Livedoid vasculopathy L95.0

Author: Prof. Dr. med. Peter Altmeyer

All authors of this article

Last updated on: 29.05.2021

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Synonym(s)

Feldacker-Hines-Kierland Syndrome; Idiopathic Atrophy blanche; livedoid vasculopathy; Livedo reticularis with summer ulcerations; Livedovasculitis; O'Leary-Montgomery-Brunsting syndrome; painful purpuric ulcers with reticulate pattering of lower extremities; PURPLE; recurrent summer ulcerations; segmental hyaline vasculitis; Skin infarction

History
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O' Leary, 1944; Feldaker, 1955; Bard and Winkelmann, 1967

Definition
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Eminently chronic, regularly recurring, thrombo-embolic occlusive disease of the cutaneous vascular plexus (see vasculopathy below), which clinically leads to a characteristic "livedo image" and, as a result of thrombotic vasculopathy of small and medium-sized skin vessels, to flashy, jagged, highly painful erosions or flat ulcers. Healing leaving flat, depigmented scars(atrophy blanche).

Brief clinical triad (LAU): Livedo racemosa, atrophieblanche, recurrent ulcers

Occurrence/Epidemiology
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Incidence: < 1/100,000 (meets the criteria of orphan disease).

Etiopathogenesis
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Idiopathic courses of the disease are often described, genetic disposition is questionable.

Relationships to lupus erythematosus, polyarteritis nodosa, phospholipid antibody syndrome, coagulation disorders or hypercoagulability (factor V Leiden mutation, prothrombin gene mutation, protein C and protein S deficiency), hyperhomocysteinemia; venous insufficiency, chronic (CVI) are described.

Manifestation
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Predominantly occurring in adolescents and younger adults (15-40 years). The disease predominantly (70-80%) affects the female sex.

Clinical features
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Reticular, deep red, livid, flat indurated plaques and erythema, with formation of bizarre, mostly very painful (not the live image but the stabbing permanent pain leads to the doctor!), therapy-resistant flat ulcers in the ankle area, especially in the summer months (summer ulcerations), which heal with 0.3-1.0 cm large, flatly sunken, splatter-like whitish scars with red accentuated edge margin (vascular ectasia). Symmetrical appearance on the lower extremities is described but is not the rule.

Laboratory
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Environmental analysis often reveals pathological coagulation parameters with porthrombotic properties such as: antiphospholipid antibodies and protein C deficiency.

Histology
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Notice. The biopsy must be performed at an early stage. It must cover the lesional area sufficiently deeply and broadly (transition from healthy to diseased) so that the triggering vascular problem can be reliably assessed in the incision. Step cuts are mandatory!

Atrophic epithelium. In the middle and deep layers of the dermis, rather sparse, perivascular, lymphocytic infiltrate as well as dilated vessels, partly bulging with erythrocytes or filled with various old, hyaline thrombi (almost obligatory phenomenon). These fibrinoid effusions lead to hyalinization and infarction of the vessel wall, with subsequent focal necrobiosis and necrosis.

No signs of leukocytoclastic vasculitis!

Direct Immunofluorescence
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Deposition of IgG, IgA,C3 and fibrin in the vessel walls.

Differential diagnosis
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Clinical differential diagnosis:

  • Poly- (Peri-)arteriitis nodosa: 1.0 - 5.0 cm large, initially coarse, usually very pressure dolent, also spontaneously painful, reddish to livid coloured plaques or nodules (iceberg phenomenon) with a tendency to painful ulceration. Histologically, the process is located at the cutis-subcutaneous border with clear inflammatory symptoms! A live image like a flash can be part of the clinical symptomatology.
  • Sneddon syndrome: Here the skin process is of systemic changes (occlusion of cerebral vessels with neurological failure symptoms). Systemic changes are always absent in livedovasculopathy! Phospholipid antibodies are detectable in more than 50% of patients!
  • Embolia cutis medicamentosa: Acute event, minutes to a few hours after an i.m. Injection (anamnesis leads to a diagnosis of exclusion!), painful, hard infiltration with lightning-figure-like skin markings. Secondary: Development of deep ulcerations which heal with bizarrely shaped atrophic scars.
  • Arteriosclerotic occlusive ulcers (see below hypertonic leg ulcer): Not infrequently grafting on the clinical picture of livedo racemosa (here underlying arteriolosclerosis), sudden (overnight) formation of haemorrhagic, jagged, very painful ulcers. Always evidence of peripheral AVK (exclusion of livedovasculopathy).
  • Calciphylaxis: Localized, mostly symmetrical picture of the razemous livedo; this is accompanied by linear or also planar, 2.0 to 20 cm large, eminently painful, hard, red or even skin-coloured plaques or nodules. Mostly also painful ulcers of different sizes (histology is diagnostic, see below).
  • Livedo reticularis (in Anglo-American usage called Livedo racemosa!): This functional disorder is best described by the term "Cutis marmorata". It is a cold-induced, large-meshed, livid marbling, which, depending on the form, disappears or appears after heating or cooling. Often peripheral acrocyanosis. The jagged "lightning figure-like" pattern of the livedo racemosa (exclusion phenomenon) is always missing. Pain is always missing (exclusion of livedovasculopathy).
  • Cutis marmorata teleangiectatica congenita: Congenital clinical picture (exclusion criterion) with asymmetrically distributed Cutis marmorata with telangiectasia and phlebectasia; often conspicuously thin, translucent (atrophic) skin with clear vein pattern.
  • Atrophie blanche: Always at the bottom of a chronic venous insufficiency (exclusion criterion). Spattered, slightly sunken, scarred areas with surrounding brown pigmentation. Mostly capillary ectasia detectable at the edges. Possible development of mostly small, rarely also the entire atrophy zone of superficial erosions or ulcers ( atrophy blanche ulcer). The clinical feature of these ulcers is a stabbing permanent pain that is not compatible with the size of the ulcer.

Histological differential diagnosis:

  • Calciphylaxis: Thrombotic dermal and subcutaneous vessels with distinct basophilic calcifications in the lumen and walls (exclusion phenomenon).
  • Dermatoliposclerosis (congestive dermatosis): Intralobular lipomembranous (membranocytic) fat necrosis and pronounced septal sclerosis. In advanced stages of dermatoliposclerosis, broad sclerosed septums with English wall-thickened capillaries and venules with PAS-positive perivascular fibrin sheaths, as well as macrophages and fibroblasts are found. In the dermis: Perivascular superficial and deep sclerosing dermatitis with wall thickened, glomeruli-like bulging vessels.
  • Leucocytoclastic vasculitis: vascular wall necrosis with fibrinoid vascular wall swelling, neutrophil infiltration and perivascular nuclear dust.
  • Thrombophlebitis migrans: Sclerosing endophlebitis (giant cell vasculitis) with complete or partial closure of the vascular lumina by thrombi. Frequent detection of giant cells...

Therapy
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Clarification of an underlying systemic disease.

General therapy
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Bed rest, strict smoking ban, discontinuation of oral contraceptives advisable.

External therapy
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Heparin-containing(e.g. Heparin-ratiopharm gel/ointment) and antiphlogistic (e.g. Voltaren Emulgel) ointment dressings in the area of erythema, in the area of ulcer phase-specific ulcer therapy. S.a.u. wound treatment.

Internal therapy
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Current treatment paradigms are based on a small evidence base, mainly on case reports and case series of low evidence (Micieli R et al. 2018). In a major review (Micieli R et al. 2018), the following ranking (by frequency of therapies mentioned) was established:

Anticoagulants were the most commonly used monotherapy and achieved a favorable response in 62 of 63 patients (98%) (Weishaupt C et al 2019).

Anabolic steroids, intravenous immunoglobulins (IVIG), and antiplatelet agents were the second, third, and fourth most commonly used therapies, respectively. The following is a priority list based on my own experience (author of this article)!

  • IVIG: According to my own experience, which has been confirmed in the meantime, prompt and long-term improvements (especially in the almost always present severe pain symptoms!) can be achieved under repetitive (4 week intervals) immunoadsorption and/or IVIG alone (high-dose immunoglobulin therapy: 0.5-1.0g-2.0/kgKG divided into 3 consecutive days i.v.).
  • Alternative: Heparin 2-3 times/day 5000-7500 IU s.c.
  • Alternative: Enoxaparin (Clexane®) 1 mg/kg bw/day. Duration of therapy adapted to symptoms, usually for about 4 weeks.
  • Alternative: Rivarobaxan (Xarelto®), initially 2 x 10 mg/day p.o. Symptom-adapted therapy with 1x10 mg/day p.o.
  • Alternative prednisolone/azathioprine: If there is no convincing improvement of the disease with these therapy regimens, immunosuppressive therapy with prednisolone (e.g. Decortin H) 100 mg/day p.o. can be started. Reduce steroid dose depending on clinic, maintenance dose of 5-10 mg/day. Combination therapy with azathioprine (e.g. Imurek®) 100 mg/day p.o. is recommended.

Not very convincing and not recommended:

  • Acetylsalicylic acid (e.g. ASS-ratiopharm) 2 times/day 500 mg p.o., also in combination with dipyridamole (e.g. Curantyl 3-5 times/day 1 drg. p.o.).
  • Sulfasalazine (e.g. azulfidine): dose gradually up to 1000 mg p.o. 3 times/day.

Note(s)
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  • The disease fulfils the criteria of an "orphan disease". This must be taken into account in all therapeutic modalities. See below Orphan Diseases, see below. Orphan drugs.
  • Randomised clinical trials are required to better establish these treatments in clinical practice.

Case report(s)
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  • A 24-year-old obese patient has been suffering since her 12th year of age from periodically, but especially in the summer months, extremely painful "open spots" on the ankle regions of both feet. These would heal again with scars after a few weeks. Over the years, the treatment was antibiotic, immunosuppressive (azathioprine and glucocorticoids in medium doses), without any demonstrable improvement in findings. Otherwise, symptomatic pain therapy with metamisol and aspirin was performed. The presentation of the patient was pain-driven.
  • Findings: On all ankles up to 8x8 cm in size, irregular, in places bizarrely limited, reddish-brown, only moderately indurated plaques are found which are interspersed with smaller (about 0.5-1.0 cm in size) whitish, bizarrely configured scarred depressions. These are accentuatedly reddened in their marginal areas. In some places livedo patterns can be seen at the edges. Furthermore there are highly painful red, 0.2-0.6 cm large erosions with and without crusts.
  • Histology: In the middle and deep layers of the dermis thin, perivascular, lymphocytic infiltrate and dilated vessels, partly filled with erythrocytes, partly with hyaline effusions (almost obligatory phenomenon). Clearly thickened vessel walls. No signs of leukocytoclastic vasculitis.
  • Other findings: No evidence of AVK or CVI. Laboratory: completely o.B.
  • Therapy: Consistent therapy with a low-molecular heparin (enoxaprin = Clexane; 1mg/kgkgKG/day s.c.). Within 10 days significant reduction of pain and healing of erosions without complications under a usual indifferent wound management). In the meantime no new erosive foci. Enoaprin therapy was discontinued after 4 weeks.

Literature
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  1. Brown-Falco O et al (1972) On azathioprine therapy of livedo racemosa with ulceration. Dermatologist 23: 136-138
  2. Calamia KT et al (2002) Livedo (livedoid) vasculitis and the factor V Leiden mutation: additional evidence for abnormal coagulation. J Am Acad Dermatol 46:133-137
  3. Feldacker M, Hines EA, Kierland RR (1955) Livedo reticularis with summer ulcerations. Arch Derm Syph 72: 31-37
  4. Fritsch P et al (1995) Livedo vasculititis. Dermatologist 46: 215-224
  5. Goerge T (2010) Low-molecular-weight heparin therapy for the treatment of livedovasculopathy. Akt DErmatol 36: 484-487
  6. Goerge T (2014) Vasculopathy and vasculitis. Act Dermatol 40: 519-522
  7. Hairston BR et al (2006) Livedoid vasculopathy. Arch Dermatol 142: 1413-1418
  8. Kerk N et al (2013) Livedoid vasculopathy - athrombotic disease. Vasa 42: 317-322
  9. Kreuter A et al (2004) Pulsed intravenous immunoglobulin therapy in livedoid vasculitis.: an open trial evaluating 9 consecutive patients. J Am Acad Dermatol 51:574-579
  10. Micieli R et al (2018) Treatment for livedoid vasculopathy: a systematic review. JAMA Dermatol 154:193-202.
  11. Monshi B et al (2014) Efficacy of intravenous immunoglobulins in livedoid vasculopathy: long-term follow-up of 11 patients. J Am Acad Dermatol 71:738-744
  12. Muller CSL et al (2016) Diagnostic and histologic features of cutaneous vasculitides/vasculopathies. Act Dermatol 42: 286-301
  13. O'Leary PA, Montgomery H, Brunsting LA (1944) Livedo reticularis: recurrent ulcerations of the ankles in the summer. Arch Dermat Syph 50: 213
  14. Sams WM (1988) Livedo vasculitis. Therapy with pentoxifylline. Arch Dermatol 124: 684-687
  15. Schanz S et al (2003) Intravenous immunoglobulin in livedo vasculitis: a new treatment option? J Am Acad Dermatol 49: 555-556
  16. Weishaupt C et al.(2019) Characteristics, risk factors and treatment reality in livedoid vasculopathy - a multicentre analysis. J Eur Acad Dermatol Venereol 33:1784-1791.

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Please ask your physician for a reliable diagnosis. This website is only meant as a reference.

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Last updated on: 29.05.2021