Steroids as Adjuvant Therapy for Acute Pharyngitis in Ambulatory Patients: A Systematic Review

RADICAL approach to systematic review on steroids as adjuvant therapy for acute pharyngitis

As proposed by the Annals Journal Club, our group of PhD students combining the courses with a traineeship in Family Medicine (“aiotho group Nijmegen”) has used our monthly research meeting to take a RADICAL approach to the systematic review by Korb and colleagues.[1] Sharing the main points of our discussion is one of the final steps in this approach.[2]

We read this article with interest. Although not explicitly suggested as a discussion item by the Annals Journal Club, the abstract of this article attracts the attention with its high quality. It is concise, with a clearly stated aim of the study, a comprehensible presentation of the main study outcomes and critical notes on the implementation in its conclusions. The authors clearly put their main question (What is the additional effect on pain reduction of steroids used in acute pharyngitis in ambulatory patients?) in the light of what is already known. Patients visiting their FP for sore throat bring in pain relief as one of the most important reasons for their visit.[3] Considering pain relief a high value in sore throat sufferers apparently provokes investigating other, less common ways to achieve this. Antibiotics are known to confer relative benefits in the treatment of sore throat (even when throat swabs are negative for Streptococcus), but their benefits are modest; they shorten the duration of symptoms by about sixteen hours overall.[4] However, the review article by Thomas et al. suggests that there are effective alternatives like paracetamol and NSAIDs for symptom relief; maybe more effective than antibiotics although the data are difficult to compare.[5] Steroids are used for symptom relief in other upper airway inflammations, mostly of allergic but also of infectious origin.[6;7] Whether the use of corticosteroids is also effective in ambulatory patients with pharyngitis is what the current systematic review aims to clarify. It is not always possible to differentiate between a pharyngitis and a tonsillitis, in fact one does often come along with the other. Looking at the search algorithm the authors provided in the Appendix, it seems that the results of their search deal with both conditions.

Although publication bias cannot be excluded, we do not criticize this study on the way the authors performed their literature search or study selection. Neither do we have reason to assume substantial researcher bias. As the authors stated, heterogeneity in the studies under review causes a problem in comparing the results. Not only variation in the type, dosage and route of administration of the steroids constitutes this difficulty, also the additional use of analgesics should be taken into account. Inspection of the abstracts of the studies learns that there is variation in the prescribed antibiotics as well. Penicillin, erythromycin, azitromycin and amoxicillin are used among adults in these studies. Most studies use the time interval until “onset of pain relief” and “pain free” as outcome measures, whereas one chooses the pain level on fixed moments after the start. The three pediatric trials all use different scales for pain measurement. Furthermore, some confounders should have been taken into account. The present study does not state which criteria for in- or exclusion were used in the trials. We do not know whether patients with or without comorbidity or fever were equally distributed among the research arms, or if their general conditions were comparable. Neither do we know whether attempts have been made to correct for the initial pain level.

Considering this difficult comparison of the study data, in our view questions can be raised towards the main finding: do steroids really provide additional benefit in symptom reduction in acute pharyngitis? Does publication bias play a role? The findings among the different studies were nonetheless consistent and significant, though small. Does a small effect, aiming at symptom reduction in a generally self-limited condition, justify the prescription of corticosteroids? And what is the meaning of the results for physicians dealing with maybe milder throat infections in family practice? Most of the ambulatory patients in the RCTs went to an emergency department, probably with a more severe pharyngitis. Remarkable is the widespread -painful- intramuscular administration of steroids when pain reduction is the ultimate purpose. We agree with the authors that criticism is appropriate. Furthermore, as antibiotic prescription for pharyngitis is not typical in The Netherlands and other European countries (as the authors and Jochen Cals[8] outlined), the results of the present study are not directly applicable to our situation. Therefore, not only the safety, but also the effectiveness of corticosteroid use without antibiotic coverage remains to be established.

The subgroup analysis offers an opportunity to contemplate the mechanism of interaction between steroids, bacterial throat infection and antibiotics in pharyngitis. Results of three studies indicate that (additional) benefit of corticosteroids can be expected when used in a proven bacterial throat infection under antibiotic coverage. On the other hand, another study found a more distinct benefit of corticosteroids when used in a throat infection with a throat swab negative for Streptococcus antigen, thus without antibiotic treatment.[9] The suggestion raised in the current systematic review that a beneficial effect of steroids on pain outcomes was not found in the group with a proven bacterial infection, was confirmed by checking the article. A fifth study did not add to our understanding. Here, subgroup analyses provided confusing findings: the presence or absence of a bacterial pathogen influences the route of administration for steroids to be successful. Probably its authors are right to state that the number of patients is too small to draw conclusions. But the lack of a plausible pathofysiologic mechanism that can be assumed to explain the additional benefit of steroids should in our view even more justify a hesitant approach in their implementation.

Acknowledgement We would like to thank Wouter van Dijk, Jaap Sijbesma, Hiske van Ravensteijn and Chris van Weel for their dedicated participation in our discussion.

Reference List

(1) Korb K, Scherer M, Chenot JF. Steroids as adjuvant therapy for acute pharyngitis in ambulatory patients: a systematic review. Ann Fam Med 2010 Jan;8(1):58-63.
(2) Stange KC, Miller WL, McLellan LA, et al. Annals Journal Club: It's time to get RADICAL. Ann Fam Med 2006;4(3):196-7. http://annfammed.org/cgi/content/full/4/3/196.
(3) van Driel ML, De Sutter SA, Deveugele M, Peersman W, Butler CC, De Meyere M, et al. Are sore throat patients who hope for antibiotics actually asking for pain relief? Ann Fam Med 2006 Nov;4(6):494-9.
(4) Del Mar CB, Glasziou PP, Spinks AB. Antibiotics for sore throat. Cochrane Database Syst Rev 2006;(4):CD000023.
(5) Thomas M, Del MC, Glasziou P. How effective are treatments other than antibiotics for acute sore throat? Br J Gen Pract 2000 Oct;50(459):817-20.
(6) Ah-See KW, Evans AS. Sinusitis and its management. BMJ 2007 Feb 17;334(7589):358-61.
(7) Mygind N, Andersson M. Topical glucocorticosteroids in rhinitis: clinical aspects. Acta Otolaryngol 2006 Oct;126(10):1022-9.
(8) Cals JWL. Symptomatic treatment for sore throat in family practice. Ann Fam Med 2010;8(1). http://www.annfammed.org/cgi/eletters/8/1/58
(9) Olympia RP, Khine H, Avner JR. Effectiveness of oral dexamethasone in the treatment of moderate to severe pharyngitis in children. Arch Pediatr Adolesc Med 2005 Mar;159(3):278-82.

Competing interests:   None declared