Acta Dermato-Venereologica 98-9CompleteContent | Page 8

842 CLINICAL REPORT Livedoid Vasculopathy: A French Observational Study Including Therapeutic Options Emma GARDETTE 1 , Philippe MOGUELET 2 , Jean David BOUAZIZ 3 , Dan LIPSKER 4 , Olivier DEREURE 5 , François LE PELLETIER 6 , Catherine LOK 7 , Thierry MAISONOBE 8 , Didier BESSIS 5 , Jacqueline CONARD 9 , Camille FRANCES 1 and Stéphane BARETE 10,11 Departments of Dermatology: 1 CHU Tenon, APHP, 3 CHU Saint Louis, APHP, Paris, 4 CHU de Strasbourg, Strasbourg, 5 CHU de Montpellier, Montpellier, 7 CHU d’Amiens, Amiens, Departments of Histopathology: 2 CHU Tenon, APHP and 6 Groupe Hospitalier Pitié-Salpêtrière, APHP, 8 Department of Neurophysiology, Groupe Hospitalier Pitié-Salpêtrière, APHP, Paris, 9 Department of Hemostasis and Vascular Biology, CHU Cochin, APHP, 10 Unit of Dermatology, Groupe Hospitalier Pitié-Salpêtrière, APHP, and 11 Inflammation-Immunopathology-Biotherapy Department, Sorbonne Universités, UPMC Univ Paris, INSERM-UMRS 959, DHU i2B, Paris, France Livedoid vasculopathy is a rare thrombotic cutaneous disease. This observational study aimed to assess the clinical and biological features of livedoid vasculopa- thy and the efficacy of treatments. Patients enrolled had typical livedoid vasculopathy both clinically and histologically. Investigation of thrombophilia was per- formed. Electromyography was undertaken in the pre- sence of symptoms suggesting peripheral neuro­pathy. Eighteen women and 8 men were included, with a mean age of 35.5 years at onset. Twenty patients had at least one thrombophilia factor. Ten patients had a peripheral neuropathy with 2 of these patients demon- strating a specific thrombo-occlusive vasculopathy on muscle biopsy. Anticoagulation with low molecular weight heparin was the most prescribed therapy and was associated with the best outcome (effective in 14 patients). Eight patients had severe disease refractory to anticoagulation and required intravenous immuno­ globulins, producing a good response in 6 patients. Key words: livedoid vasculopathy; peripheral neuropathy; throm­ bosis of dermal vessels; thrombophilia; low molecular weight heparin; intravenous immunoglobulins. Accepted May 4, 2018; Epub ahead of print May 8, 2018 Acta Derm Venereol 2018; 98: 842–847. Corr: Dr. Stéphane Barete, MD, PhD, Department of Dermatology, Hôpital Pitié-Salpêtrière, 47-83 Boulevard de l’Hôpital, FR-75013 Paris, France. E-mail: [email protected]. L ivedoid vasculopathy (LV) is a chronic disease mani- festing as recurrent necrotic and painful lower limb ulcerations. These resolve leaving atrophic porcelain- white scars with surrounding telangiectasias known as atrophie blanche (AB). The estimated incidence is 1:100,000 individuals, predominantly affecting young to middle-aged females, with a sex ratio of 3:1 (1, 2). Histopathology reveals a vaso-occlusive disorder with intraluminal thrombosis of dermal vessels without leu- kocytoclastic vasculitis (1, 3). The exact mechanism of this entity is unknown but underlying thrombophilia with abnormalities of coagulation or fibrinolysis, is observed in up to 50% of patients (2, 4). Plasminogen activator inhibitor-1 (PAI-1) is a major inhibitor of fibrinolysis. The 4G/5G polymorphism of the PAI-1 promoter gene results in enhanced transcription and the 4G allele is doi: 10.2340/00015555-2965 Acta Derm Venereol 2018; 98: 842–847 SIGNIFICANCE Livedoid vasculopathy is a chronic thrombotic disease of the skin microcirculation resulting in painful ulcers mainly af- fecting the lower legs. This study presents a French cohort of patients with livedoid vasculopathy. It describes clinical, histological characteristics and outcome of patients. It no- tably shows a frequent thrombophilia background. Nerve damage can be associated with cutaneous manifestations. These data also confirm that heparin or oral anticoagulants are able to achieve a complete response. Refractory cases can be treated with intravenous immunoglobulins. associated with increased PAI-1 levels. Impaired fib- rinolysis through PAI-1 involvement was observed in several studies, related to increased levels of PAI-1 antigen (5), enhanced activity (6) or 4G polymorphism of the promoter gene (7). Recently, a few cases have reported peripheral neuro- pathy in association with LV, most often mononeuritis multiplex (8–15). Most treatments are based on anticoagulation (1, 3). Several retrospective studies and case reports have shown a good response to intravenous immunoglobulins (IVIG) in refractory patients (16–19). However, in the absence of large prospective controlled studies, there is no recom- mendation on the dose or duration of medication and as such the optimal therapeutic regimen is unknown. We performed an observational multicenter study in France reviewing the diagnosis and management of pa- tients with LV. We aimed to assess the clinical and histo- logical features of LV, to identify related coagulopathies including plasma antigenic levels and 4G polymorphism of PAI-1, neurological involvement, therapeutic mana- gement and patient outcome. METHODS Study design and inclusion criteria This observational study was conducted in 6 different French dermatology departments between 2006 and 2015. Patients included in the study presented with typical LV based on both clinical symptoms (recurrent ulcers of the leg, livedo reticularis, AB) and histology (thrombosis of dermal vessels). The exclusion This is an open access article under the CC BY-NC license. www.medicaljournals.se/acta Journal Compilation © 2018 Acta Dermato-Venereologica.