CLINICAL CASE
Skin reactions to clonidine: not just a local problem. Case report
M. A. Crivellaro, P. Bonadonna, A. R. Dama, G. E. Senna and G. Passalacqua*
Servizio Allergologico. Ospedale Civile Maggiore di Verona. Verona. *Allergy & Respiratory Diseases. Dept. of Internal Medicine. Genoa University. Italy.
Correspondence:
Giovanni Passalacqua, MD
Allergy & Respiratory Diseases,
Dpt. Internal Medicine
Pad. Maragliano, L.go R. Benzi 10
16132 Genoa. Italy
Hypertension is the most frequent disease and a proportionally great number of antihypertensive drugs is commercially available for its treatment. Therefore, it is not surprising that allergic reactions due to these drugs may occur and that allergists have sometimes to face such a problem; for instance, ACE-inhibitors are known to be responsible for recurrent angioedema in adult and elderly people (1). We report herein a case of skin reaction due to both topical and systemic administration of clonidine, a widely used antihypertensive drug.
We describe a 47 year old female, who had a 7-year history of moderate hypertension. Several unsatisfactory attempts to control blood pressure were made with diuretics, betablockers and calcium antagonists alone or in combination. In 1997, a clonidine transdermal therapeutic system (Adesipress TTS-2TM) was prescribed. After 2 months of treatment, a pruritic erythematous vesiculation (eczema-like) appeared at the sites of application. Because of the adverse reaction and the substantial uneffectiveness, the treatment was interrupted. One year later, a new attempt with oral clonidine (1 capsule 0.3 mg once daily) was made. Since the 3rd day a generalized maculopapular rash, promptly exacerbating after each dose, appeared and the treatment had to be stopped. At the beginning of 1999 the patient needed emergency care for symptomatic hypertension: diuretics and calcium antagonists were given without any result. Therefore, intravenous clonidine 0.150 mg was administered: this latter treatment promptly reduced blood pressure, but it was followed within about 30 minutes by a severe generalized maculo-papular reaction, requiring systemic steroids and antihistamines.
After this latter episode, the patient was referred to our center. A patch test was then performed. It resulted negative for the contact allergy standard panel and for the clonidine transdermic system support (without active principle), whereas a strong positive reaction was elicited (++D2/++D3) by the transdermal commercial preparation containing clonidine (Fig. 1). A provocation test with systemic clonidine was judged neither ethical nor necessary, since the unequivocal clinical documentation.
Figure 1.--Results of the patch test (48 hrs) with the transdermal system either containing or not the active principle (clonidine).
Clonidine is a weak sensitizer in animals (2), nevertheless occlusion and prolonged skin contact may induce a delayed hypersensitivity (3). In fact, transdermic clonidine was reported to be very frequently (14-38%) responsible for contact allergic dermatitis (4). This may be due to a sensitizing complex (clonidine plus acetaldehyde) formed during manifacturing (5). On the contrary, contact dermatitis from excipients of transdermal systems was reported rarely (6). In the case described above, clonidine seemed to be the only responsible, since reactions occurred following local, oral and intravenous administration. Noteworthy and at variance with the majority of reports (6, 7) in our patient clonidine evoked the same reactions, irrespective of the administration route. Therefore, this case cannot be simply defined as "contact dermatitis" to clonidine and more complex mechanisms seem to be involved. Our findings support that patch testing to both clonidine and the components of the transdermal system are useful in the investigation of local reactions to clonidine. Moreover, oral or parentheral therapy with clonidine should be approached with caution in patients showing local reactions and positive patch tests to clonidine.
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