RTP was approved in July 2007 in US. In the patient information web site of RTP, it is recommended to apply to clean, dry, hairless, intact skin for every 24 hours at the same time of day and not to apply to skin that is red, irritated, or has cuts.
Clinical experience suggests that the most common form of skin irritation is erythema caused by removal of the patch, which normally resolves after a short period of time(17). In order to reduce the frequency of skin reactions, daily rotation of patch has been recommended. In the IDEAL trial, the signs or symptoms that were most frequently reported as moderate or severe were erythema (redness; 8% for the 9.5 mg/24 h rivastigmine patch, up to 4% for placebo) and pruritus (itching; 7% for the 9.5 mg/24 h rivastigmine patch, up to 3% for placebo)(16).
Drugs may elicit a considerable variety of clinical signs, often affecting the skin and the mucous membranes. The most common are maculopapular exanthemas and urticaria, more rarely pustules, vasculitic lesions, and lichenoid lesions may also be observed. Although these side effects are related with systemic administration of drugs, topical drugs may also cause side effects.
Topical drug applications are develeoping by technologic developments. Patch applications are called transdermal therapeutic system (TTS). As TTS supply many advantages like drug delivery in a rate-controlled manner, sustained plasma concentrations and avoiding first pass metabolism(11). There TTS forms of many drugs such as hormones, nicotine, nitroglycerine and analgesics. By the increased use of this systems new drug reactions related to application site are reported(10,11,14,15,18). TTS-treatment may induce contact allergies to pharmaceutic agents, as has already been described in other observations on allergies to haptens(6). Also, TTSs can induce sensitisation in many ways. As long-time occlusion, irritation and repeated application of the allergen to the same skin location will maximize the development of hypersensitivy reaction. The mechanism of IgE-mediated reactions is well investigated, but the mechanisms of T-cell-mediated drug hypersensitivity are not well understood.
During the RTP treatment, our patient was also under the treatment of metoprolol, lisinopril and amlodipine for hypertension. No interaction with metoprolol, amlodipine or lisinopril has been reported for RTP. However, erythema multiforme associated with metoprolol succinate and amlodipine therapies and angioedema and erythroderma associated with lisinopril therapy have been reported(1,2,3,9). Because of the potential skin side effects of these agents, it is controversial whether the skin lesions of our patient are related with antihypertensive treatment and/or RTP. It can also be argued that these antihypertensive agents may have caused hypersensitization to RTP. We think that histological and morphological characteristics, locations and the time of onset of the patient's lesions are suggestive for the skin reaction secondary to RTP. Although the lesions are not limited to the sites to where the RTP was applied, this may be the result of systemic effect of rivastigmine due to a specific sensitization in our patient. Grieco et al. have reported a 75-year-old male patient with recurrent lesions in previous application skin sites who was under the treatment of RTP(8). They suggested this clinical condition as a specific sensitization to RTP.
The characteristic feature that differs our case from the previously reported RTP-induced skin reactions is that in our patient, the eruptions were occurred not only in the application sites but also in the non-application sites which were not under the direct effect of RTP. This condition also supports the specific sensitization to RTP and generalization of sensitization by continued contact with the antigen.
Although the data supports a favourable skin tolerability profile for the RTP, physicians must be avare of possible unexpected skin reactions after the application. To our knowledge, this is the first case of RTP induced vasculitic skin eruption which was located both in application and non-application sites.
Received by: 05 May 2011
Accepted: 03 August 2011
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