LivedovasculopathyL95.0

Eminently chronic, regularly recurrent, thrombo-embolic occlusive disease of the cutaneous vascular plexus (see vasculopathy below), which clinically leads to a characteristic "livedo" appearance and, as a result of the thrombotic vasculopathy of small and medium-sized skin vessels, to lightning-figure-like, jagged, highly painful plaques, erosions or flat ulcers. Healing leaving bizarrely configured, flat, depigmented scars(atrophie blanche).

Brief clinical triad (LAU): Livedo racemosa, atrophieblanche, ulcersrecurrently.

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

Idiopathic disease courses 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) have been described.

Sato-Matsumura et al (2000) reported on two individuals with factor XII deficiency who had livedovasculopathy and painful ulcers curis that improved dramatically after anticoagulant therapy. They postulated that factor XII deficiency may lead to a hypercoagulative state in some individuals, predisposing them to painful ulcers and painful livedo syndrome (in the presence of as yet unexplained secondary irritants).

Predominantly occurring in adolescents and younger adults (15.-40. LJ). The disease affects predominantly (> 75%) the female sex.

Reticular, deep red, livid, flat indurated plaques and erythema, with formation of bizarre, usually 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.

An environmental analysis often reveals pathological coagulation parameters with prothrombotic properties such as: antiphospholipid antibodies and a protein C deficiency.

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!

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 image 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...

Successes have been described with the following therapy modalities:

• According to our own experience, which has been confirmed in the meantime, prompt and long-term improvements (especially in the almost always existing severe pain symptoms!) can be achieved under repetitive (4 weeks intervals) immunoadsorption and/or IVIG alone (high-dose immunoglobulin therapy: 0.5-1.0g-2.0/kgkgKG divided over 3 consecutive days i.v.). Long-term therapy should be carried out with factor Xa inhibitors, which can alternatively be used as primary therapy.
• Alternative: Factor Xa inhibitors. Numerous study reports are available(Rivaroxaban, Apixaban)
• Alternative: Heparin 2-3 times/day 5000-7500 IU s.c.
• Alternative: Enoxaprin (Clexane) 1 mg/kg bw/day. Symptom-adapted therapy duration, usually for about 4 weeks.
• Alternative: If there is no convincing improvement of the disease under these therapy regimes, an immunosuppressive therapy with prednisolone (e.g. Decortin H) 100 mg/day p.o. can be applied. Reduce steroid dose depending on the clinic, maintenance dose of 5-10 mg/day. A combination therapy with azathioprine (e.g. Imurek) 100 mg/day p.o. is recommended.
• Not very convincing: 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.).
• Not very convincing: Sulfasalazine (e.g. Azulfidine) can be dosed gradually up to 1000 mg p.o. 3 times/day.

The disease fulfills the criteria of an "orphan disease". This must be taken into account for all known therapeutic modalities. See below Orphan Diseases. Orphan drugs.

• 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.

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