| BackgroundLivedoid vasculopathy(LV)is currently considered to be a chronic and recurrent vaso-occlusive cutaneous disorder that typically manifests as livedo racemosa,painful ulcerations and white atrophic scars on the lower extremities.LV is relatively rare and easily misdiagnosed as cutaneous small vessel vasculitis,cutaneous polyarteritis nodosa,or antiphospholipid syndrome.Histopathologically,LV is characterized by occlusion of vessels in the dermis by fibrin deposition and intravascular thrombosis,as well as fibrinoid degeneration of the vessel walls.The current mainstream view is that LV is a vaso-occlusive disease without vasculitic changes.The treatment of LV is still challenging and long-term outcomes are unsatisfactory,due to the protracted disease course and the lack of standard protocols or guidelines for the treatment.Objectives(1)To analyze the clinical appearance,histological features and laboratory test results in a cohort of Chinese patients with LV retrospectively,and then to analyze atypical clinical characteristics of LV and make clear whether lymphocytic vasculitis exists in LV.(2)To analyze previous treatment options of our patients retrospectively and evaluate their treatment outcomes.To access the clinical efficacy and safety of sequential anticoagulant therapy prospectively.Methods(1)A total of 358 cases were identified from our database from January 2010 to October2022.All cases had clinically and pathologically confirmed diagnoses of LV.Clinical data and results of laboratory tests and histopathological examination were collected and analyzed.(2)Follow-up information including treatment options and efficacy was obtained through outpatient follow-up or telephone and analyzed.(3)From January 2022 to September 2022,19 hospitalized patients with active LV were enrolled and received the regimen of sequential subcutaneous nadroparin followed by oral rivaroxaban.Changes in pain and skin involvement were evaluated using a numerical rating scale and composite clinical scores,respectively.Adverse events occurred during the treatment period were also recorded.The efficacy and safety of sequential anticoagulant therapy was then analyzed.Results1.Clinical features:A total of 358 patients with LV were included in this study,including105(29.3%)males and 253(70.7%)females,with a median age of 23 years.One hundred and eighty-seven(52.2%)cases occurred between the ages of 11 and 25 years.Active ulcers were observed in 291(81.3%)patients when they first visited our department.The ankle area was the most commonly affected location,followed by the distal anterior lower leg and the lateral dorsum of the foot.Among 161(45.0%)patients who presented livedo racemosa,126(78.3%)patients revealed localized livedo racemosa which was limited to the lower extremities,and another 35(21.7%)cases showed diffuse livedo racemosa,involving not only the lower extremities but also the buttocks,trunk,or upper extremities.Sixty-four(17.9%)patients had pigmented purpuric dermatosis-like lesions,47 of whom presented with annular purpura.Twelve(3.4%)patients had stasis dermatitis-like skin lesions.Sixteen(4.5%)patients showed signs of peripheral nerve injury including numbness and tingling occurred on the skin of distal extremities.2.Pathological features:Fibrinoid degeneration of the vessel walls was observed in 326(91.1%)cases by HE staining,and intravascular thrombosis was found in 276(77.1%)cases.Vascular involvement occurred mainly in the superficial dermis(91.9%),and sometimes in the deep dermis(61.7%)or subcutaneous tissue(37.4%).Only a sparse or no perivascular lymphocytic infiltration was found in 221(61.7%)cases,while 137(38.3%)cases showed lymphocytic vasculitis.Medium-sized blood vessels were involved in 48(35.0%)cases,and small-sized blood vessels were involved in 89(65.0%)cases.Immunochemical staining of tissue sections with lymphocytic vasculitis showed lymphocytic infiltration dominated by CD4~+T lymphocytes and CD8~+T lymphocytes.CD4~+T lymphocytes were slightly more than CD8~+T lymphocytes.Staining for cytotoxic granule proteins including perforin,granzyme B and TIA-1 was negative.Direct immunofluorescence examination was performed in 84 cases,66 of whom were positive for immune complex deposition.Complement component 3(93.9%)was the most common immunoreactant,followed by Ig M(60.6%).The most common pattern was immunoreactants deposition in the vessel walls(84.8%).3.Treatment and follow-up:Anticoagulants were the most commonly used drugs for the treatment of LV,followed by systemic glucocorticoids,antiplatelet drugs,immunosuppressive agents and traditional Chinese medicine.Follow-up information was available for 250(69.8%)patients,41(16.4%)of whom achieved long-term remission with the absence of new ulcers for more than 4 years,59(23.6%)of whom had not developed new ulcers for more than 2 years,and 150(60.0%)of whom still had active ulcers within 2years.Among 118 patients who presented with livedo racemose,22(18.6%)patients demonstrated an improvement of livedo racemosa,while 96(81.4%)patients showed no signs of any improvement or still presented progressive livedo racemosa.NRS scores of 19patients who received the regimen of sequential subcutaneous nadroparin followed by oral rivaroxaban before and after 1,4,8,and 12 weeks of treatment were(4.79±1.58),(2.63±1.21),(1.68±1.29),(0.79±1.08),(0.32±0.58)points respectively,showing a gradual decreasing trend(F=68.16,P<0.001).The composite clinical scores of 19 patients before and after 4,8,and 12 weeks of treatment were(6.05±1.02),(3.16±1.26),(2.05±1.55),(1.00±1.33)points respectively,showing a gradual decreasing trend(F=48.02,P<0.001).The only observed adverse event was transient elevation of serum liver enzymes which was reported by 5 patients after nadroparin treatment.Conclusions1.The mean age at onset in Chinese patients is relatively young,and the peak age of onset is 11 to 25 years.The skin manifestations of LV are diverse.In addition to typical skin presentations including livedo racemosa,ulcerations and atrophie blanche on the lower extremities,atypical skin lesions including pigmented purpuric dermatosis-like lesions,stasis dermatitis-like skin lesions and generalized livedo racemosa are also observed.Signs of peripheral nerve injury including numbness and tingling sensations affecting the skin of distal extremities should be noticed by clinicians.2.The pathological manifestations of LV mainly include fibrinoid degeneration of the vessel walls and intravascular thrombosis in the upper dermis,sometimes involving the deep dermis or subcutaneous tissue,with only a slight or no perivascular lymphocytic infiltration.However,lymphocytic vasculitis with perivascular infiltration mainly of CD4~+T lymphocytes and CD8~+T lymphocytes was also observed in some cases.The vasculitis primarily impacts small-to medium-sized blood vessels.The most common pattern of immunoreactants deposition was the deposition of C3 and Ig M in the vessel walls.3.Currently,standardized treatment options for LV are still missing.Anticoagulants are the most commonly used and most effective drugs during the active period of the disease;however,the long-term outcome of patients remains unsatisfactory.The regimen of sequential nadroparin followed by rivaroxaban provides rapid pain relief and promotes ulcer healing.The most commonly adverse event is a transient elevation of serum liver enzymes which requires careful monitoring. |
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