Livedoid Vasculopathy: Successful Treatment with Tofacitinib

Abstract

Dear Editor, A 43-year-old woman presented to our rheumatology clinic with a 4-year history of painful ulcerated lesions over the dorsal surface of her feet and ankles with intermittent serous discharge from ulcers and a burning sensation of the distal extremities. The patient did not have features of systemic rheumatic disease (sicca symptoms, Raynaud’s phenomenon, fever, polyarthralgia, photosensitivity, oral ulcers, and skin thickening) or any nodules/rashes preceding the ulcers. She was nondiabetic with no history of deep-vein thrombosis, peripheral gangrene, or recurrent abortions. Physical examination revealed multiple stellate ulcers, with irregular erythematous margins, firm and tender edges, and scanty serous discharge with no fixation to underlying muscle [Figure 1a]. All peripheral pulses were normal. There was no lymphadenopathy, varicose veins, thickened nerves, or calf tenderness. Neurological examination was normal.Figure 1: Clinical images of leg ulcers: (a) Pretreatment and (b) Posttreatment; Photomicrographs of skin lesion, (c) Thrombosed vessel in the mid-dermis with mild perivascular inflammation (H and E, ×100), and (d) The same in high-power view (H and E, ×400)Her investigation showed normal complete blood count, liver and renal function, and coagulation profile. Erythrocyte sedimentation rate was 30 mm/h, C-reactive protein 8.1 mg/l, glycated hemoglobin 5.6, and normal urinalysis. Hepatitis B surface antigen, antibody to hepatitis C virus, and human immunodeficiency virus serology (1 and 2) were negative. Antinuclear antibody, rheumatoid factor, antibody to cyclic citrullinated protein, antineutrophil cytoplasmic antibody, and thrombophilia profile were negative. Chest X-ray, Doppler ultrasound, and nerve conduction study of the lower limbs were normal. A clinical diagnosis of livedoid vasculopathy (LV) was suspected. Skin biopsy showed hyalinized degeneration of the subintimal layer of mid-dermal vessels along with intraluminal thrombosis, extravasation of red blood cells, and mild perivascular lymphocytic infiltration [Figure 1c and d] – features typical of LV. The patient initially received antiplatelets, prednisolone (40 mg daily tapered to 5 mg daily over 6 months, then stopped), methotrexate (15 mg/week for 2 years), and warfarin (3–4 mg/day for 6 months) with no significant benefit. We commenced her on tofacitinib 5 mg twice daily as a monotherapy. The pain subsided in 1 month, and the ulcers healed over the next 2 months [Figure 1b]. LV is a chronic, painful, thrombo-occlusive cutaneous vasculopathy and characteristically heals with stellate porcelain-white scars called “atrophie blanche.”[1] It is typically seen in late-adolescent or middle-aged females, and histopathology is confirmatory.[2] Associations include connective tissue diseases, hypercoagulable states, thrombophilia, and malignancy. However, 20% of cases may have no such associated disease as was observed in our case.[3] A mean diagnosis delay of 5 years is reported in the literature (4 years in our case). Recent studies have shown the role of inflammation and vasculitis in the pathophysiology of LV.[4] Antiplatelets, anticoagulants, fibrinolytics, colchicine, dapsone, and vasodilators have been used with good response. In refractory cases, the efficacy of steroids, immunosuppressants, intravenous immunoglobulins, antibody to tumor necrosis factor, and rituximab have been reported. This suggests the role of inflammation in refractory LV. Tofacitinib, being pan–Janus kinase (JAK) inhibitor, controls vascular inflammation effectively through its anticytokine mechanism. Jia et al. reported successful use of tofacitinib in refractory LV.[5] Similarly, Han and Tu reported that baricitinib was also effective.[6] Our patient had already failed antiplatelets, anticoagulants, steroids, and methotrexate. Hence, we instituted tofacitinib therapy and observed a dramatic clinical response. Complete healing of ulcers took 2 months, and there was no recurrence in 1 year of follow-up. The optimum duration of treatment of LV remains unknown; however, JAK inhibitors are promising drugs for refractory LV. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understands that her name and initials will not be published, and due efforts will be made to conceal her identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.