Autoimmune Scleroderma

The definition of an overlap syndrome dictates that the criteria for diagnosis of both disorders (in the present context, of PM/DM and of some other connective tissue disorder), are fulfilled. It is not unexpected that those syndromes which overlap with PM/DM are also either known autoimmune conditions or ones in which an autoimmune basis is strongly suspected. The association of these disorders with PM/DM syndromes may not materially alter the basic histopathological featmes expected in PM/DM but some differences may be identifiable. The disorders most frequently associated with an overlap syndrome are rheumatoid arthritis, systemic lupus erythematosis, scleroderma, and mixed connective tissue disease. 

A recent report by the National Institutes of Health estimated that at 14 to 22 million people in the United States are affected by an autoimmune disease.1 As a group, these diseases represent a leading cause of death among women under age 65, with systemic lupus erythematosus, multiple sclerosis, and type 1 diabetes being the major sources of this impact on mortality.2 The autoimmune thyroid diseases, type 1 diabetes and rheumatoid arthritis are the most common of the autoimmune diseases (Table 25.1).3-5 Most autoimmune diseases disproportionately affect women. In the thyroid diseases, primary biliary cirrhosis, scleroderma, systemic lupus erythematosus, and Sjogren s syndrome, more than 85% of patients are female, but it is not known why the female predominance is so high in these specific diseases. 

For some autoimmune diseases, little is known about environmental factors involved in the initiation or progression of the disease. For other diseases, however, considerable research has been conducted on one or more types of exposures. Most epidemiologic studies of environmental influences have focused on multiple sclerosis, rheumatoid arthritis, scleroderma, systemic lupus erythematosus, and small vessel vasculitis, but experimental studies using murine models of these diseases is limited (Table 25.1). 

Occupational exposure to silica dust has been identified as a risk factor for several systemic autoimmune diseases. This literature dates back almost 100 years, to the description by Bramwell of diffuse scleroderma in stone masons.26 Rheumatoid arthritis and scleroderma in miners were described in the 1950s, and more formal cohort studies of miners and of granite workers were conducted in the 1980s. Other studies focusing on silicosis patients, and several case-control studies of these diseases and of Wegner... 

Diphenylhydantoin, which has been demonstrated to cause autoimmune phenomena in man (SLE, vasculitis and scleroderma and skin) has also been tested (via drinking water for 6 months) in genetically predisposed mice (C57BL/6-lpr/lpr strain) but the compound depressed rather than increased the levels of ANA (55 and section 4.1, below). In another study [56], a slight shift towards a Th2 response was demonstrated as an increase in the KLH-induced production of IL-4 and IgE (IgE was detected by direct ELISA, which makes these data suspect) in a 4 weeks exposure study. In this same study, proliferative responses of splenocytes to KLH (using spleen cells of KLH-sen-sitized mice), mitogens (ConA, LPS) or anti-CD3 were also reduced, possibly through interference with accessory cell function. 

Earnshaw, W.C. and Rothfield, N. (1985) Identification of a family of human centomere proteins using autoimmune sera from patients with scleroderma. Chromosoma 91, 313-321. 

Autoimmune disease There have been rare reports of various autoimmune diseases (eg, scleroderma, systemic lupus erythematosus, rheumatoid arthritis) in... 

The effectiveness of immunosuppressive drugs in autoimmune disorders varies widely. Nonetheless, with immunosuppressive therapy, remissions can be obtained in many instances of autoimmune hemolytic anemia, idiopathic thrombocytopenic purpura, type 1 diabetes, Hashimoto s thyroiditis, and temporal arteritis. Improvement is also often seen in patients with systemic lupus erythematosus, acute glomerulonephritis, acquired factor VIII inhibitors (antibodies), rheumatoid arthritis, inflammatory myopathy, scleroderma, and certain other autoimmune states. 

In the autoimmune diseases scleroderma and systematic lupus erythematosus antigens to nuclear proteins or nucleic acids are present in the blood. 

Tetracyclines also seem to have anti-inflammatory and immunomodulating effects.53,71 Although the exact reasons for these effects are unclear, tetracyclines have been used in a variety of noninfectious diseases with an inflammatory or autoimmune basis, including scleroderma and rheumatoid arthritis.71 Clinical studies will continue to investigate how these drugs can be used effectively in the long-term management of chronic disease. 

Autoimmune responses seem to be the underlying basis for a number of diseases, including rheumatoid arthritis, diabetes mellitus, myasthenia gravis, systemic lupus erythematosus, scleroderma, polymyositis/der-matomyositis, and several other disorders.25,27,44 As indicated previously, it is not exactly clear what factors cause autoimmune responses, as well as why certain individuals are more prone to autoimmune-related diseases. Nonetheless, drugs that suppress the immune system can limit damage to various other tissues, and these drugs may produce dramatic improvements in patients with diseases that are caused by an autoimmune response. 

Silica exposure has been associated with increased incidences of scleroderma, a condition manifested by hardened, rigid connective tissue. In this respect, it is believed that silica acts by an adjuvant mechanism in which it enhances the autoimmune response caused by other agents, such as silicones or paraffin.8... 

Similar MAT may enter clinical trials in a variety of other rheumato-logic conditions, including scleroderma, for which the success of current treatments is extremely limited. Another autoimmune disease that has already been studied, though not extensively and only in early phases, is psoriatic arthritis, and it appears as if this disease will respond to similar measures as rheumatoid arthritis. 

Autoimmune haemolytic anaemia Idiopathic thrombocytopenic purpura Rheumatoid arthritis Scleroderma... 

Sjogren s Syndrome. SS is an autoimmune disorder characterized by the triad of dry eye, dry mouth (xerostomia), and a connective tissue disease. At least two components of the triad need to be present for the diagnosis of SS to be made. Primary SS, an exocrinopathy, is characterized by a lymphocytic infiltration and subsequent destruction of salivary and lacrimal glandular tissues. Symptoms include both dry eyes and dry mouth. Secondary SS includes dry eyes or xerostomia, plus a connective tissue disease, most frequently rhemnatoid arthritis but also lupus, scleroderma, polyarteritis, or other related diseases. Unfortimately, there is no cure for SS at this time. Clinical trials using oral immunomodulatory agents have produced mixed results. 

The main adverse effects of ethosuximide include gastrointestinal disturbances, anorexia, dizziness, fatigue, drowsiness, headache, mood and behavioral disturbances, dyskinesias, and hiccups (1). Skin rashes (including Stevens-Johnson syndrome), systemic lupus eiythemato-sus, scleroderma, nephrotic sjmdrome, blood dyscrasias, liver dysfunction, and autoimmune thjroiditis are rare. 

Scleroderma, an autoimmune disease involving the vascular system, has been associated with exposure to chlorinated ethylene compounds related to PERC, but the reports are not definitive. 

Prolonged TCE exposure has been associated with impairment of peripheral nervous system function, persistent neuritis and temporary loss of tactile sense and paralysis of the fingers after direct solvent contact. Chromosomal effects have been reported in those involved in the use of TCE for degreasing and symptoms of systemic lupus erythematosis have been reported after chronic TCE exposure. In addition, organic dementia has been noted after occupational exposure to TCE and there have been some reports of an association between exposure and scleroderma, an autoimmune disease. 

Exposures to xenobiotics have been associated with the onset of several autoimmune diseases. Lupus (systemic lupus erythematosus or SLE), scleroderma (systemic sclerosis), rheumatoid arthritis, and other maladies... 

Scleroderma (SSc) is a chronic autoimmune disease characterized by excessive deposition of collagen and fibrosis (formation of scar tissue) in the skin and other body organs. Though the local manifestation of this disease is not serious, systemic sclerosis (SS), the serious manifestation, can be fatal. Since exposures to the same chemicals have been associated with both variants of this disease, they are discussed together. 

There are numerous forms of arthritis, including fibromyalgia, gout, lupus, and scleroderma. The two most common types are osteoarthritis and rheumatoid arthritis. Osteoarthritis is a joint disease, but rheumatoid arthritis damages the connective tissue and is considered an autoimmune disease, meaning that the body s immune system mistakenly attacks healthy tissue, not just pathogens such as viruses or bacteria. 

This case of herbs complementing technology is not an isolated incidenti have had similar experiences with other conditions. For example, although best treated initially by Western medicine, traumatic head injuries have responded well to adjunctive herbal therapies, as have various cancers, heart disease, and autoimmune disorders such as lupus, ankylosing spondylitis, and scleroderma. 

X-linked agamma-globulinaemia (XLA) lack of mature immunoglobulin-producing B cells Mutations in Bruton s tyrosine kinase (BTK) Arthritis, dermatomyositis, autoimmune haemolytic anaemia (AIHA), scleroderma... 

In 1981-1982, an epidemic spread across Spain, which was eventually labelled the toxic oil syndrome by the World Health Organization (WHO). In less than two years, at least 20 096 people were afflicted by and 356 people died from toxic oil syndrome (Philen et al., 1997 Philen Dicker, 2000). Women, especially those less than 40 years of age, were affected more severely than men 61% of the victims and 66% of the deaths were women (Sanchez-Porro Valades et al., 2003). Toxic oil syndrome has striking similarities to autoimmune diseases, particularly scleroderma. In addition, it resembles eosinophilia myalgia syndrome and diffuse fasciitis with eosinophilia. Toxic oil syndrome-associated manifestations evolved from initiating vasculitis to eosinophilia in the acute phase and then sicca syndrome, neuropathy, scleroderma, Raynaud phenomenon, and musculoskeletal inflammation in the chronic phase (Kaufman Krupp, 1995). More than 70% of toxic oil syndrome patients presented with eosinophilia, regardless of age or sex. 

It is notable that cadmium as well as mercury and gold can initiate or aggravate autoimmune manifestations in normal or autoimmune-prone animals, respectively. It would seem likely that these heavy metals have the same effects on humans, presumably by a similar mechanism. Autoimmune manifestations induced by heavy metals include lupus-type nephritis, autoimmune haemolytic anaemia, and skin diseases, such as pemphigus and scleroderma-like lesion. Some manifestations of immune-mediated nephritis and elevation of circulating autoantibodies have been noted in case-studies of persons exposed to gold and cadmium as well as mercury (Ohsawa, 1993 Bigazzi, 1994, 1999). 

---