Acute pharyngitis, characterized by inflammation of the pharynx and surrounding lymphoid tissue, is a common affliction, accounting for up to 5% of pediatric office visits and 40 million annual adult visits to medical facilities nationwide. It is a frequent presenting complaint among emergency department patients. Although most cases produce only mild to moderate discomfort and minimal systemic effects, acute pharyngitis can be incapacitating with prostration and inability to swallow. The current standard approach to therapy includes antibiotics when indicated, analgesics, and antipyretics. Standard antibiotic therapy is aimed at treating Streptococcus to prevent the immunologic sequelae of rheumatic fever and glomerulonephritis, as well as the local suppurative complications of peritonsillar and retropharyngeal abscess. ^1-4 However, only 10% to 30% of adolescent and adult pharyngitis appears to be streptococcal. ^4-6 Present standard therapy fails to attack aggressively the inflammatory component of this syndrome.

The painful symptoms of acute pharyngitis result from upper airway inflammation. Accordingly, we hypothesized that treatment of this inflammatory component might provide symptomatic relief. in a recent study, a single large dose of corticosteroid reduced the overall severity of moderate to severe croup in the first 12 hours. ⁷ Early and aggressive use of steroids has been shown to be effective in the treatment of severe bronchospasm in reactive air-disease, ^8,9 where inflammation is increasingly recognized as an important component. Glucocorticoids are potent anti-inflammatory agents that have been used successfully to modulate the inflammatory response to both infection and immunologically mediated diseases. Parenteral administration of a single large dose of glucocorticoids is well tolerated without substantial ill effects in most patients. ¹⁰ Anecdotal recommendations for use of steroid therapy in acute pharyngitis appear in the literature, but formal studies are lacking. We developed a prospective human study to evaluate the efficacy of a single IM dose of a long-acting corticosteroid as an adjuvant in the treatment of severe, acute pharyngitis.

During a five-month period (November 1990 through March 1991), all patients presenting to our urban, community hospital ED with a complaint of "sore throat" were considered for inclusion in the study. Entrance criteria included age of 12 to 65 years, visible tonsillar exudate, severe odynophagia or dysphagia, and either fever or cervical adenopathy. Patients with history of cancer, diabetes mellitus, AIDS, recent steroid use or intolerance to steroids, suspected peritonsillar abscess, oral thrush, or ulcerative pharyngitis were excluded.

All patients gave informed consent, and in the case of minors, parental consent was obtained as well. The protocol was approved by our hospital institutional review board.

Patients meeting entrance criteria and giving consent were randomized prospectively by random number table to treatment with either 10 mg dexamethasone IM (10 mg/mL or 1 mL saline placebo IM. Syringes for injection were prepared in the pharmacy and were visually indistinguishable, so that physicians, nurses, and patients were blinded to the study drug. All patients were supplied with a ten-day course of either 500 mg Pen-VK or 333 mg erythromycin base, both to be taken three times daily with food. Antibiotic choice was at the discretion of the treating physician. No throat cultures were performed nor were any other attempts made to differentiate pathogens.

At enrollment, patients graded their initial pain on a visual-analog scale 15 cm long and scored from 0 to 3.0 in 0.5-cm increments, indicating severity of pain. All patients were weighed, and a standardized questionnaire that included incidence of vomiting and/or diarrhea as well as duration of symptoms was completed. A thorough physical examination was completed on each patient. Follow-up was obtained by the authors using a standardized questionnaire, through a combination of telephone calls, return visits, and mail-in questionnaires, to ascertain patients' response to treatment, pain medication use, and incidence of side effects.

Statistical analysis was performed using two-tailed Student's t-test or Wilcoxin rank sum test for interval data and c ² testing for nominal data. P < .05 was considered significant.

Fifty-eight patients were enrolled in the study, with 31 randomized to the steroid group and 27 to the control group. Twenty-four-hour follow-up was obtained on 51 patients (26 steroid, 25 control). Data are summarized (Table). At entry, the groups were indistinguishable with regard to age, sex, weight, antibiotic assignment, analgesic use, or initial pain score.

Compared with baseline, patients in both groups exhibited significant improvement in pain score at 24 hours (P < .05). Steroid-treated patients displayed a greater degree of pain relief than those receiving placebo as evidenced by a reduction in pain score by 1.8 ± 0.8 in the steroid group compared with 1.2 ± 0.9 in the placebo group (P < .05). Time to onset of pain relief was also faster in steroid-treated patients who demonstrated relief beginning at 6.3 ± 5.3 hours, compared with 12.4 ± 8.5 hours in patients receiving placebo (P < .01).

Twenty-six patients were available for reevaluation at seven days (13 in each group). The time required for patients to become pain-free was evaluated in this sample and indicated that steroid-treated patients were free of pain sooner than placebo-treated patients (13.0 ± 11.4 hours versus 35.4 ± 17.9 hours, respectively; P <.02).

No side effects attributable to the dexamethasone were observed. Analgesic use, including type and strength of pain medication, number of doses, and pill counts, did not differ between the steroid and placebo groups. Gastrointestinal disturbances (nausea, vomiting, or diarrhea) were reported by nine of 19 (47%) patients receiving erythromycin compared with only four of 32 (12 %) patients receiving penicillin (P < .01).

Antibiotic therapy for acute exudative pharyngitis fails to provide prompt symptomatic relief. This is not surprising because most of these infections are nonbacterial in etiology, ⁵ and the acute symptoms result from inflammation that responds slowly to antibiotic treatment even in cases with a bacterial etiology.⁴ Indeed, large populations are required to demonstrate that antibiotic treatment shortens the duration of symptoms from bacterial pharyngitis.

Table.

The current study attempted to evaluate the effectiveness of corticosteroids in ameliorating the inflammatory component of acute exudative pharyngitis. More rapid and more potent pain relief was demonstrated in patients treated with corticosteroids. The observed differences between groups were clinically important. Patients treated with dexamethasone felt better faster and were free of pain on average 20 hours more rapidly than those who received a placebo. The most effective corticosteroid agent and dosing regimen are not known. Dexamethasone was chosen for this study because it has a biologic half-life of 36 to 72 hours ¹⁰ and high potency. The 10-mg dose provides elevated corticosteroid levels above baseline for five to seven days and provides a physiologic taper by drug metabolism. ¹⁰ Our sample size was too small to evaluate a dose response curve based on patient weight.

We chose to study patients with visible exudate, along with the clinical criteria of severe odynophagia or dysphagia, and fever or cervical adenopathy, to define a population that clearly had severe acute pharyngitis. This is not to imply that patients lacking some of these clinical criteria would not benefit from corticosteroids as an adjuvant in their treatment. However, a larger study with more open inclusion criteria would be necessary before extrapolating the results of our present investigation.

The patients in the current trial were not evaluated to determine the etiology of their pharyngitis. Cultures, as well as acute and convalescent antibody titers, may be useful to determine if some particular etiologies respond more (or less) favorably to corticosteroids. Post-treatment cultures also may be important to ensure that single-dose corticosteroids do not interfere with clearance of bacterial pathogens. A trial of orally administered corticosteroids seems reasonable to determine if this route achieves similar efficacy as parenteral therapy. Finally, although no complications were observed in our study, a larger sample population is needed to assess the impact of corticosteroids on the incidence of local infectious complications of pharyngitis such as peritonsillar abscess.

IM dexamethasone appears effective as an adjuvant to antibiotic therapy in the treatment of acute, severe exudative pharyngitis in that it reduces the duration and severity of pain in these patients. Further studies are indicated to evaluate various dosage regimens as well as to assess the effects of steroids on the incidence of culture-proven cures and potential complications.