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Perineural granulomatous inflammation: a potential harbinger of perineural invasion in cutaneous squamous cell carcinoma

systemic steroids, thus prolonging time to anticoagulation treatment. Once the diagnosis of LV is confirmed, continuous prevention of the occurrence of new lesions and pain reduction are the paramount therapeutic goals. Treatment is challenging and case reports from the literature suggest predominantly low-molecular-weight heparin and warfarin as therapeutic options. However, due to the chronicity of LV, patients complain about daily subcutaneous injections of heparin, and rural living may impede regular testing in warfarin therapy. Recently, rivaroxaban, an oral direct inhibitor of factor Xa, has been proven to be superior in thromboprophylaxis to enoxaparin in the RECORD (Regulation of Coagulation in Orthopedic Surgery to Prevent Deep Venous Thrombosis and Pulmonary Embolism) trials. We therefore hypothesized that in LV this oral drug should prevent occurrence of further microcapillary thrombosis, ulceration and scarring, thus reducing pain and increasing patients’ quality of life. Here, we report the clinical and subjective outcomes of three patients with biopsy-confirmed diagnosis of active LV treated with a daily dose of rivaroxaban 10 mg. The patients were all female, aged 15–24 years and had suffered from recalcitrant LV for at least 3 years. All patients had elevated levels of lipoprotein(a), an independent risk factor for cardiovascular events recently associated with LV. Apart from LV, the patients were healthy and no concomitant medication was given. Reduction of ischaemic pain – the earliest marker of disease activity – as assessed by a visual analogue scale was the primary endpoint. Secondary endpoints included incidence of new ulcerations and the results of biochemical monitoring (liver enzymes, full blood count) as a measure of safety during rivaroxaban treatment. Both occurrence of pain and skin infarctions were significantly reduced by week 4 of rivaroxaban treatment (Fig. 1c,d). Of particular note, pain was already significantly reduced within 1 week of treatment, indicating a successful prevention of further cutaneous ischaemia (Fig. 1b). There were no adverse events, especially with regard to haemorrhages, and all patients ranked rivaroxaban as more tolerable than previous treatments. All patients therefore continued rivaroxaban therapy and, as of now (up to 1 year of therapy), there has been no recurrence of LV in any patient under therapy. In summary, our observations indicate a new therapeutic role for direct factor Xa antagonism, as rivaroxaban successfully prevents cutaneous infarctions and ulcerations in patients with LV, showing a prompt and continuous response. Owing to the limited number of patients enrolled and the open-label nature of the study, confirmatory trials are required.