Volume 87 Number 6, part I
Letters to the Editor
Table I. S e r u m lipid m e a s u r e m e n t s
Patient - (11 mo) Normal diet Low-fat diet Father - (27 yr) Mother - (18 yr)
Serum cholesterol (mg/dl)
Serum triglycerides (mg/dl)
110 154 158 158
633 200 103 83
10 03
mechanisms involved in this causal relationship remain unexplained. Morad R. Ameri, M.D. M. Alebouyeh, M.D. M. Ziai, M.D. Departments' of Pediatrics and Pediatric Hematology Reza Pahlavi Medical Center Tehran, Iran Rex B. Corm, M.D. Department of Laboratory Medicine The Johns Hopkins Hospital Baltimore, M d 21205 REFERENCES
radiologic evidence of right hip joint subluxation. Ocular fundi were normal. Laboratory data. The hemoglobin was 4.4 gm/dl, hematocrit 12.5%, red blood cells 1,440,000/mm ~, and reticulocyte count 3%. The peripheral blood smear revealed anisocytosis, poikilocytosis, hypochromia, target ceils, polychromasia, and many nucleated red cells (60/100 white blood ceils). The direct Coombs test was negative; erythrocyte glucose-6-phosphate dehydrogenase activity was normal. Serum iron was 93 and total iron-binding capacity 317/~gm/dl. The bone marrow showed marked erythroid hyperplasia With normal myelo- and thrombopoiesis. No foam ceils were observed. A test for Heinz bodies was negative. The fetal hemoglobin elution test ~ revealed abundant numbers of hemoglobin F containing cells. Hemoglobin electrophoresis on cellulose acetate ~ separated two major anodic bands, identified as hemoglobin A1 and hemoglobin F. There was also a minor band consisting of hemoglobin A2. Hemoglobin F constituted 65% of the total hemoglobin as determined by alkali denaturation. 9 Hematologic examination of the parents indicated both had heterozygous beta thalassemia. The patient's serum had a creamy appearance; lipid studies were done with the patient on a normal and on a low-fat diet (20% of daily caloric requirement provided by fat). Serum triglycerides were elevated with the patient on a normal diet. They became normal after the child had received a low-fat diet for eight days (Table I). An intravenous heparin test (8 units heparin/kg body weight) was carried out 17 days after reinstitution of a normal diet. A reduction in serum triglycerides from 272 to 32 mg/dl occurred within 10 minutes after heparin administration. DISCUSSION Hypertriglyceridemia in a patient with thalassemia major might be a coincidence or might be secondary to the severe anemia seen in untreated patients. Normal serum lipid studies in the parents as well as the disappearance of the creamy layer and decrease in serum triglycerides after institution of a low-fat diet are suggestive of type I hyperlip.oproteinemia. Administration of heparin intravenously tO the propositns, however, lowered the plasma triglycerides significantly in a short time, proving the presence oflipoprotein l!pase. This suggests the secondary nature of the hypertriglyceridemia in our patient. Follow-up studies after multiple blood transfusions to maintain the hemoglobin level at about 10 gm/dI showed nearly normal serum triglycerides. These observations indicate that the hypertriglyceridemia was due to chronic, severe anemia, although the pathologic
1.
2.
3.
4.
Rama Rao AVSS, Indira BK, and Ramanujiah D: Hypertriglyceridemia in thalassemia major, J Indian Med Assoc 59:15, 1972. Betke K, and Sanguansermsri T. Zytologische Blutfarbstoffdifferenzierung, Munch Med Wochenschr 114:I099, 1972. Kohne Von E, Alebouyeh M, and Kleihauer E: Electrophoretischer Nachweis normaler und anormaler Haemoglobine, Fortschr Med 91:100, 1973. Singer K, Chernoff AI, and Singer L: Studies on abnormal hemoglobins. 1. Their demonstration in sickle cell anemia and other hematologic disorders by means of alkali denaturation, Blood 6:413, 1951.
Myositis associated with influenza A infection To the Editor: Mason and Keller 1 reported acute transient myositis associated with an influenza B epidemic, but viral studies were not done in the children they observed. They proposed an "association between influenza a n d acute transient myositis." We have recently observed a child who had acute myositis in whom an influenza A viral infection was documented by viral isolation and serology. CASE REPORT
Patient R. C., a 2 6/12-year-old black male, was admitted because of refusal to walk of one day's duration. One day prior tO admission, he had nasal congestion, rhinorrhea, and fever, but he was ambulatory. There was no history of trauma, abdominal pain, or urinary or fecal incontinence. The admission temperature was 39~ he was moderately irritable, had painful calf muscles, and refused to support his weight or walk. There was no rash, lumbosacral tenderness,
From the Edward Mallinckrodt Department of Pediatrics, Washington University School of Medicine and The Divisions of Infectious Diseases and Neurology at St. Louis Children's Hospital. Supported in part by United States Public Health Service Grant No NS-05633 and the Allen P. and Josephine B. Green Foundation, Mexico, Mo.
1004
Letters to the Editor
abdominal tenderness, joint pain, or skeletal abnormalities. Neurologic examination was normal, as were skeletal radiographs. On admission, the erythrocyte sedimentation rate (ESR) was 20 m m / h r , serum glutamic oxaloacetic transaminase 158 units, and creatine phosphokinase (CPK) 182 units (normal 0-12 units). The serum concentration of CPK increased to 370 units on the day following admission. Eleven days after admission when he was discharged the serum CPK value was 54 units. Seventeen days, 66 days, and 75 days after discharge the serum concentrations of CPK were 86 units, 66 units, and 55 units, respectively. The ESR increased to 35 m m / h r 7 days after admission and subsequently decreased to 21 mm/hr. Nasopharyngeal culture obtained during his hospitalization yielded influenza virus. Complement fixation serum antibodies for influenza A increased from < 1:4 on 1/13/75 to 1:8 on 1/29/75. The patient was walking normally three days after admission and became afebrile five days after admission. Subsequently, he has remained asymptomatic despite the persistently elevated but decreasing serum concentrations of creatine phosphokinase. DISCUSSION Influenza infection is often associated with a diffuse myalgia in addition to the classic respiratory symptoms, fever, and prostration. Myositis, a less common event, was described by Lundberg 2 in 1957 and Middleton and associates3 in 1970. Dietzman and associates~ and Mason and Keller I have described myositis in association with influenza B infections. Mejlszenkier and associates ~ described a 5-year-old girl with influenza A infection, documented by serology alone, in whom a transient myositis of the gastrocnemius muscles occurred. Leslie L. Barton, M.D. Efias G. Chalhub, M.D. St. Louis Children's Hospital 500 S. Kingshighway St. Louis, Mo. 63110 REFERENCES
1. Mason W, and Keller E: Acute transient myositis with influenza-like illness, J PEDXATR86:813, 1975. 2. Lundberg A: Myalgia crnris epidemica, Acta Paediatr 46:18, 1957. 3. Middleton PJ, Alexander RM, and Szymanski MT: Severe myositis during recovery from influenza, Lancet 2:533, 1970. 4. Dietzman DE, Schaller J, Ray CG, and Reed ME: Myositis associated with influenza B infections, Pediatr Res 8:423, 1974. 5. Mejlszenkier JD, Safran AP, Healy J J, Embree L, and Ouellette EM: The myositis of influenza, Arch Neurol 29:441, 1973.
Acute leukemia following anticancer treatment To the Editor: Development of malignant neoplasia subsequent to anticancer therapy has been listed as a late complication of radiotherapy and/or of chemotherapy. 1-3 However, as demonstrated by tlae
The Journal of Pediatrics December 1975
occurrence of multiple primary tumors in individuals, an increased host susceptibility may be responsible for second tumors2 The differentiation between multiple spontaneous tumors in susceptible individuals and drug-induced malignancy is tenuous at best. The following case report appears of interest, since acute leukemia developed following radiotherapy and long-term single-agent chemotherapy in a child in whom ,an increased host susceptibility could not be demonstrated. The child was treated for rhabdomyosarcoma which retrospectively turned out to be benign fibromatosis. CASE REPORT
A 3 X 2 X 4 cm sized tumor, removed from the lateral quarter of the suprascapular soft tissue of a 6-months-old male infant, was histologically classified as rhabdomyosarcoma. Treatment locally with radiotherapy (RT) and systemically with cyclophosphamide (CP) was initiated (RT: over a 6 cm circular field, including the upper lateral quadrant of the scapula but excluding the thymus and mediastinum; the skin dose was 6,000 rads in 48 days; CP: 3-5 mg/kg orally every 2-3 days for 26 months; total dose 19 gin). At age 7 1A years acute undifferentiated leukemia (AUL) was diagnosed. The spleen was palpated below the iliac crest, dyspnea was caused by bilateral mediastinal masses outside the former irradiation field. White blood count was 174,000/mm ~. Acid phosphatase staining o f blasts was positive. Immunologic investigations gave normal results. After the diagnosis of AUL was confirmed, the slides of the original tumor were reviewed, and the original diagnosis o f rhabdomyosarcoma had to be changed to benign fibromatosis. DISCUSSION Second tumors in long-term survivors of childhood cancer probably occur in more than 5% of cases? They may arise independently as synchronous or serial multiple tumors in unduly susceptible hosts. In other instances, preceding radiotherapy 2 or long-term oral treatment with alkylating agents ~has been suspected as oncogenic factors. The carcinogenic potential of cyclophosphamide was proved in animal experiments? Recently, it was shown that patients with Hodgkin disease who receive both intensive radiation and chemotherapy are at higher risk for second malignancies than are those who receive only one of the forms of therapy? In our patient a coincidental occurrence o f benign fibromatosis, anticancer treatment, and leukemia cannot be ruled out, but seems highly improbable. A causal relationship between radiochemotherapy and subsequent leukemia is at least an equally plausible hypothesis. Peter Gutjahr, M.D. Pediatric Oneology and Hematology J. Spranger, M.D. Head of the Department of Pediatrics The Johannes-Gutenberg University D 6500 Mainz Federal Republic of Germany REFERENCES
VT, Arseneau JC, Whang-Peng J, 1. Canellos GP, de u and Johnson REC: Second malignancies complicating
Letters to the Editor
Table I. S e r u m lipid m e a s u r e m e n t s
Patient - (11 mo) Normal diet Low-fat diet Father - (27 yr) Mother - (18 yr)
Serum cholesterol (mg/dl)
Serum triglycerides (mg/dl)
110 154 158 158
633 200 103 83
10 03
mechanisms involved in this causal relationship remain unexplained. Morad R. Ameri, M.D. M. Alebouyeh, M.D. M. Ziai, M.D. Departments' of Pediatrics and Pediatric Hematology Reza Pahlavi Medical Center Tehran, Iran Rex B. Corm, M.D. Department of Laboratory Medicine The Johns Hopkins Hospital Baltimore, M d 21205 REFERENCES
radiologic evidence of right hip joint subluxation. Ocular fundi were normal. Laboratory data. The hemoglobin was 4.4 gm/dl, hematocrit 12.5%, red blood cells 1,440,000/mm ~, and reticulocyte count 3%. The peripheral blood smear revealed anisocytosis, poikilocytosis, hypochromia, target ceils, polychromasia, and many nucleated red cells (60/100 white blood ceils). The direct Coombs test was negative; erythrocyte glucose-6-phosphate dehydrogenase activity was normal. Serum iron was 93 and total iron-binding capacity 317/~gm/dl. The bone marrow showed marked erythroid hyperplasia With normal myelo- and thrombopoiesis. No foam ceils were observed. A test for Heinz bodies was negative. The fetal hemoglobin elution test ~ revealed abundant numbers of hemoglobin F containing cells. Hemoglobin electrophoresis on cellulose acetate ~ separated two major anodic bands, identified as hemoglobin A1 and hemoglobin F. There was also a minor band consisting of hemoglobin A2. Hemoglobin F constituted 65% of the total hemoglobin as determined by alkali denaturation. 9 Hematologic examination of the parents indicated both had heterozygous beta thalassemia. The patient's serum had a creamy appearance; lipid studies were done with the patient on a normal and on a low-fat diet (20% of daily caloric requirement provided by fat). Serum triglycerides were elevated with the patient on a normal diet. They became normal after the child had received a low-fat diet for eight days (Table I). An intravenous heparin test (8 units heparin/kg body weight) was carried out 17 days after reinstitution of a normal diet. A reduction in serum triglycerides from 272 to 32 mg/dl occurred within 10 minutes after heparin administration. DISCUSSION Hypertriglyceridemia in a patient with thalassemia major might be a coincidence or might be secondary to the severe anemia seen in untreated patients. Normal serum lipid studies in the parents as well as the disappearance of the creamy layer and decrease in serum triglycerides after institution of a low-fat diet are suggestive of type I hyperlip.oproteinemia. Administration of heparin intravenously tO the propositns, however, lowered the plasma triglycerides significantly in a short time, proving the presence oflipoprotein l!pase. This suggests the secondary nature of the hypertriglyceridemia in our patient. Follow-up studies after multiple blood transfusions to maintain the hemoglobin level at about 10 gm/dI showed nearly normal serum triglycerides. These observations indicate that the hypertriglyceridemia was due to chronic, severe anemia, although the pathologic
1.
2.
3.
4.
Rama Rao AVSS, Indira BK, and Ramanujiah D: Hypertriglyceridemia in thalassemia major, J Indian Med Assoc 59:15, 1972. Betke K, and Sanguansermsri T. Zytologische Blutfarbstoffdifferenzierung, Munch Med Wochenschr 114:I099, 1972. Kohne Von E, Alebouyeh M, and Kleihauer E: Electrophoretischer Nachweis normaler und anormaler Haemoglobine, Fortschr Med 91:100, 1973. Singer K, Chernoff AI, and Singer L: Studies on abnormal hemoglobins. 1. Their demonstration in sickle cell anemia and other hematologic disorders by means of alkali denaturation, Blood 6:413, 1951.
Myositis associated with influenza A infection To the Editor: Mason and Keller 1 reported acute transient myositis associated with an influenza B epidemic, but viral studies were not done in the children they observed. They proposed an "association between influenza a n d acute transient myositis." We have recently observed a child who had acute myositis in whom an influenza A viral infection was documented by viral isolation and serology. CASE REPORT
Patient R. C., a 2 6/12-year-old black male, was admitted because of refusal to walk of one day's duration. One day prior tO admission, he had nasal congestion, rhinorrhea, and fever, but he was ambulatory. There was no history of trauma, abdominal pain, or urinary or fecal incontinence. The admission temperature was 39~ he was moderately irritable, had painful calf muscles, and refused to support his weight or walk. There was no rash, lumbosacral tenderness,
From the Edward Mallinckrodt Department of Pediatrics, Washington University School of Medicine and The Divisions of Infectious Diseases and Neurology at St. Louis Children's Hospital. Supported in part by United States Public Health Service Grant No NS-05633 and the Allen P. and Josephine B. Green Foundation, Mexico, Mo.
1004
Letters to the Editor
abdominal tenderness, joint pain, or skeletal abnormalities. Neurologic examination was normal, as were skeletal radiographs. On admission, the erythrocyte sedimentation rate (ESR) was 20 m m / h r , serum glutamic oxaloacetic transaminase 158 units, and creatine phosphokinase (CPK) 182 units (normal 0-12 units). The serum concentration of CPK increased to 370 units on the day following admission. Eleven days after admission when he was discharged the serum CPK value was 54 units. Seventeen days, 66 days, and 75 days after discharge the serum concentrations of CPK were 86 units, 66 units, and 55 units, respectively. The ESR increased to 35 m m / h r 7 days after admission and subsequently decreased to 21 mm/hr. Nasopharyngeal culture obtained during his hospitalization yielded influenza virus. Complement fixation serum antibodies for influenza A increased from < 1:4 on 1/13/75 to 1:8 on 1/29/75. The patient was walking normally three days after admission and became afebrile five days after admission. Subsequently, he has remained asymptomatic despite the persistently elevated but decreasing serum concentrations of creatine phosphokinase. DISCUSSION Influenza infection is often associated with a diffuse myalgia in addition to the classic respiratory symptoms, fever, and prostration. Myositis, a less common event, was described by Lundberg 2 in 1957 and Middleton and associates3 in 1970. Dietzman and associates~ and Mason and Keller I have described myositis in association with influenza B infections. Mejlszenkier and associates ~ described a 5-year-old girl with influenza A infection, documented by serology alone, in whom a transient myositis of the gastrocnemius muscles occurred. Leslie L. Barton, M.D. Efias G. Chalhub, M.D. St. Louis Children's Hospital 500 S. Kingshighway St. Louis, Mo. 63110 REFERENCES
1. Mason W, and Keller E: Acute transient myositis with influenza-like illness, J PEDXATR86:813, 1975. 2. Lundberg A: Myalgia crnris epidemica, Acta Paediatr 46:18, 1957. 3. Middleton PJ, Alexander RM, and Szymanski MT: Severe myositis during recovery from influenza, Lancet 2:533, 1970. 4. Dietzman DE, Schaller J, Ray CG, and Reed ME: Myositis associated with influenza B infections, Pediatr Res 8:423, 1974. 5. Mejlszenkier JD, Safran AP, Healy J J, Embree L, and Ouellette EM: The myositis of influenza, Arch Neurol 29:441, 1973.
Acute leukemia following anticancer treatment To the Editor: Development of malignant neoplasia subsequent to anticancer therapy has been listed as a late complication of radiotherapy and/or of chemotherapy. 1-3 However, as demonstrated by tlae
The Journal of Pediatrics December 1975
occurrence of multiple primary tumors in individuals, an increased host susceptibility may be responsible for second tumors2 The differentiation between multiple spontaneous tumors in susceptible individuals and drug-induced malignancy is tenuous at best. The following case report appears of interest, since acute leukemia developed following radiotherapy and long-term single-agent chemotherapy in a child in whom ,an increased host susceptibility could not be demonstrated. The child was treated for rhabdomyosarcoma which retrospectively turned out to be benign fibromatosis. CASE REPORT
A 3 X 2 X 4 cm sized tumor, removed from the lateral quarter of the suprascapular soft tissue of a 6-months-old male infant, was histologically classified as rhabdomyosarcoma. Treatment locally with radiotherapy (RT) and systemically with cyclophosphamide (CP) was initiated (RT: over a 6 cm circular field, including the upper lateral quadrant of the scapula but excluding the thymus and mediastinum; the skin dose was 6,000 rads in 48 days; CP: 3-5 mg/kg orally every 2-3 days for 26 months; total dose 19 gin). At age 7 1A years acute undifferentiated leukemia (AUL) was diagnosed. The spleen was palpated below the iliac crest, dyspnea was caused by bilateral mediastinal masses outside the former irradiation field. White blood count was 174,000/mm ~. Acid phosphatase staining o f blasts was positive. Immunologic investigations gave normal results. After the diagnosis of AUL was confirmed, the slides of the original tumor were reviewed, and the original diagnosis o f rhabdomyosarcoma had to be changed to benign fibromatosis. DISCUSSION Second tumors in long-term survivors of childhood cancer probably occur in more than 5% of cases? They may arise independently as synchronous or serial multiple tumors in unduly susceptible hosts. In other instances, preceding radiotherapy 2 or long-term oral treatment with alkylating agents ~has been suspected as oncogenic factors. The carcinogenic potential of cyclophosphamide was proved in animal experiments? Recently, it was shown that patients with Hodgkin disease who receive both intensive radiation and chemotherapy are at higher risk for second malignancies than are those who receive only one of the forms of therapy? In our patient a coincidental occurrence o f benign fibromatosis, anticancer treatment, and leukemia cannot be ruled out, but seems highly improbable. A causal relationship between radiochemotherapy and subsequent leukemia is at least an equally plausible hypothesis. Peter Gutjahr, M.D. Pediatric Oneology and Hematology J. Spranger, M.D. Head of the Department of Pediatrics The Johannes-Gutenberg University D 6500 Mainz Federal Republic of Germany REFERENCES
VT, Arseneau JC, Whang-Peng J, 1. Canellos GP, de u and Johnson REC: Second malignancies complicating
