Transcript 投影片 1

報告者：fellow 1 陳筱惠
指導醫師：方基存教授
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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
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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
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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
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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.
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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.
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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.
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A reduction in prednisone dosage, a lower
occurrence of flare-ups, and a decrease in
activity of the disease
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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
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Essential fatty acids: Omega-3 fish oil
Inhibit the abnormal autoimmune activity of the Band T-Lymphocytes and abnormal interleukin
expression.
 The mice were injected with sheep cells that induced an
overactive immune response, the formation of plaqueforming 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.
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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.
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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
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 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.
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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
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Vitamin A
 May enhance antibody- dependent cell-mediated
cytotoxicity, natural killer cell activity, and IL-2
response
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Antioxidants: vitamin C, b-carotene, and
selenium
 May decrease the anti-DNA antibody titers and
lymphoproliferation in mice
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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.
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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
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The “thunder god” vine, Tripterygium wilfordii Hook
F (TWHf)
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Active component, but toxicity origin: triptolide
 Pharmacokinetics in animal model:
▪ Rats, Cmax 10mins, half life 15-20mins
▪ Oral bioavailability: 72.08%。
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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.
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Side effect: stomach upset, diarrhea, skin
rash, change in skin pigmentation, infertility
in men and amenorrhea in woman
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Cordyceps Sinesis:
 Effective in reducing anti-DNA titers and
prolonging the life span of lupus mice
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Lingzhi:
 Prevent autoantibody formation and prolong
survival in NZB/NZW F1 mice
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Antioxidant effect: ginkgo, garlic
Anti-platelet effect: garlic, bilbery, Dongquai,
ginseng, turmeric, meadowsweet
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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.
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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
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SLEDAI score (urine analysis, hemogram,
liver/renal function, C3, C4, ESR, and antidsDNA) 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.
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Few well-designed randomised
placebocontrolled clinical trials
demonstrating the efficacy of TCM
 Toxicity: nephrotoxic
 Dosing
 drug interactions between herbs and Western
medicines
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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.
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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.