Natural Remedies For Scleroderma
SclerodermaReviewNatural Remedies for SclerodermaAlan R. Gaby, MDAbstractScleroderma is an autoimmune disease of theconnective tissue characterized by fibrosisand thickening of various tissues. It can belimited to the skin or affect multiple organs,and its course ranges from slowly to rapidlyprogressive. Penicillamine, glucocorticoids, andother drugs are used to treat scleroderma, butnone of these treatments has a high degree ofefficacy. This article reviews several promisingnatural treatments for scleroderma, includingpara-aminobenzoic acid, vitamin E, vitamin D,evening primrose oil, estriol, N-acetylcysteine,bromelain, and an avocado/soybean extract.(Altern Med Rev 2006;11(3):188-195)IntroductionScleroderma (also called systemic sclerosis)is an autoimmune disease of the connective tissue.It is characterized by fibrosis in the skin and internal organs, resulting in thickening and hardening ofthe involved areas. There are two main subtypes ofscleroderma: diffuse and limited. Diffuse scleroderma affects the skin and multiple organs and can berapidly progressive and fatal. Limited sclerodermaprogresses more slowly. It often manifests as variouscomponents of a clinical pattern called the CRESTsyndrome (calcinosis cutis, Raynaud’s phenomenon,esophageal involvement, sclerodactyly, and telangiectasia) (Figure 1). The disease may also be confinedto the skin, without involvement of other organs, inwhich case it is called morphea or linear scleroderma.Medications used to treat scleroderma include penicillamine and other immunosuppressive agents, colchicine, and glucocorticoids. Table 1 illustrates thescleroderma subtypes.Page 188Dietary FactorsPathological changes in the gastrointestinal tract in patients with scleroderma can resultin reduced colonic motility and prolonged transittime, which may lead to a state of chronic colonicpseudo -obstruction. In case reports, four patientswith scleroderma developed severe abdominal painafter initiation of a high-fiber diet for the treatment ofconstipation; three of these patients required hospitalization.1 The authors of this report suggested that,for patients with scleroderma, any increase in dietaryfiber intake should be undertaken cautiously and introduced gradually.Environmental FactorsScleroderma can be induced by exposureto a number of different chemical agents, includingorganic solvents, plastics, certain drugs, silica powder, and silicone. In patients with chemical-inducedscleroderma, eliminating the source of exposure (i.e.,changing occupation, removing silicone breast implants) might favorably influence the course of thedisease. A detoxification (depuration) program aimedat reducing the body burden of xenobiotic chemicalscould conceivably slow or reverse the disease process, since such treatment has been beneficial in thetreatment of other autoimmune diseases.2PABAPara-aminobenzoic acid (PABA) appears tohave an antifibrotic action, suggested by its beneficial effect in patients with Peyronie’s disease and Dupuytren’s contracture. Zarafonetis reported in 1948Alan R. Gaby, MD – Private practice 17 years, specializing in nutritionalmedicine; past-president, American Holistic Medical Association; contributingeditor, Alternative Medicine Review; author, Preventing and ReversingOsteoporosis (Prima, 1994) and The Doctor’s Guide to Vitamin B6(Rodale Press, 1984); co-author, The Patient’s Book of Natural Healing(Prima, 1999); contributing medical editor, The Townsend Letter forDoctors and Patients since 1985.Correspondence address: 301 Dorwood Drive, Carlisle, PA 17013Alternative Medicine Review u Volume 11, Number 3 u 2006Copyright 2005 Thorne Research, Inc. All Rights Reserved. No Reprint Without Written Permission. Alternative Medicine Review Volume 10, Number 4 December 2005
ReviewSclerodermathat PABA, usually administeredFigure 1. CREST Syndromeas potassium para-aminobenzoate(KPAB), was an effective treatment for scleroderma. In patientswho received this treatment, theskin gradually became softer andTelangiectasiathinner, with consequent increased(dilated capillariesrange of motion.3 In 1961, this samein the face, hands,or mouth)investigator presented data on 104consecutive patients treated with12 g KPAB daily. Ninety-sevenpatients (93.3%) showed moderateto-considerable improvement of theinvolved skin. Some patients had acomplete remission; in those cases,therapy was discontinued for up to8.5 years without a recurrence. Mostpatients, however, showed somesigns of residual activity and treatment was continued indefinitely.4In 1988-1989, Zarafonetiset al presented a retrospective analysis of 390 scleroderma patients whohad received adequate treatmentwith KPAB. “Adequate treatment”was defined in the analysis as 12 or12.5 g per day for three months to20.6 years (average, 4.2 years). Therate of decline in pulmonary function (vital capacity) was significantly less in these patients than in thosewho had been inadequately treatedor never treated with KPAB.5 Inaddition, five-year (88.5% versus69.8%) and 10-year (76.6% versus56.6%) survival rates were significantly higher in adequately treatedpatients than in those who had never been treated.6While other investigatorshave confirmed the effectiveness ofPABA or KPAB,7,8 a double-blindtrial found that administration of12 g KPAB daily for 48 weeks had no effect on theskin lesions of scleroderma.9 However, the patients inthat study had longstanding disease (mean duration,8.67 years), which may have been too advanced torespond to KPAB.Alternative Medicine Review u Volume 11, Number 3 u 2006Esophagitis (reflux as a resultof poorly functioning musclesin the esophagus)Raynaud’sphenomenon(spasm of thearterioles inthe fingers,toes, nose,tongue, or ears)Calcinosis(calcium deposits underthe skin of knees, elbows,or fingers appear as hardwhitish nodules)Sclerodactyly(thickening and tightnessof skin on the fingersor toes makes themlook shiny and puffy)Page 189Copyright 2005 Thorne Research, Inc. All Rights Reserved. No Reprint Without Written Permission. Alternative Medicine Review Volume 10, Number 4 December 2005
SclerodermaReviewTable 1. Scleroderma SubtypesSubtypeCharacteristicsDiffuserapidly progressiveLimitedslowly progressive (may include calcinosiscutis, Raynaudʼs phenomenon, esophagealinvolvement, sclerodactyly, andtelangiectasia)Localized to the skinmorphea, linear sclerodermaAlthough KPAB was well tolerated by mostscleroderma patients, this compound is not innocuous. Rare cases of hepatotoxicity and one death dueto toxic hepatitis have been reported in patients receiving large doses of PABA or KPAB. Fever or rashmay occur at doses greater than 12 g per day. Largedoses may also cause hypoglycemia; treatment shouldtherefore be interrupted during periods in which foodintake is inadequate.Vitamin EOxidative stress was significantly increasedin patients with scleroderma compared with healthycontrols, suggesting that free-radical-induced oxidative injury occurs in scleroderma.10 Antioxidants suchas vitamin E might, therefore, be beneficial. VitaminE is also believed to stabilize lysosomal membranes,potentially inhibiting events involved in the autoimmune process.11 In addition, vitamin E may have anantifibrotic action, suggested by its beneficial effectin patients with Peyronie’s disease and Dupuytren’scontracture.In case reports, vitamin E supplementationresulted in improvements in the skin of sclerodermapatients, although non-dermatological aspects of thedisease did not improve.12-15 Various components ofscleroderma, including morphea, calcinosis cutis,and Raynaud’s phenomenon, responded to vitaminE. The dose of vitamin E in these reports rangedfrom 200-1,200 IU per day. In some cases, vitamin Ewas also applied topically. One patient successfullyPage 190treated was a 45-year-old male with Raynaud’s phenomenon, probable early scleroderma, and ulceration and gangrene of the fingertips. He received 800IU oral vitamin E daily and applied the vitamin (50IU per mL) to the ulcerated fingers twice daily. Theulcerations became less painful after two weeks andhealed almost completely within one month.16Vitamin DA 1940 report described three patients withlocalized scleroderma who improved after treatmentwith vitamin D2 at a dose of 10,000-12,500 IU perday for 1-3 months.17 That report did not attract muchinterest, possibly because of the potential for highdose vitamin D2 to cause toxic effects. More recently,several studies have demonstrated the effectivenessof orally administered 1,25-dihydroxycholecalciferol(calcitriol), the biologically active form of vitamin D,as a treatment for scleroderma. Calcitriol has severalactions that might be expected to slow or reverse thedisease process, including immunoregulatory effectsand inhibition of fibroblast growth and collagen synthesis.A 35-year-old woman with a two-year history of localized scleroderma was given calcitriol forsix months. The initial dose was 0.25 mcg per day forone week, increased by 0.25 mcg per day each weekuntil a dosage of 1.25 mcg daily was reached in thefifth week. Thereafter, 0.5 mcg per day was given forfour months. After six months of treatment, the skinlesions had almost completely resolved.18Alternative Medicine Review u Volume 11, Number 3 u 2006Copyright 2005 Thorne Research, Inc. All Rights Reserved. No Reprint Without Written Permission. Alternative Medicine Review Volume 10, Number 4 December 2005
ReviewThree patients with generalized morphea received 0.5-0.75 mcg calcitriol daily. After 3-7 monthsof treatment, joint mobility improved and skin extensibility increased. No adverse effects were seen. Theimprovement persisted after discontinuation of therapy during a 1- to 2-year follow-up period.19Seven children (ages 3-13 years) with linearscleroderma received 0.25 mcg calcitriol daily for oneweek; this was increased every week to a maximumof 0.5-1.25 mcg per day, depending on body surfacearea and response to treatment. Dietary calcium intake was restricted to 600 mg daily. Five of sevenpatients showed good-to-excellent improvement oftheir lesions. One patient had a partial relapse after19 months, but responded well to a second course oftherapy. No significant side effects were seen. Theauthors suggested that calcitriol be tried for at leastthree months in children with linear scleroderma before introducing more aggressive therapy. If improvement is seen, this treatment may be continued for 6-9months.20Eleven scleroderma patients were treatedwith 0.25 mcg calcitriol daily during the first week;calcitriol was increased by 0.25 mcg daily each weekuntil urinary or serum calcium levels became elevated. The mean final dose was 1.75 mcg per dayand the maximum dose was 2.5 mcg per day. Aftertreatment periods ranging from six months to threeyears, significant improvements in skin thickness andextensibility were observed. No serious side effectswere seen except for transient hypercalciuria (alwaysbelow 350 mg per day), which responded to a temporary reduction in the dosage.21Twenty patients with morphea were randomlyassigned to receive, in double-blind fashion, calcitriol(0.75 mcg per day for six months, followed by 1.25mcg per day for three months) or placebo for ninemonths. The severity of the skin condition decreased19 percent in the calcitriol group and 29 percent inthe placebo group (difference not significant).22Thus, most but not all clinical trials haveshown that calcitriol treatment improves the skinmanifestations of scleroderma. However, in additionto being expensive, calcitriol can cause hypercalcemia, hypercalciuria, and other side effects requiringfrequent monitoring with laboratory tests. Whilecalcitriol treatment would be worthwhile in selectedSclerodermacases, vitamin D3 (cholecalciferol) might be a viablealternative for many patients, even though it has notbeen subjected to clinical trials. In addition to beinginexpensive and less toxic than vitamin D2, vitaminD3 is 3.4-9.4 times as potent in humans as vitaminD2.23 The vitamin D2 dosage range of 10,000-12,500IU per day reported to be effective against scleroderma would correspond to approximately 1,100-3,700IU of vitamin D3 daily. Studies in healthy humanssuggest that 4,000 IU vitamin D3 per day for 2-5months is a safe level of intake.24 Patients receivinghigh-dose vitamin D3 for long periods of time andthose being treated with calcitriol should be monitored for signs of toxicity.Evening Primrose OilEvening primrose oil (EPO) contains a highconcentration of gamma-linolenic acid (GLA), whichis a precursor to prostaglandin E1 (PGE1). In patientswith Raynaud’s phenomenon associated with scleroderma, intravenously administered PGE1 increasedcapillary blood flow and appeared to promote ulcerhealing.25 Because PGE1 is unstable and must be administered intravenously, an effective orally activealternative would be desirable.Four women with scleroderma of 5-13 years’duration received 1 g EPO three times daily for oneyear. Pain in the hands and feet was reduced, ulcers healed, and skin texture and telangiectasia improved.26Twenty-one patients with Raynaud’s phenomenon (with or without scleroderma) received, indouble-blind fashion (randomization not specified),6 g EPO per day, providing 540 mg GLA daily, orplacebo for eight weeks. The EPO group experiencedfewer attacks than the placebo group, and the difference reached statistical significance at six and eightweeks (p 0.03). Patients with Raynaud’s phenomenon associated with scleroderma appeared to be morelikely to improve with EPO, compared with patientswith Raynaud’s disease and no evidence of a connective tissue disorder.27In a double-blind study, 25 patients withscleroderma received a placebo or a preparation containing EPO and fish oil for six months. The numberand duration of attacks of Raynaud’s phenomenondecreased in both groups, but there was no significantAlternative Medicine Review u Volume 11, Number 3 u 2006Page 191Copyright 2005 Thorne Research, Inc. All Rights Reserved. No Reprint Without Written Permission. Alternative Medicine Review Volume 10, Number 4 December 2005
SclerodermaReviewdifference between groups.28 The authors concludedthat EPO/fish oil did not improve vascular symptomsin patients with scleroderma; however, the conclusion is open to question for two reasons. First, the“placebo” in the study was sunflower oil, a source oflinoleic acid, which can be converted in vivo to GLA.It is possible, therefore, that both EPO/fish oil andthe placebo were beneficial. Second, the EPO/fish oilpreparation also provided 30 mg lithium per day. Because lithium appears to interfere with essential fattyacid metabolism,29 it may have blocked a beneficialeffect of EPO/fish oil.Although more definitive studies need to beconducted, the available evidence suggests that EPOmay be beneficial in the treatment of scleroderma andthe associated Raynaud’s phenomenon.EstriolSeveral lines of evidence led a group of investigators to consider estriol as a possible treatment forscleroderma: the condition affects women primarily,it sometimes improves during pregnancy, urinary estriol levels rise during late pregnancy, and estriol hasa softening effect on the uterine cervix. Two women(ages 48 and 59 years, respectively) with sclerodermawere treated with estriol for 10 months. The first patient received 10 mg per week subcutaneously; thesecond received 2 mg per day orally, followed by 1020 mg per week subcutaneously, after the oral dosewas discontinued because of urticaria. Skin softeningwas noted on all involved areas in both patients, andwas accompanied by increased mobility of large andmedium-sized joints, a lessening of cyanosis on fingers and extremities, and marked histologic improvement of affected skin.30Until more is known, it would seem reasonable to reserve estriol therapy for postmenopausalwomen or for premenopausal women with evidenceof estrogen deficiency.N-AcetylcysteineTwenty patients with Raynaud’s phenomenon secondary to scleroderma received a five-daycontinuous infusion of N-acetylcysteine during thewinter, starting with a loading dose of 150 mg per kgbody weight given over two hours, followed by 15mg per kg body weight per hour for the remainder ofPage 192the treatment period. During the ensuing eight weeks,the frequency and severity of attacks decreased significantly compared with baseline. Of the 17 patientswith digital ischemic ulcers, eight experienced complete healing. Side effects were considered by the authors of the study to be minor and reversible.31S-AdenosylmethionineFifteen patients with scleroderma received600 mg S-adenosylmethionine per day intravenouslyfor two months, followed by 400 mg three times perday orally. After four months, 10 patients showed asignificant improvement in skin induration. In threepatients who underwent skin biopsy, a significant reduction in the thickness of the dermal layer was seen.No improvement was seen in esophageal disease or inRaynaud’s phenomenon.32BromelainA 32-year-old woman with early biopsyproven scleroderma was treated with enteric-coatedbromelain (Ananase), first 160 mg per day and later80 mg per day. After three months, she was able toclose her hand 85 percent, compared with 50 percent before treatment. Swallowing function, whichhad been impaired for several years, also improved.These improvements were maintained during a oneyear total treatment period.33The product used in this study is no longercommercially available. Non-enteric-coated bromelain would presumably be partially inactivated bygastric enzymes after ingestion. While clinical experience suggests that currently available bromelainproducts do have biological activity, dosage comparisons with Ananase are difficult.Avocado/Soybean ExtractOne practitioner has reported good resultsusing an unsaponifiable fraction of avocado/soybean(ASU [Piascledine 300; Pharmascience Laboratories,Courbevoie, France]) in more than 100 patients withextensive plaque-like morphea or linear scleroderma.If treatment was initiated at an early stage of linearscleroderma, then contractures, atrophy, and deformities of the extremities were avoided. The usual doseof ASU was 300 mg daily for six months, but somepatients were treated for 1-2 years. In severe cases,Alternative Medicine Review u Volume 11, Number 3 u 2006Copyright 2005 Thorne Research, Inc. All Rights Reserved. No Reprint Without Written Permission. Alternative Medicine Review Volume 10, Number 4 December 2005
SclerodermaReviewTable 2. Alternative Treatments for SclerodermaTREATMENTDOSAGERATIONALEFiberUse with cautionDecreased colonic motilityPara-aminobenzoic Acid(PABA)12 g/day KPABA (potassiumPABA)Anti-fibroticVitamin E200-1,200 IU/day orally; topicalapplicationAntioxidant; anti-fibroticVitamin D0.25-1.25 mcg/day calcitriol OR1,000-4,000 IU/day D3(not studied)Immunoregulatory; inhibitionof fibroblast growth andcollagen synthesisGLA (sources: blackcurrant, borage, or eveningprimrose oil)540 mg/day GLA (evening primroseoil used in the studies)Converts to prostaglandin E1to increase capillary flow anddecrease inflammation; especially for patients with concomitant Raynaud’s phenomenonEstriol2 mg/day orally OR 10-20mg/week subcutaneouslyMechanism unknownN-acetylcysteineIV infusion of 15-150 mg/kg/hourfor five daysMechanism unknownS-adenosylmethionine(SAMe)IV infusion of 600 mg/day followedby 400 mg three times dailyMechanism unknownBromelain80-160 mg/day enterically coatedMechanism unknownAvocado/Soybean Extract(unsaponifiable)300-600 mg/dayMechanism unknownZinc/Copper15-60 mg/day zinc; 1-4 mg/daycopperCorrect a deficiency600 mg per day was used. No side effects were observed.34The interpretation of this report is complicated by the fact that the patients were given procainepenicillin before starting treatment with ASU. According to some researchers, an infectious agent mayplay a role in the causation of scleroderma,35 and thedisease has been reported to improve after treatmentwith penicillin alone.36Z
none of these treatments has a high degree of efficacy. This article reviews several promising natural treatments for scleroderma, including para-aminobenzoic acid, vitamin E, vitamin D, evening primrose oil, estriol, N-acetylcysteine, bromelain, and an avocado/soybean
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autoimmune diseases, such as antiphospholipid, antineutro-phil cytoplasmic, and antimitochondrial antibodies, also have been described in patients with scleroderma. This review will summarize the var
The Natural Remedies Encyclopedia Home remedies for over 500 diseases and disorders. Back in the old days, the pioneers were practical-minded people.
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