Acute digital ischemia due to lupus vasculitis successfully treated with anifrolumab

Anifrolumab, a monoclonal antibody against the type I interferon receptor, has shown high efficacy against active systemic lupus erythematosus (SLE), including skin manifestations in clinical trials.1 However, the efficacy of anifrolumab for severe organ manifestations remains unclear. We present a first case of an SLE patient exhibiting acute digital ischemia and gangrene with lupus vasculitis successfully treated with anifrolumab in combination with glucocorticoids and anticoagulants. A 31-year-old Japanese woman was referred to our hospital for discoloration of her fingers and toes. The patient also had fever, oral ulcers, alopecia, livedo reticularis, and erythema of the lower extremities. Nine days before visiting our department, she noticed dark purple discoloration on her left toes, which progressed to her right toes and fingers within a few days (Figure 1a,b). The complete blood count was normal, the serum C-reactive protein level was 4.15 mg/dL (reference, < 0.1), and the antinuclear antibody was positive (1:1280, speckled pattern). No hypocomplementemia was observed. Anti-ds DNA antibody was positive at 61 U/mL, and results for anti-ribonucleoprotein (RNP) antibody and lupus anticoagulant (LA) were positive; anticardiolipin immunoglobulin G and M antibodies and anticardiolipin/β2 glycoprotein I antibody were negative. Skin biopsy of the palpable and painful erythema on the left lower extremity showed cutaneous vasculitis with fibrinoid necrosis and vascular occlusion with thrombosis in small arteries or arterioles (Figure 1c–h). No other organ involvement was evident. The patient was diagnosed with acute digital ischemia because of lupus vasculitis with thrombosis. Oral prednisolone (PSL) 30 mg/day with hydroxychloroquine combined with anticoagulants, including warfarin preceded by low-molecular-weight heparin, was started because of the coexistence of lupus vasculitis and secondary antiphospholipid antibody syndrome were considered. Considering the influence on fertility, cyclophosphamide was not administered, and mycophenolate mofetil was deemed intolerant due to gastrointestinal symptoms. Therefore, intravenous infusions of anifrolumab 300 mg every 4 weeks, were added. Although ischemic changes were observed in all fingers and toes, 1 month after the start of treatment, the discoloration improved and changed to redness on most digits, except the right fifth finger and the left second toe, which unfortunately showed gangrene (Figure 1i,j). PSL was tapered off, and the patient has experienced no recurrences while continuing anifrolumab for a year. To the best of our knowledge, this represents the first report to suggest the efficacy of combining anifrolumab with glucocorticoids and anticoagulants for a patient with acute digital ischemia due to lupus vasculitis. The pathogenesis of peripheral ischemia of SLE is complicated: capillary spasm and vasospasm associated with Raynaud's phenomenon, vasculitis, atherosclerosis, and thrombosis associated with anti-phospholipid antibodies.2 Cutaneous vasculitis was observed in 30% of SLE patients,3 and five of seven (71%) patients with digital gangrene of SLE showed cutaneous vasculitis.2 Therefore, vasculitis is not an uncommon cause of digital ischemia in SLE patients. Anticoagulation therapy is required when digital ischemia caused by vascular thrombosis or arteriosclerosis is suspected, but if vasculitis is involved in the pathogenesis of digital ischemia, as in the present patient, immunosuppressive therapy is also needed. No treatment strategies are available for digital ischemia, including the selection of immunosuppressants or biologics. Recent studies indicated type I interferon activity was associated with cutaneous vasculitis.4 Another report showed the prompt efficacy of anifrolumab for refractory chilblain lupus lesions and livedo reticularis: the former reflects type 1 interferon activity, and the latter suggests cutaneous ischemia including vasculitis.5 Anifrolumab, therefore, may be a therapeutic option for cutaneous vasculitis that prevents the progression of digital gangrene. The corresponding author obtained written informed consent from the patient and retained the signed consent forms. Patient details were anonymized as much as possible.