Correspondence

Iron Deficiency in Children

N Engl J Med 1993; 329:1741-1742December 2, 1993

Article

To the Editor:

In an excellent discussion of iron deficiency, Oski (July 15 issue)1 did not mention the existence of the serious yet reversible complication of increased intracranial pressure leading to pseudotumor cerebri. As early as the 1880s and 1890s, Gowers2 and subsequently Bannister3 and others made the association of iron-responsive anemia (then termed “chlorosis”) and papilledema (then termed “retinopapillitis” or “optic neuritis”). Their patients were young women with severe headaches, visual symptoms, and iron-deficiency anemia, presenting acutely with papilledema and increased intracranial pressure, or what we now know to be pseudotumor cerebri4. Because of the papilledema and headaches, these patients were often initially thought to have brain tumors3. However, the institution of iron therapy reversed the illness.

We recently treated a 36-year-old woman who presented with severe headaches and blurred vision. Ophthalmoscopy demonstrated papilledema with preserved visual acuity and fields. Serial hematocrits were in the low 20s, accompanied by a very low serum iron level and a high total iron-binding capacity. Cranial computed tomography (and subsequent magnetic resonance imaging) showed slit-like ventricles and no mass lesion. The cerebrospinal fluid opening pressure was more than 300 mm of water on two occasions, with normal glucose protein levels and normal cell counts. Ancillary investigations were negative, and the anemia was attributed to menometrorrhagia. Long-term treatment with iron led to resolution of the symptoms, return of serum iron concentrations to low normal levels, and reversal of the papilledema. The patient was then lost to follow-up for two years, during which she failed to comply with treatment. She recently presented with a relapse of symptoms and recurrence of pseudotumor. Iron treatment was resumed, with subsequent resolution of signs and symptoms.

Lubeck summarized 11 cases of papilledema caused by iron-deficiency anemia (range of patients' ages, 14 to 33)4. The mechanism may be related to abnormal hemodynamics, as in other states of increased blood flow to the brain. Anemia may lead to reversible bulging of the fontanelles in infants with iron deficiency,5 rather than papilledema.

Patients with iron-deficiency anemia and headache should undergo a careful examination of the optic fundi to rule out papilledema, since this can lead to visual loss if left untreated.

Misha Pless, M.D.
Stuart A. Lipton, M.D., Ph.D.
Harvard Medical School, Boston, MA 02115

5 References

1. 1

   Oski FA. Iron deficiency in infancy and childhood. N Engl J Med 1993;329:190-193
   Full Text | Web of Science | Medline

2. 2

   Gowers WR. Optic neuritis in chlorosis. BMJ 1881;1:796-797
   CrossRef | Medline

3. 3

   Bannister HM. Chlorosis and retinopapillitis. J Nerv Ment Dis 1898;25:874-881
   CrossRef

4. 4

   Lubeck MJ. Papilledema caused by iron-deficiency anemia. Trans Am Acad Ophthalmol Otolaryngol 1959;63:306-310
   Medline

5. 5

   Fishman RA. Cerebrospinal fluid in diseases of the nervous system. 2nd ed. Philadelphia: W.B. Saunders, 1992:147.
   

To the Editor:

In the recent excellent review of iron deficiency in children by Oski, we were surprised by the omission of any mention of pica. Pica is defined as the abnormal, persistent, compulsive ingestion of food or non-food substances1. This symptom, and particularly pagophagia -- the habit of chewing ice -- has long been recognized as a symptom of iron deficiency2.

The relation between pica and iron deficiency has been debated by proponents of pica as a causal factor in iron deficiency and proponents of pica as a result of iron deficiency due to largely undetermined mechanisms. Pica has been documented worldwide, and its prevalence in the United States is underestimated. The substances ingested vary geographically -- probably because of ethnic differences and food preferences. Pica is also thought to be more common among children.

Pica may be associated with lead poisoning, which may cause iron deficiency and which is a serious health hazard to young children.

Martin H. Ellis, M.D.
James D. Levine, M.D.
New England Deaconess Hospital, Boston, MA 02115

2 References

1. 1

   Sayetta RB. Pica: an overview. Am Fam Physician 1986;33:181-185
   Web of Science | Medline

2. 2

   Rector WG Jr. Pica: its frequency and significance in patients with iron-deficiency anemia due to chronic gastrointestinal blood loss. J Gen Intern Med 1989;4:512-513
   CrossRef | Web of Science | Medline

To the Editor:

The review by Oski includes a misunderstanding about heme iron and the absorption of non-heme iron. Heme iron itself does not promote the absorption of non-heme iron. The absorption of non-heme iron from a meal is improved by the presence of meat, fish, or chicken. The effect relates specifically to muscle protein and is probably due to the production of digestion intermediates -- the so-called meat factor -- that act as ligands in the formation of soluble iron complexes1,2.

Berit Borch-Iohnsen, Ph.D.
Institute of Nutrition Research, University of Oslo, N-0316 Oslo, Norway

2 References

1. 1

   Bothwell TH, Baynes RD, MacFarlane BJ, MacPhail AP. Nutritional iron requirements and food iron absorption. J Intern Med 1989;226:357-365
   CrossRef | Web of Science | Medline

2. 2

   Slatkavitz CA, Clydesdale FM. Solubility of inorganic iron as affected by proteolytic digestion. Am J Clin Nutr 1988;47:487-495
   Web of Science | Medline

Author/Editor Response

Dr. Oski replies:

To the Editor: Pseudotumor cerebri was omitted from the discussion of iron deficiency because it is a manifestation of anemia rather than a specific finding of iron-deficiency anemia1. In similar fashion, pica was not mentioned because it too is not a specific symptom of iron deficiency. Pica may be caused by a variety of nutritional deficiencies and psychological factors and has even been cured by intramuscular injections of saline2. I thank Borch-Iohnsen for the suggestion that the “meat factor” explains the effect of heme iron on the absorption of non-heme iron. Others have suggested alternative mechanisms3.

Frank A. Oski, M.D.
Johns Hopkins University School of Medicine, Baltimore, MD 21287

3 References

1. 1

   Davies-Jones GAB, Preston FE, Timperley WR. Neurological complications in clinical haematology. Oxford, England: Blackwell Scientific, 1980:1-6.
   

2. 2

   Lanzkowsky P. Investigation into the aetiology and treatment of pica. Arch Dis Child 1959;34:140-148
   CrossRef | Web of Science | Medline

3. 3

   Cook JD, Monsen ER. Food iron absorption in human subjects. III. Comparison of the effect of animal proteins on nonheme iron absorption. Am J Clin Nutr 1976;29:859-867
   Web of Science | Medline

Citing Articles (3)

Citing Articles

1. 1

   Christine E. Chamberlain, Edmond FitzGibbon, Eric M. Wassermann, John A. Butman, David Kettl, Doug Hale, Allan D. Kirk, Roslyn B. Mannon. (2005) Idiopathic intracranial hypertension following kidney transplantation: A case report and review of the literature. Pediatric Transplantation 9:4, 545-550
   CrossRef

2. 2

   Claudio Sandoval, Somasundaram Jayabose, Alvin N. Eden. (2004) Trends in diagnosis and management of iron deficiency during infancy and early childhood. Hematology/Oncology Clinics of North America 18:6, 1423-1438
   CrossRef

3. 3

   Gloria A. Otero, Francisco B. Pliego-Rivero, Graciela Contreras, Josefina Ricardo, Thalı́a Fernández. (2004) Iron supplementation brings up a lacking P300 in iron deficient children. Clinical Neurophysiology 115:10, 2259-2266
   CrossRef