Case series of recalcitrant livedoid vasculopathy treated with rivaroxaban

Livedoid vasculopathy (LV) is a chronic disease with a dynamic course, manifesting as recurrent, painful ulceration and scarring of the legs.1 The pathogenesis is not well known, but is thought that dermal thrombosis plays a primary role. Various systemic coagulopathies, including antiphospholipid syndrome, dysproteinaemias, genetic thrombophilic disorders, such as Factor V Leiden (R506Q) mutation, deficiency in protein C or S, hyperhomocysteinaemia, and other disorders of abnormal platelet activation or fibrinolysis have also been observed in patients with LV.2 Case reports predominantly suggest low‐molecular‐weight heparin and warfarin as therapeutic options, based on the underlying pathophysiological phenomena of the vasculopathy with microthrombosis.1 However, no studies have provided a consensus for the optimal LV treatment. The most recent data suggest that the oral Factor X inhibitor rivaroxaban can successfully prevent cutaneous ulcerations and ischaemic pain in patients with LV.3 The objective of our study was to analyse the effectiveness of rivaroxaban for treating LV. Outpatients diagnosed clinically and histologically with LV from April 2014 to June 2015 were assessed for enrolment. Three patients (one man and two women; mean age 42.6 years, range 41–44) were enrolled in the study (Table 1). They all had recalcitrant LV, with the range of disease duration being 1–16 years. None of the patients had any relevant medical history. Several treatments, including aspirin, systemic corticosteroid, pentoxifylline, and immunoglobulins had been used, but the symptoms and skin lesions waxed and waned without complete remission. Blood tests were conducted to exclude other systemic coagulopathies, and the results for all three patients were normal. Summary of clinical findings in patients treated with rivaroxaban for livedoid vasculopathy Summary of clinical findings in patients treated with rivaroxaban for livedoid vasculopathy The three patients were treated with 10 mg of rivaroxaban daily. Treatment responses were evaluated using a visual analogue scale and the total number of ulcers. Rivaroxaban treatment resulted in clinical improvement in all three patients. After 1 week of rivaroxaban treatment, mean pain score decreased from 6.7 to 4.7 and then to 1.3 in 5 weeks (Fig. 1). The three patients had a mean of 11 ulcerated lesions prior to rivaroxaban administration, which disappeared after 2.5 months of treatment. Patients 1 and 3 have now been taking rivaroxaban monotherapy for > 1 year, and so far, patient 1 has maintained complete remission for the longest period (11 months), since being diagnosed with LV 16 years ago (Fig. 2). Ischaemic pain and ulcerations decreased significantly in all three patients during rivaroxaban treatment, thus increasing patient quality of life. No adverse events, such as haemorrhage, were observed. Change in mean ischaemic pain of the three patients with livedoid vasculopathy during treatment, and clinical improvement of patient 3. VAS, visual analogue scale. Patient 1: livedoid vasculopathy (a) before, and (b) 2 and (c) 4 months after rivaroxaban treatment. Rivaroxaban inhibits Factor Xa and Factor Xa/Factor Va complex (prothrombinase) activities, preventing conversion of prothrombin to thrombin.4 Rivaroxaban is tolerated better than heparin and warfarin therapy, which require daily subcutaneous injections and regular blood testing, respectively. Rivaroxaban can be taken at a fixed dose without routine monitoring because the pharmacokinetics and pharmacodynamics are predictable.4 In our study, all three patients ranked rivaroxaban as the most satisfactory treatment they had been given. The study is limited by the small study numbers. In addition, patient 2 also received additional treatment, including 8 mg methylprednisolone and pentoxyfilline. Further randomized controled studies including a long‐term follow up and more cases are needed. A phase II multicenter trial with rivaroxaban for treating LV was recently conducted in Germany.5 Conflict of interest: the authors declare that they have no conflicts of interest.