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Signs and Symptoms of Iron Deficiency

(Wintrobe's Clinical Hematology, 11th Edition, 2004)

Iron deficiency anemia, like all anemias, is not a disease but a manifestation of disease, and the clinical presentation may include features of the underlying disease process as well as those of the deficiency state. Many patients, however, seek medical attention because of symptoms of anemia alone. In a study from the 1960s, this mode of presentation was observed in 63% of 371 patients (220). Only 16% visited the physician because of symptoms of the disease causing the anemia. In the remaining 21%, anemia was discovered at the time of evaluation for an unrelated complaint.
The onset of iron deficiency anemia is usually insidious, and the progression of symptoms is gradual. As a result, patients accommodate remarkably well to advancing anemia and may delay a visit to their physicians for prolonged periods.
Iron deficiency impairs growth in infancy, and the growth rate is restored when the deficiency is corrected (188). In one group, 78 of 156 iron-deficient children fell below the twenty-fifth percentile of expected weight.
Iron deficiency anemia can be associated with irritability, palpitations, dizziness, breathlessness, headache, and fatigue. Fatigue is a particularly common complaint among patients. It is clear that even latent iron deficiency (i.e., iron deficiency without any anemia at all) may result in fatigue (302). A group of 44 nonanemic women reporting fatigue were treated both with iron and with placebo in random order. Symptomatic improvement in women receiving iron was significantly better than that of women given the placebo but only in women whose iron stores were depleted. Other investigators have been unable to confirm this observation (303,304), but many practitioners have cared for patients with recurrent iron deficiency who could tell when their stores became depleted because of symptoms that preceded anemia.
Despite the lack of symptoms at rest, investigators have demonstrated that even mild degrees of iron deficiency anemia impair muscular performance, as measured by standardized exercise tests (189,305,306). Total exercise time, maximal workload, heart rate, and serum lactate levels after exercise are all affected adversely in proportion to the degree of anemia. Furthermore, work performance and productivity at tasks requiring sustained or prolonged activity are impaired in iron-deficient subjects and improve when iron is administered (307,308). As a result, measures directed toward iron nutrition of a work force can produce important economic dividends, more than offsetting the costs of the treatment program (189,307).
Abnormalities in muscle metabolism are noted even when deficiency is mild (309). Blood lactate levels were measured in mildly iron-deficient female athletes after standardized exercise tests. Peak lactate levels fell significantly after 2 weeks of iron treatment. This observation led to the suggestion that iron deficiency forces the muscles to depend to a greater extent on anaerobic metabolism than occurs in normal subjects. In contrast, no abnormalities of muscle function were noted in six nonanemic patients with long-standing iron deficiency, induced for the treatment of polycythemia vera (310).
Animal studies confirm that muscle function is disturbed in iron deficiency. The spontaneous activity level of iron-deficient rats decreased (311), and short-term exercise tolerance in treadmill running tests was reduced (181,182,312,313), even at mild degrees of deficiency (314). These abnormalities could not be explained by anemia alone, because they persisted after anemia was corrected by exchange transfusion (181,182). All were corrected promptly when iron was administered.
A variety of behavioral disturbances has been observed in iron-deficient children (188,315,316,317,318 and 319). These children have been reported to be irritable and disruptive, with short attention spans and a lack of interest in their surroundings. Neurologic development in infants (320) and scholastic performance in older children (321) may be impaired. Cognitive performance is defective in iron-deficient rats (322). All of these behavioral abnormalities are ameliorated with the initiation of iron therapy.
The ability to maintain body temperature on exposure to cold is impaired in iron-deficient patients (323) and animals (324). Occasional patients experience neuralgia pains, vasomotor disturbances, or numbness and tingling. In children, iron deficiency has been associated with neurologic sequelae, including developmental delay, ischemic stroke, increased intracranial pressure, papilledema, and the clinical picture of pseudotumor cerebri (325). The pathogenesis is probably complex, involving severe anemia, thrombocytosis, and reduced levels of tissue iron enzymes.
Patients with long-standing iron deficiency may develop a constellation of symptoms characterized by defective structure or function of epithelial tissue. Especially affected are the nails, the tongue and mouth, the hypopharynx, and the stomach. These epithelial lesions tend to occur together in the same patients at the same time (326,327) but also may occur as isolated findings.
In iron-deficient subjects, the fingernails may become brittle, fragile, or longitudinally ridged, but these findings are quite nonspecific. Alterations more typical of iron deficiency are nail thinning, flattening, and ultimately the development of koilonychia, concave or “spoon-shaped” nails. Koilonychia is now rarely seen in clinical practice, but of 400 babies attending a well-baby clinic in West Virginia before 1970, 5.5% had koilonychia, and nearly all of these infants appeared to be iron-deficient (328). Koilonychia is a relatively nonspecific finding, which can also result from prolonged, repeated exposure to hot soapsuds and other caustic agents.
Oral abnormalities, including atrophy of the lingual papillae, are the most common of iron deficiency–induced epithelial changes. These may present as soreness or burning of the tongue, either spontaneously or stimulated by food or drink, and by varying degrees of redness (326). The filiform papillae over the anterior two-thirds of the tongue are the first to atrophy and may disappear completely. In severe cases, fungiform papillae also may be affected, leaving the tongue completely smooth and waxy or glistening (329). These changes are generally reversed after 1 to 2 weeks of iron therapy. Angular stomatitis, characterized by ulcerations or fissures at the corners of the mouth, is a less specific sign of iron deficiency, and it also occurs in riboflavin and pyridoxine deficiencies.
Вадим Валерьевич.