The association of sore throat and psoriasis might be explained by histologically distinctive tonsils and increased expression of skin-homing molecules by tonsil T cells.

Recent studies have highlighted the involvement of the palatine tonsils in the pathogenesis of psoriasis, particularly among patients with recurrent throat infections. However, the underlying immunological mechanism is not well understood. In this study we confirm that psoriasis tonsils are infected more frequently by ß-haemolytic Streptococci, in particular Group C Streptococcus, compared with recurrently infected tonsils from patients without skin disease. Moreover, we show that tonsils from psoriasis patients contained smaller lymphoid follicles that occupied a smaller tissue area, had a lower germinal centre to marginal zone area ratio and contained fewer tingible body macrophages per unit area compared with recurrently infected tonsils from individuals without skin disease. Psoriasis patients' tonsils had a higher frequency of skin-homing [cutaneous lymphocyte-associated antigen (CLA(+) )] CD4(+) and CD8(+) T cells, and this correlated significantly with their frequency of blood CLA(+) T cells. The psoriasis patients also had a higher frequency of tonsil T cells expressing the interleukin (IL)-23 receptor that was expressed preferentially by the CLA(+) T cell population. In contrast, recurrently infected tonsils of individuals without skin disease had a higher frequency of tonsil T cells expressing the activation marker CD69 and a number of chemokine receptors with unknown relevance to psoriasis. These findings suggest that immune responses in the palatine tonsils of psoriasis patients are dysregulated. The elevated expression of CLA and IL-23 receptor by tonsil T cells may promote the egression of effector T cells from tonsils to the epidermis, suggesting that there may be functional changes within the tonsils, which promote triggering or exacerbation of psoriasis.

The role of the palatine tonsils in the pathogenesis and treatment of psoriasis.

Psoriasis is a common chronic skin disease with strong genetic associations and environmental triggers. Patients with psoriasis develop sore throats much more frequently than nonpsoriatic individuals and it is well documented that streptococcal throat infections can trigger the onset of psoriasis, and such infections cause exacerbation of chronic psoriasis. It is now generally accepted that psoriatic lesions are caused by abnormal reactivity of specific T lymphocytes in the skin. However, it has been shown in recent years that activation of specific immunity is always preceded by activation of nonspecific innate immune mechanisms, and that abnormalities in the innate immune system can cause dysregulation in specific immune responses. Here we explore the possible immune mechanisms that are involved in the link between infection of the tonsils and this inflammatory skin disease. Moreover, we survey the literature and discuss the suitability of tonsillectomy as a treatment for psoriasis.

Do non-steroidal anti-inflammatory drugs influence chronic inflammation? The effects of piroxicam on chronic antigen-induced arthritis in rats.

OBJECTIVE: The effects of non-steroidal anti-inflammatory drugs (NSAIDs) on acute inflammation have been thoroughly investigated. NSAIDs are, however, also prescribed for patients with chronic inflammation, such as rheumatoid arthritis (RA), and objective improvement suggestive of anti-inflammatory action from NSAIDs has not been convincingly shown in chronic RA. An antigen-induced arthritis (AIA) model was used to investigate the effects of piroxicam on chronic inflammation. METHODS: AIA was induced by injecting methylated bovine serum albumin (mBSA) into the knee joints of previously immunized rats that were treated orally with the NSAID piroxicam or with saline. This treatment was started either before AIA was induced or after it had reached a chronic phase. The findings were recorded by clinical and histological assessment of the joints. RESULTS: The piroxicam group developed significantly less acute and subsequent chronic knee joint inflammation but this was only evident if the drug was administered prior to the intra-articular mBSA injections. Piroxicam treatment that was initiated during the chronic inflammation did not have any clinical effect, whereas short-term corticosteroid treatment abolished the chronic inflammation. Moreover, histological analysis of the chronic inflammation revealed significantly more inflammatory changes in the piroxicam group compared with the control group. CONCLUSIONS: Piroxicam treatment had no beneficial effects on the chronic stable inflammation in this model and might even delay histological resolution. As the anti-inflammatory effect of piroxicam is restricted to acute inflammation, the use of NSAIDs during periods of chronic stable arthritis in humans, such as in RA, may need to be investigated.

The effects of tobacco smoking and rheumatoid factor seropositivity on disease activity and joint damage in early rheumatoid arthritis.

OBJECTIVE: To study the effect of tobacco smoking and rheumatoid factor (RF) isotypes on disease activity and joint damage in early rheumatoid arthritis (RA). METHODS: One hundred early RA patients were followed prospectively for 2 yr. They were evaluated at recruitment and at 6 and 24 months. Sociodemographic information included smoking history, and radiographs of hands and feet were obtained. RF was monitored by IgM- and IgA-specific RF enzyme-linked immunosorbent assay and by agglutination, and serial measurements were also obtained for C-reactive protein. The influence of tobacco smoking and RF positivity on disease outcome was evaluated using multivariate analysis. Covariates for the regression analysis included sex, age, coffee consumption and IgA-RF positivity. RESULTS: A gradient of increase in disease activity was observed from never smokers to former smokers to current smokers during the 2 yr of observation, defined by number of swollen joints (SJC), tender joints (TJC) and visual analogue scale for pain (P<0.001, P=0.02 and P=0.005, respectively), but smoking status did not influence radiological progression. Ever smokers were more often IgA RF positive (P<0.05). IgA RF-positive patients had more active disease (SJC P=0.002, TJC P=0.01) and showed more radiological progression (P<0.0001) compared with IgA RF-negative patients. Of the RF-positive patients 22% had elevated IgM RF without IgA RF and these patients showed similar disease activity and radiological joint progression to the RF-negative patients. None of these associations were explained by possible confounders. CONCLUSION: Tobacco smoking has an adverse effect on patients with early RA and this is possibly immunologically mediated. IgM RF does not predict poorer prognosis in RA unless it is associated with a concomitant elevation of IgA RF.

Increased frequency of C4B*Q0 alleles in patients with Henoch-Schönlein purpura.

Henoch-Schonlein purpura (HSP) is a vasculitis of unknown aetiology, possibly involving immune complexes. The complement system is essential for the clearance of immune complexes. Our aim was to explore the hypothesis that patients with HSP have abnormal complements, contributing to the development of the disease. The study included 56 patients diagnosed with HSP at the Children's Hospital, Iceland between 1984 and 2000, and 98 blood donors as controls. Serum levels of immunoglobulin A, C4A, C4B and mannan-binding lectin were measured and compared between the two groups. C4 null alleles were significantly more common in HSP patients than in controls (P = 0.018) and were carried by 66.1% of the patients compared with 41.2% of the controls. This difference was due to an increased frequency of C4B*Q0 allele in the HSP group (0.25 versus 0.11 in the control group; P = 0.002). The fact that the majority of our patients carried a C4 null allele indicates that children with C4 deficiencies may have an increased risk of developing HSP. This may reflect inadequate complement activity and possibly present an opportunity to identify patients at risk of developing serious morbidity associated with HSP.