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From the Townsend Letter
December 2014

Not Skin Deep: Psoriatic Arthritis and the Complications of Systemic Inflammation Seen with Psoriasis
by Sara Wood, ND
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Another primary anti-inflammatory herb is curcumin, an extract from turmeric. Unlike nettles and boswellia, this herb doesn't appear to affect TNF-a levels; however, it inhibits PGE2 production at sites of inflammation and suppresses IL-1, which not only decreases joint inflammation in PsA, but also blocks osteoclasts and decreases bone destruction, a problematic and typically irreversible effect of the disease.37
   
Because of the close connection between stressful events and flare-ups or worsening of symptoms with both psoriasis and psoriatic arthritis, management and modulation of the stress response is often an important part of a comprehensive treatment plan. As mentioned, PsA patients have been shown to have a blunted HPA response to stress.38 One of the primary physiologic roles of cortisol is to aid in the control or blunting of an immune response. When cortisol levels are elevated, or when pharmaceutical glucocorticoids are employed, suppression of the immune system is seen. Conversely, when the HPA axis is dampened and cortisol output is diminished, the immune system has lost one of its gatekeepers and autoimmune disease is common. Herbs that fall into the general category of adaptogens include (but are not limited to) Rhodiola rosea, Schisandra chinensis, Eleutherococcus senticosus, and Glycyrrhiza glabra (licorice root). These therapies aid in the production of cortisol and with patients' ability to cope with life-stress symptoms.39,40 Additional considerations for supporting a healthy stress response are B vitamins, specifically pantothenic acid (B5) to support normal adrenal cortex function and pyridoxine (B6) to modulate a healthy stress response.41,42 Voluntary, slow deep breathing acts to reset the autonomic nervous system and calm a stress response and should be an important part of any stress management system.43
   
Not only can the inflammatory processes lead to psoriatic arthritis and irrevocably damage the joints, there is also a significantly increased risk of cardiovascular disease and metabolic syndrome in psoriasis patients due to the active inflammatory activity. A recent meta-analysis concluded that psoriasis is associated with an estimated 11,500 major adverse cardiovascular events each year.44 Because inflammation often goes on "behind the scenes" until irreversible damage has occurred, regular screening for cardiovascular and articular changes is needed in patients with psoriasis as well as those with a family history of psoriasis. Treatment should always include efforts to limit systemic inflammation, and there are many alternative therapies and lifestyle modifications that can be used in lieu of or in addition to pharmaceutical management of these conditions. The National Psoriasis Foundation reports that patient satisfaction with their current treatment is under 50% and natural therapies are among their top searched for terms, indicating that there is significant need for an integrative treatment approach. It's important that neither patients nor physicians ignore the underlying immune dysfunction that occurs with psoriasis. As with many degenerative conditions, preventative measures and early intervention are key to successful outcomes. It turns out that psoriasis, like beauty, is not skin deep.

Figure 2: Examples of common conventional and alternative therapies and their mechanisms for treating psoriatic arthritis and systemic inflammation. (pdf)

Notes
1.      Taylor W, Gladman D, Helliwell P, et al. Classification criteria for psoriatic arthritis: development of new criteria from a large international study. Arthritis Rheum. 2006;54(8):2665–2673.
2.      Helliwell PS, Wright V. PsA: clinical features. In: Klippel JH, Dieppe PA, eds. Rheumatology. London: Mosby; 1998:6.21.1–6.21.8.
3.      Vandooren B, Noordenbos T, Ambarus C, et al. Absence of a classically activated macrophage cytokine signature in peripheral spondylarthritis, including psoriatic arthritis. Arthritis Rheum. 2009;60(4):966–975.
4.      Veale DJ, Ritchlin C, FitzGerald O. Immunopathology of psoriasis and psoriatic arthritis. Ann Rheum Dis. 2005;64(Suppl II):ii26–ii29.
5.      Ritchlin C, Haas-Smith SA, Hicks D, et al. Patterns of cytokine production in psoriatic synovium. J Rheumatol. 1998;25(8): 1544–1552.
6.      Menter A, Gottlieb A, Feldman SR, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis: Section 1. Overview of psoriasis and guidelines of care for the treatment of psoriasis with biologics. J Am Acad Dermatol. 2008;58(5):826–850.
7.      Ibid.
8.      Haribhai D, Williams JB, Williams CB. A requisite role for induced regulatory T cells in tolerance based on expanding antigen receptor diversity. Immunity. 2011;35(1): 109–122.
9.      Nash P, Clegg DO. Psoriatic arthritis therapy: NSAIDs and traditional DMARDs. Ann Rheum Dis. 2005;64(Suppl):ii74–ii77.
10.    Ibid.
11.    Schett G, Sloan VS, Schafer P. Apremilast: A novel PDE4 inhibitor in the treatment of autoimmune and inflammatory diseases. Ther Adv Musculoskelet Dis. 2010;2(5): 271–278.
12.    Leavitt M. New oral drug for psoriasis inches closer to the market [online article]. National Psoriasis Foundation. http://www.psoriasis.org/advance/new-oral-drug-for-psoriasis-inches-closer-to-the-market. Accessed Aug 30, 2014.
13.    Rahman P, Elder JT. Genetic epidemiology of psoriasis and psoriatic arthritis. .Ann Rheum Dis. 2005;64:ii37–ii39.
14.    Gladman DD, Anhorn KAB, Schachter RK, Mervart H. HLA antigens in psoriatic arthritis. J Rheumatol. 1986;13:586–592.
15.    Eastmond CJ. Genetics and HLA antigens. In: Wright V, Helliwell P, eds. In: Baillière's Clinical Rheumatology. Psoriatic Arthritis. London: Ballière Tindall; 1994;8:263–276.
16.    Heller MM, Lee ES, Koo, JY. Stress as an influencing factor in psoriasis. Skin Therapy Letter. 2011;16(5).
17.    Richards HL, Ray DW, Kirby B, et al. Response of the hypothalamic-pituitary-adrenal axis to psychological stress in patients with psoriasis. Br J Dermatol. 2005 Dec;153(6):1114–1120.
18.    Olivieri I, Padula A, D'Angelo S, Scarpa R. Role of trauma in psoriatic arthritis. J Rheumatol. 2008;35;2085–2087.
19.    Bruce IN, Silman AJ. The aetiology of psoriatic arthritis. Rheumatology. 2001;40(4): 363–366.
20.    Lee YK, Mazmanian SK. Has the microbiota played a critical role in the evolution of the adaptive immune system? Science. Dec. 24, 2010;330(6012)1768–1773.
21.    Gorbach SL. Chapter 95: Microbiology of the gastrointestinal tract. In: Baron S, ed. Medical Microbiology. 4th ed. Galveston, TX: University of Texas Medical Branch at Galveston; 1996.
22.    O'Mahony C et al. Commensal-induced regulatory T cells mediate protection against pathogen-stimulated NF-kappaB activation. PLoS Pathog. 2008;4:e1000112.
23.    Mazmanian SK, Liu CH, Tzianabos AO, Kasper DL. An immunomodulatory molecule of symbiotic bacteria directs maturation of the host immune system. Cell. 2005;122:107–118.
24     S. Hooda BMV, Boler MCR, Serao JM, et al. 454 Pyrosequencing reveals a shift in fecal microbiota of healthy adult men consuming polydextrose or soluble corn fiber. J Nutr. 2012;142(7):1259.
25.    Panush RS, Stroud RM, Webster EM. Food-induced (allergic) arthritis. Inflammatory arthritis exacerbated by milk. Arthritis Rheum. 1986;29(2):220–226.
26.    Lindqvist U, Rudsander A, Bostrom A, et al. IgA antibodies to gliadin and coeliac disease in psoriatic arthritis. Rheumatology. 2002;41(1):31–37.
27.    Fitzgerald K, Hyman M, Swift K. Psoriatic arthritis. Glob Adv Health Med. 2012;1(4):54–61.
28.    Gil A. Polyunsaturated fatty acids and inflammatory diseases. Biomed Pharmacother. 2002;56(8):388–396.
29.    Mori TA, Beilin LJ. Omega-3 fatty acids and inflammation. Curr Atheroscler Rep. 2004;6(6):461–467.
30.    Gregori S, Casorati M, Amuchastegui S, et al. Regulatory T cells induced by 1 alpha,25-dihydroxyvitamin D3 and mycophenolate mofetil treatment mediate transplantation tolerance. J Immunol. 2001;167:1945.
31.    Hewison M. Vitamin D and the immune system: new perspectives on an old theme. Endocrinol Metab Clin North Am. 2010;39(2):365–379.
32.    Touma Z, Eder L, Zisman D. Seasonal variation in vitamin D levels in psoriatic arthritis patients from different latitudes and its association with clinical outcomes. Arthritis Care Res (Hoboken). 2011;63(10):1440–1447.
33.    Riehemann K et al. Plant extracts from stinging nettle (Urtica dioica), an antirheumatic remedy, inhibit the proinflammatory transcription factor NF-kappaB. FEBS Lett. 1999;8:442(1):89–94.
34.    Chrubasik S et al. Evidence for antirheumatic effectiveness of Herba Urticae in acute arthritis: a pilot study. Phytomedicine. 1997;4:105–108.
35.    Gayathri B, Manjula N, Vinaykumar KS, Lakshmi BS, Balakrishnan A. Pure compound from Boswellia serrata extract exhibits antiinflammatory property in human PBMCs and mouse macrophages through inhibition of TNF alpha, IL-1beta, NO and MAP kinases. Int Immunopharmacol. 2007;7:473–482.
36.    Siddiqui MZ. Boswellia Serrata, A potential antiinflammatory agent: An overview. Ind J Pharm Sci. 2011;73(3):255–261.
37.    Funk JL, Frye JB, Oyarzo JN, et al. Efficacy and mechanism of action of turmeric supplements in the treatment of experimental arthritis. Arthritis Rheum. 2006;54(11):3452–464.
38.    Heller et al. Op cit.
39.    Al-Dujaili EA, Kenyon CJ, Nicol MR, Mason JI. Liquorice and glycyrrhetinic acid increase DHEA and deoxycorticosterone levels in vivo and in vitro by inhibiting adrenal SULT2A1 activity. Mol Cell Endrocrinol. 2011;336(1–2):102–109.
40.    Edwards D, Heufelder A, Zimmermann A. Therapeutic effects and safety of Rhodiola rosea extract WS® 1375 in subjects with life-stress symptoms–results of an open-label study. Phytother Res. 2012;26(8):1220–1225.
41.    Jaroenporn S, Yamamoto T, Itabashi A. Effects of pantothenic acid supplementation on adrenal steroid secretion from male rats. Biol Pharm Bull. 2008;31(6):1205–1208.
42.    Gaby AR. Vitamin B6. In: Nutritional Medicine. Concord, NH: Fritz Perlberg Publishing; 2011:80–87.
43.    Jerath R, Edry JW, Barnes VA, Jerath V. Physiology of long pranayamic breathing: neural respiratory elements may provide a mechanism that explains how slow deep breathing shifts the autonomic nervous system. Med Hypotheses. 2006;67(3):566–571.
44.    Armstrong EJ, Harskamp CT, Armstrong AW. Psoriasis and major adverse cardiovascular events: A systematic review and meta-analysis of observational studies. J Am Heart Assoc. 2013;2:e000062

Sara Wood, NDDr. Wood grew up in Colorado and obtained her undergraduate degree in biochemistry from Colorado College. An enthusiasm for science but a passion for people led her to medicine, and a desire to treat the cause of disease, not just the symptoms, led her to naturopathy. After completing her doctorate at the National College of Naturopathic Medicine, Dr. Wood stayed in Oregon and has a private practice focused on endocrine imbalance, digestive dysfunction, immune support, and cardiovascular health.
In addition to her clinical practice, Dr. Wood is a staff physician with Labrix Clinical Services Inc., where she educates physicians and health care providers around the country about hormonal balancing through development of educational materials, contributions to a webinar series, and lectures at local and national conferences. In 2008 she coauthored a book on andropause titled His Change of Life: Male Menopause and Healthy Aging with Testosterone.

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