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Pigmented lesions of incontinentia pigmenti in a neonate
Volume 83 Number 3
bances, chiefly neutropenia, may be seen. Isolated thrombocytopenia has been reported in three adult patients1-3; it has not been previously noted in children.
CASE R E P O R T An 8-month-old male infant was admitted to St. Louis Children's Hospital on June 3, 1971, with a chief complaint of pneumonia unresponsive to antibiotic therapy. Physical examination revealed a malnourished Oriental boy. Positive physical findings included a choroidal lesion in the right eye, diffuse rhonchi, and minimal hepatosplenomegaly. Neurologic examination was within normal limits. Laboratory data included: hemoglobin 9.9 Gin. per 100 ml., hematocrit 31 per cent, and total white blood cell count 18,000 with a normal differential and 300,000 platelets per cubic millimeter. Chest radiographs revealed a large left hilar mass compressing the left main stern bronchus, paratracheal adenopathy, and miliary lesions scattered throughout all lung fields. Urinalysis was entirely normal, but Mycobacterium tuberculosis grew from this specimen subsequently Three gastric aspirates grew Myeobacterium tuberculosis. On the day of admission therapy was initiated with isoniazid'(15 mg. per kilogram per day), para-aminosalicylic acid (300 mg. per kilogram per day), and streptomycin (40 mg. per kilogram per day). Clinical improvement and radiographic resolution of disease occurred, but on the twentythird hospital day profuse epistaxis was noted. No bleeding site was identified. Prothrombin activity was 100 per cent, bleeding and clotting times were normal, a Coombs test was negative, but a platelet count was only 38,000 per cubic millimeter. A platelet count obtained two days previously was 280,000 per cubic millimeter. A bone marrow aspirate had normal cellularity with normal megakaryocytes. The maturation of white and red blood cells was.normal with a slight shift to the left in myeloid elements. Widespread tuberculosis required continuation of antituberculous therapy; thus only para-aminosalieylic acid was discontinued. Platelet counts obtained daily for the next six days varied between 40,000 and 70,000 per cubic millimeter but increased to 260,000 on the thirtieth hospital day. Therapy with isoniazid is ongoing. Streptomycin administration was discontinued three months following discharge, at which time treatment with Rifampin was initiated. Prior to use of Rifampin, cautious readministration of para-aminosalicylic acid was attempted but was followed within four hours by a drop in platetet count from 250,000 to 80,000 per cubic millimeter. Platelet count returned to normal four days later.
DISCUSSION Thrombocytopenia following para-aminosalicyclic acid administration has 'been documented previously only in adults, l"a Thrombocytopenia
Letters to the Editor
503
was noted in association with paraaminosalicylic acid therapy, abated five days following discontinuation of para-aminosalicylic acid despite continued administration of streptomycin and isoniazid, and reoccurred promptly following rechallenge of the patient with para-aminosalicylic acid. This sequence of events strongly suggests that the thrombocytopenia was a direct consequence of para-aminosalicylic acid administration. Platelet destruction following para-aminosalicylic acid administration has been suggested by previous reports in the literature, 1-3 and in one case a circulating antibody to a glycine-conjugated metabolite of para-aminosalicylic acid was documented. 3 AIthough specific platelet antibodies were not sought, platelet destruction is the most likely cause of thrombocytopenia in the present case.
Ralph D. Feigin, M.D. ~ Harold F. Zarkowsky, M.D. William Shearer, Ph.D., M.D. Donald C. Anderson, M.D. The Edward Mallinekrodt Department o[ Pediatrics Washington University School o[ Medicine and the Divisions of Infectious Diseases and Hematology at St. Louis Children's Hospital St. Louis, Mo. 63110 ~Reclpient of a Research Career Development Award No. 1K04AI46%6 from the National Institute of Allergy and Infectious Diseases.
REFERENCES 1. Wurzet, H. A., and Maycock, R. L.: Thrombocytopenia induced by sodium para-aminosalicylic acid, J. A. M. A. 153: 1094, 1953. 2. Gregg, J. A., and Maycock, R. L.: Thrombocytopenia induced by administration of sodium para-aminosalieylate, J. A. M. A. 172: 1909, 1960. 3. Eisner, E. V., and Kasper, K.: Immune thrombocytopenia due to a metabolite of para-aminosalicylic acid, Am. J. Med. 53: 790, 1972.
Pigmented lesions of incontinentia pigmenti in a neonate To the Editor: The following case report illustrates the unusual occurrence of pigmented lesions of incontinentia pigmenti in a newborn infant who has
504
Letters to the Editor
The Journal of Pediatrics September 1973
keratosis, mild degeneration of the basal cell layer, and focal edema of the upper dermis. No eosinophil-filled intraepidermal vesicles were seen. The cutaneous scaling disappeared during the first two weeks of life. The patient is now 4 months of age and has not developed vescicular, bullous, or verrucous skin lesions. The pigmented areas have faded slightly. DISCUSSION
Fig. 1. Patient N. M. at 3 days of age. Note the typical pigmented lesions of incontinentia pigmenti and the mild scaling over the left arm. failed to develop other definite stages of cutaneous involvement. CASE REPORTS Patient N. M., a 3,470 Gin. black female infant, was the product of a full-term, uncomplicated pregnancy. Her brother, sister, and mother were in good health and had never had abnormalities of the skin, hair, nails, or teeth, The rest of the family history was negative for congenital anomalies or cutaneous disorders. Two years prior to the birth of the patient, her mother had a spontaneous abortion at 9 weeks' gestation. Physical examination revealed bilateral areas of cutaneous hyperpigmentation arranged in whorls and streaks over the trunk and extremities (Fig. 1). Mild skin inflammation and scaliness were present, particularly over the antecubital fossae. No vesicles or bullae were noted. The hair, nails, and eyes were normal. Laboratory data included a White blood cell count of 15,000 per cubic millimeter with a normal differential count including 2 per cent eosinophils. Chest roentgenogram and electrocardiogram were normal. Skin biopsy findings were interpreted as being compatible with the clinical diagnosis of incontinentia pigmenti; there was increased melanin in dermal melanophages, hyper-
Incontinentia pigmenti is a rare cutaneous disorder which is often associated with dystrophic nails, alopecia, ocular abnormalities, and delayed or malformed dentition. 1-a Seizures, mental retardation, cardiac defects, and skeletal deformities occur less often. 1, a These anomalies need not be evident in the neonatal period, so the physician must be aware of their occurrence and should look for them in the older affected child. The disease is inherited as an X-linked dominant trait and is lethal in most affected male fetuses who are aborted spontaneouslyY The characteristic skin findings often appear in stages. Vescicular or bullous lesions associated with cutaneous inflammation are usually present at the time of birth and persist for several months. This stage is nsualIy foliowed by verrucous lesions which may produce skin atrophy after healing. The third stage is characterized by pigmented lesions arranged in whorl-like patterns over large areas of the body. These pigmented areas may persist fgr several years but eventually disappear completely. There is no clear demarcation between these three stages; at times atl types of skin changes may occur simultaneously. 1-s The clinical appearance of the skin lesions is characteristic; a skin biopsy may be helpful in confirming the diagnosis, particularly in unusual or atypical cases. The pathologic findings of skin in incontinentia pigmenti have been previously, described.~, In view of the negative family history for incontinentia pigmenti, the infant may represent the product of a new mutation, Alternatively, it is possible that the patient's mother exhibited subclinical disease, demonstrating genetic heterogeneity as defined by the Lyon~ hypothesis. The present case of incontinentia pigmenti documents the unusual occurrence of pigmented lesions at the iime of birth, a phenomenon which has not been emphasized in recent reviews of this topic?, a We speculate that this infant may have had other stages of involvement of the skin during imrauterine life. The mild scaling and inflammation of the skin which were present during the first two weeks of life may have represented
Volume 83 Number 3
Letters to the Editor
resolution of vescicular lesions developed in utero. We cannot be certain of this, as the skin biopsy findings were not diagnostic of this stage of the disease.
Robert J. Lerer, M.D. Richard A. Ehrenkranz, M.D. A. G. M. Campbell, M.B., F.R.C.P. Department of Pediatrics Yale University School of Medicine Yale-New Haven Hospital New Haven, Conn. 06510 REFERENCES
1. Carney, R. G., and Carney, R. G., Jr.: Incontinentia pigmenti, Arch. Dermatol. 102: 157, 1970. 2. Gordon, H., and Gordon, W.: Incontinentia pigmenti: Clinical and genetical studies of two familial cases, Dermatologica 140: 150, 1970. 3. Morgan, J. D.: Incontinentia pigmenti (BlochSulzberger syndrome), Am. J. Dis. Child. 122: 294, 1971. 4. Lyon, M. F.: Sex chromatin and gene action in the mammalian X-chromosome, Am. J. Hum. Genet. 14: 135, 1962.
Hypoglycemia in small-forgestational age infants To the Editor: Although the pathophysiotogy of neonatal hypoglycemia is still not well understood, much has recently been learned about carbohydrate metabolism in the fetus and newborn infant. A great deal of the experimental work has, of necessity, been carried out in laboratory animals. Although species differences obviously exist, much of the knowledge gained is applicable to the human being. In a recent review on hypoglycemia in infancy and childhood, Pagliara and associates 1 discussed the predisposition of small-for-gestational age neonates to the development of hypoglycemia. They followed circulatory levels of certain metabolites in these infants from birth through the first 24 hours of llfe and found a pattern highly suggestive of a maturationaI delay in the hepatic gluconeogenic enzymatic apparatus. These re-
505
sults are in agreement with our in vitro findings in an experimental model of intrauterine growth retardation2 In these studies, liver slices taken fi'om small-for-date newborn rats three hours after spontaneous delivery showed an impaired glucose production from labeled alanine. On the basis of this observation, we postulated that inadequate postnatal development of hepatic gluconeogenesis may play a contributory role in the susceptibility of small-for-date infants to develop hypoglycemia during the early period Iollowing delivery. The rapid falt in liver glycogen after birth suggests that it is mobilized to maintain the blood glucose level. When these reserves, which are known to be smaller in intrauterine growth-retarded neonates,x, ~ are exhausted, glucose production from noncarbohydrate substrates, such as amino acids and glycerol, is of utmost importance. Glucagon and catecholamines play an important role in the induction of the gluconeogenic enzymatic mechanism.~ Thus inappropriate secretion of these hormones, or impaired enzyme induction, may cause the above-mentioned delay in maturation of hepatic gluconeogenesis.
Menachem Nitzan, M.D. Department o[ Pediatrics and Rogoff-WelIcome Trust Medical Research Institute Beilinson Medical Center Tel Aviv University Medical School Petah Tikva, Israel REFERENCES
1. Pagliara, A. S., Karl, I. E., Haymond, M., and Kipnis, D. M.: Hypoglycemia in infancy and childhood. Part I, J. P~DIATm 82: 365, 1973. 2. Nitzan, M., and Groffman, H.: Hepatic gluconeogenesis and lipogenesis in experimental intrauterine growth retardation in the rat, Am. J. Obstet. Gynecol. 109: 623, 1971. 3. Shelley, H. J.: Carbohydrate reserves in the newborn infant, Br. Med. J. 1: 273, 1964. 4. Nitzan, M., and Groffman, H.: Metabolic changes in experimental intrauterine growth retardation: Blood glucose and liver glycogen in dysmature and premature newborn rats, Isr. J. Med. Sci. 6: 697, 1970. 5. Yeung, D., and Oliver, I. T.: Factors affecting the premature induction of phosphopyruvate carboxylase in neonatal rat liver, Biochem. J. 108: 325, 1968.
bances, chiefly neutropenia, may be seen. Isolated thrombocytopenia has been reported in three adult patients1-3; it has not been previously noted in children.
CASE R E P O R T An 8-month-old male infant was admitted to St. Louis Children's Hospital on June 3, 1971, with a chief complaint of pneumonia unresponsive to antibiotic therapy. Physical examination revealed a malnourished Oriental boy. Positive physical findings included a choroidal lesion in the right eye, diffuse rhonchi, and minimal hepatosplenomegaly. Neurologic examination was within normal limits. Laboratory data included: hemoglobin 9.9 Gin. per 100 ml., hematocrit 31 per cent, and total white blood cell count 18,000 with a normal differential and 300,000 platelets per cubic millimeter. Chest radiographs revealed a large left hilar mass compressing the left main stern bronchus, paratracheal adenopathy, and miliary lesions scattered throughout all lung fields. Urinalysis was entirely normal, but Mycobacterium tuberculosis grew from this specimen subsequently Three gastric aspirates grew Myeobacterium tuberculosis. On the day of admission therapy was initiated with isoniazid'(15 mg. per kilogram per day), para-aminosalicylic acid (300 mg. per kilogram per day), and streptomycin (40 mg. per kilogram per day). Clinical improvement and radiographic resolution of disease occurred, but on the twentythird hospital day profuse epistaxis was noted. No bleeding site was identified. Prothrombin activity was 100 per cent, bleeding and clotting times were normal, a Coombs test was negative, but a platelet count was only 38,000 per cubic millimeter. A platelet count obtained two days previously was 280,000 per cubic millimeter. A bone marrow aspirate had normal cellularity with normal megakaryocytes. The maturation of white and red blood cells was.normal with a slight shift to the left in myeloid elements. Widespread tuberculosis required continuation of antituberculous therapy; thus only para-aminosalieylic acid was discontinued. Platelet counts obtained daily for the next six days varied between 40,000 and 70,000 per cubic millimeter but increased to 260,000 on the thirtieth hospital day. Therapy with isoniazid is ongoing. Streptomycin administration was discontinued three months following discharge, at which time treatment with Rifampin was initiated. Prior to use of Rifampin, cautious readministration of para-aminosalicylic acid was attempted but was followed within four hours by a drop in platetet count from 250,000 to 80,000 per cubic millimeter. Platelet count returned to normal four days later.
DISCUSSION Thrombocytopenia following para-aminosalicyclic acid administration has 'been documented previously only in adults, l"a Thrombocytopenia
Letters to the Editor
503
was noted in association with paraaminosalicylic acid therapy, abated five days following discontinuation of para-aminosalicylic acid despite continued administration of streptomycin and isoniazid, and reoccurred promptly following rechallenge of the patient with para-aminosalicylic acid. This sequence of events strongly suggests that the thrombocytopenia was a direct consequence of para-aminosalicylic acid administration. Platelet destruction following para-aminosalicylic acid administration has been suggested by previous reports in the literature, 1-3 and in one case a circulating antibody to a glycine-conjugated metabolite of para-aminosalicylic acid was documented. 3 AIthough specific platelet antibodies were not sought, platelet destruction is the most likely cause of thrombocytopenia in the present case.
Ralph D. Feigin, M.D. ~ Harold F. Zarkowsky, M.D. William Shearer, Ph.D., M.D. Donald C. Anderson, M.D. The Edward Mallinekrodt Department o[ Pediatrics Washington University School o[ Medicine and the Divisions of Infectious Diseases and Hematology at St. Louis Children's Hospital St. Louis, Mo. 63110 ~Reclpient of a Research Career Development Award No. 1K04AI46%6 from the National Institute of Allergy and Infectious Diseases.
REFERENCES 1. Wurzet, H. A., and Maycock, R. L.: Thrombocytopenia induced by sodium para-aminosalicylic acid, J. A. M. A. 153: 1094, 1953. 2. Gregg, J. A., and Maycock, R. L.: Thrombocytopenia induced by administration of sodium para-aminosalieylate, J. A. M. A. 172: 1909, 1960. 3. Eisner, E. V., and Kasper, K.: Immune thrombocytopenia due to a metabolite of para-aminosalicylic acid, Am. J. Med. 53: 790, 1972.
Pigmented lesions of incontinentia pigmenti in a neonate To the Editor: The following case report illustrates the unusual occurrence of pigmented lesions of incontinentia pigmenti in a newborn infant who has
504
Letters to the Editor
The Journal of Pediatrics September 1973
keratosis, mild degeneration of the basal cell layer, and focal edema of the upper dermis. No eosinophil-filled intraepidermal vesicles were seen. The cutaneous scaling disappeared during the first two weeks of life. The patient is now 4 months of age and has not developed vescicular, bullous, or verrucous skin lesions. The pigmented areas have faded slightly. DISCUSSION
Fig. 1. Patient N. M. at 3 days of age. Note the typical pigmented lesions of incontinentia pigmenti and the mild scaling over the left arm. failed to develop other definite stages of cutaneous involvement. CASE REPORTS Patient N. M., a 3,470 Gin. black female infant, was the product of a full-term, uncomplicated pregnancy. Her brother, sister, and mother were in good health and had never had abnormalities of the skin, hair, nails, or teeth, The rest of the family history was negative for congenital anomalies or cutaneous disorders. Two years prior to the birth of the patient, her mother had a spontaneous abortion at 9 weeks' gestation. Physical examination revealed bilateral areas of cutaneous hyperpigmentation arranged in whorls and streaks over the trunk and extremities (Fig. 1). Mild skin inflammation and scaliness were present, particularly over the antecubital fossae. No vesicles or bullae were noted. The hair, nails, and eyes were normal. Laboratory data included a White blood cell count of 15,000 per cubic millimeter with a normal differential count including 2 per cent eosinophils. Chest roentgenogram and electrocardiogram were normal. Skin biopsy findings were interpreted as being compatible with the clinical diagnosis of incontinentia pigmenti; there was increased melanin in dermal melanophages, hyper-
Incontinentia pigmenti is a rare cutaneous disorder which is often associated with dystrophic nails, alopecia, ocular abnormalities, and delayed or malformed dentition. 1-a Seizures, mental retardation, cardiac defects, and skeletal deformities occur less often. 1, a These anomalies need not be evident in the neonatal period, so the physician must be aware of their occurrence and should look for them in the older affected child. The disease is inherited as an X-linked dominant trait and is lethal in most affected male fetuses who are aborted spontaneouslyY The characteristic skin findings often appear in stages. Vescicular or bullous lesions associated with cutaneous inflammation are usually present at the time of birth and persist for several months. This stage is nsualIy foliowed by verrucous lesions which may produce skin atrophy after healing. The third stage is characterized by pigmented lesions arranged in whorl-like patterns over large areas of the body. These pigmented areas may persist fgr several years but eventually disappear completely. There is no clear demarcation between these three stages; at times atl types of skin changes may occur simultaneously. 1-s The clinical appearance of the skin lesions is characteristic; a skin biopsy may be helpful in confirming the diagnosis, particularly in unusual or atypical cases. The pathologic findings of skin in incontinentia pigmenti have been previously, described.~, In view of the negative family history for incontinentia pigmenti, the infant may represent the product of a new mutation, Alternatively, it is possible that the patient's mother exhibited subclinical disease, demonstrating genetic heterogeneity as defined by the Lyon~ hypothesis. The present case of incontinentia pigmenti documents the unusual occurrence of pigmented lesions at the iime of birth, a phenomenon which has not been emphasized in recent reviews of this topic?, a We speculate that this infant may have had other stages of involvement of the skin during imrauterine life. The mild scaling and inflammation of the skin which were present during the first two weeks of life may have represented
Volume 83 Number 3
Letters to the Editor
resolution of vescicular lesions developed in utero. We cannot be certain of this, as the skin biopsy findings were not diagnostic of this stage of the disease.
Robert J. Lerer, M.D. Richard A. Ehrenkranz, M.D. A. G. M. Campbell, M.B., F.R.C.P. Department of Pediatrics Yale University School of Medicine Yale-New Haven Hospital New Haven, Conn. 06510 REFERENCES
1. Carney, R. G., and Carney, R. G., Jr.: Incontinentia pigmenti, Arch. Dermatol. 102: 157, 1970. 2. Gordon, H., and Gordon, W.: Incontinentia pigmenti: Clinical and genetical studies of two familial cases, Dermatologica 140: 150, 1970. 3. Morgan, J. D.: Incontinentia pigmenti (BlochSulzberger syndrome), Am. J. Dis. Child. 122: 294, 1971. 4. Lyon, M. F.: Sex chromatin and gene action in the mammalian X-chromosome, Am. J. Hum. Genet. 14: 135, 1962.
Hypoglycemia in small-forgestational age infants To the Editor: Although the pathophysiotogy of neonatal hypoglycemia is still not well understood, much has recently been learned about carbohydrate metabolism in the fetus and newborn infant. A great deal of the experimental work has, of necessity, been carried out in laboratory animals. Although species differences obviously exist, much of the knowledge gained is applicable to the human being. In a recent review on hypoglycemia in infancy and childhood, Pagliara and associates 1 discussed the predisposition of small-for-gestational age neonates to the development of hypoglycemia. They followed circulatory levels of certain metabolites in these infants from birth through the first 24 hours of llfe and found a pattern highly suggestive of a maturationaI delay in the hepatic gluconeogenic enzymatic apparatus. These re-
505
sults are in agreement with our in vitro findings in an experimental model of intrauterine growth retardation2 In these studies, liver slices taken fi'om small-for-date newborn rats three hours after spontaneous delivery showed an impaired glucose production from labeled alanine. On the basis of this observation, we postulated that inadequate postnatal development of hepatic gluconeogenesis may play a contributory role in the susceptibility of small-for-date infants to develop hypoglycemia during the early period Iollowing delivery. The rapid falt in liver glycogen after birth suggests that it is mobilized to maintain the blood glucose level. When these reserves, which are known to be smaller in intrauterine growth-retarded neonates,x, ~ are exhausted, glucose production from noncarbohydrate substrates, such as amino acids and glycerol, is of utmost importance. Glucagon and catecholamines play an important role in the induction of the gluconeogenic enzymatic mechanism.~ Thus inappropriate secretion of these hormones, or impaired enzyme induction, may cause the above-mentioned delay in maturation of hepatic gluconeogenesis.
Menachem Nitzan, M.D. Department o[ Pediatrics and Rogoff-WelIcome Trust Medical Research Institute Beilinson Medical Center Tel Aviv University Medical School Petah Tikva, Israel REFERENCES
1. Pagliara, A. S., Karl, I. E., Haymond, M., and Kipnis, D. M.: Hypoglycemia in infancy and childhood. Part I, J. P~DIATm 82: 365, 1973. 2. Nitzan, M., and Groffman, H.: Hepatic gluconeogenesis and lipogenesis in experimental intrauterine growth retardation in the rat, Am. J. Obstet. Gynecol. 109: 623, 1971. 3. Shelley, H. J.: Carbohydrate reserves in the newborn infant, Br. Med. J. 1: 273, 1964. 4. Nitzan, M., and Groffman, H.: Metabolic changes in experimental intrauterine growth retardation: Blood glucose and liver glycogen in dysmature and premature newborn rats, Isr. J. Med. Sci. 6: 697, 1970. 5. Yeung, D., and Oliver, I. T.: Factors affecting the premature induction of phosphopyruvate carboxylase in neonatal rat liver, Biochem. J. 108: 325, 1968.