Amantadine-induced livedo reticularis

An 80-year-old woman with a history of vascular parkinsonism, dementia, and orofacial dyskinesia presented to the general medicine clinic with a 2-week history of decreased appetite. The patient had been taking amantadine (100 mg daily) for 6 years. Vital signs were blood pressure 128/81 mm Hg, heart rate 92 beats/min, and temperature 36.2°C. Examination showed orofacial dyskinesia and livedo reticularis on the ears and lower extremities (Figure 1). The patient’s appetite improved after hydration. Because amantadine-induced livedo reticularis can occasionally progress to skin ulceration even when asymptomatic, we discontinued the drug. By day 3, the livedo reticularis on the patient’s ears had resolved (Appendix 1, available at www.cmaj.ca/lookup/doi/10.1503/cmaj.251495/tab-related-content); it was still present in the lower extremities, but only when her legs were in a dependent position. We restarted amantadine because of worsening dyskinesia, but 11 days later, the livedo reticularis recurred on the ears, trunk, and lower extremities, without any improvement in dyskinesia. The rash was unresponsive to warming, and antiphospholipid antibodies (lupus anticoagulant, anticardiolipin, and anti-β2-glycoprotein I), tested for secondary causes of livedo reticularis, were negative. We diagnosed amantadine-induced livedo reticularis and discontinued amantadine permanently. The livedo reticularis had completely resolved at 6-month follow-up.

Figure 1:

(A) Livedo reticularis on the ear and (B) lower extremities of an 80-year-old woman with vascular parkinsonism, dementia, and orofacial dyskinesia.

Amantadine is a well-known cause of livedo reticularis,¹ with an incidence of 7.6% in a recent open-label trial.² Livedo reticularis usually occurs several months to years after initial administration.³ The rash most commonly affects the lower extremities; ^3,4 to our knowledge, ear involvement has not been previously reported, so awareness of this atypical site may facilitate earlier recognition of amantadine-associated livedo reticularis. Depletion of catecholamines at peripheral nerve terminals has been hypothesized to induce venodilation,^4,5 potentially explaining livedo reticularis, its poor response to rewarming, and dependency-related worsening. In our patient, this mechanism could account for the shorter time to recurrence after rechallenge, particularly if re-exposure occurred before catecholamine stores had fully recovered. The decision to continue amantadine should be individualized;³ in this patient, restarting amantadine provided no clinical benefit. The rash typically resolves within 6 months after discontinuation of amantadine.³