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Congenital syphilis: Subtle presentation of fulminant disease
Congenital syphilis: Subtle presentation of fulminant disease Michelle L. Bennett, MD, Annette W. Lynn, MD, Lawrence E. Klein, MD, and Katherine S. Balkowiec, MD Columbia, South Carolina The incidence of congenital syphilis has experienced a fourfold to fivefold increase in 6 years. It is a completely preventable disease whose clinical spectrum ranges from asymptomatic infection, to fulminant sepsis, to death. Congenital syphilis was diagnosed in a 6-week-old infant whose mother was negative for the disease by prenatal screen. The otherwise well child presented with a generalized, papulosquamous eruption of 3 weeks' duration but within hours multisystem failure developed from overwhelming treponemal sepsis. Factors related to increased incidence, problems in serodiagnosis, manifestations of the early versus late forms of the disease, and recommendations for evaluation and treatment are illustrated by this patient and are discussed. (J Am Acad Dermatol 1997;36:351-4.) Of patients with congenital syphilis reported to the Centers for Disease Control, only 30% are born with symptoms, 1 and clinical evidence of disease is often subtle or nonspecific. Therefore early detection can be a problem. 2 W e present a case of congenital syphilis that was undetected at birth but was later diagnosed because of a persistent eruption that preceded multisystem organ failure from overwhelming treponemal sepsis.
CASE REPORT A 30-year-old woman, gravida 3 para 2, received routine prenatal care beginning at 16 weeks' gestation. The results of the usual prenatal laboratory studies and examinations were within normal limits. Labor began spontaneously at term, but a cesarean section was performed because of thick meconium-stained amniotic fluid, fetal distress, and the mother's history of a previous stillbirth. Delivery was uncomplicated, birth weight was 2900 gm (25th percentile), and Apgar scores were 8 and 9. Histologic examination of the placenta revealed acute chorioamnionitis, but the mother and infant remained free of
ORTHO This article is made possible through an educational grant
from the Dermatological Division, Ortho Pharmaceutical Corporation. From the Depamnent of Dermatology, University of South Carolina. Reprint requests: Annette W. Lynn, MD, Department of Dermatology, University of South Carolina, 2 Richmond Medical Park, #500, Columbia, SC 29203. Copyright © 1997 by the American Academy of Dermatology, Inc. 0190-9622/96 $5.00 + 0 16/4/77694
symptoms and were discharged after normal postpartum recovery. Except for mild colic, the postnatal course was unremarkable until an eruption developed when the infant was 3 weeks of age. The mother first noticed an erythematous papule in the infant's left axilla. Within a week, similar lesions were widely distributed. Three weeks later examination revealed a generalized papulosquamous eruption of 2.5 to 5 mm, erythematous, annular to ovoid plaques with a fine, white scale, as well as ruptured bullae with an eroded base, and hyperpigmented macules at sites of resolving lesions (Fig. 1). The palms and soles contained erythematous dome-shaped papules that were devoid of scale. Soft, white, loosely adherent Candida-likeplaques were present on the tongue and buccal mucosa. The child seemed otherwise well. A biopsy specimen of a representative lesion was obtained, and blood was drawn for rapid plasma reagin (RPR) test. Fourteen hours later the child presented to the Emergency Department with irritability, listlessness, dyspnea, and decreased urine output. Temperature was 36.5 ° C, heart rate was 120, respiratory rate was 40, and blood pressure was 134/116. Examination of the moderately distressed infant revealed jaundice, diffuse purpura on the lower extremities, and the previously described eruption. Respirations were agonal. The heartbeat was irregular, with intermittent bradycardia. The abdomen was distended, with marked ascites and hepatosplenomegaly. Laboratory studies revealed hyponatremia (Na+ 118), hyperkalemia (K+ 7.6), severe hypoglycemia (glucose 6), and metabolic acidosis (pH 7.0; CO2 35; O2 142; HCO3 10; O2 saturation 98% on room air). Hematologic derangements included leukocytosis (32,000 white blood
351
352
Fig. 1. Generalized papulosquamous eruption of 3 weeks' duration.
cells) with left shift (29% bands) and monocytosis (13%), anemia (hematocrit and hemoglobin 6/18), and thrombocytopenia (24,000 platelets). Liver dysfunction with coagulopathy was evident by prolonged prothrombin time/ partial thromboplastin time (33/93), low albumin level (1.8), low cholesterol level (56), and elevated liver function test findings (AST 437, ALT 247, GGT 1716, LDH 3030, alkaline phosphatase 1117). Radiographs showed cardiomegaly, mild pulmonary edema, and a markedly enlarged liver and spleen. The infant was intubated, rehydrated, admitted to pediatric intensive care, and placed on mechanical ventilation. Soon after admission, the results of the blood test and biopsy were received. The RPR titer was 1:512, and the fluorescent treponemal antibody absorption test (FI'A-ABS) was reactive. The biopsy specimen showed only mild dermoepidermal junction effacement and spongiosis, some perivascular chronic inflammation, and rare plasma cells; Steiner stain revealed abundant spirochetes, most numerous in the epidermis (Fig. 2). Long-bone radiographs showed a lamellated periosteal reaction. Intravenous administration of aqueous penicillin G (50,000
Journal of the American Academy of Dermatology February 1997
Fig. 2. Biopsy specimen at high power revealed numerous epidermal spirochetes. (Steiner stain. Original magnification x800.)
U/kg every 6 hours for 21 days) was started for congenital syphilis with subsequent multisystem organ failure. Cerebrospinal fluid RPR was negative, TORCH titers were normal, and HIV and cytomegalovirus tests were nonreactive. Within hours, the patient became hypotensive and oliguric renal failure developed. She was treated with continuous arteriovenous hemoflltration. Renal function was regained in 2 weeks. After 133 days of hospitalization, the child was discharged in stable condition with continued reactive airway disease, developmental delay, gastric reflux requiring J-tube feedings, and hematuria that was improving.
DISCUSSION The incidence of congenital syphilis is increasing) In 1988, 691 cases in infants less than 1 year old were reported to the Centers for Disease Control (CDC). 4 By 1990 this reached 2841, 4 and by 1993 it was 3209. 5 This increase parallels the increase of syphilis in adults and can be attributed especially to lack of
Journal of the American Academy of Dermatology Volume 36, Number 2, Part 2
prenatal care and illegal drug use. 6 Prostitution, HIV infection, failure to perform screening tests, maternal reinfection, treatment failures with benzathine penicillin, and reduced resources for syphilis control are also important. 7,8 Moreover, the C D C ' s 1988 revised presumptive case definition for congenital syphilis led to more case reports than in the past. 9 The risk of fetal transmission is estimated to be as high as 70% to 100% for untreated early syphilis 1° and is related to the timing of infection. Infection of the fetus before the fourth month of gestation is rare, and the risk decreases after the earlier stages of maternal infection.l l The CDC recommends serologic screening for syphilis at the onset of prenatal care and repeat tests for high-risk pregnancies. 12 Serodiagnosis is not without difficulty, however.13 The prozone phenomenon, occurring in 1% to 2% of cases of secondary syphilis, results in false-negatives. It is overcome by serum dilution, but this is not routinely done. 14 In addition, early disease or immune deficiency may produce a seronegafive but infectious state. 5, 15 The same problems impede infant diagnosis, but antibody titers are even less reliable because of passively transferred maternal IgG. 16 These problems point to the inadequacy of a single maternal V D R L or R P R determination during pregnancy, especially if done during the fn'st trimester, 17 and support follow-up testing 2 weeks postpartum.18 Congenital syphilis exists in two forms. The early form appears before 2 years of age, often with a generalized papulosquamous eruption that includes the palms and soles. 19 Rhinorrhea, periostitis, osteochondrifts, hepatosplenomegaly, lymphadenopathy, and failure to thrive are also common, 19, 20 but the spectrum ranges from asymptomafic infection to fulminant disease. The mortality rate for the severely ill is still almost 20%. 21 The life-threatening manifestations that can occur, all of which were present in our patient, include fulminant hepatitis, hematologic derangements, respiratory failure, acidosis, nephrosis, anasarca, and secondary infections. 21 Stillbirth occurs in 30% to 40% of cases, and funisitis, plancenfitis, hydrops, growth retardation, preterm labor, and premature rupture of membranes occur in utero at an increased rate. 6, 22 The late form manifests after 2 years of age with frontal bossing, saddle nose, Hutchinson' s teeth, mulberry molars, Clutton's joints, saber shins, and neurologic and other abnormalities), 16 A definitive diagnosis of congenital syphilis is
353 made when Treponemapallidum is identified in infected tissue; diagnosis by any other means is presumptive.4,23, 24 Evaluation of a presumptive case should include treatment history of the mother, physical examination of the infant, serologic testing, cerebrospinal fluid analysis, long-bone radiography, placental examination with specific antibody staining, and other tests as clinically indicated. 24, 25 For treatment, 10 to 14 days of aqueous crystalline or procaine penicillin G is recommended over singledose benzathine penicillin, which has been associated with treatment failures. Erythromycin is not an acceptable altemative. 5 Frequent examinations after treatment should be made with serologic testing to assure declining titers by 3 months and nonreactivity by 6 to 12 months plus retreatment if titers fail to decline. 21,24'25
REFERENCES
1. Grossman KL, Rasmussen JE. Recent advances in pediatric infectious disease and their impact on dermatology. J Am Acad Dermatol 1991;24:379-89. 2. Rosenfeld SR, Weinert CR Jr, Kahn B. Congenital syphilis; a case report. J Bone Joint Surg Am 1983;65:115-9. 3. McFarlin BL, Bottoms SF, Dock BS, et al. Epidemic syphilis: maternal factors associated with congenital infection. A m J Obstet Gynecol1994;170:535-40. 4. Reyes MP, Akhras J. Dealing with maternal and congenital syphilis. Contemp OB/GYN 1995;6:52-62. 5. Stoll BJ. Congenital syphilis: evaluation and management of neonates born to mothers with reactive serologic tests for syphilis. Pediatr Infect Dis J 1994;13:845-53. 6. Ricci JM, Fojaco RM, O' Sullivan MJ. Congenital syphilis: the University of Miami/Jackson Memorial Medical Center experience, 1986-1988. Obstet Gynecol 1989;74:687-93. 7. Stamos JK, Rowley AH. Timely diagnosis of congenital infections, Pediatr Clin North Am 1994;41:1017-33. 8. Wood VD, Rana S. Congenital syphilis presenting as desquamative dermatitis. J Fam Pract 1992;35:327-9. 9. Stoll BJ, Lee FK, Larsen S, et al. Clinical and serologic evaluation of neonates for congenital syphilis: a continuing diagnostic dilemma. J Infect Dis 1993;167:1093-9. 10. Lowy G. Sexually transmitted diseases in children. Pediatr Dermatol 1992;9:329-34. 11. Johnson PC, Farnie MA. Testing for syphilis. Dermatol Clin 1994;12:9-17. 12. Sanchez PJ, Wendel GD, Norgard MV. Congenital syphiris associated with negative results of maternal serologic tests at delivery. Am J Dis Child 1991;145:967-9. 13. Morbidity and Mortality Report Centers for Disease Control: Syphilis and congenital syphilis---United States, 19851988. Arch Dermatol 1988;124:1485-6. 14. Berkowitz KM, Stampf K, Baxi L, et al. False negative screening tests for syphilis in pregnant women. N Engl J Med 1990;322:270-1. 15. Dorfman DH, Glaser JH. Congenital syphilis presenting in infants after the newborn period. N Engl J Med 1990; 323:1299-302.
Journal of the American Academy of Dermatology February 1997
354 16. Ikeda MK, Jenson HB. Evaluation and treatment of congenital syphilis. J Pediatr 1990;117:843-52. 17. Janner D. Failure to thrive and anasarca in a young infant. Pediatr Infect Dis J 1990;9:519. 18. Vohra K. Missed case of congenital syphilis. J Natl Med Assoc 1991;83:864. 19. Noppakun N, Hendrick SJ, Raimer SS, et al. Palmoplantar milia: sequelae of early congenital syphilis. Pediatr Dermatol 1986;3:395-8. 20. Tunnessen W W Jr. Picture of the month: congenital syphiris. Am J Dis Child 1992;146:115-6. 21. Wright MS, Tecklenburg FW. Critical illness in congeni-
22.
23. 24.
25.
tal syphilis after the newborn period. Clin Pediatr (Phila) 1992;31:247-51. Parker CR Jr, Wendel GD. The effects of syphilis on endocrine function of the fetoplacental unit. Am J Obstet Gynecol 1988;159:1327-31. Lawrence P, Saxe N. Bullous secondary syphilis. Clin Exp Dermatol 1992;17:44-6. Morbidity and Mortality Report Centers for Disease Control: 1993 sexually transmitted diseases treatment guidelines 1993;42:40-4. Mascola L, Pelosi R, Blount JH, et al. Congenital syphilis revisited. Am J Dis Child 1985;139:575-80.
CASE REPORT A 30-year-old woman, gravida 3 para 2, received routine prenatal care beginning at 16 weeks' gestation. The results of the usual prenatal laboratory studies and examinations were within normal limits. Labor began spontaneously at term, but a cesarean section was performed because of thick meconium-stained amniotic fluid, fetal distress, and the mother's history of a previous stillbirth. Delivery was uncomplicated, birth weight was 2900 gm (25th percentile), and Apgar scores were 8 and 9. Histologic examination of the placenta revealed acute chorioamnionitis, but the mother and infant remained free of
ORTHO This article is made possible through an educational grant
from the Dermatological Division, Ortho Pharmaceutical Corporation. From the Depamnent of Dermatology, University of South Carolina. Reprint requests: Annette W. Lynn, MD, Department of Dermatology, University of South Carolina, 2 Richmond Medical Park, #500, Columbia, SC 29203. Copyright © 1997 by the American Academy of Dermatology, Inc. 0190-9622/96 $5.00 + 0 16/4/77694
symptoms and were discharged after normal postpartum recovery. Except for mild colic, the postnatal course was unremarkable until an eruption developed when the infant was 3 weeks of age. The mother first noticed an erythematous papule in the infant's left axilla. Within a week, similar lesions were widely distributed. Three weeks later examination revealed a generalized papulosquamous eruption of 2.5 to 5 mm, erythematous, annular to ovoid plaques with a fine, white scale, as well as ruptured bullae with an eroded base, and hyperpigmented macules at sites of resolving lesions (Fig. 1). The palms and soles contained erythematous dome-shaped papules that were devoid of scale. Soft, white, loosely adherent Candida-likeplaques were present on the tongue and buccal mucosa. The child seemed otherwise well. A biopsy specimen of a representative lesion was obtained, and blood was drawn for rapid plasma reagin (RPR) test. Fourteen hours later the child presented to the Emergency Department with irritability, listlessness, dyspnea, and decreased urine output. Temperature was 36.5 ° C, heart rate was 120, respiratory rate was 40, and blood pressure was 134/116. Examination of the moderately distressed infant revealed jaundice, diffuse purpura on the lower extremities, and the previously described eruption. Respirations were agonal. The heartbeat was irregular, with intermittent bradycardia. The abdomen was distended, with marked ascites and hepatosplenomegaly. Laboratory studies revealed hyponatremia (Na+ 118), hyperkalemia (K+ 7.6), severe hypoglycemia (glucose 6), and metabolic acidosis (pH 7.0; CO2 35; O2 142; HCO3 10; O2 saturation 98% on room air). Hematologic derangements included leukocytosis (32,000 white blood
351
352
Fig. 1. Generalized papulosquamous eruption of 3 weeks' duration.
cells) with left shift (29% bands) and monocytosis (13%), anemia (hematocrit and hemoglobin 6/18), and thrombocytopenia (24,000 platelets). Liver dysfunction with coagulopathy was evident by prolonged prothrombin time/ partial thromboplastin time (33/93), low albumin level (1.8), low cholesterol level (56), and elevated liver function test findings (AST 437, ALT 247, GGT 1716, LDH 3030, alkaline phosphatase 1117). Radiographs showed cardiomegaly, mild pulmonary edema, and a markedly enlarged liver and spleen. The infant was intubated, rehydrated, admitted to pediatric intensive care, and placed on mechanical ventilation. Soon after admission, the results of the blood test and biopsy were received. The RPR titer was 1:512, and the fluorescent treponemal antibody absorption test (FI'A-ABS) was reactive. The biopsy specimen showed only mild dermoepidermal junction effacement and spongiosis, some perivascular chronic inflammation, and rare plasma cells; Steiner stain revealed abundant spirochetes, most numerous in the epidermis (Fig. 2). Long-bone radiographs showed a lamellated periosteal reaction. Intravenous administration of aqueous penicillin G (50,000
Journal of the American Academy of Dermatology February 1997
Fig. 2. Biopsy specimen at high power revealed numerous epidermal spirochetes. (Steiner stain. Original magnification x800.)
U/kg every 6 hours for 21 days) was started for congenital syphilis with subsequent multisystem organ failure. Cerebrospinal fluid RPR was negative, TORCH titers were normal, and HIV and cytomegalovirus tests were nonreactive. Within hours, the patient became hypotensive and oliguric renal failure developed. She was treated with continuous arteriovenous hemoflltration. Renal function was regained in 2 weeks. After 133 days of hospitalization, the child was discharged in stable condition with continued reactive airway disease, developmental delay, gastric reflux requiring J-tube feedings, and hematuria that was improving.
DISCUSSION The incidence of congenital syphilis is increasing) In 1988, 691 cases in infants less than 1 year old were reported to the Centers for Disease Control (CDC). 4 By 1990 this reached 2841, 4 and by 1993 it was 3209. 5 This increase parallels the increase of syphilis in adults and can be attributed especially to lack of
Journal of the American Academy of Dermatology Volume 36, Number 2, Part 2
prenatal care and illegal drug use. 6 Prostitution, HIV infection, failure to perform screening tests, maternal reinfection, treatment failures with benzathine penicillin, and reduced resources for syphilis control are also important. 7,8 Moreover, the C D C ' s 1988 revised presumptive case definition for congenital syphilis led to more case reports than in the past. 9 The risk of fetal transmission is estimated to be as high as 70% to 100% for untreated early syphilis 1° and is related to the timing of infection. Infection of the fetus before the fourth month of gestation is rare, and the risk decreases after the earlier stages of maternal infection.l l The CDC recommends serologic screening for syphilis at the onset of prenatal care and repeat tests for high-risk pregnancies. 12 Serodiagnosis is not without difficulty, however.13 The prozone phenomenon, occurring in 1% to 2% of cases of secondary syphilis, results in false-negatives. It is overcome by serum dilution, but this is not routinely done. 14 In addition, early disease or immune deficiency may produce a seronegafive but infectious state. 5, 15 The same problems impede infant diagnosis, but antibody titers are even less reliable because of passively transferred maternal IgG. 16 These problems point to the inadequacy of a single maternal V D R L or R P R determination during pregnancy, especially if done during the fn'st trimester, 17 and support follow-up testing 2 weeks postpartum.18 Congenital syphilis exists in two forms. The early form appears before 2 years of age, often with a generalized papulosquamous eruption that includes the palms and soles. 19 Rhinorrhea, periostitis, osteochondrifts, hepatosplenomegaly, lymphadenopathy, and failure to thrive are also common, 19, 20 but the spectrum ranges from asymptomafic infection to fulminant disease. The mortality rate for the severely ill is still almost 20%. 21 The life-threatening manifestations that can occur, all of which were present in our patient, include fulminant hepatitis, hematologic derangements, respiratory failure, acidosis, nephrosis, anasarca, and secondary infections. 21 Stillbirth occurs in 30% to 40% of cases, and funisitis, plancenfitis, hydrops, growth retardation, preterm labor, and premature rupture of membranes occur in utero at an increased rate. 6, 22 The late form manifests after 2 years of age with frontal bossing, saddle nose, Hutchinson' s teeth, mulberry molars, Clutton's joints, saber shins, and neurologic and other abnormalities), 16 A definitive diagnosis of congenital syphilis is
353 made when Treponemapallidum is identified in infected tissue; diagnosis by any other means is presumptive.4,23, 24 Evaluation of a presumptive case should include treatment history of the mother, physical examination of the infant, serologic testing, cerebrospinal fluid analysis, long-bone radiography, placental examination with specific antibody staining, and other tests as clinically indicated. 24, 25 For treatment, 10 to 14 days of aqueous crystalline or procaine penicillin G is recommended over singledose benzathine penicillin, which has been associated with treatment failures. Erythromycin is not an acceptable altemative. 5 Frequent examinations after treatment should be made with serologic testing to assure declining titers by 3 months and nonreactivity by 6 to 12 months plus retreatment if titers fail to decline. 21,24'25
REFERENCES
1. Grossman KL, Rasmussen JE. Recent advances in pediatric infectious disease and their impact on dermatology. J Am Acad Dermatol 1991;24:379-89. 2. Rosenfeld SR, Weinert CR Jr, Kahn B. Congenital syphilis; a case report. J Bone Joint Surg Am 1983;65:115-9. 3. McFarlin BL, Bottoms SF, Dock BS, et al. Epidemic syphilis: maternal factors associated with congenital infection. A m J Obstet Gynecol1994;170:535-40. 4. Reyes MP, Akhras J. Dealing with maternal and congenital syphilis. Contemp OB/GYN 1995;6:52-62. 5. Stoll BJ. Congenital syphilis: evaluation and management of neonates born to mothers with reactive serologic tests for syphilis. Pediatr Infect Dis J 1994;13:845-53. 6. Ricci JM, Fojaco RM, O' Sullivan MJ. Congenital syphilis: the University of Miami/Jackson Memorial Medical Center experience, 1986-1988. Obstet Gynecol 1989;74:687-93. 7. Stamos JK, Rowley AH. Timely diagnosis of congenital infections, Pediatr Clin North Am 1994;41:1017-33. 8. Wood VD, Rana S. Congenital syphilis presenting as desquamative dermatitis. J Fam Pract 1992;35:327-9. 9. Stoll BJ, Lee FK, Larsen S, et al. Clinical and serologic evaluation of neonates for congenital syphilis: a continuing diagnostic dilemma. J Infect Dis 1993;167:1093-9. 10. Lowy G. Sexually transmitted diseases in children. Pediatr Dermatol 1992;9:329-34. 11. Johnson PC, Farnie MA. Testing for syphilis. Dermatol Clin 1994;12:9-17. 12. Sanchez PJ, Wendel GD, Norgard MV. Congenital syphiris associated with negative results of maternal serologic tests at delivery. Am J Dis Child 1991;145:967-9. 13. Morbidity and Mortality Report Centers for Disease Control: Syphilis and congenital syphilis---United States, 19851988. Arch Dermatol 1988;124:1485-6. 14. Berkowitz KM, Stampf K, Baxi L, et al. False negative screening tests for syphilis in pregnant women. N Engl J Med 1990;322:270-1. 15. Dorfman DH, Glaser JH. Congenital syphilis presenting in infants after the newborn period. N Engl J Med 1990; 323:1299-302.
Journal of the American Academy of Dermatology February 1997
354 16. Ikeda MK, Jenson HB. Evaluation and treatment of congenital syphilis. J Pediatr 1990;117:843-52. 17. Janner D. Failure to thrive and anasarca in a young infant. Pediatr Infect Dis J 1990;9:519. 18. Vohra K. Missed case of congenital syphilis. J Natl Med Assoc 1991;83:864. 19. Noppakun N, Hendrick SJ, Raimer SS, et al. Palmoplantar milia: sequelae of early congenital syphilis. Pediatr Dermatol 1986;3:395-8. 20. Tunnessen W W Jr. Picture of the month: congenital syphiris. Am J Dis Child 1992;146:115-6. 21. Wright MS, Tecklenburg FW. Critical illness in congeni-
22.
23. 24.
25.
tal syphilis after the newborn period. Clin Pediatr (Phila) 1992;31:247-51. Parker CR Jr, Wendel GD. The effects of syphilis on endocrine function of the fetoplacental unit. Am J Obstet Gynecol 1988;159:1327-31. Lawrence P, Saxe N. Bullous secondary syphilis. Clin Exp Dermatol 1992;17:44-6. Morbidity and Mortality Report Centers for Disease Control: 1993 sexually transmitted diseases treatment guidelines 1993;42:40-4. Mascola L, Pelosi R, Blount JH, et al. Congenital syphilis revisited. Am J Dis Child 1985;139:575-80.