Systemic allergic reaction due to intranasal budesonide

To the Editor,

Topical corticosteroids are frequently recognised as a cause of allergic contact dermatitis but in only few cases the administration of intranasal corticosteroids has been reported as the cause of systemic allergic reaction.^1–6

A 34-year-old non-atopic woman started treatment with nasal budesonide for a common cold. On the second day of treatment the patient developed, 8 h after the administration of 256 mcg (two puff per nostril each time), lips, nose, and eyelid angioedema and pruritic urticarial papules in face, chest and arms. The symptoms remitted gradually over 3–4 days after treatment with hydroxyzine. Previously the patient had tolerated nasal budesonide without adverse effects.

Prick and intradermal test were performed with a battery of corticosteroids (hydrocortisone, methylprednisolone, budesonide, triamcinolone, deflazacort and dexamethasone) (Table 1) with the excipients carboxymethylcellulose, Tween 80, and benzylalcohol. Prick tests were considered positive when a wheal of more than 3 mm in diameter was present 15 min later. When prick test responses were negative 0.02–0.05 ml of the reagent solution was injected intradermally. Readings were made 20 min after injection. Results were considered positive when wheal and erythema greater than 5 mm were present. Positive control for prick and intradermal tests were done with histamine, at 10 mg/ml and 1 mg/ml respectively. Sterile 0.9% saline was used as a negative control. Ten non-atopic and ten atopic subjects were also tested as a control.

Table 1.

A, B, C: Groups of the Coopman classification.

Corticosteroids	Prick test	Intradermal test (1/100)	Intradermal test (1/10)
Hydrocortisone (A)	100 mg/ml	1 mg/ml	10 mg/ml
Methylprednisolone (A)	40 mg/ml	0.4 mg/ml	4 mg/ml
Budesonide (B)	0.25 mg/ml	0.0025 mg/ml	0.025 mg/ml
Triamcinolone (B)	40 mg/ml	0.4 mg/ml	4 mg/ml
Dexamethasone (C)	4 mg/ml	0.04 mg/ml	0.4 mg/ml
Deflazacort (B)	30 mg/ml	–	–

Patch tests conveyed in petrolatum were performed with the same battery of corticosteroids. The patches were placed on normal skin on the patient's back and removed after 2 days. Visual reading was carried out on day 2, day 3, and on day 7. Reactions were scored according to the International Contact Dermatitis Research Group.⁷

Single-blind, placebo-controlled tests with other corticosteroids were performed to evaluate a possible cross-reactivity.

Prick tests with corticosteroids battery and excipients were negative. Intradermal test with budesonide was positive at 48 h and negative with the rest of tested corticosteroids and excipients. In all control subjects, prick and intradermal tests were negative.

Patch tests were positive only with budesonide at 48 h (day 2) showed a +++ reaction and persisted on day 3 (+++) and on day 7 (++).

Single-blind, placebo-controlled challenge tests with intravenous hydrocortisone and deflazacort (oral) were performed with good tolerance.

We report a case of systemic allergic reaction after the administration of intranasal budesonide confirmed by positive results in patch and intradermal test and without cross-reactivity with others corticosteroids. The prevalence of corticosteroid-induced allergic contact dermatitis ranges from 0.2% to 6% according to the different patient series. In only few cases the administration of intranasal corticosteroids has been reported as the cause of hypersensitivity systemic symptoms and as in our case report, budesonide is the most commonly corticosteroid implicated.⁸ On the basis of stereochemistry, corticosteroids are classified into five groups: A, B, C, D1, and D2. Substances from the same group are thought to cross-react although this is not universally accepted.^9,10 In particular, corticosteroids in group B (such as budesonide) have been shown to cross-react not only with members of their own group but also with the corticosteroids in group D.^8–10 Our patient tolerated hydrocortisone (group A) and deflazacort (group B) without problems.

Corticosteroid allergy has very important therapeutic consequences; therefore it is necessary to offer a safe alternative to these patients demonstrating tolerance to other corticosteroids.