The Use of Elastocompressive Therapy in a Patient With Acroangiodermatitis of the Lower Limb

Disclosure: This work was supported by the ARRD (Associazione Romana Ricerca Dermatologica).

Acroangiodermatitis is a vasoproliferative disease of the lower limbs associated with congenital or acquired vascular alterations. It is clinically characterized by circumscribed, slowly-evolving, red violaceous or dusky macules, papules, or plaques.^1,2

This condition closely mimics Kaposi’s sarcoma in regard to clinical and histopathological features. For this reason it is also called pseudo-Kaposi sarcoma.¹ Immunolabeling makes the two diseases different: endothelial marker CD34, von Willebrand’s factor, and Ulex European agglutinin I lectin are not present in acroangiodermatitis.³

There are two main clinical variants of acroangiodermatitis—the Mali type, associated with venous hypertension, and the Stewart-Bluefarb type, associated with arteriovenous malformation or acquired (iatrogenic) arteriovenous fistula (in patients with chronic renal failure).Vascular alterations may be associated with A) paralysis of the affected limb;B) damage of vessels after amputation and poorly fitting prosthesis or intravenous (IV) drug abuse; C) carriage of the thrombophilic 20210A mutation in the prothrombin gene; D) Klippel-Trénaunay syndrome.^4–6

Therapeutical options consist of corrective arteriovenous shunts through embolization or surgery, surgical ligation of vessels, or elastic compression therapy in chronic venous insufficiency. Anticoagulant therapy is useful in patients with thrombophilic alterations.¹

Case Study

A 63-year-old white man, with an erythematous redviolaceous macule on the anterior tibial region of the right leg in part covered by yellow-brownish crusts presented to the authors’ facility (Figure 1).

Prior to presentation at the author’s facility, the patient had undergone surgical interventions for bladder polyposis and was given a permanent bladder catheter. The patient also had a duodenal ulcer that was controlled with oral esomeprazole.

A cutaneous biopsy of the lesion was performed and the histopathology image showed hyperkeratosis of the epidermis, presence of new vessels in lobular arrangement, and hemosiderin deposits in the papillar and the upper part of the reticular dermis (Figure 2). Diagnosis of acroangiodermatitis was made.

After several months, the erythematous area extended to the external and internal malleolar regions of the right leg and became completely covered by crusts. Upon removal,an intensely erythematous,exuding,malodorous, exulcerated skin was seen (Figures 3–5).

Laboratory assays showed mild reduction of hemoglobin (11.8), hematocrit (36.7), MCV (70.7%), ferreamia (35.8), ferritin (9), and elevation of transferrin (408). Although hepatitis C virus (HCV) antibodies resulted positive (1.26 s/co), quantitative and qualitative dosage for HCV-RNA by polymerase chain reaction (PCR) was negative. Autoantibodies (ANA, p-ANCA, c-ANCA), anticardiolipin, and cryoglobulins were not present. Inflammation signs (ie, VES, PCR, rheumatoid factor) were normal. A thrombophilic screening showed only a mild reduction of APTT (24 sec or 0.85 ratio), while PT, fibrinogen, ATIII, protein C,protein S,and APCR were normal.Mutations for Leiden’s factor V (G16961A1),methylene tetrahydrofolate reductase (MTHFR, C677T), and prothrombin (G20210A) by PCR were not found.

Several bacterial cultures from the lesion were taken and showed growth of several microorganisms:

• Escherichia coli, Proteus species, Enterococcus faecalis— treated with systemic antibiotic therapy ampicillin and imipenem

• E coli, Proteus mirabilis, Staphylococcus aureus— responsive to topical gentamicin and systemic cefepime

• P mirabilis and S aureus—treated with topical gentamicin.

Venous duplex examination showed bilateral insufficiency of internal saphenous, collateral, and perforant veins. Additionally, two erythematous lesions covered by brownish crusts were present on the inferior left leg (Figure 6).

Selective compression treatment was used on the right inferior leg using an adhesive elastic bandage up to the thigh because the patient refused surgical intervention. After 3 months, a significant reduction of the erythematous component and macula dimension was obtained (Figure 7).Complete regression of the involved lateral and medial malleolar area was also achieved. Removal of the crusted lesion and the topical antibiotic therapy were sufficient for a clear improvement of the left limb.

Discussion

Reactive angioproliferations are benign vascular disorders of the skin of which acroangiodermatitis and angioendotheliomatosis are the best known.²

Acroangiodermatitis, associated with congenital and acquired vascular diseases, is a rare condition that affects the lower limbs and is clinically characterized by purple macular plaques that occasionally ulcerate.^1,2

In 1964, Kopf and Gonzalez⁷ first described a condition they termed congenital dysplastic angiopathy. One-year later, Mali et al⁸ introduced the term acroangiodermatitis to describe peculiar mauve-colored macules and plaques developing on the extensor surface of the feet in 18 patients with chronic venous insufficiency. In 1967, Stewart,⁹ and Bluefarb and Adams,¹⁰ independently reported the same condition described by Mali et al,⁸ but this time it was associated with congenital arteriovenous malformation (AVM). In 1974, Earhart et al¹¹ reported a case associated with congenital AVM and suggested the name pseudo-Kaposi sarcoma, because of the clinical and histopathological similarity with early Kaposi’s sarcoma.

Acroangiodermatitis can be categorized as a congenital type and an acquired type. In the first group, there are the Stewart-Bluefarb Syndrome and the Klippel-Trenaunay-Weber Syndrome, both characterized by unilateral lesions and clinical signs of A-V shunt (pain, edema, varices, limb hypertrophy, hyperthermia, hyperhidrosis, and a vascular mass with a palpable thrill).^1,4 The acquired forms are A) Mali acroangiodermatitis with bilateral lesions that are usually symmetrical and accompanied by signs of chronic venous insufficiency (swelling, stasis dermatitis, and hyperpigmentation); B) acroangiodermatitis due to iatrogenic A-V shunts in hemodialytic patients with slow-evolving lesions after a latent period of 2 months to 7 years from initial shuntplacement; C) acroangiodermatitis associated with paralyzed limbs and amputation stumps.^1,4,5

Recently, cases of acroangiodermatitis have been described in patients with thrombophilic 20210A mutation in the prothrombin gene and in the methylene tetrahydrofolate reductase C677T allele.^6,12

Although the etiology is still unknown, there are two theories. The first theory proposes that proliferation of fibroblasts and small vessels is secondary to high perfusion rate in tissues. The second supposes that PGE1 or a heparin-like factor, which has angiotensin promoting activity, is responsible for the lesion development. A possible role of microtrauma has been suggested by Pfleger and others.^13,14

Recent reports show local increases of vascular endothelial growth factors (VEGF) in hypoxic conditions, which play an important part in angiogenesis. Products released during mast cell degranulation, such as heparin, histamine, and TNF-α, are responsible of neoangiogenesis by stimulation of the stem cell factor (SCF).¹⁵

Histopathologic picture usually shows, 1) a mild acanthosis with some hyperkeratosis of the epidermis; 2) a slight proliferation of endothelial cells with genesis of new thick-walled vessels, often in lobular arrangement,in the edematous papillary dermis. The vessels are usually invested by pericytes. In addition, marked red blood cell extravasation, hemosiderin pigment deposition, dermal fibrosis, and perivascular superficial infiltrate (lymphocytes, histiocytes, and eosinophiles) may be present.^1–4 In contrast to Kaposi’s sarcoma, the vessels are regular, the lack of vascular slates are not present, and collagen bundles dissected by new vascular channels and pleomorphic hyperchromatic spindle cells are absent.^1,4

Immunolabeling helps distinguish pseudo-Kaposi’ssarcoma from Kaposi’s sarcoma. In pseudo-Kaposi’s sarcoma the endothelial marker CD34 is completely absent in the perivascular cells, while the Factor VIII associated antigen is present in endothelial cells. In Kaposi’s sarcoma, both endothelial and perivascular cells are positive for CD34 antigen and Ulex European agglutinin I lectin (UEA I lectin), while the Factor VIII associate antigen is absent.^3,16 Histopathology and immunolabeling provides elements to differentiate acroangiodermatitis from other vasoproliferative disorders, as shown in Table 1.

EcocolorDoppler scan, MRI angiography, and arteriography are useful in detecting chronic venous insufficiency or an arteriovenous shunt—laboratory testing must investigate for alterations of antithrombin III, protein C, protein S, and for the presence of mutations in the prothrombin G20210A and methylene tetrahydrofolate reductase (MTHFR) C677T genes.^5,12,17–19 Acroangiodermatitis therapy is based on the correction of associated diseases: A) chronic venous insufficiency, corrected by surgical ligature of the vessels and elastic support, or elastic compression alone, as in the present case; B) the AVM corrected by embolization, sclerotherapy, or surgery.^1,19 In the case of thrombophilic alterations, anticoagulant oral therapy is sufficient for the resolution of the cutaneous disease.^6,12,19

Complete regression following therapy with dapsone and support stockings has been reported.⁴ Stanozolol and erythromycin have also been used successfully in the treatment of this condition.^20,21 Their exact mode of action is still unknown, but erythromycin appears to have anti-inflammatory effects, and has shown to inhibit the chemotaxis of leukocytes, monocytes, and eosinophiles.¹