中 西醫 combined conference 2012.02.08

1. 報告者：fellow 1 陳筱惠 指導醫師：方基存教授 中西醫combined conference2012.02.08

2. Most patients with SLE need long-term treatment with glucocorticoids and immunomodulators to control disease activity. • Prolonged complete remission in lupus is rare. • Side effects of current treatment: • Steroid: central obesity, moon face, buffalo hump, wasting of th extremities, osteoporosis, avascular necrosis of bone, and infection.

3. Antimalarial drugs: macular damage and myopathy • Azathioprine: myelosuppression, hepatotoxicity, and lymphoproliferative disorders • Cyclophosphamide: immunosuppression, infertility, and bladder cancer

4. Complementary and alternative therapies (CATs): • Diets and vitamins • Herbal medicines • Acupuncture • Chiropractice • Folk medicine • Massage • Spiritual healing Lupus (2010) 19, 1425–1429.

5. Nutrients and vitamins Journal of Renal Nutrition, Vol 10, No 4 (October), 2000: pp 170-183

6. Dehydroepiandrosterone (DHEA) • Cholesterol-pregnenolone pathway, an intermediate to androstenediol and androstenedione • SLE: predominantly female-based disease, high levels of estrogen metabolites and inactivation of already low levels of testosterone • DHEA levels are also low in the serum of SLE patients. Alternative Medicine Review; Volume 6, Number 5 2001

7. Immunoregulatory effects: • Enhance IL-2 production and the subsequent proliferation of T-helper 1 cells • An decrease in anti-DNA antibodies in mouse models • Shift toward T-helper 1 dominance results in a decrease in pro-inflammatory cytokines.

8. Antiresorptive effect that may counteract bone damage caused by corticosteroids • A double-blind, placebo-controlled, clinical trial of dehydroepiandrosterone in severe systemic lupus erythematosus. Lupus 1999;8:181-187. • Bone mineral density levels were also found to have a direct correlation to DHEA levels. • The association of dehydroepiandrosterone sulphate levels with bone mineral density in systemic lupus erythematosus. Clin Exp Rheumatol 1997;15:387-392.

9. A reduction in prednisone dosage, a lower occurrence of flare-ups, and a decrease in activity of the disease • Dehydroepiandrosterone in systemic lupus erythematosus. Results of a double-blind, placebo-controlled, randomized clinical trial. Arthritis Rheum 1995;38:1826-1831 • Treatment of systemic lupus erythematosus with dehydroepiandrosterone: 50 patients treated up to 12 months. J Rheumatol 1998;25:285-289 • Side effects: acne and mild hirsutism

10. Essential fatty acids: Omega-3 fish oil • Inhibit the abnormal autoimmune activity of the B- and T-Lymphocytes and abnormal interleukin expression. • The mice were injected with sheep cells that induced an overactive immune response, the formation of plaque-forming cells, abnormal IL-1 and IL-2 activity, proteinuria, and subsequent death. • Mice fed a diet containing fish oil had lower levels of proteinuria, decreased abnormal cytokine and interleukin activity, and better survival rates than mice fed corn oil diets. • Effect of fish oil diet on immune response and proteinuria in mice. Proc Natl Sci Counc Repub China B 1991;15:105-110.

11. Suppress macrophage activity and the production of cyclooxygenase metabolites that contribute to renal damage in a mouse lupus model. • A fish oil diet rich in eicosapentaenoic acid reduces cyclooxygenase metabolites, and suppresses lupus in MRL-lpr mice. J Immunol 1985;134:1914-1919.

12. Decrease in arachidonic acid and its resultant inflammation • HDL levels were raised, while triglyceride and VLDL levels were lowered. LDL levels were not altered significantly.  the potential to make an impact in controlling atherosclerotic plaquing • Omega-3 fatty acid dietary supplementation in systemic lupus erythematosus. Kidney Int 1989;36:653-660.

13. Flaxseed oil: 70% omega-3 fatty acids • Mice fed diets supplemented with flaxseed oil had reductions in anti-cardiolipin and anti-DNA antibodies. • Effective in lupus patients with nephritis • Serum 1evels of creatinine were reduced and creatinine clearance rates were improved. • 30 g/day seemed to be the most beneficial dosage. • Flaxseed: a potential treatment for lupus nephritis. Kidney Int 1995;48:475-480. • Inhibit platelet aggregation and delay proteinuria • Abrogation of MRL/lpr lupus nephritis by dietary flaxseed. Am J Kidney Dis 1993;22:326-332.

14. Vitamins D • Decreased vitamin D levels may be linked to the lack of sunlight exposure in most SLE patients due to their increased photosensitivity. • Immunoregulatory function: inhibit lymphocyte activation and cytokine release

15. Vitamin A • May enhance antibody- dependent cell-mediated cytotoxicity, natural killer cell activity, and IL-2 response • Antioxidants: vitamin C, b-carotene, and selenium • May decrease the anti-DNA antibody titers and lymphoproliferation in mice

16. The long-term effects of dietary and vitamins therapy in humans with SLE have not been determined as yet, and require elucidation through further study.

17. Chinese medicine • TCM as immunosuppressive agents. • Demethylzelasteral (TZ-93), a triterpenoid isolated from the root cortex of TWHf, the plant alkaloid berbamine, and the hydrophobic extract of a Chinese herbal decoction, CMX-13 • Prolong allograft survival in experimental animal models of heart, skin and single lung transplants • Zemaphyte: a decoction of 10 herbs • Atopic dermatitis in both children and adults Ann Acad Med Singapore 2000; 29:11-6

18. The “thunder god” vine, Tripterygium wilfordii Hook F (TWHf) • Active component, but toxicity origin: triptolide • Pharmacokinetics in animal model: • Rats, Cmax 10mins, half life 15-20mins • Oral bioavailability: 72.08%。

19. Inhibit mitogen-stimulated lymphoproliferation • Inhibit production of proinflammatory cytokines by monocytes and lymphocytes, as well as prostaglandin E2 production via the cyclooxygenase, COX-2 – by its active derivatives • Prednisone requirements were reduced by 50 percent by subjects taking TwHF. • The effects of traditional antirheumatic herbal medicines on immune response cells. J Rheumatol 1997;24:436-441.

20. Side effect: stomach upset, diarrhea, skin rash, change in skin pigmentation, infertility in men and amenorrhea in woman

21. Cordyceps Sinesis: • Effective in reducing anti-DNA titers and prolonging the life span of lupus mice • Lingzhi: • Prevent autoantibody formation and prolong survival in NZB/NZW F1 mice • Antioxidant effect: ginkgo, garlic • Anti-platelet effect: garlic, bilbery, Dongquai, ginseng, turmeric, meadowsweet

22. Since SLE is a heterogeneous disease involving a variety of organs, different herbal remedies may be required for the relief of symptoms arising from different organs.

23. Dan-Chi-Liu-Wei combination (DCLWC) with conventional therapy in SLE patients • Double-blind and randomized controlled trial, 66 SLE patients: • SLE disease activity index (SLEDAI) score of 2-12 • Steroid (measured with prednisolone) daily dose < 20 mg/d • SLEDAI score (urine analysis, hemogram, liver/renal function, C3, C4, ESR, and anti-dsDNA) and steroid dose at 0, 3, 6 months

24. After 6 months of study, the C4 and blood urea nitrogen level revealed a statistically significant difference in either group. • There was a tendency toward a decreased SLEDAI score in the experimental group (p=0.083) but not in the control group (p=0.867) • The steroid dose was not statistically significant in either group. • Renal function and liver function revealed no statistically significant statistics changes in either group.

25. Few well-designed randomised placebocontrolled clinical trials demonstrating the efficacy of TCM • Toxicity: nephrotoxic • Dosing • drug interactions between herbs and Western medicines

26. Acupuncture • Pain management: • Acupuncture for systemic lupus erythematosus: a pilot RCT feasibility and safety study. Lupus 2008; 17: 1108–1116. • 24 SLE patients • After 6 weeks of treatment, 40% of patients who received acupuncture had 30% improvement on standard measures of pain. • No serious side effects or adverse events were found.

27. Conclusion • Chinese herbs or other treatments are encouraged at the stage when SLE disease activity is lower or stable in renal manifestations. • Herb remedies may be added to replace Western medicine or to reduce the steroid dosage. • However, herbal therapy or CATs may not be safe in patients with rheumatic or immune disease and close monitoring is still indicated.

28. Thanks for your listening