Psoriasis Awareness Month: focus on psoriasis arthritis – Dr Nina Bailey

Psoriasis is an immune-mediated, chronic, inflammatory disease affecting about 80 million people worldwide. It is not life threatening, but those with psoriasis may have a higher incidence of diabetes, psoriatic arthritis, heart disease, and depression.  According to Arthritis Research UK, the prevalence of psoriasis in this country is about 2%, and of those individuals, the prevalence of psoriatic arthritis is about 14%.

Psoriatic arthritis usually affects adults, but occasionally children can develop the disease. Psoriatic arthritis is a hyperproliferative and inflammatory arthritis that involves both the skin and joints, resulting in significant quality of life impairment, joint deformity and psychosocial disability.

Psoriatic arthritis is distinct from rheumatoid arthritis (RA) and is closely associated with psoriasis. Patients generally test negative for RA factor (an antibody produced by plasma cells and found in around 70% of cases of RA). The condition differs from RA in that the pattern of joint involvement is commonly asymmetric, and involves the joints at the very tip of the fingers and toes, often with corresponding nail lesions. In psoriatic arthritis, affected joints are tighter, contain less fluid and are less tender than those in RA. The inflammatory process is similar in the skin and joints, with treatments comprising of a combination of oral and topical anti-inflammatory drugs, as well as disease-modifying drugs.   Individuals, beyond the physical symptoms associated with the condition, often have to endure the stigma that is the consequence of a general misunderstanding by the public.

Numerous cytokines are believed to play an important role in triggering cell proliferation and sustaining joint inflammation in psoriatic arthritis. Cytokines are small proteins that are secreted by specific cells of the immune system, stimulating specific inflammatory processes that result in the migration and activation of further immune cells called ‘T cells’.  T cells can be divided according to the cytokines they produce. Th1 cells mainly secrete cytokines that support cellular immunity against diseases caused by viruses and bacteria.  In contrast, Th2 cells produce (primarily) cytokines that are responsible for stimulating the production of other immune cells, called ‘B cells’, that are involved in the production of antibodies.   It is the imbalance between the Th1 and Th2 subtypes that is thought to lead to the development of different autoimmune disorders, and that Th1 cells play a direct role in the development of psoriatic arthritis.  Tumour necrosis factor (TNFα) is one of several pro-inflammatory cytokines produced by Th1 cells that has been implicated in the development of both psoriasis and psoriatic arthritis. Newer strategies for the treatment of psoriatic arthritis have therefore focused on modifying Th1 cells in this disease, either by inhibiting cytokine secretion or activity, inhibiting Th1 cell activation, or by directly eliminating any activated Th1 cells.

It is becoming increasingly clear that whilst inflammation can be modified by pharmaceutical means, inflammation can also be directly influenced by dietary modifications.   The type of fat, or fatty acid, in the diet can modulate T cell proliferation and therefore the production of cytokines by specific T cells. The fatty acEmail%3Aid composition of T cells, and other immune cells, is altered according to the fatty acid composition of the diet, and this alters the capacity of those cells to produce a variety of immune and inflammatory modulating products.  A high fat diet can impair T cell function; cell culture and animal feeding studies certainly indicate that very specific fatty acids influence T cell proliferation and the production of cytokines very differently.   Among these fatty acids, the long chain omega-3 fatty acids, especially eicosapentaenoic acid (EPA), appear to be the most potent when included in the diet, and it appears that fish oil, which contains EPA, down-regulates the Th1-type response which is associated with chronic inflammatory disease.   However, very high intakes of fatty acids are necessary to induce these effects.

Th1-type cytokines are more sensitive to the effects of fatty acids than Th2-type cytokines, and the long-chain omega-3 fatty acids, EPA in particular, appear to be the most potent fatty acids in this regard. The effect of EPA on cytokine production appears to be exerted through effects on cytokine gene expression.  Interestingly, the ability of omega-3 fatty acids to shift away from a Th1-type response has been suggested as a primary factor in explaining the low incidence of inflammatory and autoimmune disorders among Greenland Eskimos, in which fish rich in EPA comprises a staple part of their diet.

Calder PCYaqoob PThies FWallace FAMiles EA. (2002) Fatty acids and lymphocyte functions. Br J Nutr. 2002 87:S31-48.

Wallace FAMiles EAEvans CStock TEYaqoob PCalder PC. (2001) Dietary fatty acids influence the production of Th1- but not Th2-type cytokines.  J Leukoc Biol. 69:449-57.

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