Autoimmune Lupus erythematosus

COPD, chronic obstructive pulmonary disease EAE, experimental autoimmune encephalomyelitis RSV, respiratory syncytial virus SLE, systemic lupus erythematosus. 

Besides anemia associated with cancer and CKD, anemia of chronic disease can result from inflammatory processes and occurs commonly in autoimmune disorders such as rheumatoid arthritis and systemic lupus erythematosus. In treating these types of anemia of chronic disease, the most important principle is treating the underlying disease. These patients also may have iron deficiency and should be treated in the manner already discussed. Erythropoietin therapy such as epoetin-alfa therapy at a dose of 150 units/kg three times a week also may be used in these patients. 

Kovacic, P.J., J.D., Systemic lupus erythematosus and other autoimmune diseases from endogenous and exogenous agents unifying theme of oxidative stress, Mini Rev. Med Chem., 3, 568, 2003. 

Other studies describe similar beneficial effects for PUFA-enriched diets to treat Crohn s disease, other inflammatory bowel diseases such as ulcerative colitis, as well as psoriasis, asthma, systemic lupus erythematosus, and multiple sclerosis [57], Thus, immunomodulation by PUFAs appears to be a promising intervention for the treatment of many autoimmune and inflammatory diseases. 

McDonagh, J.E. and Isenberg, D.A., Development of additional autoimmune diseases in a population of patients with systemic lupus erythematosus, Ann. Rheum. Dis., 59, 230, 2000. 

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). 

One of the primary reasons ultraviolet radiation is of interest in the context of autoimmune diseases is because of induction of photosensitive cutaneous lesions (cutaneous lupus erythematosus)82 and dermatomyositis.83 A recent global evaluation of the frequency of dermatomyositis and associated autoantibodies in referral centers around the world showed a positive correlation with the intensity of ultraviolet irradiation at those locations.84... 

Strong mechanistic evidence from rodent models of autoimmune disease of viral or other infectious agents affecting autoimmunity or progression to overt disease, but harder to demonstrate in humans. Enterovirus (Coxsackie virus) focus of epidemiologic studies in type 1 diabetes, Epstein-Barr virus focus of epidemiologic studies in multiple sclerosis and systemic lupus erythematosus. 

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

Autoimmune disorders Development or exacerbation of autoimmune disorders, including myositis, hepatitis, idiopathic thrombocytopenic purpura, psoriasis, rheumatoid arthritis, interstitial nephritis, thyroiditis, and systemic lupus erythematosus have been reported in patients receiving alpha interferon. 

Outcomes of in vitro methods or simple in vivo methods such as the PLNA, only indicate whether a compound can sensitize the immune system. They do not predict whether a compound can induce an autoimmune disease. For that disease models are warranted. However, most disease models, as mentioned, will often require predisposed animal strains such as systemic lupus erythematosus (SLE)-prone mice [81, 82]. Often models using autoimmune-prone mice or rats (including the BN rat) are considered too sensitive and are for that reason undesired by various stakeholders (i.e., pharmaceutical industries, regulatory agencies). 

Polyspecific Response Associated with CNS Autoimmune Diseases. The oligoclonal, intrathecally synthesized IgG contains numerous specific antibodies and autoantibodies. Antibodies are frequently found with specificities against measles, the rubella virus and the varicella-zoster virus, but seldom against the herpes simplex virus. The occurrence of one, two, or three of these antibodies is referred to as the MRZ reaction. The corresponding antigens are not present in these cases. The MRZ reaction is typical of multiple sclerosis as well as cerebral lupus erythematosus and is a chronically evolving immune process (F5, KIO, S16). 

The autoimmune rheumatic diseases consists of Rheumatoid Arthritis (RA), Spondylarthritis (SpA), Systemic Lupus Erythematosus (SLE), Polymyositis, Dermatomyositis, Polymyalgia Rheumatica, Acute Temporal Arteritis, Giant Cell Arteritis, Behcet s Disease, Sjorgren s Syndrome, Felty s Syndrome and Mixed Connective Tissue Disease (MCTD). Spondylarthritis (SpA) can be subdivided in Reactive Arthritis (ReA), Ankylosing Spondylitis (AS), Psoriatic Arthritis (PsA), Arthritis associated with the inflammatory bowel diseases are Crohn s disease and Ulcerative Colitis (IBD), Undifferentiated SpA (UspA) and Sacro-ilitis, Juvenile SpA and Acute Anterior Uveitis (AAU). 

Pathophysiologically, there is little difficulty in recognizing disseminated intravascular coagulation and then treating this on merit. Much more frequent are immunologically mediated mechanisms that may be secondary to underlying collagen-vascular diseases such as systemic lupus erythematosus or where the defect exists in isolation and the process is defined as primary, idiopathic or autoimmune. 

Topical corticosteroids are most useful in inflammatory dermatoses, such as eczematous dermatitis and psoriasis they may also be helpful in other skin diseases that have a prominent inflammatory component, such as autoimmune blistering diseases (e.g., bullous pemphigoid and pemphigus vulgaris) and lupus erythematosus. 

Dapsone is approved for the treatment of an autoimmune blistering skin disease, dermatitis herpetiformis. This intensely pruritic eruption is characterized histologically by a dense dermal infiltration of neutrophils and subepidermal blisters. Other skin diseases in which dapsone is helpful are linear immunoglobulin A (IgA) dermatosis, subcorneal pustular dermatosis, leukocytoclastic vasculitis, and a variety of rarer eruptions in which neutrophils predominate, including some forms of cutaneous lupus erythematosus. 

Cyclosporine appears to have promise in the treatment of autoimmune diseases. It has a beneficial effect on the course of rheumatoid arthritis, uveitis, insulin-dependent diabetes, systemic lupus erythematosus, and psoriatic arthropathies in some patients. Toxicity is more of a problem in these conditions than during use in transplantation, since higher doses of cyclosporine are often required to suppress autoimmune disorders. 

---