CASE REPORT

Iron Deficiency Anemia and Papilledema

Rapid Resolution with Oral Iron Therapy

Richard Stoebner,* MD, Roger Kiser, MDf and Jack B. Alperin$

T h e r e h a v e b e e n seve ra l case r e p o r t s of

p a p i l l e d e m a a s s o c i a t e d w i t h i r o n de f i c i ency

a n e m i a . W i t h o n e e x c e p t i o n , al l h a v e b e e n

w o m e n w i t h a n a v e r a g e age o f 18 yea rs

(1-4). T h e f o l l o w i n g is a d e s c r i p t i o n of a

p a t i e n t w i t h p a p i l l e d e m a a n d i r o n def ic ien-

cy a n e m i a . S i g n i f i c a n t r e s o l u t i o n of t he

p a p i l l e d e m a o c c u r r e d w i t h i n 7 days of ins t i -

t n t i n g t h e r a p y w i t h o ra l i r o n .

CASE REPORT A 19-~ear-old female complained of generalized

weakness and dizziness when assuming an erect posture, These symptoms became so troublesome that she was confined to bed. She denied epistaxis, hemoptysis, hematemesis, melena and hematuria. She described a normal menstrual history and had never been pregnant. Recently. she had noted an unusually great desire to cat ice (5), and, in addition, described a long history of chronic con- sumption of laundry starch (6). She denied the ingestion of any drugs, and there was no family history of anemia. Physical examination disclosed an obese female who weighed 188 lb, was 62 in. in height and had marked pallor. A sinus tachycardia of 115 beats/rain was present. Her blood pressure,

From the l)i,,isions of Gastroenterology and Hematology, Department of Internal Medicine, University of Texas Medical Branch, Galveston, Tex.

Sponsored in part by DHEW 5T01 AM 05304-08 and DHED." 5T01 AM 05208.

Address for reprint requests: R. Stoebner, MD, l)epartment of Medicine, University of Texas Medi- cal Branch. Galveston. Tex.

*NIH Fellow in Gastroenterology, Department of Internal Medicine, University of Texas Medical Branch.

]Resident in Internal Medicine, University of Texas Medical Branch,

.+Assistant Professor, Department of Internal Medicine, University of Texas Medical Branch.

respiration and tenlperature wine llorma]. Li~er, spleen and lymph nodes were not palpahle. Exam- ination of the eyes revealed bilateral papilledema with no hemorrhage or exudates (Fig 1). There was a grade II/VI systolic murmur at the cardiac apex. Rectal and pelvic examinations revealed no abnormalities. The remainder of the physical ex- amination, including neurologic examination, was within normal limits.

A hemogram obtained on admission showed hemoglobin 5.0 g/100 ml, hematocrit 20%, ervthro- cvtes 2.6 million/cu mm and reticulocytes2.2%. The calculated erythrocyte indices were MCV 75 cu mm, MCH 19 /z#g and MCHC 25 g/100 ml. Microscopic exantination of Wright's-stained blood smears dis- closed hypochrmnic and microcytic erythrocytes. Leukocvtes and platelets were normal. Serum iron and total binding capacity measured 20 and 332 mg/100 ml, respectively. Examination of a Kingsley's-stained sternal bone marrow aspirate revealed a maturation arrest in erythropoiesis at the pol)chromatophilic normoblast stage of develop- merit. Furthermore, no hemosiderin deposits were found in the bone marrow when the aspirate was stained with Prussian blue. Electrophoresis of a hemolysate showed no hemoglobinopathy. Qnanti- tative analysis of the hemoglobin disclosed 2.1% hemoglobin A.., less than 1% fetal hemoglobin and the remainder, hemoglobin A.

Repeated stool examinations were negative for occult blood. An upper gastrointestinal series denlonstrated an nicer crater in the duodenum. Proctoscopic and barium examination of the colon shmved no abnormalities. An electroencephalogram, brain scan with Tc ~ pertechnetate and roentgeno- grams of the skull were all normal except for slight demineralization of the dorsum sella. Normal meas- urements in serum of calcium, phosphorus, electro- lyres and total proteins were obtained. Also normal were serum protein electrophoresis and tests of thyroid, renal and hepatic function. The patient refused a lumbar puncture.

Therapy with ferrous sulfate..'300 mg three times

D;gestive Diseases, Vol. 15, No. 10 (October 1970) 919

STOEBNER ET AL

Fig 1. Photograph of ocular fundus prior to therapy demonstrates marked papilledema.

Fig 2. Photograph of ocular fundus taken 7 days after instituting iron therapy demonstrates significant resolution of papilledema.

a day, was instituted with a dramatic response. Beginning resolution of the papilledema was noted 72 hr after the onset of iron therapy and the papilledema was ahnost completely resolved on the seventh day of therapy (Fig 2). The reticulocvte count at this time had climbed to 11%. hnprove- merit in the papilledema was coincident with improvement of the patients subjective weakness and dizziness. Two months after starting iron therapy, the patient was asymptomatic, papilledema

had disappeared, and the blood count was normal, An examination 5 months later rc~ealed no abnor- malities.

D I S C U S S I O N

A wel l k n o w n p h e n o m e n o n is ti le r a p i d

d i s a p p e a r a n c e o f w e a k n e s s a n d e x t r e m e

f a t i g u e a f t e r i r o n is a d m i n i s t e r e d to pa-

t i en t s w i t h i r o n def ic iency , S y m p t o m s in

920 Digestive Diseases, Vol. 15, No. 10 (October 1970)

IRON DEFICIENCY

many patients have improved after only 24 hr of therapy and before the hemoglobin concentrat ion increased (7-10). Previous reports, describing patients with iron defi- ciency anemia and papil ledema, have not commented on the rapidity with which papil ledema was resolved after blood trans- fusion or t reatment with iron (1,4, 7, 11). The improvements in our pat ient 's pap- illedema began shortly after iron replace- ment started and was independent of the hemoglobin level. Ninety-six hours after beginning therapy, there was significant resolution of the papil ledema; however, the hemoglobin concentrat ion was 5.7 g/100 ml which represented little change from the value on admission. After 7 days of iron therapy, the papi l ledema was near- ly gone, the reticulocyte count had reached a value of 11 percent, and the hemoglobin measured 6.3 g/100 mI.

Papil ledema is very rare in iron deficien- cy anemia, and the cause is unknown. Capriles described 4 patients, all females with iron deficiency anemia and papillede- ma, who responded satisfactorily to oral iron therapy. He postulated that iron defi- ciency could cause cerebral edema and pap- illedema by carbon monoxide intoxica- tion through the formation of carboxyhe- moglobin and blocking of the cytochrome system (11). Jacobs (7) observed that some patients with severe iron deficiency anemia do not have detectable levels of cytochrome oxidase (an iron-containing enzyme) in the buccal mucosa; however, a re turn to nor- mal levels occurred within 24 hr after in- travenous iron therapy. Beutler (8) meas- ured cytochrome oxidase in the tissue of iron-deficient rats. He found decreased leve!s in the kidney, but enzyme levels in the heart were normal.

T h e studies of Jacobs and Beutler, plus the observations made by Capriles and the patient reported herein, suggest that de-

pletion of an i ron-containing enzyme in the brain may be impor tan t in the develop- ment of papi l ledema in some patients with iron-deficiency aneinia. Resolut ion of the papi l ledema shortly after beginning iron replacement may coincide with regener- ation of the deficient enzyme. Jacobs (12) found normal levels of cytochrome C (an- other i ron-containing enzyme) in the brain of iron-deficient rats, but he did not meas- ure cytochrome oxidase. Fur ther studies, which include measurements of several iron-containing enzymes in nervous tissue, may provide clues to the etiology of pap- il ledema in patients with iron-deficiency anenlia.

S U M M A R Y

A young female with papi l ledema and iron deficiency anemia is described. T h e papi l ledema was resolved rapidly alter oral iron therapy was initiated,

R E F E R E N C E S

1. Lubeck M J: Papilledema caused by iron deficiency anemia. Trans 3.mer Acad 01211- thai Otolaryng 63:306-310, 1959

'2. Hamihon JB: A case of chloro~is with ocular complication. Brit J Ophthal 20:I8- '22. 1936

3. Gowers WR: ()/)tic neuritis in thlorosis. Brit Med J 1:796, 1881

4. Schwaber JR, Blumberg AG: Papilledema associated with blood loss anemia. Ann Intern Med 55:1004-1007, 1961

5. Reynolds RD: Pagophagia and iron deft- ciency anemia. Ann Intern Med 69:435-440. 1968

6. Edwards CH: Clay and cornstarch eating women..I Amer Diet Ass 35:81(1-815, 1959

7. Jacobs A: Iron containing enzymes in the buccal epithelium. Lancet 2:1331-1333. 1961

8. Beutler E: Iron enzymes in iron deficiency. IV. Cytochrome oxidase in rat kidney and heart. Acta Haemat 21:371-377, 1959

9. Beutler E: Iron enzymes in iron deficiency. VII. Oxygen consumption measurement in

Digestive Diseases, Vol. 15, No. 10 (October 1970) 921

STOEBNER ET AL

iron deficient subjects. Amer J Med Sci 239:759-765, 1960

10. Beutler E, Fairbanks VE, Fahey JL: Clin- ical disorders of iron metabolism. New York, Grune and Stratton, 1963

11. Capriles L: Intracranial hypertension and iron deficiency anemia. Arch Neurol 9:147- 153, 1963

12. Jacobs A: Tissue changes in iron deficiency. Brit J Haemat I6:1-4, 1969

922 Digestive Diseases, Vol. 15, No. 10 (October 1970)