970
7.
8.
9.
10.
II.
Brief clinical and laboratory observations
viral coproantibodies in breast-fed infants, Pediatrics 39:202, 1967. Middleton PJ, Petrie M, Hewitt CM, Szymanski MT, and Tam JS: Counterimmunoelectro-osmophoresis for the detection of infantile gastroenteritis virus (orbi-group) antigen and antibody, J Clin Patho129:191, 1976. Blacklow NR, Echeverria P, and Smith DH: Serological studies with reovirus-like enteritis agent, Infect Immun 13:1563, 1976. Schmitz H, and Enders G: Cytomegalovirus as a frequent cause of Guillain-Barre syndrome, J Med Virol 1:21, 1977. Thouless ME, Bryden AS, and Flewett TH: Rotavirus neutralization by human milk, Br Med J 2: 1390, 1977. Simhon A, and Mata L: Anti-rotavirus antibody in human colostrum, Lancet 1:39, 1978.
The Journal of Pediatrics December 1978
12.
Yolken R, Kim HW, Clem T, Wyatt RG, Kalica AR, Chanock RM, and Kapikian AZ: Enzyme-linked immunesorbent assay (ELISA) for detection of human reovirus-like agent of infantile gastroenteritis, Lancet 2:263, 1977. 13. Snodgrass DR, and Wells PW: Rotavirus infection in lambs: studies on passive protection, Arch Virol 52:201, 1976. 14. Matthews THJ, Nair CDG, Lawrence MK, and Tyrrell DAJ: Antiviral activity in milk of possible clinical importance, Lancet 2: 1387, 1976. 15. Raptopoulou-Gigi M, Marwick K, and McClelland DBL: Antimicrobial proteins in sterilised human milk, Br Med J 1: 12, 1977.
Cold weather and rhabdomyolysis Mark A. Raifman, M.D., Far Rockaway, N. Y., Moshe Berant, M.D., Hadera, Israel, and Carl Lenarsky, M.D., Far Rockaway, N. Y.
RHABDOMYOLYSIS is an uncommon condition which may have serious consequences, such as severe electrolyte imbalance, cardiac arrhythmias, renal failure, and respiratory failure.' The clinical presentation is frequently nonspecific. Reports on rhabdomyolysis do not list exposure to cold as one of the causes of this condition. This report describes three instances of rhabdomyolysis asso-
Laboratory investigation as well as family and past history failed to disclose any of the factors that are usually considered in a patient with an attack of rhabdomyo 'g'sis. However, a detailed history of the youngster's activities on the day of admission revealed that he had spent one and one-half hours standing at a bus stop. dressed in a short overcoat, thin trousers, tube socks, and sneakers. That day was dry, with temperatures around -SoC and winds of 20 miles per hour.
ciated with exposure to cold weather. CASE REPORTS Patient 1. A 15-year-old boy was referred to the emergency room at Peninsula Hospital Center as "rule out nephrotic syndrome," because of bilateral ankle edema and 2+ protein in the urine. Blood pressure on admission was 120170 mm Hg. The positive physical findings were limited to the lower extremities, with painful and tender symmetric swelling of the legs and ankles. The overlying skin was normal and was cool to touch. There was no evidence of any vascular incompetence and peripheral pulses were equal and palpated bilaterally. Urinalysis showed 2+ protein, was slightly benzidine positive, and had no cells or casts on microscopic examination. The color of the urine was not noted. Results of tests for blood urea nitrogen, creatinine, electrolytes, proteins, cholesterol, and total lipids were all normal. Serum phosphorus concentration was 5.8 mg/dl, and calcium 10.1 mg/dl; SOOT was 180 units, LDH 800 units, and CPK was initially 3,400 units and rose to 5,200 units on the following day. From the Department of Pediatrics, Peninsula Hospital Center. • Reprint address: Department of Pediatrics, Peninsula Hospitai Center, For Rockaway, NY 11691.
See related article, p, 1015. Abbreviations used: SOOT: serum glutamic oxaloacetic transaminase LDH: lactate dehydrogenase CPK: creatine phosphokinase Patient 2. A 4-year-old girl was referred with a diagnosis of "acute rheumatic fever." She had awakened that morning with swelling and severe pain in both feet and ankles. The patient was one of eight children of an indigent family, living in a shabby, unheated home. The evening before admission the child had been stepping into puddles covered with thin' ice and went to sleep without taking off her wet socks and sneakers. The temperature that night was below the freezing point. Physical examination showed her to be unable to stand because of the pain in her feet. Her ankles and her feet were swollen and exquisitely tender. The overlying skin appeared normal, without lesions, and was ice cold to touch. There were no other abnormal findings. The urine had a slightly pink tinge, contained 2+ protein with a positive benzidine test. Blood counts and renal function studies were all normal. The serum potassium concen-
0022-3476/78/120970+02$00.20/0 © 1978 The C. V. Mosby Co.
Volume 93 Number 6
tration was 6.2 rnfiq/l. SGOT was 200units, LDH 900 units, and CPK levels reached 6,800 units. Patient 3. A generally healthy 16-year-old girl came to our emergency room with severely painful and swollen feet and ankles. Over the last 24 hours she had been seen twice at another hospital and was thought to have "an infection of the ankles." The patient had stayed with a friend for the last two weeks in an unheated apartment, where it was freezing cold, reflecting the inclement weather and the low temperatures which prevailed at the time. Once a day she would go out to the store, wearing slippers and thin socks which she did not change upon returning to the apartment, despite their becoming wet. Before going to bed, this girl used to put on two pairs of socks overthose she had worn during the day. Five days before her admission, the patient had noticed that her feet tended to become "numb and weak" and two days before admission her feet and ankles became increasingly painful and swollen. On examination, there was no evidence of systemic illness. Both feet and ankles were affected.They were exquisitely tender, with nonpitting edema. There were no signs of inflammation and the skin was intact. Results of an urinalysis was normal. the serum level of CPK was 5,500 units. All three patients followed a benign course. Treatment with bed rest and gentle warmingof the lower extremities allowed full clinical recovery over three to four days. Urinalysis and renal function tests were normal, and serum enzyme levels were normal at follow up three weeks later.
DISCUSSION The clinical findings along with transient proteinuria, positive urine benzidine tests, and high serum enzyme levels are all consistent with the diagnosis of rhabdomyo 1ysis, albeit with minimal myoglobinuria.' The muscular damage, while causing dramatic clinical and laboratory features, was not extensive enough to cause visibly apparent myoglobinuria. To have overt myoglobinuria, at least 200 gm of muscle must be severely damaged." Less massive muscle injury will not produce the telltale pinkto-brown discoloration of the urine and may, therefore, go unrecognized. Exposure to cold has been overlooked by reviews and classifications of rhabdornyolysis.': 2. '-7 Reiner et al" described a patient who developed rhabdomyolysis with acute renal failure after lying unconscious on frozen ground for half an hour following a "syncopal attack associated with tonic muscular contractions"; the authors interpreted the rhabdomyolysis as seizure related, and did not refer to the possibility that cold induced the episode of muscle necrosis. Rowland and Penn' stated that among their 38 patients with myoglobinuria, none was associated with hypothermia; however, one of their patients had five episodes of myalgia and pigmenturia "all associated with exercise (prolonged walking and cycling) and usually in cold
Brief clinical and laboratory observations
97]
weather." In another, rhabdomyolysis ensued from "presumed carbon monoxide intoxication," but the report described this 16-year-old girl as having been admitted "in coma on a cold Sunday morning" and having been unconscious in her car the whole night. The omission of cold as a cause of rhabdomyo lysis in its own right is possibly due to the assumption that the effect of cold is mediated by ischemia, which is a wellrecognized etiologic agent of muscle necrosis.' Experimental evidence," however, demonstrates that the pathologic changes in the muscles induced by cold differ from those caused by ischemia. One major difference is borne out by the observation that, although the necrotic changes ill muscle provoked by ischemia involve the whole bundle which has become deprived of its blood supply, the muscle damage induced by the immersion of a rabbit's leg ill a cold alcohol bath is layered; the most severe degree of structural damage appears in the outer layers of muscle tissue, i.e., those nearest to the cold bath, and the mildest damage occurs in the inner layers, i.e., those farthest from the injurious agent. Furthermore, the depth of the severely affected layers can be altered at will by manipulating the severity of the exposure to cold. Such layering of the lesions from the surface according to severity cannot be explained on a vascular basis; thus the injury from cold is a direct one on the cells and represents thermal damage to muscle. The children described here are examples of muscle damage associated with exposure to cold. Since cold is a preventable injurious agent, it should be included in the classification of the etiologic factors of rhabdomyolysis. REFERENCES 1. Rowland LP, and Penn AS: Myoglobinuria, Med Clin
North Am 56:1233,1972. 2. Robotham JL, and Haddow JE: Rhabdornyolysis and myoglobinuria in childhood, Pediatr Clin North Am 23:279. 1976. 3. Berenbaum MD, Birch CA, and Moreland JD: Paroxysmal myoglobinuria, Lancet 1:892, 1955. 4. Favara BE, Vawter GF, Wagner R, Kevy S, and Porter EG: Familial paroxysmal rhabdornyolysis in children. A myoglobinuric syndrome Am J Med 42:19/i, 1967. 5. Savage DCC, Forbes M, and Pearce OW: Idiopathic rhabdomyolysis, Arch Dis Child 46:594, 1971. 6. Kagen LJ: Myoglobinuric syndromes, Am J Med Sci 264:141, 1972. 7. Cifuentes E, Norman ME, Schwartz MW, Maley B, and Bason W: Myoglobinuria with acute renal failure in children, Clin Pediatr 15:63, 1976. 8. Reiner L, Konikoff N, Altschulc MD, Dammin GJ, and Merrill JP: Idiopathic paroxysmal myoglobinuria, Arch Intern Med 97:537, 1956. 9. LewisRB, and Moen pW: Further studies on the pathogenesis of cold-induced muscle necrosis, Surg Gynecol Obster 95:543, 1952.
7.
8.
9.
10.
II.
Brief clinical and laboratory observations
viral coproantibodies in breast-fed infants, Pediatrics 39:202, 1967. Middleton PJ, Petrie M, Hewitt CM, Szymanski MT, and Tam JS: Counterimmunoelectro-osmophoresis for the detection of infantile gastroenteritis virus (orbi-group) antigen and antibody, J Clin Patho129:191, 1976. Blacklow NR, Echeverria P, and Smith DH: Serological studies with reovirus-like enteritis agent, Infect Immun 13:1563, 1976. Schmitz H, and Enders G: Cytomegalovirus as a frequent cause of Guillain-Barre syndrome, J Med Virol 1:21, 1977. Thouless ME, Bryden AS, and Flewett TH: Rotavirus neutralization by human milk, Br Med J 2: 1390, 1977. Simhon A, and Mata L: Anti-rotavirus antibody in human colostrum, Lancet 1:39, 1978.
The Journal of Pediatrics December 1978
12.
Yolken R, Kim HW, Clem T, Wyatt RG, Kalica AR, Chanock RM, and Kapikian AZ: Enzyme-linked immunesorbent assay (ELISA) for detection of human reovirus-like agent of infantile gastroenteritis, Lancet 2:263, 1977. 13. Snodgrass DR, and Wells PW: Rotavirus infection in lambs: studies on passive protection, Arch Virol 52:201, 1976. 14. Matthews THJ, Nair CDG, Lawrence MK, and Tyrrell DAJ: Antiviral activity in milk of possible clinical importance, Lancet 2: 1387, 1976. 15. Raptopoulou-Gigi M, Marwick K, and McClelland DBL: Antimicrobial proteins in sterilised human milk, Br Med J 1: 12, 1977.
Cold weather and rhabdomyolysis Mark A. Raifman, M.D., Far Rockaway, N. Y., Moshe Berant, M.D., Hadera, Israel, and Carl Lenarsky, M.D., Far Rockaway, N. Y.
RHABDOMYOLYSIS is an uncommon condition which may have serious consequences, such as severe electrolyte imbalance, cardiac arrhythmias, renal failure, and respiratory failure.' The clinical presentation is frequently nonspecific. Reports on rhabdomyolysis do not list exposure to cold as one of the causes of this condition. This report describes three instances of rhabdomyolysis asso-
Laboratory investigation as well as family and past history failed to disclose any of the factors that are usually considered in a patient with an attack of rhabdomyo 'g'sis. However, a detailed history of the youngster's activities on the day of admission revealed that he had spent one and one-half hours standing at a bus stop. dressed in a short overcoat, thin trousers, tube socks, and sneakers. That day was dry, with temperatures around -SoC and winds of 20 miles per hour.
ciated with exposure to cold weather. CASE REPORTS Patient 1. A 15-year-old boy was referred to the emergency room at Peninsula Hospital Center as "rule out nephrotic syndrome," because of bilateral ankle edema and 2+ protein in the urine. Blood pressure on admission was 120170 mm Hg. The positive physical findings were limited to the lower extremities, with painful and tender symmetric swelling of the legs and ankles. The overlying skin was normal and was cool to touch. There was no evidence of any vascular incompetence and peripheral pulses were equal and palpated bilaterally. Urinalysis showed 2+ protein, was slightly benzidine positive, and had no cells or casts on microscopic examination. The color of the urine was not noted. Results of tests for blood urea nitrogen, creatinine, electrolytes, proteins, cholesterol, and total lipids were all normal. Serum phosphorus concentration was 5.8 mg/dl, and calcium 10.1 mg/dl; SOOT was 180 units, LDH 800 units, and CPK was initially 3,400 units and rose to 5,200 units on the following day. From the Department of Pediatrics, Peninsula Hospital Center. • Reprint address: Department of Pediatrics, Peninsula Hospitai Center, For Rockaway, NY 11691.
See related article, p, 1015. Abbreviations used: SOOT: serum glutamic oxaloacetic transaminase LDH: lactate dehydrogenase CPK: creatine phosphokinase Patient 2. A 4-year-old girl was referred with a diagnosis of "acute rheumatic fever." She had awakened that morning with swelling and severe pain in both feet and ankles. The patient was one of eight children of an indigent family, living in a shabby, unheated home. The evening before admission the child had been stepping into puddles covered with thin' ice and went to sleep without taking off her wet socks and sneakers. The temperature that night was below the freezing point. Physical examination showed her to be unable to stand because of the pain in her feet. Her ankles and her feet were swollen and exquisitely tender. The overlying skin appeared normal, without lesions, and was ice cold to touch. There were no other abnormal findings. The urine had a slightly pink tinge, contained 2+ protein with a positive benzidine test. Blood counts and renal function studies were all normal. The serum potassium concen-
0022-3476/78/120970+02$00.20/0 © 1978 The C. V. Mosby Co.
Volume 93 Number 6
tration was 6.2 rnfiq/l. SGOT was 200units, LDH 900 units, and CPK levels reached 6,800 units. Patient 3. A generally healthy 16-year-old girl came to our emergency room with severely painful and swollen feet and ankles. Over the last 24 hours she had been seen twice at another hospital and was thought to have "an infection of the ankles." The patient had stayed with a friend for the last two weeks in an unheated apartment, where it was freezing cold, reflecting the inclement weather and the low temperatures which prevailed at the time. Once a day she would go out to the store, wearing slippers and thin socks which she did not change upon returning to the apartment, despite their becoming wet. Before going to bed, this girl used to put on two pairs of socks overthose she had worn during the day. Five days before her admission, the patient had noticed that her feet tended to become "numb and weak" and two days before admission her feet and ankles became increasingly painful and swollen. On examination, there was no evidence of systemic illness. Both feet and ankles were affected.They were exquisitely tender, with nonpitting edema. There were no signs of inflammation and the skin was intact. Results of an urinalysis was normal. the serum level of CPK was 5,500 units. All three patients followed a benign course. Treatment with bed rest and gentle warmingof the lower extremities allowed full clinical recovery over three to four days. Urinalysis and renal function tests were normal, and serum enzyme levels were normal at follow up three weeks later.
DISCUSSION The clinical findings along with transient proteinuria, positive urine benzidine tests, and high serum enzyme levels are all consistent with the diagnosis of rhabdomyo 1ysis, albeit with minimal myoglobinuria.' The muscular damage, while causing dramatic clinical and laboratory features, was not extensive enough to cause visibly apparent myoglobinuria. To have overt myoglobinuria, at least 200 gm of muscle must be severely damaged." Less massive muscle injury will not produce the telltale pinkto-brown discoloration of the urine and may, therefore, go unrecognized. Exposure to cold has been overlooked by reviews and classifications of rhabdornyolysis.': 2. '-7 Reiner et al" described a patient who developed rhabdomyolysis with acute renal failure after lying unconscious on frozen ground for half an hour following a "syncopal attack associated with tonic muscular contractions"; the authors interpreted the rhabdomyolysis as seizure related, and did not refer to the possibility that cold induced the episode of muscle necrosis. Rowland and Penn' stated that among their 38 patients with myoglobinuria, none was associated with hypothermia; however, one of their patients had five episodes of myalgia and pigmenturia "all associated with exercise (prolonged walking and cycling) and usually in cold
Brief clinical and laboratory observations
97]
weather." In another, rhabdomyolysis ensued from "presumed carbon monoxide intoxication," but the report described this 16-year-old girl as having been admitted "in coma on a cold Sunday morning" and having been unconscious in her car the whole night. The omission of cold as a cause of rhabdomyo lysis in its own right is possibly due to the assumption that the effect of cold is mediated by ischemia, which is a wellrecognized etiologic agent of muscle necrosis.' Experimental evidence," however, demonstrates that the pathologic changes in the muscles induced by cold differ from those caused by ischemia. One major difference is borne out by the observation that, although the necrotic changes ill muscle provoked by ischemia involve the whole bundle which has become deprived of its blood supply, the muscle damage induced by the immersion of a rabbit's leg ill a cold alcohol bath is layered; the most severe degree of structural damage appears in the outer layers of muscle tissue, i.e., those nearest to the cold bath, and the mildest damage occurs in the inner layers, i.e., those farthest from the injurious agent. Furthermore, the depth of the severely affected layers can be altered at will by manipulating the severity of the exposure to cold. Such layering of the lesions from the surface according to severity cannot be explained on a vascular basis; thus the injury from cold is a direct one on the cells and represents thermal damage to muscle. The children described here are examples of muscle damage associated with exposure to cold. Since cold is a preventable injurious agent, it should be included in the classification of the etiologic factors of rhabdomyolysis. REFERENCES 1. Rowland LP, and Penn AS: Myoglobinuria, Med Clin
North Am 56:1233,1972. 2. Robotham JL, and Haddow JE: Rhabdornyolysis and myoglobinuria in childhood, Pediatr Clin North Am 23:279. 1976. 3. Berenbaum MD, Birch CA, and Moreland JD: Paroxysmal myoglobinuria, Lancet 1:892, 1955. 4. Favara BE, Vawter GF, Wagner R, Kevy S, and Porter EG: Familial paroxysmal rhabdornyolysis in children. A myoglobinuric syndrome Am J Med 42:19/i, 1967. 5. Savage DCC, Forbes M, and Pearce OW: Idiopathic rhabdomyolysis, Arch Dis Child 46:594, 1971. 6. Kagen LJ: Myoglobinuric syndromes, Am J Med Sci 264:141, 1972. 7. Cifuentes E, Norman ME, Schwartz MW, Maley B, and Bason W: Myoglobinuria with acute renal failure in children, Clin Pediatr 15:63, 1976. 8. Reiner L, Konikoff N, Altschulc MD, Dammin GJ, and Merrill JP: Idiopathic paroxysmal myoglobinuria, Arch Intern Med 97:537, 1956. 9. LewisRB, and Moen pW: Further studies on the pathogenesis of cold-induced muscle necrosis, Surg Gynecol Obster 95:543, 1952.
