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Original Article |

Toxic Shock Syndrome and Rhinosinusitis in Children FREE

Kenny H. Chan, MD; Tania L. Kraai, MD; Gresham T. Richter, MD; Sharon Wetherall, MD; James K. Todd, MD
[+] Author Affiliations

Author Affiliations: Departments of Otolaryngology (Drs Chan, Kraai, Richter, and Wetherall) and Pediatrics (Dr Todd), University of Colorado School of Medicine and The Children's Hospital of Denver; Division of Otolaryngology–Head and Neck Surgery, University of New Mexico, Albuquerque (Dr Kraai); Division of Pediatric Otolaryngology, Arkansas Children's Hospital, Little Rock (Dr Richter); and Department of Anesthesia, Brigham and Women's Hospital, Boston, Massachusetts (Dr Wetherall).


Arch Otolaryngol Head Neck Surg. 2009;135(6):538-542. doi:10.1001/archoto.2009.55.
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Objective  To determine the association between toxic shock syndrome (TSS) and rhinosinusitis in children.

Design  Eighteen-year retrospective review of medical records.

Setting  Tertiary children's hospital.

Patients  A total of 76 patients were identified as having TSS. Twenty-three of them were also diagnosed as having either acute or chronic rhinosinusitis, with no other source of infection in 17 cases.

Interventions  Of the 23 patients with TSS and rhinosinusitis, 10 were admitted to the intensive care unit, 4 required pressors, and 6 received surgical intervention. Surgical intervention for sinus disease included bilateral antral lavage in 5 patients and bilateral maxillary antrostomy and ethmoidectomy in 1 patient.

Main Outcome Measures  Patients with TSS and rhinosinusitis were identified using a rigorous set of definitions and detailed data pertaining to history, imaging studies, microbiologic studies, and hospital course.

Results  Correlation of the data revealed 4 patients who met the criteria for proven TSS and proven rhinosinusitis, 2 patients who met the criteria for probable TSS and proven rhinosinusitis, 7 patients who met the criteria for proven TSS and possible rhinosinusitis, and 3 patients who met the criteria for probable TSS and possible rhinosinusitis.

Conclusions  Rhinosinusitis was found to be the primary cause of TSS 21% of the time in this series. Rhinosinusitis should be considered the primary cause of TSS when another site of infection has not been identified. Once the link is made, prompt otolaryngology consultation and sinus lavage should be considered.

Toxic-shock syndrome (TSS) was first described in pediatric patients by Todd et al1 in 1978. Several years later, the syndrome gained widespread recognition as a disease associated with menstruation and tampon use.2 Although not as publicized, numerous other risk factors have been established for TSS in association with focal infections, such as surgical wound infections (notably after rhinologic surgery and nasal packing), postpartum and postabortion infections, and a wide variety of connective tissue lesions. The association between TSS and rhinosinusitis has been less well characterized in the literature, with only a few case reports having been published to date.38

The criteria for the diagnosis of TSS were originally established by the Centers for Disease Control and Prevention and were subsequently revised by Reingold et al9 in 1982. Reingold and colleagues' algorithm for diagnosis stipulates that 4 of 4 diagnostic criteria must be present for proven TSS and that 3 of 4 diagnostic criteria must be present for probable TSS (Table 1). The 3 hallmark clinical signs include fever, erythrodermatoid rash, and hypotension. Also, a diverse set of multisystem derangements may be present. In a large proportion of TSS cases, the pathogenesis involves Staphylococcus aureus infection.1,10Streptococcus pneumoniae and Streptococcus pyogenes have also been reported as potential causes of TSS, 3 cases of which were described in patients with rhinosinusitis.4,5,7,11 The clinical course of TSS in most cases is a fulminant one, requiring pressor support and fluid resuscitation for cardiovascular collapse. The mortality rate of TSS is reported to be less than 3% for staphylococcal infections and anywhere from 30% to 70% for streptococcal infections.12

Table Graphic Jump LocationTable 1. Summary of Criteria for Toxic Shock Syndrome (TSS)a

The current understanding of TSS due to rhinosinusitis in children is poorly understood, and the frequency of this occurrence is unknown owing to a lack of cases in the medical literature. A review of 130 cases of nonmenstrual TSS did not identify rhinosinusitis as a potential cause. However, 13 cases had an unknown infectious source, 6 were described as miscellaneous, and 34 had incomplete information and could not be further categorized, for a total of 53% of the cases.13 This high percentage of unknown causes raises the question as to whether rhinosinusitis could have been the cause in some of these cases. Our goal was to explore this relationship through an 18-year retrospective review of the medical records at a tertiary children's hospital starting in 1982, the year that Reingold et al9 established a working definition for TSS. We describe a child with TSS and rhinosinusitis to illustrate the typical hospital course in a case involving this association.

An 8-year-old boy presented to the emergency department with a history of intermittent fevers, vomiting, sore throat, rash, and refusal to walk. He had been healthy until 6 days before admission, when the fevers, pharyngeal erythema, strawberry tongue, and vomiting had begun. His pediatrician made a presumptive diagnosis of streptococcal pharyngitis, and amoxicillin therapy was initiated. The antibiotic therapy was discontinued 3 days later, when the patient's throat culture was found to be negative for organisms.

On presentation to the emergency department, the patient was febrile, hypotensive, and tachycardic. He was promptly admitted to the pediatric intensive care unit (ICU) with a presumptive diagnosis of TSS and was started on an intravenous regimen of nafcillin sodium, clindamycin, and cefotaxime sodium. Because of hypotension, treatment with dopamine hydrochloride was also initiated. A septic workup consisting of blood, urine, and cerebrospinal fluid cultures was performed, and no bacterial growth was identified. Additional laboratory tests showed a white blood cell count of 19 000/μL (to convert to ×109/L, multiply by 0.001). A chemistry panel, including liver function tests, revealed normal values. In the absence of a source for the septic shock in this case, computed tomography of the sinuses was performed, and the results showed substantial mucosal thickening in both the maxillary and the ethmoidal sinuses as well as the left frontal sinus, while mild thickening was seen in the sphenoidal sinus. Furthermore, a bilateral bubbly appearance was noted over the maxillary sinus mucosa, suggesting acute disease. The patient was taken to the operating room 36 hours after the intravenous antibiotics were administered, and bilateral antral irrigation was performed. A Gram stain of the sinus aspirate was unremarkable, and the aerobic and anaerobic cultures were subsequently negative for organisms. In the immediate postoperative period, the dopamine dosage was cut in half. The septic shock resolved, and the patient was discharged from the hospital within 96 hours. A follow-up computed tomogram obtained 4 weeks after his discharge showed complete resolution of the mucosal thickening, supporting the impression that acute sinusitis was the basis for the TSS in this case. It also suggests that this patient did not have chronic rhinosinusitis prior to this hospitalization.

Appropriate institutional review board approval was obtained. The primary and secondary discharge diagnoses of medical records at The Children's Hospital, Denver, Colorado, from January 1983 to December 2000 were searched using International Classification of Diseases, Ninth Revision (ICD-9), diagnostic codes for toxic shock syndrome (040.82), shock (639.5), acute sinusitis (461), and chronic sinusitis (473). The medical records of all potential subjects were reviewed based on the criteria of Reingold et al,9 as detailed below. All cases not meeting the criteria were excluded. Demographic and clinical data were recorded in all relevant cases.

The definitions of proven and probable TSS as defined by Reingold and colleagues9 were used in the analysis of the TSS status of all potential participants (Table 1). Proven TSS was defined as meeting 4 of the 4 criteria, and probable TSS was defined as meeting 3 of the 4 criteria. If a patient had a positive culture result other than that of the paranasal sinus, he or she was excluded from the study. Furthermore, the rhinosinusitis status of the potential cases was defined as proven or probable. Probable rhinosinusitis was defined as imaging studies (plain radiography or computed tomography) that showed 4 mm or more of mucosal thickening in the maxillary sinus, air-fluid levels in any of the sinuses, or total opacification of any paranasal sinus. Proven rhinosinusitis required a positive result on Gram stain and/or culture in addition to the radiographic changes noted above. A positive Gram stain result was defined as microbiology laboratory notations of either organisms or polymorphonuclear cells.

Based on the ICD-9 code search, 76 patients were identified as having TSS as either the primary (n = 65) or the secondary (n = 11) diagnosis. Twenty-three of these patients were also diagnosed as having either acute or chronic rhinosinusitis. A total of 53 cases that failed to meet the criteria of Reingold and colleagues9 for TSS were excluded. Of the 23 patients who met the ICD-9 code criteria for TSS and rhinosinusitis, 11 met Reingold and coworkers' criteria for proven TSS, and 5 met the criteria for probable TSS (Table 2). Sinus imaging of the 23 patients who met ICD-9 criteria for both TSS and rhinosinusitis revealed that 9 patients had proven rhinosinusitis and 13 patients had probable rhinosinusitis (Table 3). A total of 7 patients were excluded from the study. One patient (No. 7) did not meet the criteria for either proven or probable TSS. Six patients had positive culture results from sites other than the paranasal sinuses, nullifying the diagnosis of TSS caused by rhinosinusitis. Furthermore, patient 16 had no imaging studies performed during his hospitalization. Correlation of the data revealed 4 patients who met the criteria for proven TSS and proven rhinosinusitis; 2 patients who met the criteria for probable TSS and proven rhinosinusitis; 7 patients who met the criteria for proven TSS and probable rhinosinusitis; and 3 patients who met the criteria for probable TSS and probable rhinosinusitis (Table 4).

Table Graphic Jump LocationTable 2. Classification of Toxic Shock Syndrome (TSS) Status of the Cohorta
Table Graphic Jump LocationTable 3. Classification of Rhinosinusitis Status of the Cohort Based on Study Criteria
Table Graphic Jump LocationTable 4. Correlation of Patients According to the Diagnosis of Proven or Probable TSS and Proven or Probable Rhinosinusitis

The average age of the patients in our study was 10 years, with a median age of 11 years. Of the 17 patients, 13 were white, 2 were Hispanic, 1 was Native American, and 1 was of unknown race. Eight patients were female and 9 were male. The average number of hospital days for the cohort was 14, with 10 of the 17 patients being admitted to the ICU. Pressor support was required in 4 patients and intubation was required in 2 patients. Surgical intervention occurred in 6 patients. Among the surgical procedures performed in the 4 subgroups, 1 patient underwent antrostomy and ethmoidectomy, and the remaining 5 patients underwent antral lavage. None of these patients are known to have encountered a surgical complication. Furthermore, we made no attempt to correlate surgical procedures with any outcome variables, because clinical outcome is multifactorial. In comparison, the average number of hospital days for the 6 patients who were excluded from the study was 17, with 3 of the 6 being admitted to the ICU. Pressor support and intubation was required in 1 of the 6 patients, and 3 patients underwent surgery.

The 4 patients with proven TSS and proven rhinosinusitis had an average hospital stay of 14 days; 3 of the 4 patients were admitted to the ICU; 2 of the 4 received pressor support; and all 4 underwent surgery. Among the 7 patients with proven TSS and probable rhinosinusitis, the average hospital stay was 4.7 days, with 4 being admitted to the ICU and only 1 receiving pressor support. None of the 7 patients received surgical intervention. There were only 2 patients who fell into the category of probable TSS and proven rhinosinusitis. They had an average hospital stay of 51.5 days; both underwent surgery; and 1 was admitted to the ICU, received pressor support, and was intubated. The 3 patients who met the criteria for probable TSS and probable rhinosinusitis had an average hospital stay of 3 days. Two of the 3 were admitted to the ICU, but none of the 3 patients received pressors, intubation, or surgical intervention.

When the patients who were included in the study were compared with those who were not included, there was little difference in the average number of hospital days. However, once admitted, the patients who were included in the study had a more tenuous hospital course. They also had a higher incidence of ICU admission, pressor administration, and intubation. The incidence of surgical intervention, however, was higher in those who were excluded. These differences may be attributable to the numbers in the study or to the finding of positive cultures from other bodily fluids. Among the 4 subgroups, the average number of days in the hospital varied, but once the patients were in the hospital, all but those in the probable TSS and probable rhinosinusitis group had similar hospital courses.

This study illustrates several salient points concerning TSS and rhinosinusitis in children. First, rhinosinusitis as the primary culprit in the pathogenesis of TSS is not a sporadic phenomenon. In fact, the frequency of this combination for this 18-year series is an impressive 21%. Fortunately, the TSS and rhinosinusitis cohort fared no differently than the total TSS group. Nonetheless, this group of children had protracted hospitalization requiring intensive care, and some of them had morbid complications.

In retrospect, it could be argued that the data set should have been more meticulous in terms of having more of the patients undergo sinus cultures, thereby obtaining a more complete microbiologic picture. The fact remains that these patients were critically ill, and imaging studies and diagnoses of rhinosinusitis might have been delayed and surgical procedures might have been likewise unsafe for some of the patients for medical reasons alone. The lack of positive culture results among those who underwent surgical procedures may be attributable to broad antimicrobial coverage in these patients soon after their admission. Increasing recognition of rhinosinusitis as a potential cause of TSS should lead to earlier diagnosis and intervention in cases involving this entity.

The signs of infection in TSS may be modest in relation to the profound multiorgan involvement. The presentation of rhinosinusitis in children can also be subtle, underscoring the importance of increasing awareness of rhinosinusitis as a potential cause of TSS, especially in patients without a clear source of infection. Numerous different superantigens produced by either streptococcal or staphylococcal infection are thought to produce the systemic effects in TSS that are mediated via cytokine stimulation of the immune system.12 Neutralizing the circulating toxins with intravenous immunoglobulin has been shown to reduce mortality.14,15 Primary treatments for TSS are aimed at eradicating the infection and thus the source of toxin production, using antibiotics and conservative surgical debridement.

The utility of performing a sinus surgical procedure in this patient population should be considered based on the current understanding of the pathogenesis of bacterial infection and toxin production in TSS. Although our experience is anecdotal, we believe that the goal of any sinus procedure in this situation is to reduce the bacterial and toxin load in a critically ill patient in the shortest amount of anesthetic time. In fact, some of our study patients underwent their antral lavages at the bedside under intravenous sedation. Therefore, addressing the maxillary sinuses is logical, and lavaging the sinuses becomes the most expeditious procedure. Endoscopic sinus procedures such as antrostomy and ethmoidectomy may be less desirable and risky in this patient population.

Because this study was a retrospective review, it was limited by the data that were present in the medical records. Although 23 patients were identified, the combination of TSS and rhinosinusitis is a rare entity, and determining the effect of interventions, including sinus lavage, could not be addressed. The study was undertaken to look at the association between TSS and rhinosinusitis in children, which seems evident based on our experience. Patients who have been described in the literature and several patients in this series were seen to have a dramatic recovery after sinus lavage; however, this outcome was not universal. The role of surgical intervention in this disease process deserves further investigation.

Toxic shock syndrome in children, though rare, occurs with certainty. It is imperative that physicians, particularly those who are providing intensive care to children, recognize that rhinosinusitis can be the sole cause of TSS in children. Prompt imaging studies of the sinuses is mandatory when no apparent cause of TSS is found. Once rhinosinusitis is diagnosed, timely otolaryngology referral should be obtained, and sinus culture and lavage should be considered if the clinical condition warrants it.

Correspondence: Kenny H. Chan, MD, Department of Pediatric Otolaryngology, The Children's Hospital, 13123 E 16th Ave, B455, Aurora, CO 80045 (chan.kennyh@tchden.org).

Submitted for Publication: May 20, 2008; final revision received September 30, 2008; accepted October 9, 2008.

Author Contributions: Dr Chan had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Chan, Richter, and Todd. Acquisition of data: Chan, Kraai, Richter, Wetherall, and Todd. Analysis and interpretation of data: Chan, Kraai, Richter, Wetherall, and Todd. Drafting of the manuscript: Chan, Kraai, Richter, and Wetherall. Critical revision of the manuscript for important intellectual content: Chan, Kraai, Richter, and Todd. Statistical analysis: Todd. Administrative, technical, and material support: Chan and Kraai. Study supervision: Chan and Richter.

Financial Disclosure: None reported.

Previous Presentation: This study was presented as a poster at the Combined Otolaryngology Spring Meeting, American Society of Pediatric Otolaryngology Section; May 3, 2008; Orlando, Florida.

Todd  JFishaut  MKapral  FWelch  T Toxic-shock syndrome associated with phage-group-I staphylococci. Lancet 1978;2 (8100) 1116- 1118
PubMed
Shands  KNSchmid  GPDan  BB  et al.  Toxic-shock syndrome in menstruating women: association with tampon use and Staphylococcus aureus and clinical features in 52 cases. N Engl J Med 1980;303 (25) 1436- 1442
PubMed
Ferguson  MATodd  JK Toxic shock syndrome associated with Staphylococcus aureus sinusitis in children. J Infect Dis 1990;161 (5) 953- 955
PubMed
Friedstrom  SRAwad  J Toxic-shock–like-syndrome due to Streptococcuspneumoniae sinusitis. Scand J Infect Dis 1999;31 (5) 509- 510
PubMed
Gallo  UEFontanarosa  PB Toxic streptococcal syndrome. Ann Emerg Med 1990;19 (11) 1332- 1334
PubMed
Griffith  JAPerkin  RM Toxic shock syndrome and sinusitis—a hidden site of infection. West J Med 1988;148 (5) 580- 581
PubMed
Hariri  MAVice  PA Septic shock and death due to occult sinusitis. J Laryngol Otol 1990;104 (12) 990
PubMed
Wood  SDRies  KWhite  GL  JrMurdock  RTPedersen  DM Maxillary sinusitis—the focus of toxic shock syndrome in a male patient. West J Med 1987;147 (4) 467- 469
PubMed
Reingold  ALHargrett  NTShands  KN  et al.  Toxic shock syndrome surveillance in the United States, 1980 to 1981. Ann Intern Med 1982;96 (6, pt 2) 875- 880
PubMed
Todd  JKFranco-Buff  ALawellin  DWVasil  ML Phenotypic distinctiveness of Staphylococcus aureus strains associated with toxic shock syndrome. Infect Immun 1984;45 (2) 339- 344
PubMed
Eriksson  BKAndersson  JHolm  SENorgren  M Epidemiological and clinical aspects of invasive group A streptococcal infections and the streptococcal toxic shock syndrome. Clin Infect Dis 1998;27 (6) 1428- 1436
PubMed
Stevens  DL The toxic shock syndromes. Infect Dis Clin North Am 1996;10 (4) 727- 746
PubMed
Reingold  ALHargrett  NTDan  BBShands  KNStrickland  BYBroome  CV Nonmenstrual toxic shock syndrome: a review of 130 cases. Ann Intern Med 1982;96 (6, pt 2) 871- 874
PubMed
Descloux  EPerpoint  TFerry  T  et al.  One in five mortality in non-menstrual toxic shock syndrome versus no mortality in menstrual cases in a balanced French series of 55 cases. Eur J Clin Microbiol Infect Dis 2008;27 (1) 37- 43
PubMed
Norrby-Teglund  AMuller  MPMcGeer  A  et al.  Successful management of severe group A streptococcal soft tissue infections using an aggressive medical regimen including intravenous polyspecific immunoglobulin together with a conservative surgical approach. Scand J Infect Dis 2005;37 (3) 166- 172
PubMed

Figures

Tables

Table Graphic Jump LocationTable 1. Summary of Criteria for Toxic Shock Syndrome (TSS)a
Table Graphic Jump LocationTable 2. Classification of Toxic Shock Syndrome (TSS) Status of the Cohorta
Table Graphic Jump LocationTable 3. Classification of Rhinosinusitis Status of the Cohort Based on Study Criteria
Table Graphic Jump LocationTable 4. Correlation of Patients According to the Diagnosis of Proven or Probable TSS and Proven or Probable Rhinosinusitis

References

Todd  JFishaut  MKapral  FWelch  T Toxic-shock syndrome associated with phage-group-I staphylococci. Lancet 1978;2 (8100) 1116- 1118
PubMed
Shands  KNSchmid  GPDan  BB  et al.  Toxic-shock syndrome in menstruating women: association with tampon use and Staphylococcus aureus and clinical features in 52 cases. N Engl J Med 1980;303 (25) 1436- 1442
PubMed
Ferguson  MATodd  JK Toxic shock syndrome associated with Staphylococcus aureus sinusitis in children. J Infect Dis 1990;161 (5) 953- 955
PubMed
Friedstrom  SRAwad  J Toxic-shock–like-syndrome due to Streptococcuspneumoniae sinusitis. Scand J Infect Dis 1999;31 (5) 509- 510
PubMed
Gallo  UEFontanarosa  PB Toxic streptococcal syndrome. Ann Emerg Med 1990;19 (11) 1332- 1334
PubMed
Griffith  JAPerkin  RM Toxic shock syndrome and sinusitis—a hidden site of infection. West J Med 1988;148 (5) 580- 581
PubMed
Hariri  MAVice  PA Septic shock and death due to occult sinusitis. J Laryngol Otol 1990;104 (12) 990
PubMed
Wood  SDRies  KWhite  GL  JrMurdock  RTPedersen  DM Maxillary sinusitis—the focus of toxic shock syndrome in a male patient. West J Med 1987;147 (4) 467- 469
PubMed
Reingold  ALHargrett  NTShands  KN  et al.  Toxic shock syndrome surveillance in the United States, 1980 to 1981. Ann Intern Med 1982;96 (6, pt 2) 875- 880
PubMed
Todd  JKFranco-Buff  ALawellin  DWVasil  ML Phenotypic distinctiveness of Staphylococcus aureus strains associated with toxic shock syndrome. Infect Immun 1984;45 (2) 339- 344
PubMed
Eriksson  BKAndersson  JHolm  SENorgren  M Epidemiological and clinical aspects of invasive group A streptococcal infections and the streptococcal toxic shock syndrome. Clin Infect Dis 1998;27 (6) 1428- 1436
PubMed
Stevens  DL The toxic shock syndromes. Infect Dis Clin North Am 1996;10 (4) 727- 746
PubMed
Reingold  ALHargrett  NTDan  BBShands  KNStrickland  BYBroome  CV Nonmenstrual toxic shock syndrome: a review of 130 cases. Ann Intern Med 1982;96 (6, pt 2) 871- 874
PubMed
Descloux  EPerpoint  TFerry  T  et al.  One in five mortality in non-menstrual toxic shock syndrome versus no mortality in menstrual cases in a balanced French series of 55 cases. Eur J Clin Microbiol Infect Dis 2008;27 (1) 37- 43
PubMed
Norrby-Teglund  AMuller  MPMcGeer  A  et al.  Successful management of severe group A streptococcal soft tissue infections using an aggressive medical regimen including intravenous polyspecific immunoglobulin together with a conservative surgical approach. Scand J Infect Dis 2005;37 (3) 166- 172
PubMed

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