Anemia and lupus

In this issue of the Journal is published the article «Pathogenic role of erythropoietin in Egyptian SLE anemic patients: Prevalence of different types of anemia in systemic lupus erythematosus». This article raises a dissertation to which we are frequently exposed in the process of diagnosis or follow-up of patients with rheumatic diseases of autoimmune origin. It is sometimes difficult to identify the cause of the anemic syndrome that accompanies these patients. The explanations of the phenomenon can be multiple and it requires an individualized approach in which it is necessary to establish whether it obeys to a manifestation proper of the entity we are facing; if it is a manifestation of the chronic inflammatory state; if it is related to a nutritional deprivation in which the iron deficit occupies the first place; if it is secondary to some comorbidity such as gastrointestinal bleeding or renal failure, or if, as is common, it has a multicausal origin in which the mechanisms outlined above are combined.¹

It is not a matter of little concern, nor should it be seen as a common issue or of minimal importance given the implications that an anemic syndrome can have on a patient with a complex disease, in whom this condition may end up compromising the cardiovascular status or deepening the intensity of the «constitutional» symptoms, sometimes poorly weighted by being framed within the group of manifestations identified as «fibromyalgia» that accompanies the majority of these patients.² It is the case of fatigue, a cardinal symptom of the patient with chronic rheumatic disease, that we are obliged to consider as an inflammatory activity of the disease and rethink, if necessary, the therapeutic approach that allows to reduce the impact that this manifestation produces in the quality of life of these patients.³

The anemia that accompanies the chronic inflammatory diseases is usually mild or moderate, and rarely the level of hemoglobin is below 10 g per liter.⁴ Approximately 50% of patients with systemic lupus erythematosus (SLE) have this type of anemia prior to starting the treatment of the disease.⁵ Finding lower values of hemoglobin obliges us to consider a different cause, especially those related to pathophysiological mechanisms altered by the chronic autoimmune disease. The anemia of systemic inflammatory disease is essentially an immune disorder with multiple alterations, in which iron homeostasis, proliferation of erythroid progenitors, reduced erythropoietin activity, and decreased erythrocyte half-life stand out.⁶

We cannot forget, in the context of patients with chronic rheumatic diseases of autoimmune origin, the anemia related to iron deficiency. In the case of SLE and its relationship with the female gender, the menstruation is an important condition that must be taken into account in the diagnosis and treatment,⁷ without underestimating situations related to gastrointestinal disorders associated with chronic consumption of non-steroidal anti-inflammatory drugs and glucocorticoids, which favor the decrease in serum iron levels secondary to bleeding from the digestive tract.⁸ It becomes necessary to rule out in every rheumatic patient in whom the use of these drugs for a long time is contemplated, the presence of an active acid-peptic disease that favors this condition. The age of the patient is another determining circumstance in the onset of the anemia.⁹ In general, few patients have anemia related to poor iron intake, and its origin is multicausal.¹⁰

It is important to take into account the effect of immunosuppressive medications in patients with diseases such as SLE or rheumatoid arthritis (RA). Immunosuppressants such as methotrexate, cyclosporine, azathioprine, leflunomide and mycophenolate exert a direct effect on the bone marrow, they reduce erythropoiesis and the half-life of erythrocytes.¹¹ New drugs, such as the inhibitors of JAK kinases (inhibitors of Janus kinases), have an intrinsic effect on the bone marrow and, to a greater of lesser extent, they have an impact on the regulatory mechanisms of the formation of the formed elements of the blood that oblige to their frequent monitoring in the patients who receive them.¹²

The article of Dr. Ahmed et al. studies the frequency of the 3 most common causes of anemic syndrome in an important group of Egyptian patients with an established diagnosis of SLE. The anemia related to chronic inflammatory status was the most frequent (41.3%), followed by the anemia secondary to iron deficiency (33.3%), and finally by the anemia of autoimmune etiology (25.3%). The authors complement the results with the relationship that anemia could have with serum erythropoietin (EPO) levels, and although in all three conditions the serum level of this hormone was higher than that found in the controls, the levels in the patients classified with anemia related to autoimmune mechanisms of the disease were significantly lower than the levels in patients with anemia due to chronic inflammation and iron deficiency.

The results obtained by Dr. Ahmed are in concordance with what was reported by other researchers. Serum levels of EPO in patients with SLE appear to be inadequate to respond properly to the degree of anemia, or the response of the bone marrow to the hormone would be diminished compared with healthy individuals.

Whatever the explanation, the reduced biological activity of EPO in patients with SLE could be a consequence of the effects of increased levels of TNF, IL-1 and toxic radicals on EPO producing cells in the kidney, as well as of the infiltration of the renal peritubular region by macrophages and T cells.^13,14

In conclusion, the anemia in patients with chronic rheumatic diseases of autoimmune origin, such as SLE and RA, should be considered as an important issue to take into account in the diagnosis, treatment and prognosis of these patients. No effort should be spared to find the origin of the condition. The recovery of serum hemoglobin levels will result in the well-being of patients and will favor the appropriate response to other therapeutic measures implemented.