[Cutaneous necrosis at apomorphine injection points]. / Nécroses cutanées localisées aux points d'injection d'apomorphine.

BACKGROUND: Apomorphine is a specific dopaminergic agonist used in the treatment of severe fluctuations of Parkinson's disease, particularly in patients on L-dopa. The drug is usually given subcutaneously, either as several daily injections or via a continuous subcutaneous delivery system. We describe two cases of localized cutaneous necrosis at the points of subcutaneous apomorphine injection. OBSERVATIONS: Two male patients presenting Parkinson's disease were treated by subcutaneous injection of apomorphine. One month later, asymptomatic necrotic lesions measuring from 2 to 5 mm appeared at the injection sites. Complete blood count, standard and advanced coagulation studies and screening tests were normal. One patient had taken acetylsalicylic acid. A skin biopsy showed normal epidermis, oedema of the papillary dermis with perivascular lymphocytic infiltrates, reticular dermal infiltrate with neutrophils, and necrosis of the reticular dermis and hypodermis in one patient, and in the other, necrosis in the epidermis, dermis, hypodermis and skin appendages, with dermal leucocytoclastic vasculitis and cytosteatonecrosis. Due to the severity of necrosis, apomorphine was stopped, resulting in improvement of skin lesions in one patient. In the second, due to the localized nature of the lesions and the improvement in the patient's quality of life since the introduction of apomorphine, the drug was continued, resulting in the appearance of new lesions, which continued to be limited to the injection sites. COMMENTS: To our knowledge, this is the first description of biopsy-proven apomorphine-induced localized skin necrosis. Reported cutaneous side effects of the drug include pruritic subcutaneous nodules corresponding to panniculitis with large numbers of eosinophils, allergic contact dermatitis, pigmented nodules resulting from oxidation of apomorphine, and nonspecific rashes. Cutaneous necrosis at injection sites could arise through various mechanisms: localized vasoconstriction ("dopamine necrosis"), direct toxicity of the injected drug, local manifestations of pre-existent coagulation disorders, immunological mechanisms or poor administration technique involving intravascular injection. The specific pharmacodynamic properties of apomorphine rule out vasomotor phenomena in the aetiology of such necrosis. Screening tests for thrombophilia were negative in the first patient. Although the underlying mechanism of this form of necrosis remains unknown, an immunological mechanism of the immune complex type could be considered aetiologically relevant on histological grounds due to the presence of vasculitis in one of the two patients.

[Bioavailability evaluation of dermocorticoids using differential infrared thermography]. / Evaluation de la biodisponibilité des dermocorticoïdes par thermographie infrarouge différentielle.

INTRODUCTION: Differential infrared thermography, proposed in this paper, is a technique based on direct observations of infrared radiations emitted by the skin. The evolution of cutaneous temperature caused by the application of dermocorticoids on healthy skin demonstrates their pharmaco-dynamic properties. MATERIALS AND METHODS: The cutaneous thermal image was recorded in real time. Image processing using subtraction function readily provided differential infrared thermographic analysis of the effects. Four activity classes of dermocorticoids had been applied on healthy skin. A test immediately carried out after dermocorticoid application on skin without occlusion and the classical skin blanching-test have been performed. RESULTS: Temperature differences between the dermocorticoids were detected within the first three hours after the application on the skin without occlusion. The dermocorticoid class II cream formulation under study induced a decrease in temperature more pronounced than the others dermocorticoids. The skin-blanching effect was more noticeable for dermocorticoids class I and II and it was not detected for class IV. DISCUSSION: Subtraction thermograms provide a means of differential imaging. Evolutive temperature differences subsequent to unique application without dermocorticoid occlusion are evidenced during a short duration (the first three hours). This may correspond to efficacy differences while classical tests of vasoconstriction analyse the cutaneous blanching induced after the 6th hour. Concerning the skin-blanching effect, results of this first investigation are not sufficient for a precise qualitative and quantitative interpretation. The main interest of differential infrared thermography is to be quantitative, without contact, continuous in real time. Differential infrared thermography is more sensitive than classical thermography. It allowed an objective evolution survey for dermocorticoids.