Soothing the Savage Throat

ACADEMIC EMERGENCY MEDICINE June 1998, Volume 5, Number 6

I COMM€NTARI €S Soothing the Savage Throat 7

cute pharyngitis is an in- A flammatory syndrome of the pharynx that is caused by several groups of microorganisms. While many cases have viral etiologies, the most significant of the common bacterial etiologies is group A P-hemolytic streptococcus (GABHS). Approximately 15% of all cases of acute pharyngitis in adults and up to 50% of all cases in children are due to this bacteria.l The severity of the illness depends on the underlying infect- ing organism and even varies among persons infected with the same organism. In severe cases, one may note a temperature >39"C, chills, severe pharyngeal pain, odynophagia, headache, and abdominal pain. Without treatment, the illness usually runs its course in 3-7 days.

Concern over acute pharyngitis increased in the 1950s, when it was discovered that rheumatic fever could be pre- vented with the prompt treatment of acute streptococcal in- fection2 Thus, the primary objective in the diagnosis of acute p haryngi tis historically has been to diagnose and treat GABHS. In the 1970s and early 1980s, interest in treating acute pharyngitis waned as the inci- dence of acute rheumatic fever plummeted. In the late 1980s, a resurgence in acute rheumatic fever, among both crowded inner- city dwellers and middle-class suburbanites,s revived interest in rapid, accurate diagnostic methods for GABHS and in various antibiotic ~eg imens .~ .~

Each year, 40 million adults visit their physicians seeking pain relief from acute pharyngitis.l Sometimes these patients seek medical advice to differen- tiate between GABHS and other bacterial or viral etiologies of pharyngitis. Rarely do they un- derstand or are they concerned

about the sequelae of the various etiologies of pharyngitis. Their reason for visiting the doctor is to obtain pain relief so they may return to their normal daily ac- tivities. Pain relief and return to function are the issues that Marvez-Valls and colleagues ad- dress in their study in this issue of Academic Emergency Medi- cine.

Marvez-Valls et al. adminis- tered IM penicillin (oral erythromycin for penicillin-allergic patients) plus either IM betamethasone or placebo to 92 patients aged 14 through 65 years who presented to the ED for treatment of exudative pharyngitis. Patients were asked to rate their pain using a standard 10- cm graded visual analog scale WAS) before receiving treatment. After treatment, patients were released home with a copy of the VAS and were called daily up to 120 hours later to ascertain pain relief, side effects from the treatment medications, and days of work and school missed. Pa- tients were encouraged to use ibuprofen or acetaminophen as needed for pain relief.6

Marvez-Valls et al. report that the mean pain score was lower and the mean decrease in pain score at 24 hours was greater in the group of patients who received betamethasone than in the group who received placebo. Furthermore, the interval until complete pain relief was significantly shorter for the patients receiving betamethasone. Unfortunately, this did not translate into a reduced number of days of school or work missed in the betamethasone group. When the authors further ana- lyzed their data, they discovered that patients with positive throat cultures for streptococcal organisms received much quicker pain relief when given

557

betamethasone rather than placebo, while patients with negative cultures who received betamethasone experienced no more pain relief at 24 and 48 hours than did culture-negative patients who received placebo. They speculate that patients with streptococcal pharyngitis (often those with acute exudative pharyngitis) in the ED may benefit from betamethasone therapy. This most recent study comple- ments an earlier study by OBrien et al., which evaluated dexamethasone vs saline IM as an adjunct for pharyngitis in 51 patients and also found the steroid group to have a greater improvement in pain score and more rapid relief of pain.7

These 2 studies suggest a po- tential role for adjunctive steroid therapy in streptococcal pharyngitis. However, several caveats should be applied to these ran- domized, prospective, double- blind, placebo-controlled clinical trials. First, a word of caution must be interjected regarding statistical significance and clinical significance. The VAS in both studies has not been validated in patients with pharyngitis. Fur- thermore, O'Brien et al.7 used a nonstandard 15-cm scale vs the standard 10-cm scale used in the current study by Marvez-Valls et a1.6 The association of changes in these pain scales with clinical significance in the pharyngitis patient is unknown. It is unclear whether one can translate Todd et a1.k findings for trauma patients to the pain of pharyngitis that is waning slowly at home, rather than quickly in the ED.* If we assume that Todd et al.'s data can be used for acute pharyngitis, the differences that Marvez-Valls et al. describe at 24 hours disappear by 48 hours. That is, at 48 hours, the 2 groups are clinically the same, although statistically differenL6 The nonstandard scale used by O'Brien et al. prohibits even this degree of specula tion.

558 COMMENTARIES Cydullca SORE THROAT

Another problem with the use of a pain scale over the phone as described in these 2 studies is that the use of the scale is likely to have been less “visual” than intended. Patients who chose a number over the phone might re- spond differently when the scale is placed in front of them. While we commonly verbally track pain responses in the ED using a ver- bal “0-to-10” scale, the relation- ship to a “visual” analog pain scale remains unclear. Unfortu- nately, the logistics of such outpatient studies make consistent response to a visual scale virtu- ally impossible. Finally, remind- ing patients of their initial pain scores may have biased the way in which they reported their sub- sequent scores. Ideally, the visual analog pain scores would be determined independently.

The more clinically significant results are the intervals until the beginning of pain relief and until complete relief. In the study by Marvez-Valls et al., patients who received betamethasone began to feel better 5 hours sooner and had eomplete pain relief 13 hours sooner than did patients receiving placebo.6 In the study by O’Brien et al., patients who received dexamethasone be: gan to feel better 6 hours sooner and had complete pain relief 20 hours sooner than did patients receiving placebo, although follow-up evaluations were more limited.7

OBrien et al. did not isolate pharyngeal pathogen^.^ Marvez- Valls et al. performed a sub- analysis of streptococcal-positive cases6 They found that the clinical improvement was even more dramatic in patients who were culture-positive. While both culture-positive and culture-negative patients who received betamethasone experienced pain relief sooner (clinically, although not statistically) than did patients who received placebo, culture- positive patients who received betamethasone were pain-free a

full day before patients who received antibiotics alone.

O’Brien et al. state that the uses of ancillary analgesia were not different for their 2 treatment groups, although these data were not published.’ Marvez-Valls et al. did not docu- ment analgesic use for fever and pain although one would expect that the group with more severe symptoms would self-medicate to a greater extent. That is, a bias against the steroid group would be anticipated, but this represents a limitation of the study.

O’Brien et al. did not evaluate the return-to-work interval for their patients.’ Marvez-Valls et al. did not find a statistical dif- ference between the numbers of days of school or work missed. However, they didn’t report whether the interval of missed schooYwork included the interval of time prior to seeking treatment.6 It would also be valuable to know how many of these inner-city patients were employed or attending school on a daily ba- sis. Patients who seek treatment on a Friday night or Saturday morning would be likely to return to work or school on the fol- lowing Monday, regardless of supplemental steroid therapy.

The finding by Marvez-Valls et al. of a differential response between culture-positive and culture-negative patients reintro- duces the issue of “strep screens” and cultures in the ED. Previous studies have shown that empiric treatment with antibiotics does not hasten the recovery in non- streptococcal pharyngi t i~ .~J~ The data of Marvez-Valls et al. suggest that betamethasone may do little for these patients, as well. Marvez-Valls et al. state that treatment in the ED is necessar- ily empiric because rapid strep tests and cultures are not always readily available.6 This is not the strategy recommended by the In- fectious Diseases Society of

acute pharyngitis.l’ However, strategies in the ED may deviate from those for established patients in an office practice, because patient follow-up is often problematic.

Is it cost-effective to use an imperfect “rapid strep” screen to identify those patients with acute streptococcal pharyngitis most likely to benefit from both antibiotics and IM steroids? The cost of most screens is $4-10, and these screens are specifically for GABHS. However, if early identification of patients with the most severe streptococcal pharyngitis enabled them to re- ceive a medication that would relieve their pain and allow them to return to work and school a full day earlier, the return on in- vestment might be reasonable.

Unfortunately, even in the trial of Marvez-Valls et al.,‘j cultures were not obtained for all patients, and no patient had a repeat culture obtained. Both studies are of inadequate sample size to determine whether the addition of betamethasone would impact the occurrence of suppu- rative and nonsuppurative complications due to streptococcal infection. Also unanswered are the effects of steroids on the interval required to achieve culture neg- ativity, on the development of an- tibodies to the bacteria, and on the rate of recurrence. However, the addition of corticosteroids to the treatment of other infections, such as meningitis,’* croup,13 and Pneumocystis carinii pneu- monia,14 has proven beneficial without introducing significant additional complications, such as worsening of infection, hyper- glycemia, or steroid psychosis. Perhaps the addition of corticosteroids to the treatment of streptococcal pharyngitis will eventually prove to be useful, as well.

Before we jump on the steroid bandwagon, future studies are recommended, in which cultures

America for the treatment of are obtained for all patients both

ACADEMIC EMERGENCY MEDICINE June 1998, Volume 5, Number 6 559

before and after treatment, analgesic use is controlled and doc- umented, and a validated pain scale is consistently used. A trial evaluating oral steroids would also be helpful because oral pred- nisone should be less costly than giving an IM injection and would eliminate the risk of unnecessary needlesticks to the hospital staff. Overall, Marvez-Valls et al. have addressed an issue that affects nearly every household at least once a year. They are to be congratulated.-RITA K. CY- DULKA, MD, Department of Emergency Medicine, MetroHeal th Medical Centel; Cleveland, OH

Keu words. pharyngitis; tonsillitis; streptococci; steroid; betamethasone.

References

1. Vukmir RB. Adult and pediatric pharyngitis: a review. J Emerg Med. 1992; 10:

2. Denny FW, Wannamaker LW, Brink WR, Rammelkamp CH Jr, Custer EA. Landmark article May 13, 1950: Preven- tion of rheumatic fever. Treatment of the preceding streptococcic infection. JAMA.

3. Hosier DM, Craenen JM, Teske DW, Wheller JJ. Resurgence of acute rheumatic fever. Am J Dis Child. 1987; 141:

4. Gerber MA, Tanz RR, Kabat W, e t al. Optical immunoassay test for group A beta-hemolytic streptococcal pharyngi-

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tis. An office-based, multicenter investi- gation. JAMA. 1997; 277:899-903. 6. Shulman ST. Evaluation of penicil- lins, cephalosporins, and macrolides for therapy of streptococcal pharyngitis. Pe- diatrics. 1996; 97(6 Pt 2):955-9. 6. Marvez-Valls EG, Ernst AA, Gray J, Johnson WD. The role of betamethasone in the treatment of acute exudative pharyngitis. Acad Emerg Med. 1998; 5:

7. O’Brien JF, Meade JL, Falk JL. Dex- amethasone as adjuvant therapy for severe acute pharyngitis. Ann Emerg Med.

8. Todd KH, Funk KG, Funk JP, Bonacci R. Clinical significance of reported changes in pain severity. Ann Emerg Med. 1996; 27:485-9. 9. Little P, Gould C, Williamson I, War- ner G, Gantley M, Kinmonth AL. Reat- tendance and complications in a random- ised trial of prescribing strategies for sore throat: the medicalising effect of prescribing antibiotics. Br Med J. 1997;

10. Peterson K, Phillips RS, Soukup J , Komaroff AL, Aronson M. The effect of erythromycin on resolution of symptoms among adults with pharyngitis not caused by group A streptococcus. J Gen Intern Med. 1997; 12:95-101. 11. Bisno AL, Gerber MA, Gwaltney J M Jr, Kaplan EL, Schwartz RH. Diagnosis and management of group A streptococcal pharyngitis: a practice guideline. Clin Infect Dis. 1997; 25574-83. 12. Rockowitz J, Tunkel AR. Bacterial meningitis. Practical guidelines for management. Drugs. 1995; 50:838-53. 13. Geelhoed GC. Croup. Pediatr Pul- monol. 1997; 23:370-4. 14. Martos A, Podzamczer D, Martinez- Lacasa J, Rufi G, Santin M, Gudiol F. Steroids do not enhance the risk of de- veloping tuberculosis or other AIDS-re- lated diseases in HIV-infected patients treated for Pneurnocystis carinii pneu- monia. AIDS. 1995; 9:1037-41.

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1993; 22~212-5.

31~350-2.

I Phar yngi tis :

How Can So Simple a Disease Be So Complex?

I

t is a common public percep- I tion that science has long ago solved the mysteries of diseases as simple as sore throat, and that the forefront of medical science has moved on to more for- midable challenges such as gene therapy, HIV vaccines, and a cure for aging. The public’s faith in medical science could be shaken if it were generally known that pharyngitis is a complex illness about which we still have much to learn. Controversy remains about some of the most

basic issues of microbial etiology, diagnosis, and preferred therapy. The public expects that physicians can reliably diagnose a “strep throat” and prescribe therapy that will not only pre- vent complications, but also quickly relieve the symptoms. In fact, accurately diagnosing the etiology of pharyngitis is diffi- cult, diagnostic testing and culture are problematic, there is disagreement about the antibiotic of choice, and antibiotic therapy of some types of pharyngitis

may not lead to more rapid resolution of symptoms. Although prevention of sequelae is an important goal, it is important to remember that the patient’s primary concern is usually prompt relief of symptoms.

In this issue of Academic Emergency Medicine, Marvez- Valls and colleagues report a study’ demonstrating that treatment with betamethasone is as- sociated with more rapid improvement of symptoms in exudative pharyngitis patients treated with antibiotics. The study provides more evidence that steroids can ameliorate pharyngitis symptoms, but it also raises many questions about how this can best be integrated into pharyngitis treatment strategies.

Many cases of exudative pharyngitis in both adults and children are due to viruses, and some may be due to other bacteria such as chlamydia and my- coplasma. The 40% rate of group A P-hemolytic streptococcus (GABHS) in this study (31/77 patients for whom cultures were detained) is higher than the rate found in most outpatient clinic studies of adults. Although GABHS can account for up to 40% of exudative pharyngitis cases in children,l some studies report GABHS rates of only about 5-10% of cases among a d ~ l t s . ~ , ~ Although the current study found a benefit in the treatment group as a whole and the group with positive cultures, it was not demonstrated for the culture-negative group. It is not clear whether steroids would be beneficial in a population with a lower proportion of cases due to GABHS.

Although acute rheumatic fever (AFtF) occurs in a small proportion of patients with streptococcal pharyngitis, fear of this complication is often what prompts physicians to treat pharyngitis with antibiotics. ARF occurred in 0.4% of children

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Soothing the Savage Throat