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Congenital varicella of the upper limb
CONGENITAL
VARICELLA OF THE UPPER A preventable disaster
LIMB
M . M . A L - Q A T T A N and H. G. T H O M S O N
From the Section of Plastic Surgery, the Hospital for Sick Children, Toronto, Ontario, Canada
Two patients with a rare form of congenital varicella involving the upper limb are described. The spectrum of disease, pathophysiology, principles of management and prevention are discussed.
Journal of Hand Surgery (British and European Volume, 1995)20B: 1:115-117 Examination of the upper limb revealed good shoulder abduction, weak flexion and extension of the elbow, no active pronation, supination or wrist flexion, but wrist extension was present. No hand movements were observed. Electromyography of the upper limb muscles showed evidence of denervation. At 1 year of age, the infant had deepening of the first web space with full thickness skin grafts. He is now 4 years old with normal stature and development and is using the right hand mainly to assist the normal limb.
Chickenpox (varicella) is uncommon in pregnancy because most women have acquired immunity from previous infection before they reach child-bearing age. Varicella during pregnancy appears to be more severe than in the non-pregnant women (Paryani and Arvin, 1986). The clinical spectrum of congenital varicella in the affected foetus is related to the time of acquiring varicella in utero and can be divided into five groups (Table 1). Case I
Case 2
A male infant was born at 42 weeks gestation to a mother who developed clinically documented varicella during the 15th week of pregnancy. The newborn baby's height, weight and head circumference were above the 90th percentile for age. Linear crusted cutaneous lesions in the distribution of the second and third thoracic dermatomes were observed on the right side of the trunk. The right upper limb was hypoplastic with rudimentary fingers and multiple healing ulcers in the hand and forearm. All skin lesions healed with conservative management. Flexion contracture of the elbow was present (Fig 1). Except for a right Horner's syndrome, ocular examination was normal. There was no evidence of any other systemic abnormalities and CT scan of the head was normal.
A female infant was born at 40 weeks gestation to a mother who clinically developed varicella during the 32nd week of pregnancy. The newborn baby's height, weight and head circumference were above the 90th percentile for age. Large necrotic ulcers were seen on the dorsum of the left hand at birth. There was no active flexion or extension of the digits or intrinsic hand function, but proximal limb strength was normal. Systemic examination showed no other abnormalities. A few days after birth, the necrotic skin was excised and the defect covered with split thickness skin graft. There was good skin graft survival with secondary extension contracture of the fingers (Fig 2). The infant was referred to our institution at 2 months of age for
Table l - - T h e spectrum of congenital varicella in relation to the time of acquiring varicella in utero
Time of acquiring varicella in utero
Clinical disease presentation in the newborn
Estimated risk of clinical disease in the newborn
First trimester (Srabstein et al, 1974; Paryani and Arvin, 1986; Magliocco et al, 1992; Pastuszak et al, 1994)
Classic (severe) congenital varicella syndrome with chorioretinitis, cerebral cortical atrophy, hydronephrosis, cutaneous defects, hypoplastic limbs, low birth weight and microphthalmia.
2-9%
Second trimester (Brice, 1976; Frey et al, 1977)
Moderate congenital varicella syndrome with relative preservation of the brain
Rare
From the beginning of the third trimester to 15 days prior to delivery (Bai and John, 1979)
Skin necrosis with or without underlying muscle and nerve involvement
Rare
5 to 15 days prior to delivery (Paryani and Arvin, 1986)
Chickenpox infection with classic rash apparent at birth or during the first few days after delivery. The course of infection is benign because transplacental antibodies are capable of ameliorating the disease.
10%
Within 5 days prior to delivery (i.e. in utero infection and delivery prior to formation of maternal antibodies; (Stagno and Whitley, 1985; Miller et al, 1989)
The newborn appears normal at birth then 10 to 15 days later, the neonate develops a fatal chickenpox infection with skin rash and disseminated visceral and central nervous system disease,
20-30%
115
116
THE JOURNAL OF HAND SURGERY VOL. 20B No. 1 FEBRUARY 1995
rehabilitation, assessment and splint fabrication. There has been no neurological recovery of the denervated muscles and the patient will probably benefit from tendon transfers later in childhood. DISCUSSION The lower limb is more commonly affected than the upper limb in congenital varicella. Newborn babies with affected upper limbs rarely present to the hand surgeon because they usually die early in infancy from associated systemic abnormalities. The disease in our patients was mainly confined to the upper limb. At 9 weeks' gestation, the upper limbs are similar to the adult form. Innervation of muscles and development of spinal anterior horn cells occur by 12 weeks of intrauterine life. Limb growth continues during the second and third trimester. The degree of hypoplasia of the affected limb will therefore depend on the time of acquiring varicella in utero (Grose and Itani, 1989). Rudimentary digits have been reported with congenital varicella acquired early in pregnancy (Savage et al, 1973). The varicella virus is known to damage the dorsal root ganglia and the anterior horn of the spinal cord (Magliocco et al, 1992) leading to both sensory
Fig 1
A 1-year-old child who was born with congenital varicella mainly affecting to the right upper limb. (a) Note the rudimentary digits and the flexion contracture of the elbow. (b) Scarred skin on the dorsum of the hand and forearm. (c) Radiological examination of the affected limb, showing the shortened ulna.
deficiencies and denervation atrophy of muscles. Autonomic nervous system involvement has been manifested by the occurrence of Homer's syndrome (Savage et al, 1973) and intestinal obstruction (McKendry and Bailey, 1973). The principles of management of congenital varicella of the upper limb are similar to those applied to other paralytic conditions. Delayed reconstruction is almost
117
CONGENITAL VARICELLA
impossible in severely hypoplastic limbs, but patients with distal limb disease will probably benefit from tendon transfers later in childhood. We think that there is under-reporting of congenital varicella, and the issue of preventive measures should be addressed. Currently, varicella-zoster immunoglobulin is recommended for susceptible adults who have been exposed, but it is not recommended routinely for pregnant women (Cunningham et al, 1993). According to Paryani and Arvin (1986), maternal risks justify the administration of the immunoglobulin to pregnant women who have no antibody to varicella in the serum. However, the effectiveness of the immunoglobulin in preventing foetal complications is unknown. We feel that congenital varicella syndrome is best prevented by the administration of the live-attenuated varicella vaccine (Bogger-Goren et al, 1982; Gershon et al, 1984) to susceptible, non-pregnant women who have no serum antibody to varicella. References
Fig 2
A 2 - m o n t h - o l d infant w i t h c o n g e n i t a l varicella m a i n l y affecting the left hand. (a) E x t e n s i o n c o n t r a c t u r e of the fingers. ( b ) The v o l a r aspect of the affected hand. (c) R a d i o l o g i c a l e x a m i n a t i o n o f the left u p p e r limb. There is irregular m i n e r a l i z a t i o n of=the r a d i u s a n d ulna.
BAI, P. V. A. and JOHN, T. J. (1979). Congenital skin ulcers following varicella in late pregnancy. Journal of Pediatrics, 94: 1: 65-67. BOGGER-GOREN, S., BABA, K., HURLEY, P., YABUUCHI, H., TAKAHASHI, M. and OGRA, P. L, (1982). Antibody response to varicella-zoster virus after natural or vaccine-induced infection. Journal of Infectious Diseases, 146: 2: 260-265. BRICE, J. E. H. (1976). Congenital varicella resulting from infection during second trimester of pregnancy. Archives of Disease in Childhood, 51: 474-476. CUNNINGHAM, F. G., MACDONALD, P. C., GANT, N. F., LEVENO, K. J. and GILSTRAP, L. C. Williams Obstetrics, 19th Edn. Norwalk, Appleton and Lange, 1993: 1282. FREY, H. M., BtALKIN, G. and GERSHON, A. A. (t977). Congenital varicella: Case report of a serologically proved long-term survivor. Pediatrics, 59: 1: 110-112. GERSHON, A. A., STEINBERG, S. P., GELB, L., GALASSO, G., BORKOWSKY, W., LARUSSA, P. and FERRARA, A. (1984). Live attenuated varicetla vaccine. Efficacy for children with leukemia in remission. Journal of the American Medical Association, 252: 3:355 362. GROSE, C. and ITANI, O. (1989). Pathogenesis of congenital infection with three diverse viruses: Varicella-zoster virus, human parvovirus and human immunodeficiency virus. Seminars in Perinatotogy, 13: 4:278 293. MAGLIOCCO, A. M., DEMETRICK, D. J., SARNAT, H. B. and HWANG, W. (1992). Varicella embryopathy. Archives of Pathology and Laboratory Medicine, 116: 181-186. MCKENDRY, J. B. L and BAILEY, J. D. (1973). Congenital variceUa associated with multiple defects. Canadian Medical Association Journal, 108: 66-67. MILLER, E., CRADOCK-WATSON, J. E. and RIDEHALGH, M. K. S. (1989). Outcome in newborn babies given anti-varicella-zosterimmunoglobulin after perinatal maternal infection with varieella-zoster virus. Lancet, 2: 371-373. PARYANI, S. G. and ARVIN, A. M. (t986). Intrauterine infection with varicella-zoster virus after maternal varicella. New England Journal of Medicine, 314: 24: 1542-1546. PASTUSZAK, A. L., LEVY, M., SCHICK, B., ZUBER, C., FELDKAMP, M., GLADSTONE, J., BAR-LEVY, F., JACKSON, E., DONNENFELD, A., MESCHINO, W, and KOREN, G. (1994). Outcome after maternal varicella infection in the first 20 weeks of pregnancy. New England Journal of Medicine, 330: 901-905. SAVAGE, M. O., MOOSA, A. and GORDON, R. R. (1973). Maternal varicella infection as a cause of fetal malformations. Lancet, 1: 352-354. SRABSTEIN, J. C., MORRIS, N., LARKE, R. P. B., DESA, D. J., CASTELINO, B. B. and SUM, E. (1974). Is there a congenital varicella syndrome? Journal of Pediatrics, 84: 2: 239-243. STAGNO, S. and WHITLEY, R. J. (1985 ). Herpes virus infections of pregnancy: Part II: Herpes simplex virus and variceUa-zoster virus infections, New England Journal of Medicine, 313: 21: 1327-1330. Accepted: 25 July 1994 H. G. Thomson, Section of Plastic Surgery The Hospital for Sick Children, Suite 1524-555 Un versity Avenue, Toronto, Ontario M5G IX8, Canada. © 1994The British Societyfor Surgery of the Hand
VARICELLA OF THE UPPER A preventable disaster
LIMB
M . M . A L - Q A T T A N and H. G. T H O M S O N
From the Section of Plastic Surgery, the Hospital for Sick Children, Toronto, Ontario, Canada
Two patients with a rare form of congenital varicella involving the upper limb are described. The spectrum of disease, pathophysiology, principles of management and prevention are discussed.
Journal of Hand Surgery (British and European Volume, 1995)20B: 1:115-117 Examination of the upper limb revealed good shoulder abduction, weak flexion and extension of the elbow, no active pronation, supination or wrist flexion, but wrist extension was present. No hand movements were observed. Electromyography of the upper limb muscles showed evidence of denervation. At 1 year of age, the infant had deepening of the first web space with full thickness skin grafts. He is now 4 years old with normal stature and development and is using the right hand mainly to assist the normal limb.
Chickenpox (varicella) is uncommon in pregnancy because most women have acquired immunity from previous infection before they reach child-bearing age. Varicella during pregnancy appears to be more severe than in the non-pregnant women (Paryani and Arvin, 1986). The clinical spectrum of congenital varicella in the affected foetus is related to the time of acquiring varicella in utero and can be divided into five groups (Table 1). Case I
Case 2
A male infant was born at 42 weeks gestation to a mother who developed clinically documented varicella during the 15th week of pregnancy. The newborn baby's height, weight and head circumference were above the 90th percentile for age. Linear crusted cutaneous lesions in the distribution of the second and third thoracic dermatomes were observed on the right side of the trunk. The right upper limb was hypoplastic with rudimentary fingers and multiple healing ulcers in the hand and forearm. All skin lesions healed with conservative management. Flexion contracture of the elbow was present (Fig 1). Except for a right Horner's syndrome, ocular examination was normal. There was no evidence of any other systemic abnormalities and CT scan of the head was normal.
A female infant was born at 40 weeks gestation to a mother who clinically developed varicella during the 32nd week of pregnancy. The newborn baby's height, weight and head circumference were above the 90th percentile for age. Large necrotic ulcers were seen on the dorsum of the left hand at birth. There was no active flexion or extension of the digits or intrinsic hand function, but proximal limb strength was normal. Systemic examination showed no other abnormalities. A few days after birth, the necrotic skin was excised and the defect covered with split thickness skin graft. There was good skin graft survival with secondary extension contracture of the fingers (Fig 2). The infant was referred to our institution at 2 months of age for
Table l - - T h e spectrum of congenital varicella in relation to the time of acquiring varicella in utero
Time of acquiring varicella in utero
Clinical disease presentation in the newborn
Estimated risk of clinical disease in the newborn
First trimester (Srabstein et al, 1974; Paryani and Arvin, 1986; Magliocco et al, 1992; Pastuszak et al, 1994)
Classic (severe) congenital varicella syndrome with chorioretinitis, cerebral cortical atrophy, hydronephrosis, cutaneous defects, hypoplastic limbs, low birth weight and microphthalmia.
2-9%
Second trimester (Brice, 1976; Frey et al, 1977)
Moderate congenital varicella syndrome with relative preservation of the brain
Rare
From the beginning of the third trimester to 15 days prior to delivery (Bai and John, 1979)
Skin necrosis with or without underlying muscle and nerve involvement
Rare
5 to 15 days prior to delivery (Paryani and Arvin, 1986)
Chickenpox infection with classic rash apparent at birth or during the first few days after delivery. The course of infection is benign because transplacental antibodies are capable of ameliorating the disease.
10%
Within 5 days prior to delivery (i.e. in utero infection and delivery prior to formation of maternal antibodies; (Stagno and Whitley, 1985; Miller et al, 1989)
The newborn appears normal at birth then 10 to 15 days later, the neonate develops a fatal chickenpox infection with skin rash and disseminated visceral and central nervous system disease,
20-30%
115
116
THE JOURNAL OF HAND SURGERY VOL. 20B No. 1 FEBRUARY 1995
rehabilitation, assessment and splint fabrication. There has been no neurological recovery of the denervated muscles and the patient will probably benefit from tendon transfers later in childhood. DISCUSSION The lower limb is more commonly affected than the upper limb in congenital varicella. Newborn babies with affected upper limbs rarely present to the hand surgeon because they usually die early in infancy from associated systemic abnormalities. The disease in our patients was mainly confined to the upper limb. At 9 weeks' gestation, the upper limbs are similar to the adult form. Innervation of muscles and development of spinal anterior horn cells occur by 12 weeks of intrauterine life. Limb growth continues during the second and third trimester. The degree of hypoplasia of the affected limb will therefore depend on the time of acquiring varicella in utero (Grose and Itani, 1989). Rudimentary digits have been reported with congenital varicella acquired early in pregnancy (Savage et al, 1973). The varicella virus is known to damage the dorsal root ganglia and the anterior horn of the spinal cord (Magliocco et al, 1992) leading to both sensory
Fig 1
A 1-year-old child who was born with congenital varicella mainly affecting to the right upper limb. (a) Note the rudimentary digits and the flexion contracture of the elbow. (b) Scarred skin on the dorsum of the hand and forearm. (c) Radiological examination of the affected limb, showing the shortened ulna.
deficiencies and denervation atrophy of muscles. Autonomic nervous system involvement has been manifested by the occurrence of Homer's syndrome (Savage et al, 1973) and intestinal obstruction (McKendry and Bailey, 1973). The principles of management of congenital varicella of the upper limb are similar to those applied to other paralytic conditions. Delayed reconstruction is almost
117
CONGENITAL VARICELLA
impossible in severely hypoplastic limbs, but patients with distal limb disease will probably benefit from tendon transfers later in childhood. We think that there is under-reporting of congenital varicella, and the issue of preventive measures should be addressed. Currently, varicella-zoster immunoglobulin is recommended for susceptible adults who have been exposed, but it is not recommended routinely for pregnant women (Cunningham et al, 1993). According to Paryani and Arvin (1986), maternal risks justify the administration of the immunoglobulin to pregnant women who have no antibody to varicella in the serum. However, the effectiveness of the immunoglobulin in preventing foetal complications is unknown. We feel that congenital varicella syndrome is best prevented by the administration of the live-attenuated varicella vaccine (Bogger-Goren et al, 1982; Gershon et al, 1984) to susceptible, non-pregnant women who have no serum antibody to varicella. References
Fig 2
A 2 - m o n t h - o l d infant w i t h c o n g e n i t a l varicella m a i n l y affecting the left hand. (a) E x t e n s i o n c o n t r a c t u r e of the fingers. ( b ) The v o l a r aspect of the affected hand. (c) R a d i o l o g i c a l e x a m i n a t i o n o f the left u p p e r limb. There is irregular m i n e r a l i z a t i o n of=the r a d i u s a n d ulna.
BAI, P. V. A. and JOHN, T. J. (1979). Congenital skin ulcers following varicella in late pregnancy. Journal of Pediatrics, 94: 1: 65-67. BOGGER-GOREN, S., BABA, K., HURLEY, P., YABUUCHI, H., TAKAHASHI, M. and OGRA, P. L, (1982). Antibody response to varicella-zoster virus after natural or vaccine-induced infection. Journal of Infectious Diseases, 146: 2: 260-265. BRICE, J. E. H. (1976). Congenital varicella resulting from infection during second trimester of pregnancy. Archives of Disease in Childhood, 51: 474-476. CUNNINGHAM, F. G., MACDONALD, P. C., GANT, N. F., LEVENO, K. J. and GILSTRAP, L. C. Williams Obstetrics, 19th Edn. Norwalk, Appleton and Lange, 1993: 1282. FREY, H. M., BtALKIN, G. and GERSHON, A. A. (t977). Congenital varicella: Case report of a serologically proved long-term survivor. Pediatrics, 59: 1: 110-112. GERSHON, A. A., STEINBERG, S. P., GELB, L., GALASSO, G., BORKOWSKY, W., LARUSSA, P. and FERRARA, A. (1984). Live attenuated varicetla vaccine. Efficacy for children with leukemia in remission. Journal of the American Medical Association, 252: 3:355 362. GROSE, C. and ITANI, O. (1989). Pathogenesis of congenital infection with three diverse viruses: Varicella-zoster virus, human parvovirus and human immunodeficiency virus. Seminars in Perinatotogy, 13: 4:278 293. MAGLIOCCO, A. M., DEMETRICK, D. J., SARNAT, H. B. and HWANG, W. (1992). Varicella embryopathy. Archives of Pathology and Laboratory Medicine, 116: 181-186. MCKENDRY, J. B. L and BAILEY, J. D. (1973). Congenital variceUa associated with multiple defects. Canadian Medical Association Journal, 108: 66-67. MILLER, E., CRADOCK-WATSON, J. E. and RIDEHALGH, M. K. S. (1989). Outcome in newborn babies given anti-varicella-zosterimmunoglobulin after perinatal maternal infection with varieella-zoster virus. Lancet, 2: 371-373. PARYANI, S. G. and ARVIN, A. M. (t986). Intrauterine infection with varicella-zoster virus after maternal varicella. New England Journal of Medicine, 314: 24: 1542-1546. PASTUSZAK, A. L., LEVY, M., SCHICK, B., ZUBER, C., FELDKAMP, M., GLADSTONE, J., BAR-LEVY, F., JACKSON, E., DONNENFELD, A., MESCHINO, W, and KOREN, G. (1994). Outcome after maternal varicella infection in the first 20 weeks of pregnancy. New England Journal of Medicine, 330: 901-905. SAVAGE, M. O., MOOSA, A. and GORDON, R. R. (1973). Maternal varicella infection as a cause of fetal malformations. Lancet, 1: 352-354. SRABSTEIN, J. C., MORRIS, N., LARKE, R. P. B., DESA, D. J., CASTELINO, B. B. and SUM, E. (1974). Is there a congenital varicella syndrome? Journal of Pediatrics, 84: 2: 239-243. STAGNO, S. and WHITLEY, R. J. (1985 ). Herpes virus infections of pregnancy: Part II: Herpes simplex virus and variceUa-zoster virus infections, New England Journal of Medicine, 313: 21: 1327-1330. Accepted: 25 July 1994 H. G. Thomson, Section of Plastic Surgery The Hospital for Sick Children, Suite 1524-555 Un versity Avenue, Toronto, Ontario M5G IX8, Canada. © 1994The British Societyfor Surgery of the Hand