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March 30, 2022

Treatment of Livedoid Vasculopathy With Baricitinib

Author Affiliations
  • 1Department of Dermatology and Venereology, Peking University First Hospital, Beijing Key Laboratory of Molecular Diagnosis on Dermatoses, National Clinical Research Center for Skin and Immune Diseases, NMPA Key Laboratory for Quality Control and Evaluation of Cosmetics, Beijing, China
JAMA Dermatol. 2022;158(5):587-589. doi:10.1001/jamadermatol.2022.0241

Livedoid vasculopathy (LV) is a rare vascular disease characterized by erythema, purpura, and painful ulcers with a reticular pattern in the lower extremities, especially on the ankle. Atrophie blanche occurs after the ulcers heal. It manifests as small, stellate, and reticulated white scars. Although the exact cause of LV remains unknown, a hypercoagulable state and endothelial cell damage are likely to be the causative factors. To our knowledge, there is no definitive treatment for LV. However, drugs that stimulate endogenous fibrinolytic activity, anticoagulation, antiplatelet activity, vasodilation, and immunosuppression have shown favorable results in some cases.1 We report 3 cases of LV that were resistant to conventional therapy and showed marked improvement following treatment with baricitinib.

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2 Comments for this article
Use of Baricitinib for Livedoid Vasculopathy- a potential treatment option but keeping watching
Jundong Huang, Master of Medicine | Department of Dermatology, Xiangya Hospital, Central South University,Hu Nan Key Laboratory of Aging Biology,Changsha, China
It is with great interest that we have read “Treatment of Livedoid Vasculopathy With Baricitinib”.We would appreciate their work in providing a potential treatment option for LV.
However, we must point out that the using of baricitinib requires more caution.Up until now, the etiopathogenesis of LV has not been fully understood and thrombophilia(thrombosis) is commonly considered to play an crucial role, which is the main reason why Livedoid vasculitis was renamed Livedoid Vasculopathy.(1)A recent meta-analysis including long-term data of baricitinib suggested incidence rates(IRs) per 100 patient-years at risk were 0.4(95% CI 0.26 to 0.45) and 0.3(95% CI 0.18 to 0.35)
for deep vein thrombosis and pulmonary embolism, respectively.(2)Although the risk is exceedingly small, there is a possibility of LV aggravation with baricitinib.Therefore, frequent reassessment of the therapeutic response and close monitoring of the coagulation function are necessarily. Moreover, there is a concern about relapse during drug withdrawal or in the summer. More controlled studies with long-term follow-up are needed to confirm the real efficacy of baricitinib.
We would point out that not all three patients received anticoagulant therapy. As mentioned before, LV is a thromboembolic disorder and the treatment recommendation should focus on anticoagulation rather than immunosuppression.A previous study conducted by Di Giacomo et al.(3) suggested a strong relationship between LV and prothrombotic state with more than half of the patients(18/34) showed laboratory abnormalities.And 84%(11/13) of LV patients, who presented intractable disease or evidence of hypercoagulable states, benefited from anticoagulant therapy(either warfarin or heparin).Another systematic review reported a higher rate of clinical benefit(62/63), suggesting anticoagulant therapy is the first-choice of LV(4).Low molecular weight haparin is commonly applied and is safer but more expensive than traditional anticoagulants.Of note, rivaroxaban, a selective factor Xa antagonist, was the most commonly used anticoagulant for LV.Because there is no need for routine coagulation testing in oral rivaroxaban.
LV can be classified as either an idiopahtic(primary) disease or secondary to other conditions, such as systemic lupus erythematosus, antiphospholipid syndrome, hypercoagulable states, or paraproteinemia. For these patients with connective tissue diseases, the outcome of anticoagulant therapy is unpredictable, while baricitinib may be a considerate alternative option. The optimal indication of baricitinib for LV needs further study.
1.Criado PR, Rivitti EA, Sotto MN, de Carvalho JF. Livedoid vasculopathy as a coagulation disorder. Autoimmun Rev. 2011;10(6):353-360. doi: 10.1016/j.autrev.2010.11.008
2.Taylor PC, Takeuchi T, Burmester GR, et al. Safety of baricitinib for the treatment of rheumatoid arthritis over a median of 4.6 and up to 9.3 years of treatment: final results from long-term extension study and integrated database. Ann Rheum Dis. 2022;81(3):335-343. doi:10.1136/annrheumdis-2021-221276
3.Di Giacomo TB, Hussein TP, Souza DG, Criado PR. Frequency of thrombophilia determinant factors in patients with livedoid vasculopathy and treatment with anticoagulant drugs--a prospective study. J Eur Acad Dermatol Venereol. 2010;24(11):1340-1346. doi:10.1111/j.1468-3083.2010. 03646.x
4.Micieli R, Alavi A. Treatment for Livedoid Vasculopathy: A Systematic Review. JAMA Dermatol. 2018;154(2):193-202. doi:10.1001/jamadermatol.2017.4374

all authors’ names:Jun-Dong Huang, MM;Wei Shi, MD
Importance of Skin Biopsy in Diagnosis of Livedoid Vasculopathy
Harish Eswaran, MD | Department of Medicine, University of North Carolina School of Medicine
We read with interest the article by Song et al. reporting on cases of livedoid vasculopathy (LV) treated with baricitinib [1]. As the authors note, baricitinib is an immune modulator targeting the JAK/STAT pathway that carries an FDA warning regarding increased thrombotic risk based on safety data from a large clinical trial of tofacitinib, a drug in a similar class [2]. The efficacy of baricitinib in LV would provide evidence for an inflammatory—rather than purely thrombotic—etiology for LV, an area of considerable debate [3]. Our main concern with the published series is that only one of the participants underwent skin biopsy. Skin biopsy is essential in the diagnosis of LV as focal dermal vessel thrombosis in the absence of inflammatory infiltrate is pathognomonic for the disorder [4]. The clinical characteristics of retiform purpura with ulceration may be found in a range of inflammatory and non-inflammatory vasculopathies of the skin [5]. It is therefore conceivable that the improvement in ulcers observed in two of the patients in this study was due to the effect of baricitinib on a vasculitis or inflammatory vasculopathy distinct from LV. Additionally, the natural history of LV is for lesions to relapse and remit, and the short-term follow-up of four months for two of the patients studied is, in our opinion, insufficient to draw meaningful conclusions regarding the efficacy of therapy. Optimal therapy for LV remains unclear due to the absence of controlled or comparative studies with long term follow-up. Clarifying the etiology of LV demands the use of standardized diagnostic criteria in published research, including skin biopsy.

1.    Song X, Tu P. Treatment of livedoid vasculopathy with baricitinib. JAMA Dermatol. Published online March 30, 2022. doi:10.1001/jamadermatol.2022.0241
2.    Ytterberg SR, Bhatt DL, Mikuls TR, et al. Cardiovascular and Cancer Risk with Tofacitinib in Rheumatoid Arthritis. N Engl J Med. 2022;386(4):316-326. doi:10.1056/NEJMoa2109927
3.    Khenifer S, Thomas L, Balme B, Dalle S. Livedoid vasculopathy: thrombotic or inflammatory disease? Clin Exp Dermatol. 2010;35(7):693-698. doi:10.1111/j.1365-2230.2009.03732.x
4.    Freitas TQ, Halpern I, Criado PR. Livedoid vasculopathy: a compelling diagnosis. Autops Case Rep. 2018;8(3):e2018034. doi:10.4322/acr.2018.034
5.    Georgesen C, Fox LP, Harp J. Retiform purpura: A diagnostic approach. J Am Acad Dermatol. 2020;82(4):783-796. doi:10.1016/j.jaad.2019.07.112

Authors: Harish Eswaran, MD(1) and Stephan Moll, MD(2)
Affiliations: 1. Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC.
2. Division of Hematology, Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC.