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Disseminated intravascular coagulopathy following fatal brown spider bite (necrotic arachnidism)
Volume 80 Number 6
Brie[ clinical and laboratory observations
10 3 5
2. Herschmann, A., Blum, R., and Lee, Y. C.: Angiographie findings in polyarteritis nodosa, Radiology 94: 147, 1970. 3. Dornfeld, L., Lecky, J. W., and Peter, J. B.: Polyarteritis and intrarenal artery aneurysms, J. A. M. A. 215: 1950, 1971. 4. Citron, B. P., Halpern, M., McCarron, M., Lundberg, G. D., McCormick, R., Pincus, I. J., Tatter, D., and Haverback, B. J.: Necrotizing angiitis associated with drug abuse, N. Engh J. Med. 283: 1003, 1970.
5. Hamburger, J.: Nephrology, vol. 2, Philadelphia, 1968, W. B. Saunders Company, p. 843. 6. Davson, J., Ball, J., and Platt, R.: The kidney in periarteritis nodosa, Quart. J. Med. 17: 175, 1948. 7. Heptinstall, R. H.: Pathology of the kidney, Boston, 1966, Little, Brown & Company, p. 509.
Disseminated i n t ra ra scu la r
at a rural lake. He was reportedly bitten by an unidentified insect. Several hours later he developed headache and vomiting. He was admitted to another hospital where a vesicle surrounded by ecchymosis was noted on his back. This area became necrotic and he developed progressive iaundice and gross hematuria over the next 24 hours. He was then referred to Children's Memorial Hospital. The physical examination revealed a pale, lethargic child who was critically ill. His blood pressure was 100/50, temperature 37.5~ C., and pulse 100. Perioral cyanosis and acrocyanosis were present, and the skin and sclerae were icteric. Located in the interscapular area was a small necrotic lesion with a 5 x 9 cm. circumferential ecchymotic area which followed a dependent pattern. There was swelling and tenderness of the sm'rounding soft tissues. Petechiae were noted over the shoulders, thighs, and buttocks. The liver was palpable 2 cm. below the right costal margin, Laboratory data included: hemoglobin, 6.8 rag. per 100 ml.; hematocrit, 11 per cent; white blood count, 22,700 per cubic millimeter with 89 per cent neutrophils, 8 per cent bands, and 3 per cent lymphocytes. The peripheral blood smear showed spherocytosis, many schistocytes, and decreased platelets. The platelet count was 25,000 per cubic millimeter by phase microscopy. The partial thromboplastin time was 77.4 seconds (normal <50 seconds), and the prothrombin time was 21.9 seconds (control 12.9 seconds). The fibrinogen was 88 mg. per cent (norreal >160 rag. per cent). The fibrin split products were 80 tag per cent (normal < 5 /xg per cent). The urine and serum had a dark brown color. The urine was positive for hemoglobin. Other laboratory studies were as follows: biHrubin, total 8.2, direct 5.3; SGOT, 583u; blood urea nitrogen, 44 rag. per cent; CO~, 15 ram. per liter; potassium, 5.4 mEq. per liter; chloride, 104 mEq. per liter~ and sodium, 135 mEq. per liter.
coagulopatby f olloMng fatal brown spider bite (necrotic aracbnidism) Hal Vorse, M.D., Paul Seccareccio, M.D., Kay Woodruff, M.D., and G.
Bennett Humphrey,
M.D., Ph.D.,
O k l a h o m a City, Okla. ALTJ~Ob'O~t the brown spider, Loxosceles reclusa, has been k n o w n to exist in the Southwestern U n i t e d States for m a n y years, 1 it was n o t associated with necrotic arachnidism until the work of Atkins a n d associates 2 in 1957. Since that time, the bite of the b r o w n recluse spider has been recognized as a frequent cause of illness in a large area of the U n i t e d States. a-6 Serious systemic symptoms may occur, particularly intravascular hemolysis a n d renal failure?. 4-s These complications are most f r e q u e n t in children a n d m a y lead to death. We have observed a child in whom disseminated intravascular coagulation was d o c u m e n t e d following systemic necrotic arachnidism.
CASE REPORT Patient J. D. was a healthy 6-year-old Cauca~.ian boy who had been pIaying under a wharf
From the Departments o[ Pediatrics and Pathology, and the Children's Memorial Hospital, University o[ Oklahoma Medical Center.
10 36
Brie[ clinical and laboratory observations
Fig. 1. Skin from bite site showing epidermal sloughing, thrombosis, and scattered inflammation. (Hematoxylin and eosin, x70.) In spite of therapy with intravenous fluids, blood, corticosteroids, and heparin, and peritoneal dialysis, the patient had a cardiorespiratory arrest five hours following admission and was not responsive to resuscitation. At necropsy, the previously described necrotic lesion was noted. Microscopically, this corresponded to an area of superficial epidermal sloughing. The underlying dermis showed necrosis and a scattered infiltrate of neutrophils and eosinophils. The small blood vessels were thrombosed and had focal necrosis of their walls (Fig. 1). The lungs were congested, edematous, and atelectatic. Special stains revealed free hemoglobin in many small blood vessels. Microthrombi were not found despite special stains for fibrin. The portal triads of the liver exhibited a striking eosinophilia, and there was an increase in eosinophils in the generally hypercellular bone marrow. The small intestine had focal areas of superficial mueosal necrosis and hemorrhage. Fibrin thrombi were not seen. A modified Van Geison stain identified hemoglobin-laden reticuloendothelial cells in the spleen. AhnoSt every renal tubule contained hemoglobin casts (Fig. 2), and the surrounding tubular epithelial cells contained large intracellular hemoglobin droplets. Many tubular epithelial cells were necrotic. There were large areas of hemorrhage, primarily in the medulla. The brain contained approximately 50 c.c. of fresh hemorrhage in the subdural space of the anterior~ middle, and posterior fossae.
The Journal o[ Pediatrics June 19'72
Fig. 2. Renal tubules containing hemoglobin casts. (Hematoxylin and eosin, x400.) COMMENT
A l t h o u g h no spider was identified in this case, L. reclusa is e n d e m i c in the area?, s, a This p a t i e n t h a d the typical local lesion. T h e area a r o u n d the bite is very painful. Initially the bite is white a n d raised, s u r r o u n d e d by an a r e a of e d e m a a n d erythema. O v e r the next 24 to 48 hours, a central a r e a of ulceration develops, a n d the s u r r o u n d i n g tissues become ecchymotic. Microscopically this area shows an extensive vasculitis with thrombosis a n d necrosis of the vessels?, 2 T h e p a t i e n t also h a d systemic symptoms of massive i n t r a v a c u l a r hemolysis. ~, s, 4, s, 7, 8 This hemolysis was manifested by clinical h e m o globinuria a n d by h e m o g l o b i n in the lungs, kidneys, a n d spleen at autopsy. A l t h o u g h fibrin t h r o m b i were not identified, the clinical coagulation studies a n d the hemorrhages in the kidneys a n d b r a i n attest to the presence of disseminated i n t r a v a s c u l a r coagulation. A l t h o u g h disseminated i n t r a v a s c u l a r coagulation has not been r e p o r t e d with necrotic arachnidism, several authors have noted t h r o m b o c y t o p e n i a ? , 5, 7 Also, dogs injected with the v e n o m of L. reclusa have t h r o m b o c y t o p e n i a a n d h e m o r r h a g e in various organs2 Severe i n t r a v a s c u l a r hemolysis secondary to a variety of causes have been well established as a triggering m e c h a n i s m
Volume 80 Number 6
Brie/ clinical a n d laboratory observations
for disseminated i n t r a v a s c u l a r coagulation?0, 1, This is most p r o b a b l y the cause of disseminated intravascular coagulation in this p a t i e n t a n d m a y explain the t h r o m b o cytopenia a n d h e m o r r h a g e s n o t e d in other cases of necrotic arachnidism. If recognized early, local a n d systemic glucocorticoids in large doses have been advocated to p r e v e n t i n t r a v a s c u l a r hemolysis? O n c e systemic symptoms occur, exchange transfusion should be considered. O n e patient who survived systemic necrotic arachnidism u n d e r w e n t exchange transfusion, s This p r o c e d u r e would theoretically accomplish the following: (1) raise the red cell volume, (2) lower the circulating free hemoglobin, (3) possibly decrease the a m o u n t of r e m a i n i n g venom, and (4) i n t e r r u p t intravascular coagulation. T h i s p a t i e n t unfortunately died before exchange transfusion could be performed. Necrotic a r a c h n i d i s m is one more cause in a growing list of disorders associated with disseminated i n t r a v a s c u l a r coagulation. I n patients with systemic symptoms secondary to L. reclusa, coagulation studies should be p e r f o r m e d early in o r d e r t h a t a p p r o p r i a t e t h e r a p y m a y be instituted should dissemin a t e d i n t r a v a s c u l a r coagulation be a p a r t of the syndrome.
G-6-PD hemolytic anemia complicating diabetic ketoaciclosir A n d r e w M. Gellady, M.D., a n d R o n a l d D. G r e e n w o o d , M.D., Chicago, Ill.
From The Children's Memorial Hospital and The Department of Pediatrics, Northwestern University Medical School. Reprint address: Andrew M. GeUady, M.D., Children's Memorial Hospital, 2300 Children's Plaza, ChleaEo, Ill. 60614.
10 3 7
REFERENCES
1. Riley, H. D., Jr., McLean, W. R., Stuart, A. G., et al.: Brown spider bite with severe hemolytic phenomenon, J, OkIa. State Med. Assoc. 57: 218, 1964. 2. Atkins, J. A., Wingo, C. W., and Plynn, J. E.: Necrotic arachnidism, Am. J. Trop. Med. 7: 165, 1958. 3. Dillaha, C. J., Janser, G. T., Honeycutt, W. M., and Hayden, C. R.: North American Loxoscelism, J. A. M. A. 188: 33, 1964. 4. Minton, S. A., and Olson, C.: A case of spider bite with severe hemolytic reaction, Pediatrics 33" 283, 1964. 5. Taylor, E. H., and Denny, W. F.: Hemolysis renal failure and sudden death presumed secondary to bite of brown recluse spider, South. Med. J. 59: 1209, 1966. 6. Flux, M., and Riley, H. D., Jr.: Necrotic arachnidism due to bite of brown spider (L. reclusa). Report of 11 cases in children. In preparation. 7. Nance, W. E.: Hemolytic anemia in necrotic arachnidism, Am. J. Med. 31" 801, 1961. 8. Nicholson, J. F., and Nicholson, B. H.: Hemolytic anemia from brown spider bite, necrotic arachnidism, J. Okla. State Med. Assoc. 55: 234, 1962. 9. Denny, W. F., Dillaha, C. J., and Morgan, P. M.: Hemotoxic effect of Loxosceles reclusus venom in vivo and in vitro, J. Lab. Clin. Med. 64: 29i, 1964. 10. McKay, D. G.: Disseminated intravascular coagulation, New York, 1965, Harper & Row, Publishers, pp. 23-62. 11. Abildgaard, C. F.: Recognition and treatment of intravascular coagulation, J. PEmATR. 74: 163, 1969.
H E M o t Y S I S from glucose-6-phosphate dehydrogenase ( G - 6 - P D ) deficiency associa t e d with diabetic ketoacidosis has been rep o r t e d b u t is not common. Patients in the pediatric p o p u l a t i o n have not been specifically cited in previous reports. CASE REPORT Patient J. W., a 10-year-old Negro boy, was apparently well until one month prior to admission, when he began to experience polyuria and polydipsia. He became lethargic two days prior to admission. Physical examination at the time of admission revealed a dehydrated child in semicomatose condition. Vital signs revealed a pulse rate of 140 per minute, Kussmaul respirations at 30 per minute, and a bIood pressure of 110/70. Initial laboratory values revealed a blood
Brie[ clinical and laboratory observations
10 3 5
2. Herschmann, A., Blum, R., and Lee, Y. C.: Angiographie findings in polyarteritis nodosa, Radiology 94: 147, 1970. 3. Dornfeld, L., Lecky, J. W., and Peter, J. B.: Polyarteritis and intrarenal artery aneurysms, J. A. M. A. 215: 1950, 1971. 4. Citron, B. P., Halpern, M., McCarron, M., Lundberg, G. D., McCormick, R., Pincus, I. J., Tatter, D., and Haverback, B. J.: Necrotizing angiitis associated with drug abuse, N. Engh J. Med. 283: 1003, 1970.
5. Hamburger, J.: Nephrology, vol. 2, Philadelphia, 1968, W. B. Saunders Company, p. 843. 6. Davson, J., Ball, J., and Platt, R.: The kidney in periarteritis nodosa, Quart. J. Med. 17: 175, 1948. 7. Heptinstall, R. H.: Pathology of the kidney, Boston, 1966, Little, Brown & Company, p. 509.
Disseminated i n t ra ra scu la r
at a rural lake. He was reportedly bitten by an unidentified insect. Several hours later he developed headache and vomiting. He was admitted to another hospital where a vesicle surrounded by ecchymosis was noted on his back. This area became necrotic and he developed progressive iaundice and gross hematuria over the next 24 hours. He was then referred to Children's Memorial Hospital. The physical examination revealed a pale, lethargic child who was critically ill. His blood pressure was 100/50, temperature 37.5~ C., and pulse 100. Perioral cyanosis and acrocyanosis were present, and the skin and sclerae were icteric. Located in the interscapular area was a small necrotic lesion with a 5 x 9 cm. circumferential ecchymotic area which followed a dependent pattern. There was swelling and tenderness of the sm'rounding soft tissues. Petechiae were noted over the shoulders, thighs, and buttocks. The liver was palpable 2 cm. below the right costal margin, Laboratory data included: hemoglobin, 6.8 rag. per 100 ml.; hematocrit, 11 per cent; white blood count, 22,700 per cubic millimeter with 89 per cent neutrophils, 8 per cent bands, and 3 per cent lymphocytes. The peripheral blood smear showed spherocytosis, many schistocytes, and decreased platelets. The platelet count was 25,000 per cubic millimeter by phase microscopy. The partial thromboplastin time was 77.4 seconds (normal <50 seconds), and the prothrombin time was 21.9 seconds (control 12.9 seconds). The fibrinogen was 88 mg. per cent (norreal >160 rag. per cent). The fibrin split products were 80 tag per cent (normal < 5 /xg per cent). The urine and serum had a dark brown color. The urine was positive for hemoglobin. Other laboratory studies were as follows: biHrubin, total 8.2, direct 5.3; SGOT, 583u; blood urea nitrogen, 44 rag. per cent; CO~, 15 ram. per liter; potassium, 5.4 mEq. per liter; chloride, 104 mEq. per liter~ and sodium, 135 mEq. per liter.
coagulopatby f olloMng fatal brown spider bite (necrotic aracbnidism) Hal Vorse, M.D., Paul Seccareccio, M.D., Kay Woodruff, M.D., and G.
Bennett Humphrey,
M.D., Ph.D.,
O k l a h o m a City, Okla. ALTJ~Ob'O~t the brown spider, Loxosceles reclusa, has been k n o w n to exist in the Southwestern U n i t e d States for m a n y years, 1 it was n o t associated with necrotic arachnidism until the work of Atkins a n d associates 2 in 1957. Since that time, the bite of the b r o w n recluse spider has been recognized as a frequent cause of illness in a large area of the U n i t e d States. a-6 Serious systemic symptoms may occur, particularly intravascular hemolysis a n d renal failure?. 4-s These complications are most f r e q u e n t in children a n d m a y lead to death. We have observed a child in whom disseminated intravascular coagulation was d o c u m e n t e d following systemic necrotic arachnidism.
CASE REPORT Patient J. D. was a healthy 6-year-old Cauca~.ian boy who had been pIaying under a wharf
From the Departments o[ Pediatrics and Pathology, and the Children's Memorial Hospital, University o[ Oklahoma Medical Center.
10 36
Brie[ clinical and laboratory observations
Fig. 1. Skin from bite site showing epidermal sloughing, thrombosis, and scattered inflammation. (Hematoxylin and eosin, x70.) In spite of therapy with intravenous fluids, blood, corticosteroids, and heparin, and peritoneal dialysis, the patient had a cardiorespiratory arrest five hours following admission and was not responsive to resuscitation. At necropsy, the previously described necrotic lesion was noted. Microscopically, this corresponded to an area of superficial epidermal sloughing. The underlying dermis showed necrosis and a scattered infiltrate of neutrophils and eosinophils. The small blood vessels were thrombosed and had focal necrosis of their walls (Fig. 1). The lungs were congested, edematous, and atelectatic. Special stains revealed free hemoglobin in many small blood vessels. Microthrombi were not found despite special stains for fibrin. The portal triads of the liver exhibited a striking eosinophilia, and there was an increase in eosinophils in the generally hypercellular bone marrow. The small intestine had focal areas of superficial mueosal necrosis and hemorrhage. Fibrin thrombi were not seen. A modified Van Geison stain identified hemoglobin-laden reticuloendothelial cells in the spleen. AhnoSt every renal tubule contained hemoglobin casts (Fig. 2), and the surrounding tubular epithelial cells contained large intracellular hemoglobin droplets. Many tubular epithelial cells were necrotic. There were large areas of hemorrhage, primarily in the medulla. The brain contained approximately 50 c.c. of fresh hemorrhage in the subdural space of the anterior~ middle, and posterior fossae.
The Journal o[ Pediatrics June 19'72
Fig. 2. Renal tubules containing hemoglobin casts. (Hematoxylin and eosin, x400.) COMMENT
A l t h o u g h no spider was identified in this case, L. reclusa is e n d e m i c in the area?, s, a This p a t i e n t h a d the typical local lesion. T h e area a r o u n d the bite is very painful. Initially the bite is white a n d raised, s u r r o u n d e d by an a r e a of e d e m a a n d erythema. O v e r the next 24 to 48 hours, a central a r e a of ulceration develops, a n d the s u r r o u n d i n g tissues become ecchymotic. Microscopically this area shows an extensive vasculitis with thrombosis a n d necrosis of the vessels?, 2 T h e p a t i e n t also h a d systemic symptoms of massive i n t r a v a c u l a r hemolysis. ~, s, 4, s, 7, 8 This hemolysis was manifested by clinical h e m o globinuria a n d by h e m o g l o b i n in the lungs, kidneys, a n d spleen at autopsy. A l t h o u g h fibrin t h r o m b i were not identified, the clinical coagulation studies a n d the hemorrhages in the kidneys a n d b r a i n attest to the presence of disseminated i n t r a v a s c u l a r coagulation. A l t h o u g h disseminated i n t r a v a s c u l a r coagulation has not been r e p o r t e d with necrotic arachnidism, several authors have noted t h r o m b o c y t o p e n i a ? , 5, 7 Also, dogs injected with the v e n o m of L. reclusa have t h r o m b o c y t o p e n i a a n d h e m o r r h a g e in various organs2 Severe i n t r a v a s c u l a r hemolysis secondary to a variety of causes have been well established as a triggering m e c h a n i s m
Volume 80 Number 6
Brie/ clinical a n d laboratory observations
for disseminated i n t r a v a s c u l a r coagulation?0, 1, This is most p r o b a b l y the cause of disseminated intravascular coagulation in this p a t i e n t a n d m a y explain the t h r o m b o cytopenia a n d h e m o r r h a g e s n o t e d in other cases of necrotic arachnidism. If recognized early, local a n d systemic glucocorticoids in large doses have been advocated to p r e v e n t i n t r a v a s c u l a r hemolysis? O n c e systemic symptoms occur, exchange transfusion should be considered. O n e patient who survived systemic necrotic arachnidism u n d e r w e n t exchange transfusion, s This p r o c e d u r e would theoretically accomplish the following: (1) raise the red cell volume, (2) lower the circulating free hemoglobin, (3) possibly decrease the a m o u n t of r e m a i n i n g venom, and (4) i n t e r r u p t intravascular coagulation. T h i s p a t i e n t unfortunately died before exchange transfusion could be performed. Necrotic a r a c h n i d i s m is one more cause in a growing list of disorders associated with disseminated i n t r a v a s c u l a r coagulation. I n patients with systemic symptoms secondary to L. reclusa, coagulation studies should be p e r f o r m e d early in o r d e r t h a t a p p r o p r i a t e t h e r a p y m a y be instituted should dissemin a t e d i n t r a v a s c u l a r coagulation be a p a r t of the syndrome.
G-6-PD hemolytic anemia complicating diabetic ketoaciclosir A n d r e w M. Gellady, M.D., a n d R o n a l d D. G r e e n w o o d , M.D., Chicago, Ill.
From The Children's Memorial Hospital and The Department of Pediatrics, Northwestern University Medical School. Reprint address: Andrew M. GeUady, M.D., Children's Memorial Hospital, 2300 Children's Plaza, ChleaEo, Ill. 60614.
10 3 7
REFERENCES
1. Riley, H. D., Jr., McLean, W. R., Stuart, A. G., et al.: Brown spider bite with severe hemolytic phenomenon, J, OkIa. State Med. Assoc. 57: 218, 1964. 2. Atkins, J. A., Wingo, C. W., and Plynn, J. E.: Necrotic arachnidism, Am. J. Trop. Med. 7: 165, 1958. 3. Dillaha, C. J., Janser, G. T., Honeycutt, W. M., and Hayden, C. R.: North American Loxoscelism, J. A. M. A. 188: 33, 1964. 4. Minton, S. A., and Olson, C.: A case of spider bite with severe hemolytic reaction, Pediatrics 33" 283, 1964. 5. Taylor, E. H., and Denny, W. F.: Hemolysis renal failure and sudden death presumed secondary to bite of brown recluse spider, South. Med. J. 59: 1209, 1966. 6. Flux, M., and Riley, H. D., Jr.: Necrotic arachnidism due to bite of brown spider (L. reclusa). Report of 11 cases in children. In preparation. 7. Nance, W. E.: Hemolytic anemia in necrotic arachnidism, Am. J. Med. 31" 801, 1961. 8. Nicholson, J. F., and Nicholson, B. H.: Hemolytic anemia from brown spider bite, necrotic arachnidism, J. Okla. State Med. Assoc. 55: 234, 1962. 9. Denny, W. F., Dillaha, C. J., and Morgan, P. M.: Hemotoxic effect of Loxosceles reclusus venom in vivo and in vitro, J. Lab. Clin. Med. 64: 29i, 1964. 10. McKay, D. G.: Disseminated intravascular coagulation, New York, 1965, Harper & Row, Publishers, pp. 23-62. 11. Abildgaard, C. F.: Recognition and treatment of intravascular coagulation, J. PEmATR. 74: 163, 1969.
H E M o t Y S I S from glucose-6-phosphate dehydrogenase ( G - 6 - P D ) deficiency associa t e d with diabetic ketoacidosis has been rep o r t e d b u t is not common. Patients in the pediatric p o p u l a t i o n have not been specifically cited in previous reports. CASE REPORT Patient J. W., a 10-year-old Negro boy, was apparently well until one month prior to admission, when he began to experience polyuria and polydipsia. He became lethargic two days prior to admission. Physical examination at the time of admission revealed a dehydrated child in semicomatose condition. Vital signs revealed a pulse rate of 140 per minute, Kussmaul respirations at 30 per minute, and a bIood pressure of 110/70. Initial laboratory values revealed a blood