of the group A
streptococci [15-17].
Bertrams et al. [24] studied the correlation of antistreptolysin
– O titre to HLA B-13 in psoriasis and suggested that the ability
of HLA B-13 negative psoriasis patients to handle streptococcal
infection might be genetically impaired as also suggested by Baker
et al. [5] that the influx of T-cells indicates the presence of
streptococcal antigens in the skin of these patients, possibly as a
result of inadequate elimination by the immune system [25]. Blok et
al. [26] demonstrated that a subgroup of psoriatics exist who are
prone to exacerbation following infections as a genetic trait
rather than a variable expression in the entire population of
psoriatics.
Immunoflurescence studies of psoriasis using monoclonal and
polyclonal antistreptococcal antibodies have been reported [27].
The published findings suggest that the streptococci product
deposition and/or the presence of antigen cross react with
streptococci in the epidermis [11].
Based on the premise that streptococci may act not only as a
triggering factor for self limiting acute guttate psoriasis, but
also as an on-going stimulus for the chronic form of the disease, a
study by Rosenberg et al. [19] deserves special mention. They
treated nine patients with streptococcal-associated psoriasis with
rifampicin-penicillin and rifampicin-erythromycin combination
therapy, to determine the effect of streptococcal eradication on
their disease. Penicillin and erythromycin were given for 10 to 14
days. Rifampicin was added to either penicillin or erythromycin
dosage schedules (600 mg daily on the final 5 days of therapy). Of
the nine patients four of whom had chronic plaque psoriasis, five
were evaluated as having an excellent response (95-100%
disappearance of lesions) and four as having a good response
(80-95% improvement), indicating that streptococcal antigens may be
involved even in persistent psoriasis. However, when Vincent et al.
[28] studied twenty patients that met the criteria of the reported
preliminary study by Rosenberg et al. [19] they concluded that
there was no apparent benefit for patients with streptococcal
associated psoriasis from a course of oral penicillin or
erythromycin with addition of rifampicin in last 5 days of 14 day
trial, as there was also no serological alteration in their
patients. However, it may be pointed out that in our trial
significant improvement in skin lesions was noted at 12 weeks of
therapy.
Considering that streptococci or its product may act as an
on-going stimulus for chronic plaque psoriasis, parenteral
benzathine penicillin was preferred for a long duration (as is
being used for rheumatic heart disease), which is further
substantiated by the significant improvement obtained only after 12
weeks of continuous treatment. The present study is open, therefore
conclusion from this report only can be preliminary, hence
controlled trials are recommended for further confirmation.
Acknowledgements
We acknowledge the work of Mr. M.C. Vyas, Statistical Assistant
Central Bureau of Health Intelligence, Jaipur who applied the
statistical test of significance in this work.
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