A 7-year-old Hispanic girl presented to the emergency department for evaluation of fever and a rash on her abdomen. She was in her usual state of good health when she developed varicella six days earlier. Her fever, initially associated with the onset of the varicella, had resolved only to reoccur 24 hours prior to admission. Her varicella was fairly mild, with only 20-30 lesions. The morning of admission, she felt sick to her stomach, which was accompanied by some emesis, and noticed one of the varicella lesions on her abdomen was especially sore.
Her past medical history was unremarkable. Her family history was positive for an older sibling having just recovered from varicella. Her immunizations were said to be up-to-date; however, that did not include varicella vaccine (Varivax, Merck).
Because she appeared moderately ill, she received some intravenous fluid boluses of normal saline, a dose of nafcillin and a dose of gentamicin in the emergency department prior to being sent for admission. Upon arrival to the floor, her examination revealed an ill-appearing 7-year-old female whose vital signs registered a fever of 102.7º F, a pulse of 147, a respiratory rate of 24 and a blood pressure of 93/56 with a capillary refill of three seconds. In addition to having numerous varicella lesions, most of which were crusting over, she also had an area of painful erythema on her mid-left abdomen measuring about 14 x 20 cm. The central portion of the lesion had a darker, purplish-black appearance (figures 1 and 2). The rest of her exam was normal. Her complete blood count was normal and blood cultures are pending.
Of the following, what's the most urgent course of action?
Even though the figures are a little out of focus, I think this patient clearly demonstrates a typical case of necrotizing fasciitis of the abdomen. As much as I hate to admit it, the most urgent need in a case like this is aggressive surgical débridement (answer A). Most of these infections are due to a rapidly progressive Streptococcus pyogenes (group A streptococcus or GAS) infection, and thorough débridement of the necrotic tissue is paramount. Delay can result in massive tissue loss and ultimately, death. Streptococcal toxic shock syndrome can also accompany the necrotizing fasciitis, which can be rapidly fatal. This patient had early evidence of shock, and GAS grew out of both blood cultures and the wound culture taken at surgery. Obviously, antibiotics are important in the management of a case like this; however, she had already received antibiotics in the emergency department, and antibiotics alone will not resolve this problem. Aggressive fluid resuscitation and intensive care is also very important.
The patient's initial antibiotic therapy in the hospital was nafcillin plus clindamycin, but was changed to penicillin G plus clindamycin after the culture results were known.
She promptly went to surgery for débridement of the necrotic material as shown in figures 3 and 4. Her repeat blood cultures were negative, and she had an unremarkable recovery. After a couple of weeks of hydrotherapy, the wound was ready for grafting (figures 5 and 6). From a cosmetic standpoint, she ended up with a significant abdominal wall defect, but at least she lived.
In 1952, Eagle suggested with a mouse model that GAS treatment failures with penicillin were possibly due to the organism going into a prolonged resting phase. This appeared to be stimulated by the presence of a large number of organisms (high inoculum), like one might see in a case of streptococcal myofasciitis. -lactams, like penicillin, kill streptococci by inhibiting cell wall synthesis, which occurs when the organism is undergoing replication.
Following this line of reasoning (the Eagle effect or inoculum effect), it seems logical to use an antimicrobial that works by another mechanism. Clindamycin works by interfering with protein synthesis at the 50S ribosome level, and, therefore, does not depend on the organism being in the replication phase. Additionally, this mechanism has the theoretical advantage of decreasing exotoxin production of the streptococci while clindamycin can also treat any anaerobic organisms that may be in the mix. In fact, clindamycin is not a bad antistaphylococcal antimicrobial also. Because of this, some experts argue that clindamycin alone could be used in cases like this. However, I still like the idea of killing streptococci by two mechanisms, at least in the acute stage of the infection. When the port of entry of the cellulitis or necrotizing fasciitis is about the groin (figure 7), I recommend adding an aminoglycoside until culture results are known since gram-negative organisms have been implicated in such cases, both alone and with streptococi. It is often difficult to distinguish between varicella-associated bacterial cellulitis (as shown on the neck of the patient in figures 8 and 9) and early necrotizing fasciitis. Cases like the one presented above are easy, but for those not so clear cut, it may be helpful to obtain an MRI of the area involved.
However, I always have our pediatric surgeons consulted first and foremost. If all are in agreement that we are dealing with cellulitis and not a deeper infection, then we treat with aggressive antibiotics as noted above and cautiously watch for progression. Figures 10 and 11 show a typical case of severe GAS cellulitis associated with varicella at admission and 36 hours later, that responded to antibiotic therapy. If there is any significant question, some surgeons may try passing a needle through the area in question while aspirating. Some feel they can distinguish between the feel of the needle as it goes through healthy vs. necrotic tissue. Others may choose to go to the operating room and take a look through an incision. Of course, the downside is leaving a scar that may not be necessary. But if you're wrong, and you sit on a case of necrotizing fasciitis, there may not be a leg or an abdomen left on which to leave a scar. This is quite a dilemma.
As noted above, these bacterial complications of varicella can be life- and limb-threatening. While the skin is the site most frequently involved, we occasionally see other suppurative complications, such as bone and joint and pulmonary infections. Figure 12 shows the chest radiograph of a child on day six of an otherwise uncomplicated case of varicella. He also presented with a secondary fever. Figure 13 is the appearance after approximately 500 cc of pus was drained, which grew pure GAS, as did the childblood. Figure 14 is after a few days of chest tube drainage and antibiotics.
Since the mid-1980s, severe GAS infections have been on the rise. When M-typing has been done, it has been mostly associated with the lower number types such as M1, M3, M4, M12, M18 and others. In children, it seems to be more commonly associated with varicella infections. It's not clear why this association exists. One popular theory is that perhaps the stress to the immune system from the varicella puts the patient at risk for the "opportunistic" strep to invade. Whatever the answer, there is a clear association, and one that is occurring more frequently than before. Lastly, there is some concern over the use of nonsteroidal anti-inflammatory agents with varicella and the risk of severe GAS disease. No scientific proof of this possible association exists, but it may be prudent to avoid these agents during varicella pending further studies.
The most common central nervous system (CNS) complication of varicella is the occurrence of cerebellar ataxia. This is usually self-limiting. However, severe encephalitis can rarely occur and can be fatal. Other uncommon CNS problems include transverse myelitis and aseptic meningitis. Varicella hepatitis, pneumonia, myocarditis, nephritis and disseminated intravascular coagulopathy are additional complications. While these problems are more likely to occur and be associated with a prolonged course in immunocompromised patients, they can also occur in otherwise normal patients. Severe manifestations are also more likely to occur in adults, especially pregnant women. And if a pregnant woman gets varicella, there is the possibility of the fetus being damaged by the infection, resulting in the congenital varicella syndrome.
Varicella, being caused by varicella zoster virus, a member of the herpesvirus family, stays with you for life, sort of like "the gift that keeps on giving," residing in the posterior root ganglion in a latent form after the primary infection.
Reactivation leads to shingles which, contrary to popular opinion, does occur in children (figure 15), and can sometimes be fairly severe (figure 16, courtesy of Bill Parry, MD.).
Once varicella occurs, there are treatments that can be used to modify the severity of the disease if started very early in the course (within 48 hours of onset). Acyclovir is the only drug approved for children. However, the drugs valacyclovir (Valtrex, Glaxo Wellcome) and famciclovir (Famvir, Smith-Kline Beecham) are available for patients 18 years and older. I would recommend consulting the 2000 Red Book or treatment recommendations. In general, the patient described above would not benefit from any anti-varicella agent since the viral infection was essentially resolved when the secondary bacterial infection was diagnosed. This will almost always be the case. Remember, if the decision is made to treat a varicella zoster infection, the dose of acyclovir is much higher than the one used for herpes simplex infections. Also remember that aspirin is contraindicated in varicella because of its association with Reye's syndrome.
As of Aug. 1, 2000, the state of Texas will require all children older than 1 year of age to be immunized against varicella, or have a history of disease. This follows many other states, and should, in my opinion, be required everywhere. The disease has an unacceptable complication rate, with treatment that is not optimal. Therefore, prevention with vaccine is the best solution.
The product available is a live-attenuated vaccine with an excellent safety record. While prevention is not 100% with the vaccine, it is almost unheard of to have a breakthrough case of severe varicella in a vaccinated patient. In fact, I am not aware of any published report of severe varicella in a vaccinated individual. The immunity derived from the vaccine appears to last at least 20 years. However, it is unclear how much the anamnestic response with exposure to wild varicella virus might contribute to the duration of immunity. Significantly reducing varicella disease, and therefore, exposure, may result in waning immunity sooner. Even if a booster is ultimately required every 10 to 20 years, it seems to me that this would be preferable to taking our chances with our children's health regarding varicella and its complications. We currently boost tetanus and diphtheria every 10 years, and should be taking an annual influenza vaccine. I think immunizations throughout life are going to be common in the near future; that is if we want to continue to improve our standard of health, prevent disease and live "the good life."
The face of varicella is usually that seen in figures 17 and 18. However, there are times when it is not so benign (figure 19), and complications seem to be increasing over the last two decades. I think we are fortunate to be able to prevent or significantly attenuate this expensive and problematic disease in our children.
I should point out that our own Philip A. Brunell, MD, chief medical editor of Infectious Diseases in Children was one of the pioneers in testing varicella vaccine in this country, and is widely regarded as one of the world's leading experts on varicella zoster virus infections.
Acknowledgments: I would like to thank Drs. Stephanie Gintherand Hari Reddy, pediatric residents at Scott and White, and Dr. Lori Wick, pediatric intensivist at Scott and White, for their assistance with this column.
For more information:
- James H. Brien, DO; Pediatric Infectious Disease; Scott and White's Children's Health Center and Texas A&M University, College of Medicine; Temple, Texas; E-mail: firstname.lastname@example.org
- Vugia DJ, Peterson CL, Meyers HB, et al. Invasive group A streptococcal infections in children with varicella in Southern California. Pediatr Infect Dis J. 1996;15:146-150.
- Peterson CL, Vugia DJ, Meyers HB, et al. Risk factors for invasive group A streptococcal infections in children with varicella: a case-control study. Pediatr Infect Dis J. 1996;15:151-156.
- Eagle H. Experimental approach to the problem of treatment failure with penicillin. I. Group A streptococcal infection in mice. Am J Med. 1952;13:389.
- Stevens DL, Gibson AE, Bergstrom R, et al. The Eagle effect revisited: efficacy of clindamycin, erythromycin, and penicillin in the treatment of streptococcal myositis. J Infect Dis. 1988;158:23-28.
- Brunell PA, Shehab Z, Geiser C, et al. Administration of live varicella vaccine to children with leukemia. Lancet. 1982;2:1069-1073.
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