Eur Arch Otorhinolaryngol (1991) 248 : 246-249

European Archives of

Oto-RhinoLaryngology © Sprmger-Verlag 1991

Clinical efficacy of budesonide in the treatment of eczematous external otitis S. Jacobsson 1, G. Karlsson 1, P. Rign6r 2, E. Sanner 2, and C. Schrewelius 3 lENT Department, M61ndal Hospital, M61ndal, Sweden 2ENT Department, Sociala Huset, G6teborg, Sweden 3Medical Department, Astra-Draco, Lund, Sweden Received July 27, 1990 / Accepted August 8, 1990

Summary. Sixty patients with mild to m o d e r a t e forms of eczematous otitis externa were treated with budesonide and placebo in a double-blind controlled study using parallel groups. Each treatment period was preceded by otomicroscopic examination and thorough cleaning of the ear canal. The symptoms and signs were assessed with a score system ranging from 0 (no symptoms/signs) to 3 (severe symptoms/signs). Budesonide treatment was associated with a reduction in severity of all symptoms recorded and a m a r k e d i m p r o v e m e n t in erythema, swelling and discharge. Mechanical cleaning of the ear canal and placebo was not a sufficient treatment for this group of patients.

Key words: Otitis externa - E c z e m a - Budesonide

The aim of this study was to compare the efficacy of the anti-inflammatory topical steroid budesonide (in a daily dose of 0.3 mg/ear) and placebo in the treatment of mild to m o d e r a t e forms of external otitis.

Patients and methods Sixty outpatients were entered into the trial, 17 men and 43 women. The age range was 16-82 years with a mean of 47 years of age. Only mild to moderate forms of otitis externa were included. Patients with totally occluded ear canals, furunculosis or fungal infections were excluded, as well as patients with fever, perichondritis, perforated ear drums or infections secondary to otitis media. The study was carried out as a double-blind placebo controlled study using parallel groups. The patients were allocated at random to active or placebo treatment. The patients were given the contents of one single-dose pipette (0.1 ml) three times daily in one or both ears for 7 days. Before the start of treatment, the ear canal

Introduction Otitis externa is not a uniform disease. The diagnosis comprises such different clinical entities as eczema and bacterial and fungal infections. T h e r e is often a combination of eczema and infection [1]. Predisposing factors are genetic (e.g., tendency to eczema, excessive wax formation), environmental (e.g., heat, humidity and swimming), traumatic (e.g., excessive cleaning of the ear canal, the use of hairpins, matches, etc. to scratch the ears), and infective (bacteria, virus or fungi) [2]. The major symptoms are itching, pain and discharge f r o m the ear. The clinical findings are e r y t h e m a of the ear canal with or without myringitis and different degrees of swelling of the ear canal with or without discharge. A d e q u a t e treatment must include mechanical (manual) aural cleaning, after which some form of topical anti-inflammatory, antibacterial or antifungal aural medications can be used [3]. Offprint requests to: S.Jacobsson, ENT Department, Mrlndal

Hospital, 431 80 Mrlndal, Sweden

Table 1. Patients discontinuing treatment Sex

Age (years)

No. of days with medication

Reason

Budesonide F 51

3

Persistent itching and pain in ear (lack of efficacy)

F

36

4

F

78

0

Subjective hearing loss and pain in left ear Drop-out for personal reasons

Placebo F

50

4

F

28

1

F

24

1

Sticky feeling in ear, headache and fever Pain in temporo-mandibular joint Patient seen twice but took no medication

S. Jacobsson et al.: Budesonide in the treatment of eczematous external otitis was suctioned thoroughly, removing wax, peeling skin and detritus. Dosage of the budesonide suspension was 1.0mg/ml and was administered as 0.1 ml doses in the single-dose pipettes. The corresponding placebo was given in a similar dose. All pipettes were placed in envelopes of identical appearance in order to maintain blindness for both the investigators and the patients. The symptoms of itching, discharge, pain and hearing loss were assessed during clinic visits and were also evaluated by the patients in daily record cards in accordance with the score system: 0 = no

symptoms; 1 = mild symptoms, present but not troublesome; 2 = moderate symptoms, discomfort experienced; 3 = severe symptoms, considerable discomfort experienced. Otomicroscopic examination was performed at the time of each patient's entry into the study and after 10 days. Any erythema, swelling of the ear canal, myringitis and discharge were observed and then assessed with the score system. Any adverse experience was reported by the patient in the daily record card and by the investigator in a case record form. Information about the seriousness, date of onset, duration, maximum intensity, action taken regarding the study drug and outcome were recorded on an adverse experience report. The World Health Organization's adverse reaction terminology was used for classification of the adverse experiences encountered. The study was conducted according to the Declaration of Helsinki and included approval from the regional ethics committee. The descriptive statistics used individual ears. For patients with bilateral external otitis, the most affected ear was used in the statistical analysis. Standard non-paired statistical methods were used; i.e., t-test, Wilcoxon test and chi-square tests.

Table 2. Demographics of enrolled patients with otitis externa (OE) Budesonide

Placebo

Total no. of patients enrolled

30

30

Sex ratio (male/female)

8/22

9/21

Age (years)

Mean Range

50 16-82

44 18-80

Weight (kg)

Mean Range

66 49-81

67 50-96

Height (cm)

Mean Range

169.7 158-185

170.1 150-193

Ethnic group (no.)

Caucasian

30

30

Duration of OE (years)

Mean Range

12.4 0-52

7.6 0-25

I T C H I N G IN W O R S E

247

Results

Sixty patients were enrolled into the study. Six patients discontinued For various reasons (Table 1). The treatment groups were compared with regard to age, weight, height, race, sex and duration of otitis externa (Table 2). Fifty of the patients enrolled in the study (25 budesonide and 25 placebo patients) had the habit of picking their ears. Thirteen patients (7 budesonide and 6 placebo patients) had a history of eczema or seborrheic dermatitis.

EAR

DISCHARGE

Mean score

FROM WORSE

EAR

Mean score -Budesonide . . . . . . . . . Placebo

~Budesonide . . . . . . . . . Placebo

1.5

,? I

I

2

I

I

4 Day number

I

I

6

H E A R I N G L O S S IN W O R S E Mean score .8

8

"I,

0 0

2

4 Day number

EAR

P A I N IN W O R S E

6

EAR

Mean score --Budesonide . . . . . . . . . Placebo

- Budesonide . . . . . . . . . Placebo

.8

.6

.2

0

I

0

2

I

I

4 Day number

Fig. 1. Diaries (symptom scores)

I

1

6

I

I

0 0

I

2

r

I

4 Day number

I

L

6

I

248

S. Jacobsson et al.: Budesonide in the treatment of eczematous external otitis

Table 3. Adverse experiences reported by the patient or observed

by the investigators during the study period No. of patients with

adverse experiences Budesonide

Placebo

External auditory canal disorders Sticky ear canal Increased amount of earwax Discomfort with application Itching following application Blood-tinged aural discharge Bad smell from ear canal

5 1 1 1 0a 1 1

6 2 1 1 2 0 0

CNS/psychiatric disorders Headache Dizziness

4 3 1

5 4 1

Hearing disorders Tinnitus

2 2

0 0

Gastro-intestinal system disorders Vomiting

0 0

1 1

Others Tenderness next to ear/temporomandibular joint dysfunction Fever Bad general condition

3

2

2 0 1

1 1 0

No. of patients entered

30

30

No. of patients with adverse experience

10

9

% of patients with adverse experience

30

27

Total number of adverse experience

14

14

a First days only of treatment About half of the patients had no definitely "worse" ear. For these patients the highest score recorded in the left and right ears was used at each visit. For the remaining patients there was a definitely worse ear at the first visit and this ear was assessed for the purpose of the study. According to the scoring system used, the mean severity was "mild" or less for most symptoms in both groups. Patients randomized to receive budesonide had on average more symptoms from pain compared to patients randomized to placebo. Itching was the symptom which gave the highest mean score in both treatment groups. The most common otomicroscopic finding at the initial examination was erythema and it was of similar severity in both groups. Budesonide treatment was associated with a reduction in the severity of all otitis externa symptoms recorded (Fig. 1). The mean reduction of the symptom scores between day 1 and day 7 ranged from 0.32 to 1.08, which was statistically significant concerning itching, discharge and hearing loss (P = 0.002 to P = 0.015) but not for pain ( P = 0.074). The mean change in the scores for the severity of symptoms in the placebo group ranged from an increase of 0.19 to a reduction of 0.23, which was n o t statistically significant.

When the scores of the four otitis externa symptoms were added to form a "combined" symptom score, a similar result was found: i.e., a statistically significant reduction (2.29) in the budesonide group (P = 0.001) and a small (0.23) but not significant reduction in the placebo group. We then determined the differences between symptom scores in the two treatment groups from day 1 to day 7. The results consistently favored the budesonide treatment. The mean differences in reducing symptoms ranged from 0.09 to 0.89. These differences were statistically significant concerning itching (P = 0.002) and discharge (P = 0.003). Otomicroscopic examinations revealed a greater reduction in the symptom scores for erythema, discharge, myringitis and swelling of the ear canal in the budesonide group as compared with the placebo group. Statistically significant differences in favor of budesonide were found for erythema (P = 0.005) and discharge (P = 0.002) when using the Wilcoxon-Mann-Whitney test, stratified by entry scores for each symptom. All adverse events during the course of the study were reported. Most of these events (Table 3) were regarded as unrelated to the treatment. This assumption was based on the patients' remarks in their diary cards.

Discussion

Local steroids are often the treatment of choice for eczematous external otitis but must always be preceded by a thorough cleaning of the ear canal and adequate visualization of the tympanic membrane. Treatment without properly cleaning will not only be insufficient but will also include the risk of missing serious ear disease [3]. However, our present investigation has shown that manual aural toilet is not sufficient treatment alone but some sort of anti-inflammatory, antibacterial or antifungal drops must be used. As only mild to moderate forms of external otitis were included and furunculosis and fungal infections were excluded a pure anti-inflammatory drug was considered to be sufficient for our study. The topical steroid budesonide has a documented effect in treating nasal allergy and asthma but has not been used previously for the treatment of external otitis. It was therefore of interest to us to determine its effect on this disease. A double-blind crossover clinical comparison with placebo was therefore carried out in 60 patients, using budesonide ear drops in 0.1 ml single-dose pipettes ( l m g / m l ) t.i.d, and matching placebo. Most of the patients in the present study had experienced external otitis several times before and were familiar with different types of ear drops. However, they had never used single-dose pipettes before, and this was a new and generally positive experience. Several patients made spontaneous notes in their daily record cards concerning the practical administration form compared to other types of ear drops. Still, other patients considered the content too small, an opinion which we are inclined to support. It is probably better to use 0.2 ml pipettes in order to achieve a more accurate and safe contact between the steroid and the affected ear canal wall.

S. Jacobsson et al. : Budesonide in the treatment of eczematous external otitis

In spite of the small dose of steroid given a marked improvement was seen in the budesonide group concerning erythema, swelling and discharge (statistically significant for controlling erythema and discharge). Budesonide treatment compared to placebo was also associated with a reduction in the severity of all symptoms recorded. The adverse reactions were few and their nature negligible. Present findings showed the topical steroid budesonide to be a good alternative for treating mild to moderate forms of external otitis. Further clinical trials are re-

249

quired, however, to make a fair comparison with other types of steroid ear drops. References 1. Buch-Rasmussen A (1979) Hydrocortisone alcoholic solution in eczematous external otitis. J Int Med Res 7:449-451 2. Goodman WS, Middleton WC (1984) The management of chronic external otitis. J Otolaryngol 13: 3 : 183-186 3. Hicks SC (1983) Otitis externa: are we giving adequate care? J R Coil G e n Pract 33 : 581-583

Clinical efficacy of budesonide in the treatment of eczematous external otitis.

Sixty patients with mild to moderate forms of eczematous otitis externa were treated with budesonide and placebo in a double-blind controlled study us...
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