A PRESENTATION ON POSSIBLE CAUSES OFANEMIA IN A PATIENT WITH RHEUMATOID ARTHRITIS BY DR JOSEPH UCHENNA VICTOR MEDICAL FACULTY GROUP 5(CLINICAL PRACTICAL SKILLS) 4TH COURSE
IntroductionPossible Causes of Anemia in RA Patient-Non-drug associated-Drug associatedConclusion
Rheumatoid arthritis is a chronic inflammatory(autoimmune) disorder that typically affects thejoints in hands and feet especially small jointscausing a painful swelling that can eventuallyresult in bone erosion and joint deformity. Asidefrom joint symptoms, anemia is the most commonproblem for people with rheumatoid arthritis. Studiesshow as many as 60% of people with rheumatoidarthritis are anemic. Anemia is a below-normal levelof hemoglobin* or hematocrit*.
Anemia can be a temporary condition, aconsequence of other health conditions, or it canbe a chronic problem. People with mild anemiamay not have any symptoms or may have onlymild symptoms. People with severe anemia mayhave problems carrying out routine activities andcan feel tired or experience shortness of breathwith activity.
Anemia and rheumatoid arthritis are linked toeach other as this can affect the bone marrow andthus the blood count. Sex, age, duration and renalfunction play important role on the developmentof anemia. Prevalence of anemia is higher inwomen (73%) than in men (38%). The prevalencealso is more frequent in younger and olderwomen, with the highest hemoglobin levels inpatients >58years.
There can be many reasons a person with rheumatoidarthritis experiences anemia. According to general classificationof causes, it can be grouped into 2 major categories;A. Non-drug associated:Non-drug associated includes, Anemia of Chronic Disease(ACD) and concomitant disease induced.B. Drug associated:In drug associated, it is noted that the anemia is not part of RAbut as a result of side-effects of drugs used in the treatment.E.g. NSAIDs, (DMARDs) Disease Mediating Anti-RheumaticDrugs: Methotrexate and other heavy metal-containing drugslike gold.
Overall, anemia in RA is classified as an anemiaof chronic disease (ACD) and it is considered themost frequent cause of anemia in RA. The anemiadevelops slowly during the first month of illness andhas been found to be associated with a higher degreeof disease activity. ACD is usually mild andnonprogressive, characterized by decreased plasmairon, decreased total iron-binding capacity, decreasediron saturation of transferrin, decreased bone marrowsideroblast, and normal or increasedreticuloendothelial iron.
One cause is inflammation associated withrheumatoid arthritis. Inflamed tissues secrete smallproteins that have effects on iron metabolism, bonemarrow, and erythropoietin production by thekidneys (a hormone that controls production of redblood cells).The development of ACD in patients suffering fromRA is related to the inflammation associated with thecondition. The increased production of inflammatorycytokines results in decreased availability oferythropoietin, decreased erythropoietic response in thebone marrow and inadequate erythropoiesis.
Numerous cytokines, including TNF, IL-1, IL-10,IFN-Υ and IL-6, mediate ACD. Hepcidin, apeptide that controls iron homeostasis, is an acutephase protein that is influenced by inflammation.Hepcidin, secondary to the effects of IL-6 is alsoassociated with ACD. IL-6 has a significant effect,through the increased production of hepcidin, ondecreased duodenal iron absorption and reducediron transport to macrophages, as well as thestorage of ferritin in macrophages.
The outline effects of cytokines due to inflammation in RA include;1.Iron utilization is impaired, with decreased serum ironand transferrin concentrations and an increased synthesisof ferritin. There is increased lactoferrin which binds andlowers serum iron.2. Reduced erythropoietin levels3. Decreased bone marrow response to erythropoietin.4. Premature destruction of red blood cells. Red blood cell lifespan may be reduced.Hence in ACD, the anemia is most often normocytic andmonochromic. Different inflammatory substances depressreticular processes causing anemia of different forms.
The degree of anemia in RA is related to theactivity of the underlying disease andinflammation. Proven effect was also observed onsecondary disease activity characteristics for thenumber of swollen joints, pain score, and patientsglobal assessment of disease activity. A combinationof rheumatoid arthritis, splenomegaly, leucopenia,pigmented spots on lower extremities, and otherevidence of hypersplenism (anemia andthrombocytopenia).
Concomitant diseases causes secondary anemia (Irondeficiency) in RA patient by causing internal bleeding orby destruction of bones which directly affectserythropoiesis and hematopoietic disorders in kidney. Theyinclude Osteoarthritis, Leucopenia, disease of thyroid gland, Canceretc.Rheumatoid arthritis as a disease may cause a warmautoimmune hemolytic anemia. The red cells are of normalsize and color (normocytic and normochromic). A low whiteblood cell count (neutropenia) usually only occurs in patientswith Feltys syndrome with an enlarged liver and spleen. Themechanism of neutropenia is complex. An increased plateletcount (thrombocytosis) occurs when inflammation isuncontrolled, as does the anemia.
Mostly results to Iron-deficiency anemia(hypochromic, microcytic ) and sometimesmegaloblastic anemia. NSAIDs and DMARDs are themain cause of drug related anemia in patient withRA. This anemia is secondary because it’s not as aresult of the disease. Pain killers, NSAIDs,Methotrexate are among drugs use in treatment of RAwhich have side effects on patients blood cell count.This iron deficiency is usually caused by gastrointestinalbleeding, or a problem getting the iron from within thebone marrow into the red blood cells.
NSAID induced bleeding (menstrual bleeding inwomen) and secondary iron deficiency while bonemarrow suppression is caused from drug therapyi.e. gold, Penicillamine, Methotrexate. Generally, theyprevent the release of iron for incorporation into redblood cells. This type of anemia is characterized bydecreased or absent iron stores, low serum ironconcentration, low transferrin saturation, and lowhemoglobin concentration or hematocrit value. Theerythrocytes are hypochromic and microcytic and theiron binding capacity is increased.
The most common causes of anemia in patients withrheumatoid arthritis are the anemia of chronic disease(ACD) and iron deficiency anemia (IDA). ACD ismore common than IDA in RA patients, occurring inup to 77% of anemic RA patients. In fact, anemia inRA patients has served as a model for the anemia ofchronic disease. Differentiating the types of anemia isimportant in planning diagnostic testing and inguiding therapy. In ACD, hemoglobin levels arehigher than in IDA, ferritin levels tend to be steady orincreasing, but if ferritin is decreased, and the anemiais hypochromic, IDA is much more likely.
It is estimated that iron deficiency anemia occurs inapproximately 23% of anemic RA patients. However, Irondeficiency anemia often coexists with ACD in RApatients. It is generally a hypochromic, microcytic anemiamost commonly due to gastrointestinal bleedingsecondary to nonsteroidal anti-inflammatory drugs(NSAIDs), or corticosteroid therapy. “It’s important torecognize that iron deficiency anemia is not part of RA.It’s the drugs we use to treat our patients, such as the NSAIDsand the DMARDs (disease-modifying antirheumatic drugs); itcan also be from the secondary effects of other concomitantconditions resulting in gastrointestinal blood loss that causesIDA in the patients.