Rheumatoid arthritis anemia

Chronic autoimmune disorders or infections, such as human immunodeficiency virus (HIV) infection or rheumatoid arthritis (anemia of chronic disease)... 

Persistent or recurrent cutaneous T-cell lymphoma Prevention of severe chemotherapy-induced thrombocytopenia Moderate to severe active rheumatoid arthritis Moderate to severe active rheumatoid arthritis Anemia related to AZT therapy in HIV-infected patients Anemia associated with chronic renal failure... 

A decrease in erythrocyte production can be multifactorial. A deficiency in nutrients (such as iron, vitamin B12, and folic acid) is a common cause that often is easily treatable. In addition, patients with cancer and CKD are at risk for developing a hypoproductive anemia. Furthermore, patients with chronic immune-related diseases (such as rheumatoid arthritis and systemic lupus erythematosus) can develop anemia as a complication of their disease. Anemia related to these chronic inflammatory conditions is typically termed anemia of chronic 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. 

At present, numerous free radical studies related to many pathologies have been carried out. The amount of these studies is really enormous and many of them are too far from the scope of this book. The main topics of this chapter will be confined to the mechanism of free radical formation and oxidative processes under pathophysiological conditions. We will consider the possible role of free radicals in cardiovascular disorders, cancer, anemias, inflammation, diabetes mellitus, rheumatoid arthritis, and some other diseases. Furthermore, the possibilities of antioxidant and chelating therapies will be discussed. 

This point of view overlooks the fact that every well and normal individual is potentially an ill individual, and the roots of disease may be present in his make-up years before there is any overt disease. A dozen young men used as normal controls may each have metabolic peculiarities that point toward a different metabolic derangement gout, multiple sclerosis, diabetes, anemia, atherosclerosis, hypertension, nephrosis, hypothyroidism, rheumatoid arthritis, rheumatic heart disease, liver cirrhosis, and myasthenia gravis, for example, and yet at the time of their use as controls these young men may show no symptoms of the disease which is to appear later in life. It seems far from safe to assume that because an individual on clinical examination seems well, all of his blood values, for example, are normal and meaningless so far as disease susceptibilities are concerned. 

History of penicillamine-related aplastic anemia or agranulocytosis rheumatoid arthritis patients with a history or other evidence of renal insufficiency pregnancy breastfeeding. 

Generalized/organ specific (lung disease, anemia, decreased blood supply) Cellular hypoxia (cyanide poisoning of electron transport chain in mitochondria) Inflammatory (pathology from abnormal inflammatory response in the body) Autoimmune and/or chronic diseases (systemic lupus erythmatosus, rheumatoid arthritis)... 

G. Other applications Epoetin alfa may find a place in the therapy of anemia of other diseases such as those associated with sickle cell disease, rheumatoid arthritis, and prematurity. In addition the potential for use in autologous blood transfusion programs merits study. 

Azathioprine and mercaptopurine appear to be of definite benefit in maintaining renal allografts and may be of value in transplantation of other tissues. These antimetabolites have been used with some success in the management of acute glomerulonephritis and in the renal component of systemic lupus erythematosus. They have also proved useful in some cases of rheumatoid arthritis, Crohn s disease, and multiple sclerosis. The drugs have been of occasional use in prednisone-resistant antibody-mediated idiopathic thrombocytopenic purpura and autoimmune hemolytic anemias. 

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. 

Leucovorin or folinic acid, a mixture of the 6R- and 6S,-diastereomers of 5-formyltetrahydrofolic acid, is an important clinical agent which may be used as a remedy for megaloblastic anemia and as an antidote for inadvertent overdosages of antifolates in patients with cancer, parasitic diseases, or autoimmune disorders such as psoriasis and rheumatoid arthritis. In view of these applications it is surprising that few significant improvements in the manufacture of leucovorin have occurred... 

In patients suffering from a wide variety of tmrelated diseases, including Hodgkins lymphoma, rheumatoid arthritis, schizophrenia, porphyria, renal tuberculosis and aplastic anemia, there is abnormal excretion of kynurenine metabolites after a test dose of tryptophan (Altman and Greengard, 1966 Coon and Nagler, 1969). It is unlikely that such disparate conditions would aU be associated with vitamin Be deficiency. Liver biopsy shows elevated tryptophan... 

A-39 Deficiency of Vitamin B6 can cause convulsions, lethargy, mental changes retardation, anemia, and skin inflammation. Deficiencies of vitamin Be are rare and usually are related to an overall deficiency of all the B-complex vitamins. Isoniazid (see niacin deficiencies above) and penicillamine (used to treat rheumatoid arthritis and cystinurias) are two drugs that complex with pyridoxal and pyridoxal phosphate resulting in a deficiency in this vitamin. 

Macrocytic anemia associated with folate deficiency has been described in patients with rheumatoid arthritis (30) and also in patients who abuse analgesic mixtures containing aspirin (30). 

Deferoxamine has a strong depressant effect on proliferation of bone marrow cultures in vitro (72). On the other hand, deferoxamine improves hemopoiesis in patients with anemia, for example in rheumatoid arthritis, hemolysis, or myelodysplastic sjmdromes, and reduces transfusion dependency (73-78). The mechanism is unknown, but increased erythropoietin responsiveness secondary to iron chelation may play a role (77). 

When used in patients without iron overload, deferoxamine can cause iron deficiency (12). In 20 patients, there were falls in ferritin concentrations in six, requiring withdrawal of deferoxamine and parenteral administration of iron dextran (12). Monitoring ferritin concentrations is therefore recommended in patients receiving deferoxamine for aluminium overload. On the other hand, the administration of deferoxamine (500mg/day by subcutaneous infusion) improves chronic anemia in patients with rheumatoid arthritis (77). This effect is thought to be achieved through increased erythropoietin responsiveness, secondary to iron chelation. Iron chelation with deferoxamine also improves hemopoiesis in patients with myelodysplastic syndromes and can reduce transfusion dependency (78). Exactly how deferoxamine works in these patients remains to be explained. 

A 62-year-old woman with rheumatoid arthritis developed swelling and pain of both knees. Aurothiomalate was given in a test dose of 12.5 mg, followed the next day by a dose of 25 mg, and then 50 mg twice weekly (total cumulative dose 137.5 mg). She had a leukocjde count of 2.2 X 10 /1, a normochromic anemia, and a normal platelet count. Her hver enzyme activities were raised. Aurothiomalate was withdrawn and about 6 weeks later her liver function tests returned to normal and her white cell count rose to 6.9 x 10 /1. 

An 80-year-old Japanese woman presented with epigastric discomfort and nausea. She had a history of hypertension, rheumatoid arthritis, iron deficiency anemia, chronic renal insufficiency, and had taken oral ferrous sulfite for 19 months. Endoscopic examination of the duodenum showed marked pigmentation of the duodenal mucosa. Histological examination showed that the pigment had histochemical features compatible with hemosiderin and was located mainly within macrophage lysosomes in the lamina propria. Ferrous sulfite was withdrawn and the pigmentation disappeared within 7 months. 

Aplastic anemia with fever and pancytopenia developed in a 29-year-old woman, probably as a reaction to tiopronin (500 mg/day), which she had taken for 71 days for seronegative rheumatoid arthritis (9). A bone marrow examination confirmed acute marrow aplasia. She recovered within 5 weeks after withdrawal. 

In addition to penicillamine nephropathy, other side effects of the drug may be related to the widespread deposition of immune complexes (Figure 3). Dense, granular immunoglobuhn deposits have been identified at the epidermodermal junction in 4 rheumatoid arthritis patients who developed toxic reactions, such as severe rashes, thrombocytopenia, aplastic anemia, and proteinuria. Three of 4 penicillamine-induced systemic lupus erythematosus syndrome patients had similar findings on skin biopsy [161]. 

Gibson J, McGirr EE, York J, Kronenberg H. Aplastic anemia in association with gold therapy for rheumatoid arthritis. Aust NZ J Med 1983 13 130-135. 

Weiss AS, Markenson JA, Weiss MS, Kammerer WEI. Toxicity of D-penicillamine in rheumatoid arthritis. A report of 63 patients including two with aplastic anemia and one with the nephritic syndrome. Am J Med 1978 64 114-120. 

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