Livedoid vasculopathy (LV) is a microvascular thrombotic skin disease leading to cutaneous infarction and chronic, recurrent painful ulcers1. Several therapeutic modalities have been used with variable success, but there are no randomized controlled trials attesting the efficacy of any treatment1. Sildenafil is a selective inhibitor of phosphodiesterase-5 (PDE5), an enzyme that inactivates cyclic guanosine monophosphate (cGMP), which mediates the effects of nitric oxid. Increased intracellular cGMP inhibits calcium entry into the cell, causing smooth muscle relaxation and exerting vasodilatatory effect. PDE5 inhibitors also have angiogenic and antithrombotic (inhibiting platelet aggregation) actions23. Treatment with sildenafil in high doses (20 to 50 mg, 3 times a day) has promoted improvement of skin lesions caused by microvascular diseases, with few adverse effects2345. Considering this, we report here the results of treatment with sildenafil in a patient with refractory LV.

On May 7th, 2015, a 46-year-old female patient, with diagnosis of LV made 15 years ago, required hospitalization due to severe pain caused by skin lesions on the lower limbs. A previous skin biopsy (2014) showed the presence of small luminal thrombi in capillaries of the upper dermis and associated mural fibrinoid necrosis, surrounding microhemorrhages, and absence of vasculitis. Laboratory tests for antinuclear and antiphospholipid antibodies were negative, and she had no history of thromboembolic events. She underwent several unsuccessful treatments in the past, including prednisone (up to 40 mg/day) and dipyridamole, along with daily dressings. At admission, she reported that the ulcers became active 2 years ago and recently evolved with deterioration in their appearance and pain. On physical examination, livedo racemosa was present along with six lesions (1 purpuric plaque and 5 ulcers with necrotic areas) on both lower limbs, whose size ranged from 1.2 cm to 10.0 cm (Fig. 1). She was taking continuously nicotinic acid 1 g/day, warfarin, 5 mg/day; pentoxifylline, 400 mg/day; prednisone, 5 mg/day; and acetylsalicylic acid, 100 mg/day during the last year, without any substantial clinical improvement.

After removal of necrotic material by mechanical and hydrogel chemical debridements, oral sildenafil (12.5 mg, twice a day) was added to the drug scheme on May 19th, with the dosage progressively increased to 25 mg, 3 times a day over 2 weeks. Amitriptyline and methadone were prescribed for pain control at discharge. Eight weeks after the start of sildenafil, the patient had a significant reduction in pain (abandoning the use of methadone) and 4 lesions were completely healed, while other 2 lesions, located on the lateral malleoli, were recovering (Fig. 1). We then started a gradual reduction of the corticosteroid dosage, and warfarin and nicotinic acid were removed from patient's prescription. The last remaining ulcer was completely healed by August 20th. She reported never have experienced a higher rate of healing before, and no treatment- related adverse event occurred. At the last contact with the patient (December 30th), she was showing no evidence of disease activity.

The present case represents the first report of use of sildenafil or any PDE5 inhibitor in the treatment of LV, suggesting the possibility of an effective treatment alternative for this disease.