Cure Arthritis Naturally

Cure Arthritis Naturally

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The treatment of SSc is challenging due to the complex disease process and the difficulty to specifically treat distinct subgroups of this relatively rare disease. Thus in 1995, an American College of Rheumatology Comittee published guidelines for the conduct of clinical trials in SSc (White et al. 1995). To date, there is no proven effective disease modifying treatment of SSc. Nevertheless, there have been significant breakthroughs in the treatment of several individual end-organ manifestations leading to improvements in patients longevity and quality of life. SSc poses a particular problem to the medical system due to the relative rarity of the disease requiring specialised care by the general practicioner. Therefore, diagnosis and care should be at least in part in the hands of specialists who have daily exposure to this disease and have access to a laboratory trained in autoimmune serology, to dermatohis-topathology, and modern diagnostic radiologic procedures (e.g. CT, MRT, angiography). Cooperation with different subspecialties is often necessary to provide optimal care due to the nature of the disease affecting other organ systems than the skin (e.g. rheumatology, pulmonary medicine, nephrology, neurology). Specialized care should be provided in a setting where the outpatient facilities have also access to hospital beds to ensure timely and appropriate treatment for patients presenting with exacerbation of their disease. Physical therapy which has access to treatment facilities to prevent loss of function is another prerequisite for these specialised facilities. Although there are single medical centers often linked to research centers which can provide care along the guidelines cited above they are usually not embedded into the medical system in a way that ensures access for patients not living in regions where these centers exist. Patient support groups which to date in part make up for these shortcomings should play an important role in communicating the special needs of these patients to society. Internet based resources will play an increasing role for the information of patients and recruitement for ongoing studies in the future (e.g. Http://, Therefore an important future aim will be to develop competence and communication based networks which ensure participation of all levels involved in the care for these patients.

Immunosuppressive Agents

D-penicillamine seems to affect both collagen and the immune system thus making it an ideal candidate to treat SSc. Interestingly, it took until the mid 90s to start a double blind randomized trial to investigate the effect of D-peni-cillamine in SSc. Unfortunately, no difference was found between a dose of 62.5 mg and 750 mg D-penicillamine daily indicating lack of efficacy (Clements et al. 1999). Also photopheresis (extracorporeal photochemotherapy) that has shown promise in several uncontrolled studies (Rook et al. 1992), failed in a recent crossover study to demonstrate a favourable effect (Enomoto et al. 1999). Several smaller trials investigated the use of cyclosporin A, which unfortunately was associated with considerable toxicity, especially nephropathy (Denton et al. 1994). Methotrexate, although its toxicity profile in patients with SSc was better than exspected, produced inconsistent results in two controlled studies (van den Hoogen et al. 1996; Pope et al. 1998).

Antifibrotic Agents

Interferon-y is the most potent cytokine known to inhibit collagen synthesis. Several uncontrolled studies applying the cytokine over up to one year have been performed to investigate the potential role of interferon-y in the treatment of SSc showing no major effect on the disease course (Hunzelmann et al. 1997). Interferon-a has also been shown to inhibit collagen synthesis (Duncan et al. 1995). However, a placebo controlled study of early diffuse SSc found no benefit for skin sclerosis and pulmonary function, but a greater mortality in the active treatment arm (Black et al. 1998). Relaxin is a pregnancy-related hormone that has tissue remodeling and antifibrotic effects. Relaxin has been tested in a phase 2 trial where in the low dose group a significant improvement of the modified Rodnan skin score was found (p = 0.049) wheras in the high dose group no such effect was seen (Seibold et al. 2000).

Organ-Specific Therapies

Skin Involvement

General measures include skin protection from cold and trauma, skin care with moistening creams, lymph drainage and active physiotherapy. Calcium channel blockers or angiotensin II receptor type 1 antagonists can be given to decrease symptoms of Raynaud's syndrome (Dziaio et al. 1999). In severe cases of finger tip ulcerations and impending digit amputation, intravenous prostacycline analogues may be of value (Zachariae et al. 1996; Pope et al. 2000). New agents as endothelin antagonists or phosphodiesterase-inhibitors are still under investigation. Ectopic calcifications or calcinosis when compromising blood circulation or causing symptoms may be removed surgically or by the use of CO2-laser (Bottomly et al. 1996). Laser (i.e. argon or flashlamp pumped dye laser) therapy is the treatment of choice to remove teleangiectasias, which may also involve the mucosa.

UV radiation (UVA1 or bath-PUVA) with small patients numbers in uncontrolled studies has been reported to be beneficial. In localized scleroderma, evidence for the efficacy of UVA1 or bath-PUVA is increasing although no double blind prospective study is available (Kerscher et al. 1996). Recent studies have shown that UVA irradiation alone, and more so in conjunction with photosensitizing agents, increases the expression, synthesis and activation of metalloproteinases. In addition, a variety of cytokines and soluble factors in vitro and in vivo are modulated by UVA and can affect connective tissue remodeling (Scharffetter et al. 1991; Herrmann et al. 1993). Clinical and ultrasound evaluation revealed that the sclerotic lesions disappeared or markedly improved during PUVA bath photochemotherapy in 13 of the 17 enrolled patients within less than three months. We have additional experience in 14 patients suffering from localized scleroderma who improved substantially from bath PUVA therapy as monitored by skin score, cutaneous elastometry and evaluation of skin thickness by ultrasound analysis (Hunzelmann et al. 1998b). In a recent publication, the therapeutic potential of UVA1 therapy has been evaluated in localized scleroderma (Stege et al. 1998). This study corroborates and extends previous observations that in vivo UVA1 irradiation exposure of healthy human skin is associated with the induction of interstitial collagenase RNA expression in situ which may play a role in the remodelling of the fibrotic connective tissue.

Musculosceletal Involvement

Musculosceletal involvement, arthralgia and musculosceletal pain being the most frequent complaints, is common in scleroderma and may lead to secondary fibromyalgia. Muscle weakness and some increase in serum creatine kinase levels are quite common. Inflammatory arthritis can occur but raises the suspicion of the presence of an overlap syndrome and only rarely results in mutilating arthritis. Corticosteroids should be avoided due to their long term side effects and association with nephropathy in higher doses (Steen et al. 1998). Non steroidal anti-inflammatory agents should also be prudently chosen due to their potential side effects on renal function, blood pressure and gastrointestinal function. The superiority of the use of cyclo-oxygenase 2 inhibitors remains to be proven.

Renal Involvement

Acute renal crisis is a serious and potentially fatal SSc complication associated with an acute reduction on cortical blood flow, hyperreninemia, hyper-

tension which occurs most likely in diffuse cutaneous scleroderma of less than four years duration. Thus regular control of blood pressure (at least twice a week) is recommended to detect acute renal involvement early on. Some patients will progress to renal failure and dialysis or renal transplantation. Chronic renal involvement is asociated with a slowly progressive obliterative vasculo-pathy. Before the advent of ACE inhibitor therapy and other improvements in the management of advanced renal disease, survival for longer than 3-6 months was almost unknown. Particularly in acute renal crisis, ACE inhibitors are the mainstay of treatment significantly prolonging patient survival (Steen et al. 1990). Additional administration of intravenous prostacyclin may be considered. Nevertheless, prognosis of established renal crisis is still relatively poor with about one third of patients progressing to renal replacement therapy. Here, a five year kidney graft survival rate of 47% was reported comparable to that of patients with SLE (Chang and Spiera 1999).

Pulmonary Involvement

Pulmonary fibrosis in SSc affects to different degrees the parenchymal and the vascular system. In early disease, inflammatory alveolitis may precede and/or accompany interstitial fibrosis leading to loss of pulmonary function as evidenced by decreased diffusing capacity and vital capacity. Bronchoalveolar lavage (in experienced hands) and high resolution chest computertomogra-phy will help to determine the degree of inflammation. Several studies indicate that alveolitis can be treated with cyclophosphamide (White et al. 2000).

Pulmonary hypertension may most prominently develop in patients with limited cutaneous scleroderma of long duration with relatively little interstitial disease determining the prognosis of these patients. Here infusion or inhalation of prostacycline analogues or endothelin antagonists may improve the outcome, which usually results in death within five years unless heart-lung transplantation is performed (Pigula et al. 1997; Badesch et al. 2000; Hoeper et al. 2000; Rubin et al, 2002).

Gastrointestinal Involvement

The gastrointestinal tract is frequently involved with a frequency for the oesophagus in about 80%, the stomach, small intestine and large intestine in about 40-70% (Sjogren 1996). The pathology is characterized both by atrophy of the smooth muscles that line the gastrointestinal tract and involvement of the myenteric nerve plexus. Main symptoms associated are heartburn, eso-phageal dysfunction in the upper gastrointestinal tract and diarrhoea due to bacterial overgrowth, fetal incontinence in the distal tract. Prokinetics (e.g. octreotide) are of limited use in severe constipation and recently, the prokine-tic cisapride has been withdrawn from the market due to associated cardiac arrythmias leading to death. Proton pump inhibitors and to a lesser extent

H2-blockers are effective in controlling reflux esophagitis apart from typical conservative measures (no late meals etc.). Bacterial overgrowth and fungal infections (e.g. candida esophagitis) can be dealt with by intermittent antimicrobial therapy and antimycotics. Rarely, teleangiectasias may also be present on the mucosa representing a potential source of occult intestinal bleeding.

Cardiac Involvement

The nature and severity of cardiac disease depends on the extent of myocar-dial fibrosis, a primary component of this disorder, and on the extent to which concurrent fibrosis of the lung and thickening and fibrosis of the small pulmonary arteries place an additional burden on the circulation. Large perfusion abnormalities on thallium scans are predictive of shortened survival and an increased number of cardiac events (Steen et al. 1996). Also, intermittent vascular ischemia is observed which probably reflects similar pathophy-siological changes as observed in the peripheral vasculature (Raynaud's syndrome). Arrhythmias are quite common in SSc but seldom meet the definition of severe arrhythmia.

Novel Therapeutic Perspectives

A number of studies are currently performed or planned to investigate the effect of new therapeutic concepts. Due to the relative rarity of these diseases and distinct subgroups, however, national and international cooperative studies will be required to prove the efficacy of these new approaches. The role of collagen as an autoantigen in SSc is not entirely proven. However, in a recent study on the use of oral administration of bovine collagen a reduction of T cell reactivity to human collagen was found accompanied by significantly improved skin thickness score and carbon monoxide diffusing capacity (McKown et al. 2000).

Recombinant technology gives now rise to the development of recombinant cytokines and anti-cytokines that may have therapeutic potential, the principle of anti-TNF-alpha therapy in rheumatoid arthritis being the most prominent example. TGF-beta as a potent stimulus of collagen synthesis is thought to drive the fibrotic process. Recent studies in a mouse model (McCor-mick et al. 1999) and in human glaucoma in the human indicate a potential for the use of TGF-beta antibodies.

Studies have been recently initiated to evaluate the beneficial effect of autologous haemopoetic stem cell transplantation in systemic lupus erythe-matosus and SSc. Previous studies showed that patients with autoimmune disease who undergo bone marrow transplant for haemopoietic or other malignancy are frequently noted to experience a remission of their autoimmune disease (Clements et al. 1997; Tyndall et al. 1997). However, to date only uncontrolled studies have been reported with divergent effects.

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Arthritis Joint Pain

Arthritis Joint Pain

Arthritis is a general term which is commonly associated with a number of painful conditions affecting the joints and bones. The term arthritis literally translates to joint inflammation.

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