報告者： fellow 1 陳筱惠 指導醫師：方基存教授

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.

Antimalarial drugs: macular damage and myopathy

Azathioprine: myelosuppression, hepatotoxicity, and lymphoproliferative disorders

Cyclophosphamide: immunosuppression, infertility, and bladder cancer

Complementary and alternative therapies (CATs): Diets and vitamins Herbal medicines Acupuncture Chiropractice Folk medicine Massage Spiritual healing

Lupus (2010) 19, 1425–1429.

Journal of Renal Nutrition, Vol 10, No 4 (October), 2000: pp 170-183

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

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.

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.

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

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.

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.

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.

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.

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

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

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.

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 adultsAnn Acad Med Singapore 2000;

29:11-6

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% 。

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.

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

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

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.

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

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.

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

Western medicines

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.

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.