Special Feature
Invasive Group A Beta-Hemolytic Streptococcal Infections and Varicella
By Leonard Friedland, MD
A vaccine for varicella was licensed in the united States in March 1995. Prior to the introduction of the vaccine, an estimated 4 million cases of varicella occurred each year, most often in children between the ages of 5 and 9 years. Primary infection with varicella-zoster virus results in chickenpox, manifested by a generalized, pruritic, vesicular rash with mild fever and systemic symptoms. Symptoms usually resolve within one week.
Table 1
Complications in Previously Well Children Hospitalized for Varicella
| Complications |
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| Skin/soft tissue infection |
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| Neurologic |
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| Respiratory |
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| Gastrointestinal |
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| Sepsis |
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Varicella is more than just an annoying, avoidable disease. Serious complications can occur. Data from the era prior to the introduction of varicella vaccine estimate that varicella causes 4000-9000 hospitalizations and an average of 100 deaths each year. According to the CDC, chickenpox kills more children and adolescents than all other diseases combined for which vaccination is routinely recommended. Patients at high risk for complications include neonates, adults, and immunocompromised hosts. It should be noted that the great majority of children who suffer complications are without underlying disease. Complications involve neurologic, respiratory, skin and soft tissue, gastrointestinal, hematologic, renal, and hepatic organ systems. Table 1 summarizes the complications noted in two recent reviews of previously well children hospitalized for varicella. Both reviews documented a recent increase in hospitalizations related to skin and soft tissue infections, especially those caused by group A beta-hemolytic streptococcal infections (GABHS).
Since the mid 1980s, we have witnessed an increased number of severe, invasive GABHS infections, including bacteremia, streptococcal toxic shock syndrome (TSS), and necrotizing fasciitis. The reason that GABHS has reappeared as an important pathogen is not entirely clear and might be the result of the re-emergence of certain serotypes (M-protein types 1 and 3), alterations in the function of streptococcal pyrogenic exotoxins, or the emergence of other virulence factors. In recent years, an increasing proportion of invasive GABHS infections in the United States have been associated with varicella.
In the April 1994 issue of Annals of Emergency Medicine, investigators in Texas reported a case series of six previously healthy children between the ages of 1 and 5 years managed over a three-month period in the winter of 1993.3 All six children had varicella infection before developing invasive GABHS infections. The following year, the incidence GABHS bacteremia at Boston Children's Hospital was retrospectively reviewed.4 Sixty three episodes of GABHS bacteremia were identified over a 4-year period. Ten cases occurred in previously healthy children with primary varicella; five of the cases occurred in 1993. In 1996, the Division of Communicable Disease Control in Southern California reported 24 cases of invasive GABHS infections in previously healthy children with primary varicella identified in the first 100 days of 1994.5 Table 2 summarizes the 40 cases included in the Texas, Boston, and California reports. The mean temperature at the time of presentation for cases 1-6 was 39.1oC, for cases 7-16 was 39.4oC, and for cases 17-40 was 39.4oC.
Table 2
Cases of Varicella-Associated Invasive GABHS Infections3,4,5
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Notes |
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Streptococcal toxic shock syndrome (TSS) |
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TSS |
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Pneumonia, empyema |
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TSS |
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TSS, erysipelas-like rash |
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Pyomyositis |
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Bacteremia |
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Bacteremia with GABHS and S. aureus |
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Bacteremia, TSS, multifocal osteomyelitis |
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Bacteremia, TSS, death |
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Bacteremia, osteomyelitis |
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Bacteremia, epiglottitis |
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Bacteremia, infected pox, periorbital cellulitis |
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Bacteremia, cellulitis |
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Bacteremia, multifocal septic arthritis |
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Bacteremia, cellulitis |
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Bacteremia, cellulitis |
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Bacteremia, TSS |
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Bacteremia |
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Bacteremia, pneumonia, empyema |
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Bacteremia, TSS, necrotizing fasciitis |
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Cellulitis |
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Cellulitis |
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Cellulitis, epiglottitis |
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Cardiopulmonary arrest with death in ED (GABHS in trachea, enlarged epiglottis) |
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Cellulitis |
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Bacteremia, necrotizing fasciitis |
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Cellulitis |
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Cellulitis |
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Bacteremia, cellulitis, coagulopathy |
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Cardiopulmonary arrest with death in clinic (GABHS in throat, leg pain, fever, vomiting) |
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Bacteremia |
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Bacteremia, cellulitis |
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Cellulitis |
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Cellulitis |
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Cellulitis |
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Death at home 4 hours after an ED visit (GABHS in CSF) |
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Cellulitis |
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Death at home (GABHS in CSF) |
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Bacteremia, infected pox |
Cases 1-6 are from reference 3, cases 7-16 are from reference 4, and cases 17-40 are from reference 5.
Two recent investigations report specifically on the association of GABHS necrotizing fasciitis and varicella. Between December 1993 and May 1995, 14 children were treated in Seattle after developing GABHS necrotizing fasciitis as a complication of primary varicella.6 The children ranged in age from 6 months to 10 years and presented with necrotizing fasciitis between days 2 and 6 of varicella (median, 3 days). The most common presenting symptoms were erythema (71%), focal pain (79%), fever (85%), and localizing swelling (71%). Pain was often described as being out of proportion to other clinical findings, and, often, there was refusal to bear weight or move an extremity. The majority of cases were not associated with overlying superinfected pox lesions, eight of the 14 were initially evaluated and discharged before returning several hours later with advancing symptoms, and five of the 14 developed TSS. A report from Nashville reviews the course of four children treated in the early 1990s after developing GABHS necrotizing fasciitis as a complication of primary varicella.7 The children ranged in age from 3 to 8 years and presented with necrotizing fasciitis on days 4, 5, 7, and 9 of varicella. Presenting symptoms included erythema, focal pain, localized swelling, and fever. All four patients had a delay in diagnosis.
There have also been anecdotal reports of a relationship between the use of nonsteroidal antiinflammatory drugs (NSAIDs) and the development of GABHS necrotizing fasciitis. In the report from Seattle of the 14 children who were treated after developing GABHS necrotizing fasciitis as a complication of primary varicella,6 five of the 14 were taking NSAIDs at the time of their initial presentation with necrotizing fasciitis. NSAIDs may contribute to the sudden onset of shock, organ failure, and fulminant evolution of soft tissue infections by inhibiting neutrophil function, augmenting cytokine production, and may also contribute to delay in diagnosis by masking signs of disease progression such as fever, pain, and swelling. Data are insufficient on which to base a clinical decision about the use or restriction of NSAIDs in children with varicella, but, it seems prudent to restrict their use.
What places previously healthy children with varicella at risk for developing invasive GABHS infections? The Los Angeles Department of Health Services designed a case-control study in order to identify potential risk factors for invasive GABHS infections in children with varicella.8 Cases included 25 children with varicella who developed invasive GABHS infections, and controls were 62 children from the same geographic area during the same time period who had uncomplicated varicella. Cases were more likely than controls to 1) be cared for in the home vs. day care; 2) report having asthma and be taking albuterol; 3) be secondary varicella cases within the household; 4) report fever above 38oC after day 2 of varicella; and 5) have contacted their doctor later than controls. Additional studies will be necessary to confirm these associations.
Conclusion
Varicella continues to result in serious and life-threatening complications in previously healthy children. Varicella is a risk factor for invasive GABHS infections. An invasive GABHS infection should be considered in any child with varicella who has 1) a higher temperature or fever persisting beyond the third day of illness or who becomes febrile after having been afebrile; 2) looks ill, has prolonged capillary refill, hypotension, tachycardia or altered mental status; 3) has skin findings of localized swelling, erythema, or focal tenderness; 4) refuses to bear weight, move an extremity, or complains of pain out-of-proportion to other clinical findings. Widespread varicella vaccine incorporation into the infant immunization schedule should decrease the incidence of varicella-related complications and should be encouraged.
References
1. Peterson CL, et al. J Pediatr 1996;129:529-536.
2. Jackson MA, et al. Pediatr Infect Dis J 1992;11: 441-445.
3. Cowan MR, et al. Ann Emerg Med 1994;23:818-822.
4. Doctor A, et al. Pediatrics 1995;96:428-433.
5. Vugia DJ, et al. Pediatr Infect Dis J 1996;15:146-150.
6. Brogan TV, et al. Pediatr Infect Dis J 1995;14:588-594.
7. Wilson GT, et al. Clin Infect Dis 1995;20:1333-1338.
8. Peterson CL, et al. Pediatr Infect Dis J 1996;15:151-156.
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