Normal erythrocyte osmotic fragility in hereditary spherocytosis

264

Clinical and laboratory observations

14. Lint TF, Gewurz H. Complement deficiencies. 9. The ninth component. Prog Allergy 1986;39:307-10. 15. Harriman GR, Esser AF, Podack ER, et al. The role of C9 in complement-mediated killing of Neisseria. J Immunol 1981; 127:2386-90. 16. Lint TF, Zeitz HJ, Gewurz H. Inherited deficiency of the ninth component of complement in man. J Immunol 1980;125:2252-7. 17. Zeitz HJ, Lint TF, Gewurz H, Gewurz A. Complement

The Journal of Pediatrics February 1989

deficiencies: 7. The seventh component. Prog Allergy

1986;39:289-94. 18. Ellison RT, Kohler F, Curd JG, Judson FN, Relier LB. Prevalence of congenital or acquired complement deficiency in patients with sporadic meningococcal disease. N Engl J Med 1983;308:913-6. 19. Leggiadro RJ, Winkelstein JA. Prevalence of complement deficiencies in children with systemic meningococcal infections. Pediatr Infect Dis 1987;6:75-6.

Normal erythrocyte osmotic fragility in hereditary

spherocytosis David Korones, MD, a n d Howard A. Pearson, MD From the Department of Pediatrics, Strong Memorial Hospital, Rochester, New York, and the Division of Pediatric Hematology/Oncology, Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut

An increase in the osmotic fragility of erythrocytes is regarded as the most helpful laboratory study in making the diagnosis of hereditary spherocytosis. One of the limitations of this test is that results are sometimes normal in cases of mild hereditary spherocytosis. This limitation can usually be overcome by incubating the erythrocytes for 24 hours at 37 ° C before measuring osmotic fragility. The incubation increases the fragility of the spherocytes while having little effect on the fragility of normal erythrocytes. 1 There have been few reported cases of normal osmotic fragility of incubated erythrocytes in patients with hereditary spherocytosis. 2-4 W e describe a child who had a normal incubated osmotic fragility test 3 weeks after an apparent aplastic crisis, but repeat testing several months later showed the expected increase in osmotic fragility.

capacity, blood lead level of 4 mg/L, and normal hemoglobin electrophoresis. The patient was evaluated by us 3 weeks later. Physical examination findings were again normal. Hemoglobin level was 12.6 gm/dl, hematocrit 36.9%, mean corpuscular volume 93 fl, and reticulocyte count 2.2%. The peripheral blood smear was normal. Results of other laboratory studies included a haptoglobin value of 0 mg/dl and normal nonincubated and incubated erythrocyte osmotic fragility (Figure). At this visit the patient's father stated that he had recently undergone extensive examination for intermittent anemia, jaundice, and splenomegaly. His hemoglobin level was 15.3 gm/dl, and his reticulocyte count was 5.2%. His peripheral blood smear showed a few spherocytes. An osmotic fragility test of his incubated red blood cells (performed at the same time as that of the patient and using the same reagents and the same technician) showed an increase in osmotic fragility. There was no other family history of anemia or jaundice.

CASE REPORT A previously healthy 2-year-old white girl, during routine screening by her pediatrician, bad a hematocrit value of 17%. Her parents had not recognized pallor or change in her behavior or level of activity. She had had no recent febrile illness. Physical examination findings were normal except for pallor. No jaundice or splenomegaly was present. Further evaluation revealed hemoglobin 5.7 gm/dl, mean corpuscular volume 90 fl, reticulocyte count 9.5%, platelet count 368,000/mm 3, and leukocyte count 9700/mm 3 with a normal cell differential count. The blood smear was described as normal except for polychromasia. Other findings included normal serum iron concentration and total iron binding

G6PD

Glucose-6-phosphate dehydrogenase

Two months later, the patient appeared well and had had no episodes of jaundice or pallor since her previous visit. Physical examination findings were again normal. Results of laboratory studies included a hemoglobin concentration of 13.1 g/dl, reticulocyte count 2.4%, and blood smear showing a number of spherocytes. A repeat erythrocyte osmotic fragility test now showed an increase in the fragility of the patient's incubated red blood cells (Figure). DISCUSSION

Submitted for publication June 14, 1988; accepted Aug. 26, 1988. Reprint requests~ David Korones, MD, Department of Pediatrics, Strong Memorial Hospital, P.O. Box 777, 60l Elmwood Ave., Rochester, NY 14642.

The spectrum of hereditary spherocytosis is broad; patients with mild illness may have no symptoms, and diagnosis is often made incidentally during routine physi-

Volume 114 Number 2

Clinical and laboratory observations

265

10/21 \

I00 Qme

Patient

o - - - o Father of Patient 8O Or)

>, o

60

w -r F--

z

40

0 a::

20

O

I

1.0

.9

•

I

.8

,-~,~!i:i:i:i:i:i:i:i;'/

.7

.6

I

I

I

I

I

.5

.4

.5

.2

.I

PERCENT S A L I N E CONCENTRATION

Figure. Osmotic fragility of erythrocytes incubated at 37 ° C for 24 hours. Solid curve labeled "'8/19" is initial result of test of patient's osmotic fragility. Solid curve labeled "'10/21 ""is test result obtained 2 months later. Dotted curve labeled "'8/19" is father's osmotic fragility curve. Range of normal incubated osmotic fragility is indicated by shaded area. Note greater percentage of hemolysis at every concentration of saline solution in father's test and patient's second test.

cal or laboratory examination. The current case is an example of disease at the mild end of the spectrum. Had the patient not had routine hemoglobin screening at the time she was anemic, diagnosis may have been delayed indefinitely. Her laboratory findings of a low hemoglobin level and an elevated reticulocyte count at the time of this screening suggest that she was recovering from an aplastic crisis. Such crises are characterized by profound anemia and reticulocytopenia; they are known complications of hereditary spherocyt0sis and in many instances are associated with parvovirus infection. 5 The reticulocytosis noted at initial presentation in our patient has been reported during convalescence from aplastic crises6 and probably represents the initial recovery of the marrow. At the time the first osmotic fragility test was performed, our patient's hemoglobin level was 12.6 gm/dl, more than twice the level it had been when she was evaluated by her pediatrician 3 weeks earlier. Thus a substantial portion of her circulating erythrocytes were young, having been produced over the previous 3 weeks. Earlier studies have shown that young erythrocytes of patients with hereditary spherocytosis have relatively normal morphologie characteristics and function; they are still discoid and demonstrate less osmotic fragility than their older counterparts2.8 As the erythrocyte mass of our patient matured, repeated passage of the erythrocytes through the spleen (so-called "splenic conditioning") resulted in the erythroeytes' gradually assuming a microspherocytic morphologic picture and an increased tendency to undergo osmotic hemolysis. At the time of the second study, the patient had a fully

compensated hemolytic anemia, her peripheral blood smear showed a number of spherocytes, and her erythroeyte osmotic fragility test showed a clear increase in fragility. This situation is analogous to that of the patient with glucose-6-phosphate dehydrogenase deficiency who is recovering from a hemolytic crisis. Young erythroeytes with normal or high G6PD activity predominate at this time and so are less likely to hemolyze. Thus a test measuring G6PD activity during recovery often shows normal enzyme activity even though the patient has G6PD deficiency. It is only after the patient has fully recovered and has more mature erythroeytes in circulation that the enzyme deficiency can be demonstrated. Clinicians should be aware that on rare occasions the osmotic fragility can be normal in patients with hereditary spherocytosis. In addition to the previously documented normal test results in patients with hereditary spherocytosis and iron deficiency~ or obstructive jaundice, ~° the clinician should consider the possibility of a falsely normal test result in a patient who has recently recovered from an aplastic crisis. The child with mild hereditary spherocytosis may come to the attention of a physician only after the increased anemia of an aplastic crisis prompts the child's parents to seek medical assistance. If an osmotic fragility test is performed at this time, results may be normal when in fact the patient has hereditary spherocytosis. In such cases this test should be repeated in several months. Prompt diagnosis of even mild hereditary spherocytosis would permit physicians to avoid extensive and unnecessary diagnostic studies for other anemias. Furthermore,

266

Clinical and laboratory observations

diagnosis would allow for more effective management of anticipated problems such as cholelithiasis and its complications, the need for splenectomy, and the examination of family members for the disease. REFERENCES

1. Hereditary spherocytosis and other hemolytic anemias associated with abnormalities of the red cell membrane. In: Wintrobe MM, Lee GR, Boggs DR, et al., eds. Clinical hematology. Philadelphia: Lea & Febiger, 1981:747-8. 2. Fukagawa N, Friedman S, Gill FM, et al, Hereditary spherocytosis with normal fragility after incubation. JAMA 1979;242:63-4. 3. Dacie JV, Mollison PL, Richardson N, et al. Atypical congenital haemolytic anemia. QJ Med 1953;22:79-99. 4. Zail SS, Krawitz P, Viljoen E, et al. Atypical hereditary spherocytosis: biochemical studies and sites of erythrocyte destruction. Br Med J 1967;13:323-34.

The Journal of Pediatrics February 1989

5. Lefrere J J, Courouce AM, Girot R, et al. Six cases of hereditary spherocytosis revealed by human parvovirus infection. Br J Haematol 1986;62:653-7. 6. Dameshek W, Bloom ML. The events in the hemolytic crisis of hereditary spherocytosis, with particular reference to the reticulocytopenia, pancytopenia and abnormal splenic mechanism. Blood 1948;3:1381-409. 7. Paolino W. Variations of the mean diameter in the ripening of the erythrocyte. Acta Med Scand 1949;136:141-7. 8. Griggs RC, Weisman R, Harris JW. Alterations in osmotic fragility related to in vivo erythrocyte aging and splenic sequestration in hereditary spherocytosis. J Clin Invest 1960;39:89-101. 9. Crosby WH, Conrad ME. Hereditary spherocytosis: observations on hemolytic mechanisms and iron metabolism. Blood 1960;15:662-74. 10. Lux SE. Disorders of the red cell membrane. In: Nathan D, Oski F, eds. Hematology of infancy and childhood. Philadelphia: WB Saunders, 1987:488-9.

Multicentric reticulohistiocytosis in a child Stephen A. Raphael, MD, Susan L. Cowdery, MD, Eric N. Faerber, MD, Harold W. Lischner, MD, H. Ralph Schumacher, MD, and Charles D. Tourtellotte, MD From the Section of Immunology and Rheumatology, Department of Pediatrics, the Department of Radiology, and the Section of Rheumatology, Department of Internal Medic!ne, Temple University School of Medicine and St. Christopher's Hospital for Children; the Department of internal Medicine, Section of Rheumatology, Albert Einstein Medical Center-Northern Division; and the Section of Rheumatology, Department of Internal Medicine, University of Pennsylvania School of Medicine and Veterans Administration Hospital of Philadelphia

Multicentric reticulohistiocytosis is a rare, easily misdiagnosed, systemic disorder of unknown cause, characterized by papulonodular skin lesions, potentially destructive arthritis, a tendency to involve multiple organs, and histopathologic studies that show large mononuclear and multinucleated giant cell infiltrations. 1-7 There is a possible association with malignancy, diabetes, hypothyroidism, hyperlipidemia, and tuberculosis.i, 2,6,8,9 All fully described cases have been in adults. W e present the first clinically described case of M R H in a child.

symmetric swelling of several distal interphalangeal joints, and nonpainful, hypopigmented wartlike intracutaneous nodules over the distal ends and periungual areas of several fingers. Subsequently, she experienced easy fatigability, increased numbers of skin nodules, and bilateral painful knee swelling. Fever, unexplained weight loss, anorexia, adenopathy, rash, signs of the Raynaud phenomenon, photosensitivity, mouth ulcers, chest pain, neurologic problems, myalgia, abdominal pain, eye irritation, loss of scalp hair, and intolerance to cold were denied. There was no MRH

Multicentric reticulohistiocytosis

[

CASE REPORT The patient, a black girl almost 14 years old, was well until 1ly2 years of age, when she noticed the simultaneous occurrence of early morning stiffness, loss of grip strength, right elbow pain,

Submitted for publication July 18, 1988; accepted Sept. 20, 1988. Reprint requests: Stephen A. Raphael, MD, St. Christopher's Hospital for Children, Section of Immunology and Rheumatology, 5th and Lehigh Ave., Philadelphia, PA 19133.

history of recent immunizations, antecedent illness, tick bite, or travel. The patient was taking no long-term medications. She was not sexually active. Growth and development had been normal. Family history revealed two well siblings and a history of intravenous drug abuse in the patient's father. Initial physical examination revealed an anxious 1l~(2-year-old pubertal black girl in no acute physical distress. Height and weight were appropriate for age. Vital signs were normal. The patient had multiple 2 to 3 mm wartlike nodules along the dorsal