Autoimmune disorder systemic lupus erythematosus

The interstitium of the kidney is also susceptible to injury from a variety of causes. Although acute interstitial nephritis is most commonly caused by medications (see Chap. 46), infections (e.g., streptococcal, leptospirosis, hantavirus, and human immimodeflciency virus), selected autoimmune disorders (systemic lupus erythematosus or mixed connective tissue disease) also may produce a similar syndrome. The presence of white blood cells (WBCs), WBC casts, and coarse granular casts in the urine aU suggest interstitial inflammation. The presence of eosinophUia and eosinophiluria also strongly suggest the presence of an interstitial nephritis. Occasionally low to moderate proteinuria can be seen on urinalysis. 

The possibility of autoimmune disorders during interferon alfa treatment has been addressed by many authors. The spectrum of interferon alfa-induced immune diseases includes organ-specific and systemic autoimmune diseases, such as thyroiditis, diabetes, hematological disorders, systemic lupus erythematosus, rheumatoid arthritis, dermatological disease, and myasthenia gravis (156). Several have been discussed in appropriate sections elsewhere in this monograph. The exact role of interferon alfa is usually difficult to ascertain, because the underlying disease, that is chronic hepatitis C, can also be associated with immune-mediated disease. 

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. 

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. 

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. 

Because of these immunosuppressant activities, hydroxychloroquine is used to treat some autoimmune disorders, eg, rheumatoid arthritis and systemic lupus erythematosus. It has also been used to both treat and prevent graft-versus-host disease after allogeneic stem cell transplantation. 

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. 

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. 

Clinical Use. Cyclophosphamide (Cytoxan, Neosar) is an anticancer alkylating agent that is commonly used in a variety of neoplastic disorders (see Chapter 36). This drug may also be helpful in suppressing the immune response in certain autoimmune diseases, such as multiple sclerosis, systemic lupus erythematosus, and rheumatoid arthritis.12 43 High doses of cyclophosphamide are also used to prevent tissue rejection in patients receiving bone marrow transplants and other organ transplants. 

Therapists also deal with the rehabilitation of musculoskeletal disorders that are caused by an autoimmune response. Many of these diseases attack connective tissues, and autoimmune diseases such as rheumatoid arthritis, dermatomyositis, and systemic lupus erythematosus are often the primary reason that patients undergo rehabilitation. Patients with a compromised immune system may develop musculoskeletal problems related to their immunodeficient state. Hence, immunomodulating drugs are frequently used in many patients receiving physical therapy and occupational therapy. 

One controlled, double-blind trial plus anecdotal evidence attest to the efficacy of chlorambucil in rheumatoid arthritis. Chlorambucil has also been used in Behef s disease, systemic lupus erythematosus, vasculitis, and other autoimmune disorders. 

Typically, serum and synovial fluid from patients contain rheumatoid factors (>80% of patients) although serum rheumatoid factors are found in other autoimmune disorders affecting connective tissues, and in some chronic infections. The presence of small joint involvement along with the presence of rheumatoid factors is usually taken as diagnostic, however other disorders, such as systemic lupus erythematosus, need to be eliminated by clinical presentation and associated laboratory observations. 

There is indirect evidence of sex differences in immunology. Women have a higher incidence of autoimmune diseases such as multiple sclerosis, rheumatoid arthritis, and systemic lupus erythematosus. The influence of sex hormones on the immune system may provide insight into these immunological disorders. For example, estrogen stimulates both humoral and cell-mediated immunity, whereas testosterone has the opposite effect (126). Therefore, it is not surprising that there is sex-dependent variability in response to immunosuppressive agents. 

There was an unexpectedly high incidence of rheumatoid and lupus-like symptoms (27 of 137 patients), namely arthralgia, arthritis, myalgia, and Raynaud s phenomenon, in patients with myeloproliferative disorders taking interferon alfa alone or combined with interferon gamma (365). However, only a minority of affected patients fulfilled the diagnostic criteria for systemic lupus erythematosus. By contrast, systemic autoimmune diseases appeared to be genuine but very rare complications of interferon alfa in chronic hepatitis C, with only one case of lupus-like syndrome and two cases of polyarthritis in a survey of 677 patients (18). 

Cytokine concentrations reflect the severity of some diseases and are markers of prognosis. This is particularly applicable for infectious diseases (bacterial sepsis and parasitological infections) and immune disorders (autoimmune diseases, such as rheumatoid arthritis and systemic lupus erythematosus, and allergic diseases, such as asthma and skin hypersensitivity). 

There is also a significantly increased incidence of IgA deficiency in patients with autoimmune or potentially autoimmune disorders, and usually it is not clear which came first. It can be argued that autoimmunity is a complication of immune imbalance subsequent to inborn IgA deficiency (H24). With inborn absence of IgA, exposure to normal human colostrum, plasma, and saliva can result in the production of antibodies to IgA. By the time such patients are discovered the etiological mechanisms are often obscured and IgA treatment is out of the question. The incidence of IgA deficiency is known to be 1-4% in the following conditions Still s disease, systemic lupus erythematosus, rheumatoid arthritis, Sjogren s disease, warm hemolytic anemia, megaloblastic anemia, idiopathic pulmonary hemosiderosis, thyrotoxicosis, and cirrhosis. 

Diaz-Borjon, A. et al. (2000) Multidrug resistance-1 (M DR-1) in rheumatic autoimmune disorders. Part II. Increased P-glycoprotein activity in lymphocytes from systemic lupus erythematosus patients might affect steroid requirements for disease control. 

Acquired von Willebrand disease is a rare bleeding disorder that is similar to the congenital form of the disease. It has been reported primarily in association with autoimmune disorders, such as systemic lupus erythematosus, lymphoproliferative disorders, and neoplastic disease. Certain medications also have been associated with acquired von Willebrand disease, including valproic acid, dextran, and ciprofloxacin. Bleeding manifestations vary frommild to severe, and the condition often resolves with treatment of the underlying disease. In the acquired disease, von Wfllebrand factor appears to be synthesized in normal amounts, but then is rapidly removed from plasma by anti-von Willebrand factor antibodies, adsorption to tumor cells, or other mechanisms. ... 

Warm autoimmune haemolytic anaemia may be either idiopathic or secondary to chronic lymphocytic leukaemia, lymphomas, systemic lupus erythematosus, or other autoimmune disorders or infections. Warm autoantibodies are responsible for 48-70% of autoimmune haemolytic anaemia cases and may occur at any age due to the secondary causes, however, the incidence increases starting around 40 years of age. There is an approximate 2 1 female predilection, possibly due to the association with other autoimmune diseases. Warm autoimmune haemolytic anaemia presents as a haemolytic anaemia of varying severity. The symptoms are those of anaemia (i.e. weakness, dizziness, fatigue, pallor, oedema, and dyspnoea on exertion) and haemolysis (i.e. jaundice, dark urine, and splenomegaly). The laboratory evaluation shows a reduced... 

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