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The case for psoriatic arthritis as reactive arthritis and psoriasis as
reactive dermatitis to streptococci
Ilyes Benchaala, Harpreet Sagar, Frank Vasey
Over 50 years ago Scandianavian authors recognized the association between group A
streptococcal pharangitis and the drop-like psoriatic plaques known as guttate psoriasis. [1]
This was typically seen in children, occasionally in adults as well. Extending the association
to other forms of psoriasis[PS] as well as psoriatic arthritis[PSA] has been controversial and
unaccepted. The argument seems to be streptococci are so ubiquitous any evidence of
immune response to them is nonspecific. This dispite control groups in studies of normal
people, other skin diseases and other forms of arthritis all showing much less immune
pertrubation to streptococci.
In the 1970s Wright [2] and the Leeds, England group took the lead in noting psoriatic
arthritis had major familial and genetic tendencies. They took the environment into
consideration in suggesting the Koebner phenomenin applied to the joints as well as the skin.
They argued psoriatic arthritis fit into the spondyloarthritis family of conditions. There was a
similar pauciarticular peripheral arthritis, similar spinal involvement, similar lack of
rheumatoid factor and increasingly similar genetic underpinnings such as B 27. The other
spondyloarthropathies include at a minimum ankylosing spondylitis, reactive arthritis to
Chlamydia and enteric food poisoning organisms, and inflammatory bowel disease arthritis .
All these important observations have stood the test of time.
However the “unified concept” was not extended to the bacterial pathogenisis of all forms of
spondyloarthritis. This dispite the near clinical identity of psoriatic arthritis to reactive
arthritis regardless of whether it is acquired sexually or enterically. This similarity extended
beyond the joints to the skin in that keratodermia blenorrhagicum of the palms and soles was
identical even histolologically to pustular psoriasis.
If you accept that psoriasis and psoriatic arthritis should have a bacterial basis on clinical
grounds, the evidence overwhelmingly favors streptococci. Both humoral and cellular
immunity involving PS/PSA and streptococci have been enhanced. Antibodies measured to
anti-streptolysin-O [3], the exotoxin Dnase B[ 4,5], streptococcal cell walls[6,7],and
peptidoglycan[7] have all been statistically elevated in controlled studies. Peptidoglycan is a
major component of gram positive bacterial cell walls. Baker [8] showed that biopsy of
psoriatic plaque and guttate skin lesions stained for GAS anti Peptidoglycan. Most of cells
stained were macrophages. Interestingly, T cells isolated from gluttate and plaque lesions
were stimulated by GAS Peptidoglycan. They displayed a restricted HLA DR isotype
suggesting an antigen specific response.
Streptococcal M protien[9,10] and other superantigens [11]have also been proposed as the
antigenic stimulus.
Altered cellular immunity to streptoc occi in PS/PSA has been well documented. Enhanced
lymphocyte activation has been measured increasingly in T lymphocytes [12,13,14,15].
Some have argued there is a lack of specificity in the response [16]. But upregulation of toll-
like receptor-2 in psoriatic mononuclear cells further supports a role for gram positive
bacteria in the pathogenesis of PS/PSA.[17].
Not only are streptococci gaining favor in PS/PSA at least among dermatologists,, bacteria
are increasingly implicated in the pathogenesis of inflammatory bowel diseaseand its
arthritis. A detailed discussion is beyond the scope here, but enterococci [formerly group D
streptococci] and adhesive ,invasive E Coli have been proposed. These observations are
Revista Latinoamericana de Psoriasis y Artritis Psoriásica 2010, 1: 76-78
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77
likely relevant in view of the 10-20 fold increase in the prevalance of psoriasis in
inflammatory bowel disease patients. The colonoscopy finding of patchy inflammation in the
wall of the colon in both PS/PSA and ankylosing spondylitis patients makes bowel bacteria
contenders for a role in both of these conditions.
Biologic plausibility for a role in PSA for streptococci is evidenced by studies of experimental
arthritis utilizing live streptococci, dead cell walls and even peptidoglycan-polysaccaride
conjugants.
Cromartie [18] showed that sonicated Group A Streptococcus (GAS) induce arthritis in rat
model. Synovial tissues were positively stained for C-carbohydrate antigen inside
monocytes.
Hammer [19] showed that transgenic HLA B27 rats developed psoriasis and arthritis in a
conventional environment but failed to develop skin lesions, bowel inflammation and arthritis
in sterile environment by Sartor [20].
If bacteria are causing PS/PSA and the other spondyloarthropathies it begs a question about
the use of antibiotics. We believe the recent work by Carter [21] on post chlamydial reactive
arthritis represents a major breakthrough. 42 patients with PCR proven CT infection in blood
or synovium and spondyloarthritis were randomized into three groups and treated for 6
months. Group 1 received doxycycline 100 mg BID with Rifampin 300mg BID. Group 2
received Azithromax 500mg twice a week after a loading dose of four tablets the first week
with rifampin 300mg BID. Group 3 received placebo. The regimins were generally well
tolerated. Because of the small numbers both antibiotic groups were a piori combined in
comparison to the placebo group. They were statistically different. [P < .05} with the
antibiotic group more improved. Perhaps even more importantly patients with an average 10
years of inflammatory arthritis the Azithromycin/rifampin group had 6 of 14 patients cured.
Cure defined rigourously as assymptomatic at 6 mos and still so at 9 months [ off antibiotics
for 3 months].
The issue of the mechanism underlying the chronic arthritis has been the subject of debate.
Were live organisms in the patient’s body/joints/immune system suggesting antibiotics might
work? Were dead organisms persisting somewhere or were the organisms entirely gone
both suggesting antibiotics would not work. Dr Carter’s study supports the fact at least in the
post chlamydial reactive arthritis patients he treated the orgasnisms were alive for 10 years.
Revista Latinoamericana de Psoriasis y Artritis Psoriásica 2010, 1: 76-78
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