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Abstract. Stewart–Bluefarb syndrome is a rare angioproliferative disorder characterised by acroangiodermatitis associated with an underlying arteriovenous ...

Phlebology http://phl.sagepub.com/ Stewart−Bluefarb syndrome: Report of five cases and a review of literature K Parsi, AA O'Connor and L Bester Phlebology published online 13 August 2014 DOI: 10.1177/0268355514548090

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Phlebology OnlineFirst, published on August 13, 2014 as doi:10.1177/0268355514548090

Review Article

Stewart–Bluefarb syndrome: Report of five cases and a review of literature

Phlebology 0(0) 1–10 ! The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/0268355514548090 phl.sagepub.com

K Parsi1,2,3, AA O’Connor1 and L Bester2,3,4

Abstract Stewart–Bluefarb syndrome is a rare angioproliferative disorder characterised by acroangiodermatitis associated with an underlying arteriovenous shunt. This condition should be differentiated from acroangiodermatitis of Mali classically described in association with chronic venous insufficiency. Patients with Stewart–Bluefarb syndrome typically present with lower leg pigmented macules, papules and plaques that can coalesce to form larger confluent patches of pigmentation. Recognition of Stewart–Bluefarb syndrome may be difficult or delayed as the cutaneous manifestations may resemble a variety of other dermatological conditions. Most commonly, acroangiodermatitis may be confused with Kaposi’s sarcoma and the condition is often referred to as ‘Pseudo-Kaposi’s sarcoma’. Acroangiodermatitis may also resemble or coexist with pigmentation of chronic venous insufficiency. As seen in this report, acroangiodermatitis may also be clinically confused with the ‘cavernous’ form of a capillary malformation. Here, we describe five patients with Stewart–Bluefarb syndrome. In one female and two male patients the diagnosis was delayed as the acroangiodermatitis closely resembled other conditions. All underlying arterio-venous communications were initially diagnosed on duplex ultrasound and confirmed with magnetic resonance angiography. Four patients were found to have a congenital arteriovenous malformation while one was diagnosed with a post-thrombotic arterio-venous fistula. Management included observation and intervention using a variety of techniques including percutaneous or trans-catheter embolisation, endovenous laser, radiofrequency ablation and foam ultrasound guided sclerotherapy. This case series highlights the challenges involved in the diagnosis and management of Stewart–Bluefarb syndrome. Given the local and systemic sequelae of high flow shunts, correct diagnosis and early detection of the underlying arterio-venous abnormality is crucial in the long-term management of these patients and in preventing the associated complications.

Keywords Catheter-based interventions, venous malformation, venous syndromes

Introduction Stewart–Bluefarb syndrome (SBS) is a rare disorder characterised by acroangiodermatitis (AAD) associated with an underlying arterio-venous malformation (AVM).1 First described by Bluefarb and Adams and later by Stewart in 1967, the term Stewart–Bluefarb Syndrome was conceived by Earhart in 1974.1–3 To date, there are approximately 26 reported cases of SBS. The clinical presentation and in particular the pigmentation and secondary skin changes of SBS can be confused with Kaposi’s sarcoma (KS) or pigmentation of chronic venous insufficiency (CVI). Identification of an underlying arterio-venous (AV) anomaly is critical as these high flow shunts can result in significant morbidities including skin ulceration, limb length discrepancy, deformity, regional osteoporosis and congestive

cardiac failure. Therefore, early detection and appropriate management of SBS is important in preventing significant secondary complications.4,5 Clinically, skin lesions of AAD appear as brown violaceous macules, papules and plaques that can 1

Department of Dermatology, St. Vincent’s Hospital, Sydney, Australia Sydney Skin and Vein Clinic, Sydney, Australia 3 University of New South Wales, Sydney, Australia 4 Department of Medical Imaging, St. Vincent’s Hospital, Sydney, Australia 2

Corresponding author: Kurosh Parsi, Dermatology, Phlebology and Fluid Mechanics Research Laboratory, St. Vincent’s Hospital Centre for Applied Medical Research, Level 8, Lowy-Packer Building, 405 Liverpool Street, Darlinghurst, NSW 2010, Australia. Email: [email protected]

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coalesce to form confluent patches of pigmentation. Individual lesions can develop verrucous change and ultimately ulcerate.4 Lower limb lesions typically occur on the extensor surfaces and in particular the dorsal aspects of the foot, ankle or calf.1–4,6 Histologically, AAD is characterised by profuse thinwalled capillaries and venules lined by a single layer of endothelial cells, erythrocyte extravasation and haemosiderin deposition in the dermis.4,7,8 There may be an associated perivascular proliferation of dermal fibroblasts and an inflammatory mononuclear infiltrate.8 AAD resembles KS and is often referred to as ‘Pseudo-KS’.2 It lacks, however, the typical histological features of KS such as the vascular slit pattern, expression of CD34þ antigen in endothelial and perivascular spindle cells, factor VIII-associated antigen in endothelial cells and human herpes virus type 8 detection.8–10 The pathogenesis of AAD is poorly understood but is thought to involve an angiogenic response to high perfusion rates and an associated increase in venous and capillary pressures.4,6,8,11 The angiogenic drive is thought to involve the angiogenic growth factors also implicated in the pathogenesis of AVMs.12 This is thought to result in a reactive endothelial hyperplasia and the typical angioproliferative histological features. In SBS, AAD is associated with an underlying AV communication resulting in retrograde high venous pressures. However, severe chronic venous hypertension in the absence of an AV shunt can also result in AAD. This variation is termed ‘acroangiodermatitis of Mali’ and was described by Mali et al. in 1965 as a ‘peculiar form of angiodermatitis (angio-dermite de Favre et Chaix) due to a chronic insufficiency of the venous network of the foot. . .’.13 It has also been reported in other contexts where there is localised high venous pressures such as in patients using suction socket prostheses.14,15 In contrast to SBS where AAD is unilateral, AAD of Mali may be bilateral. Furthermore, histological changes in AAD of Mali are typically limited to the superficial dermis while in SBS these changes may extend to the deeper dermis.6 Here, we present a case series of five patients with SBS. The underlying AV communication was diagnosed on duplex ultrasound and confirmed by angiography in combination with magnetic resonance angiography (MRA) or computed tomography angiography (CTA). Interventional modalities used included trans-catheter or percutaneous embolisation, endovenous laser ablation (EVLA; Biolitec 1470 nm, Biolitec Biomedical Technology, Jena, Germany), radiofrequency ablation (RFA; Covidien ClosureFast, Covidien, San Jose, CA, USA) and ultrasound guided sclerotherapy (UGS). Embolic agents used included ethanol (Ethilbloc, Dehydrated Alcohol, Phebra, NSW, Australia), sodium tetradecyl sulphate (STS,

supplied as FIBRO-VEIN 3%, Australian Medical and Scientific, Chatswood, NSW, Australia) and polidocanol (POL, supplied as AETHOXYSKLEROL 3%; Chemische Fabrik Kreussler, Wiesbaden, Germany).

Case reports Patient 1: AVM of the great toe A 14-year-old female presented with a 4-year history of asymptomatic right great toe discolouration on a background of recurrent onychocryptosis for which she had undergone a wedge excision. There was no other significant past personal or family history of vascular anomalies. She was on no regular medications but took supplements including probiotics and vitamin D. On examination, the right great toe was larger than the contralateral digit (Figure 1(a)). There was a plaque of brown violaceous pigmentation proximal to the nail bed on the dorsum of the right great toe. The area was tender to touch but no excessive warmth could be discerned. The other toes appeared normal to examination. A skin biopsy of the pigmentation showed clusters of small vessels (capillaries and venules) within the papillary dermis associated with prominent haemosiderin deposition throughout the papillary and reticular dermis. These features were consistent with AAD (Figure 1(b)). Duplex ultrasound detected an AVM measuring 25 mm  6.6 mm on the dorsal aspect of the distal phalanx of the right great toe. The lesion was composed of minimally compressible vascular channels that demonstrated a mix of low resistance, high diastolic, pulsatile flow (Figure 1(c)). The feeding arteries were in communication with the digital artery which demonstrated low resistance high flow and a normal calibre. A nidus was located at the base of the nail bed. Magnetic resonance (MR) of the right foot showed a volar mass with flow voids enveloping the distal phalanx of the right great toe and heterogeneous enhancement with contrast consistent with an AVM (Figure 1(d)). She was diagnosed with AAD secondary to an underlying AVM consistent with SBS. Considering the anatomical position of the lesion, the young age of the patient and lack of functional morbidity, conservative management was recommended. This included annual clinical examinations, orthopaedic assessment, photography and ultrasound measurements of the lesion size and flow characteristics.

Patient 2: Diffuse AVM of the anterolateral calf A 24-year-old female presented with a lifelong history of painful pruritic patchy pigmentation of the left anterolateral calf. This lesion was previously biopsied

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Figure 1. Case 1. (a) Violaceous pigmented plaque proximal to the nail bed extending across the enlarged right great toe. (b) Skin biopsy demonstrating clusters of small vessels within the papillary dermis and a prominent haemosiderin deposition suggestive of acroangiodermatitis. (c) Duplex ultrasound demonstrating low resistance high phasic flow in the distal phalanx of the right great toe. (d) Magnetic resonance imaging demonstrating a volar mass with flow voids and heterogeneous contrast enhancement. Arrow indicates region of high signal intensity.

twice with inconclusive findings. There was also one previous unsuccessful attempt at treating the cutaneous lesions with cryotherapy. Her past personal and family history was unremarkable. She was on no regular medications. On examination, there was patchy violaceous pigmentation on the left anterolateral calf (Figure 2(a)). The area was warm on palpation and demonstrated pulsatile flow on continuous-wave Doppler examination. There was no soft tissue or bony hypertrophy. There was an area of cutaneous necrosis overlying one of the distal lesions. Skin biopsy showed increased vascularity throughout the dermis with lobular clusters of capillary-like

vessels in the upper, mid and lower dermis and larger vessels in the lower dermis presumed to be feeder vessels. Abundant haemosiderin pigmentation was present. The findings were consistent with AAD. Duplex ultrasound localised a diffuse pattern of vascularity in the subcutaneous tissue underlying the cutaneous lesions. Some of the vessels were large enough (1–2 mm) to be confused with subcutaneous varicose veins although non-compressible. Colour and spectral Doppler examination detected a mixture of high and low velocities consistent with mixed arterial and venous flow (Figure 2(b)). The feeding arteries were noted to arise from the lateral calf perforators and communicated with the anterior tibial artery (ATA).

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Figure 2. Case 2. (a) Multiple pigmented violaceous lesions on the anterolateral left shin. (b) Duplex ultrasound of the lateral calf lesion demonstrating a mixture of high and low flow consistent with mixed arterial and venous flow. (c) Series of radiograms demonstrating two arteriovenous malformations (AVMs) in the mid and distal calf each with small arterial feeders from the anterior tibial artery (ATA). Arrows indicate the ATA (A) and the two malformations (B).

The draining veins were in communication with the superficial anterior tibial vein proximally. The surrounding subcutaneous tissue appeared hyperechoic consistent with fibrotic changes. MRA showed two vascular anomalies in the midand distal anterolateral calf, each with small arterial feeders from the ATA (Figure 2(c)). Both lesions demonstrated a vascular blush prior to early venous filling. No significant angiographic evidence of an arterial steal from the foot was seen. These findings were consistent with two AVMs. She was diagnosed with SBS and underwent three intervention sessions. The lesions were accessed percutaneously from the venous side and occluded using EVLA (1470 nm) combined with foam UGS. STS 1.5% was used for larger vessels and POL 0.5% for smaller and more superficial ones. Six months following

the last intervention, she was asymptomatic and there was some reduction in pigmentation.

Patient 3: AVM of the foot A 23-year-old female presented with a left lower limb vascular anomaly initially thought to represent Klippel–Trenaunay syndrome (KTS). At the age of 10, she developed brownish discolouration and large prominent veins over the dorsal aspect of the left foot. A leg length discrepancy in favour of the left leg was diagnosed and the growth plates were subsequently removed. A test dose of laser to treat the pigmentation of the left medial foot had resulted in worsening of the skin discolouration. Verrucous change of the first and second toes subsequently occurred over time. There was no significant past personal or family history. Current

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medications included esomeprazole and the combined oral contraceptive pill (cyproterone acetate with ethinyloestradiol). On examination, there was patchy brown pigmentation on the medial aspect and dorsum of the left foot extending to the first and second digits. There was no associated warmth or a palpable mass (Figure 3(a)). An initial skin biopsy showed multiple lobules of ectatic thin and thick-walled vessels with intervening dermis demonstrating abundant haemosiderin deposition. These changes were reported to represent a ‘capillary and venous haemangioma consistent with a cavernous form of a port-wine stain’. Duplex ultrasound demonstrated reflux in the left great saphenous system but not involving the lateral superficial venous system as expected in KTS. Deep veins were all competent. A compressible vascular malformation consistent with a venous malformation (VM) was located on the anterolateral and medial aspects of the foot (Figure 3(b)). An initial MR of the left leg demonstrated a vascular malformation involving the anterior tibial and peroneal vessels extending from the knee and becoming more prominent at the ankle. Given these findings, the patient was diagnosed with a combined capillary–venous malformation and was treated for the venous component. She underwent several interventions that included EVLA and UGS. Hyperkeratosis and verrucous changes were treated with liquid nitrogen cryotherapy and topical salicylic acid. Although the clinical appearance of the foot improved, the skin lesions remained pigmented. Given the limited clinical response to interventions, a missed diagnosis of SBS was suspected. The lesion was biopsied again and further imaging was organised. Repeat biopsy showed lobular aggregates of small vessels in the dermis with intervening fibrosis and haemosiderin pigmentation consistent with AAD (Figure 3(c)). MRA of the left foot demonstrated a small AVM, with a nidus measuring 30 mm  18 mm  40 mm, fed by the medial plantar artery (Figure 3(d)). She was diagnosed with SBS and further intervention for the underlying AVM was planned.

On examination, he presented with visible varicosities in the left medial lower leg. There were violaceous pigmented patches on the medial aspect of the left ankle associated with small patches of venous eczema (Figure 4(a)). There was no evidence of lipodermatosclerosis or atrophie blanche or other trophic skin changes of CVI. His clinical stage of clinical etiological anatomical pathological (CEAP) classification was C4a. Duplex ultrasound of the left leg showed no evidence of chronic changes associated with deep vein thrombosis (DVT). There was extensive incompetence of the deep venous system including the femoral, popliteal and all calf veins. In addition, there was incompetence of the residual superficial veins including the small saphenous vein (SSV) and medial calf and ankle tributaries of the GSV. He underwent three uneventful procedures to treat the superficial venous incompetence of the left leg including one session of EVLA for the SSV incompetence and two sessions of foam USG using STS 1.5% to treat the remaining tributaries. A post-operative follow-up was organised at 12 weeks. Clinically, the dermatitis had resolved although the pigmentation was persistent. Duplex study of the left leg demonstrated good occlusion of the majority of the treated vessels. However, a small AVF communicating between the posterior tibial artery (PTA) and the posterior tibial vein (PTV) 6 cm proximal to the medial malleolus was detected (Figure 4(b)). This anomaly was not detected pre-operatively. MRA of the left ankle confirmed the presence of this malformation. There was a leash of vessels in the subcutaneous tissue overlying the medial aspect of the leg and a dilated vascular structure adjacent to the PTV (Figure 4(c)). Time resolved imaging showed early filling of these vessels. The patient was diagnosed with SBS. The AVF was embolised over three sessions with ultrasound guided RFA, sclerotherapy with STS 3% and embolisation using 100% ethanol. On follow-up 3 years later, the AV communication could not be detected on duplex ultrasound. Clinically, the patient was asymptomatic and there was a noticeable reduction in pigmentation.

Patient 4: AV fistula (AVF) of the ankle

Patient 5: Acquired AVF of the medial calf

A 39-year-old male presented with a history of dilated veins since the age of 12. He complained of left medial ankle cutaneous changes such as dermatitis and pigmentation. Previous management had included stripping of the left great saphenous vein (GSV) followed by EVLA and foam UGS of a post-operative GSV recurrence. There was no past personal or family history of venous thrombosis. He was on no regular medications.

A 63-year-old male presented with an 18-year history of left lower limb varicosities associated with pruritus and nocturnal cramps. He had a complex past venous history consisting of two previous episodes of left leg DVT. The first was a popliteal vein thrombosis for which he was heparinised and commenced on warfarin for 3 months. One year later, he developed a major thromboembolic event which included DVT of the femoral, popliteal and calf veins, pulmonary embolism,

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Figure 3. Case 3. (a) Patchy violaceous-brown pigmentation of the medial aspect and the dorsum of the left foot extending to the first and second digits. (b) Patient was initially thought to have a venous malformation (VM) based on duplex finding of a compressible vascular lesion of the foot demonstrating low flow. (c) Repeat skin biopsy demonstrating lobular aggregates of small vessels in the dermis with intervening fibrosis and haemosiderin deposition consistent with acroangiodermatitis. (d) Sequence of images from magnetic resonance angiography (MRA) of the left foot demonstrating an arteriovenous malformation (AVM) fed by the medial plantar artery (MPA). The nidus is visible during the arterial phase (image 1). Arrows indicate the anterior tibial artery (ATA; A), the posterior tibial artery (PTA; B), the MPA (C) and the AVM nidus (D) showing high signal intensity. Wash out of the nidus and evidence of early venous filling is seen in images 2 and 3. Image 4 depicts the venous phase with arrows indicating the anterior (ATV; E) and the posterior tibial veins (PTV; F).

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Figure 4. Case 4. (a) Pigmentation and venous eczema in the left medial ankle. (b) Duplex ultrasound using Power Doppler demonstrating an abnormal communication between the left distal posterior tibial artery (PTA) and the posterior tibial vein (PTV). (c) Sequence of images from magnetic resonance angiography (MRA) of the left foot. Image 1 demonstrates the arterial phase with arrows indicating the anterior tibial artery (ATA; A), the posterior tibial artery (PTA; B) and a leash of vessels representing the nidus of the AVM (C). Images 2–4 demonstrate the venous filling. Image 4 demonstrates the venous drainage with arrows indicating the paired posterior tibial veins (PTVs; D) and the anterior tibial veins (ATVs).

portal vein and superior mesenteric vein thrombosis. A thrombophilia screening demonstrated homozygous polymorphism for methylene tetrahydrofolate reductase gene in association with a slightly raised serum homocysteine levels (17.4 mmol/l [4–14]). Two further thrombophilia screenings a number of years later had confirmed the previous findings. No concurrent malignancy was diagnosed at the time and there was no family history of venous thromboembolism (VTE) or hypercoagulable states. His past medical history included a total thyroidectomy for a benign thyroid mass, renal calculus, ulcerative oesophagitis, oesophageal varices and hiatus hernia. His regular medications included warfarin (Coumadin), thyroxine and esomeprazole. He was a heavy drinker but denied smoking. On examination, there was pigmentation and atrophie blanche posterior to the left medial malleolus and macular pigmentation in the more proximal calf areas (Figure 5(a)). The left calf circumference was larger than the contralateral side by about 3 cm. His clinical stage of CEAP classification was C4b. Duplex ultrasound demonstrated incompetence of the left superficial venous system with reflux in the great and SSVs as well as incompetence in the deep venous system with reflux in the distal femoral vein.

There was also a non-occlusive tongue of thrombus in the popliteal vein with extension of webbing to one pair of medial gastrocnemius veins, consistent with previous venous thrombosis. He was diagnosed with venous insufficiency secondary to post-thrombotic syndrome. He was advised to reduce his alcohol intake, stay on warfarin and commence on folic acid 5 mg daily to reduce the serum homocysteine levels. He subsequently underwent an uneventful EVLA and foam UGS to treat the superficial venous disease. During his routine post-operative ultrasound DVT screening, a possible AV communication was suspected. The fistula measured approximately 5 mm  8 mm and was located over the medial aspect of the left leg approximately 14 cm proximal to the medial malleolus. Doppler examination demonstrated high diastolic, low resistance phasic flow within the patent channels. Colour Doppler demonstrated aliasing within the fistula indicative of turbulence (Figure 5(b)). A CTA of the left leg was organised which showed a tortuous prominent PTV coursing along the PTA medially in the proximal to mid portion. There was an intimate alignment of the two vessels but no distinct communicating channel could be discerned on CTA.

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Figure 5. Case 5. (a) Violaceous macules and papules and atrophie blanche of the left medial ankle. (b) Colour Doppler demonstrating the posterior tibial vein (PTV) with prominent aliasing. (c) Sequence of images from magnetic resonance angiography (MRA) of the left calf. Image 1 demonstrates the arterial phase with arrows indicating the posterior tibial artery (PTA; A), and the peroneal artery (B). Images 2–4 demonstrate the early venous filling. Arrows indicate the anterior tibial artery (ATA; C), the paired posterior tibial veins (PTVs; D), the peroneal veins (E) and the anterior tibial vein (ATV, F). Image 4 demonstrates corkscrewing of vessels (G), fistulous communication (H) and malformed vessels (I).

Given the inconclusive findings of CTA, an MRA was organised. This study showed early venous filling at the proximal third of the PTV compatible with the presence of a fistula between the peroneal artery and the PTV (Figure 5(c)). Skin biopsies of the left medial ankle and anterior shin showed prominent lobular vascular proliferation in the superficial and upper reticular dermis and extensive haemosiderin deposition consistent with AAD. He subsequently developed an acute DVT in this limb in the context of warfarin non-compliance and excessive alcohol consumption. In view of these events and the thromboembolic risk factors, he was not considered a good candidate for embolisation and it was decided to monitor the AVM. On follow-up 4 years after the first presentation, the clinical presentation remained stable with no deterioration of the skin signs.

Discussion We present five patients with SBS in whom AAD was associated with an underlying AV communication. Cases 1 and 2 presented with unilateral patchy violaceous pigmentation and were promptly diagnosed with SBS. In these patients AAD was diagnosed on skin biopsy and the subsequent imaging localised the underlying AVM. By contrast, the diagnosis in cases 3–5 was delayed. Case 3 was referred with a presumed diagnosis of KTS and the AAD was thought to represent a cavernous form of a CM (port wine stain). Case 4 had a lifelong history of venous disease and presented with varicose veins, dermatitis and pigmentation. Case 5 had a significant past history of VTE and presented with clinical signs of post-thrombotic syndrome. These three patients were later diagnosed with SBS. In Case 3,

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we suspected a missed diagnosis of SBS given the lack of clinical response to intervention. In Cases 4 and 5, the underlying AVM was incidentally found on duplex examination. As evident from cases presented here, it may be quite difficult to discern SBS from CVI based on subtle clinical signs. In SBS, cutaneous lesions may present as violaceous brown macules, papules, plaques or nodules that can coalesce, become verrucous or ulcerate.4 By contrast, pigmentation of CVI presents with diffuse patches. Furthermore, patients with SBS may present with soft tissue or bony hypertrophy secondary to the underlying AV shunt.4 These features are not consistently present and in this cohort, bony hypertrophy was only seen in Cases 1 and 3. Features of an underlying pulsatile mass such as cutaneous warmth, an audible bruit, a palpable thrill or a difference in pulses can also be absent.4 In such patients, the maculopapular morphology and the violaceous tint of the pigmentation may be the only physical signs of AAD. Even in patients presenting with typical lesions, the diagnosis of AAD must be confirmed by biopsy. Samples should be collected from lesions with typical clinical signs, otherwise the biopsy may be inconclusive. Historically, SBS has been associated with underlying congenital AVMs. Here we present an association with an acquired non-traumatic AVF in Case 5. This patient presented with a history of recurrent DVTs involving the left lower limb deep veins including the calf veins where he subsequently developed an AVF. There was no history of a congenital malformation and prior to the DVT, he was asymptomatic and had no manifestations of a congenital vascular anomaly such as limb size discrepancy or the associated skin changes. The onset of left lower limb changes including the cutaneous lesions followed the onset of the DVT. There was also no history of a blunt or penetrating trauma to the region. Although an asymptomatic congenital AVF cannot be ruled out, the AV communication in this case most likely represented an acquired non-traumatic AVF. These fistulae may form at the site of an acute venous thrombosis and possibly arise from the vasa vasorum. Yakes reported four patients with acquired AVFs associated with chronic venous thrombosis.16 Stenting of diseased vein segments proved successful in eliminating numerous AVFs in the vein wall. Other previous cases have been reported in the context of May–Thurner syndrome where an iliofemoral venous thrombosis was followed by a nontraumatic acquired AVF at the site of thrombosis.16 The mechanism involves post-thrombotic phlebitis resulting in damage to the vessel wall and formation of a fistula communicating with the adjacent vessels. Case 4 presented with ‘varicose veins’ since the age of 12. He had a combined deep and superficial venous

insufficiency in the absence of a history or ultrasound features of a previous DVT. The primary venous insufficiency in this case would represent a truncular VM involving major named vessels.17 The AVF in this case was most likely congenital as there was no history of an acquired cause such as trauma or thrombosis. These findings are consistent with a combined venous/ arteriovenous vascular malformation. In combined vascular malformations, AV anomalies can be found in association with other congenital malformations.17 We used the non-invasive modality of duplex ultrasound to identify and localise all five AV anomalies. Diagnostic evaluation of SBS should include a combination of baseline minimally invasive investigations which may incorporate other modalities. Duplex ultrasound is the first line modality due to its non-invasive nature and widespread availability.18 On B-mode ultrasound, AVMs are non- to minimally compressible vascular channels incorporating very little soft tissue mass. The surrounding tissues may be hyperechoic due to fibrosis. The key Doppler feature of AVM is a low resistance, high diastolic pulsatile flow.18 A nidus would generate turbulence which will be detected on Doppler as aliasing. MRA and CTA are used to confirm the duplex diagnosis of AVMs. In patients presented here, the presence of all AVMs was confirmed by MR imaging. MR is helpful in confirming the diagnosis as well as establishing the location and extent of the lesion. MR has a superior capability in imaging soft tissue, better spatial resolution and a wider field of view than ultrasound.10,18 CTA may be considered an alternative to MRA although in Case 5 presented here, CTA failed to detect the abnormality. In general, MRA is a better modality to diagnose AVMs of the soft tissue in comparison to CTA which is better in diagnosing lesions involving bone, bowel or lung. CT is also an alternative to MR in patients with cardiac or respiratory failure due to faster image acquisition and in patients who have contraindications to sedation or MR.19 Time resolved MRA is more likely to identify an AV communication compared with CTA which is not time resolved. The hallmark of AVMs on MRA is early venous filling proportional to the severity of the anomalous AV connections.5,18 Prompt diagnosis of an underlying AVM is a crucial aspect of the management of patients presenting with AAD. AVMs can cause local pathology such as soft tissue hypertrophy and skin ulceration as well as systemic problems including congestive cardiac failure.4,5 When left undiagnosed, the underlying AVM may cause bony changes such as cortical thinning and demineralisation, regional osteoporosis, limb length discrepancy and deformity.4,5 In addition, patients may undergo numerous procedures for a presumed

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underlying venous disease. Hence, SBS and its underlying AVM should be diagnosed promptly and managed accordingly.4,5 Quite importantly, patients need to be educated on their diagnosis and may require counselling. A definitive treatment of SBS is directed towards obliterating the underlying AVM.6 This may be achieved by selective embolisation, endovenous ablative techniques, sclerotherapy or surgery.4,20 An ill-planned embolisation or surgical intervention can result in acute exacerbation and worsening of the AVM and in extreme cases can result in amputation of the affected digit or limb.4–6 Conservative management includes regular monitoring and treatment of any complications such as ulceration, haemorrhage and infections. Topical steroids, oral antibiotics (erythromycin), dapsone and heparan sulphate have been suggested as medical therapies in the management of SBS-associated ulcers but their value and efficacy is not established.21 As seen in Case 3, verrucous change and pigmentation may be managed with cryotherapy, salicylic acid and topical bleaching agents.17 Monitoring should incorporate limb size (length and circumference) measurements with appropriate orthopaedic referrals, photography and duplex ultrasound examinations.4,20 In summary, we present five cases of SBS. We highlight the characteristic clinical, histological and imaging features of this rare condition and emphasise the diagnostic and management challenges facing clinicians. SBS is a rare but important dermatological condition that should be considered in the differential diagnosis of patients presenting with violaceous pigmentation of lower limbs.

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Acknowledgements We would like to thank Prof. Hugo Partsch (Vienna, Austria) for advice on Stewart–Bluefarb syndrome and Dr John Pereira for comments on angiographic images.

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Conflict of interest None declared. 18.

Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

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References 1. Bluefarb SM and Adams LA. Arteriovenous malformation with angiodermatitis. Stasis dermatitis simulating Kaposi’s disease. Arch Dermatol 1965; 62: 176–181. 2. Earhart RN, Aeling JA, Nuss DD, et al. Pseudo-Kaposi sarcoma. A patient with arteriovenous malformation and skin lesions simulating Kaposi sarcoma. Arch Dermatol 1974; 110: 907–910. 3. Stewart WM. Fausse angiosarcomatose de Kaposi par fistules arterioveinulaires multiples. Bull Soc

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franc¸ dermatol syphiligr 1967; 74: 664–665. (Article in French). Larralde M, Gonzales V, Mariette R, et al. Pseudokaposi sarcoma with arteriovenous malformation. Pediatr Dermatol 2001; 18: 325–327. Smiddy PF, Molloy MP, Flanagan N, et al. PseudoKaposi’s sarcoma: The association of arterio-venous malformations with skin lesions resembling Kaposi’s sarcoma. Australas Radiol 2001; 45: 225–227. Hueso L, Llombart B, Alfaro-Rubio A, et al. StewartBluefarb syndrome. Actas Dermo-sifiliograficas 2007; 98: 545–548. Rao B, Unis M and Poulos E. Acroangiodermatitis a study of ten cases. Int J Dermatol 1994; 33: 179–183. Turk BG, Turk UO, Alioglu E, et al. Stewart-Bluefarb syndrome: A case report with angiographic findings. J Dermatol 2009; 36: 415–418. Kanitakis J, Narvez D and Claudy A. Expression of the CD34 antigen distinguishes Kaposi’s sarcoma from pseudo-Kaposi’s sarcoma (Acroangiodermatitis). Br J Dermatol 1996; 134: 44–46. Krengel S, Goerdt S, Kruger K, et al. Kaposiform HHV8 negative acroangiodermatitis in chronic venous insufficiency. Hautarzt 1999; 50: 208–213. Agrawal S, Rizal A and Agrawal CS. Pseudo-Kaposi’s Sarcoma (Stewart-Bluefarb type). Int J Dermatol 2005; 44: 136–138. Atri D, Larrivee B, Eichmann A, et al. Endothelial signalling and the molecular basis of arterivenous malformation. Cell Mol Life Sci 2014; 71: 867–883. Mali JW, Kuiper JP and Hamers AA. Acro-angiodermatitis of the foot. Arch Dermatol 1965; 92: 515–518. Armenores P, James CL, Weightman W, et al. Acroangiodermatitis in a lower leg amputee related to suction socket use. Australas J Dermatol 2013; 54: e37–e39. Badell A, Marcoval J, Graells J, et al. Kaposi-like acroangiodermatitis by a suction-socket prosthesis. Br J Dermatol 1994; 131: 915–917. Yakes W. Acquired non-traumatic peripheral arteriovenous fistula. J Vasc Interv Radiol 2014; 25: S52. Lee BB, Baumgartner I, Berlien P, et al. Diagnosis and treatment of venous malformations consensus document of the International Union of Phlebology (UIP): Updated 2013. Int Angiol, Epub ahead of print 25 February 2014, http://www.ncbi.nlm.nih.gov/pubmed/24566499. Brenner S and Martinez de Morentin E. What’s new in pseudo-Kaposi sarcoma. J Eur Acad Dermatol Venereol 2001; 15: 382–384. Moukaddam H, Pollak J and Haims AH. MRI characteristics and classification of peripheral vascular malformation. Skeletal Radiol 2009; 38: 535–547. Lee BB, Baumgartner I, Berlien HP, et al. Consensus document of the International Union of Angiology (IUA) 2013. Current concept on the management of arterio-venous management. Int Angiol 2013; 32: 9–36. Hayek S, Atiyeh B and Zgheib E. Stewart-Bluefarb syndrome: Review of the literature and case report of chronic ulcer treatment with heparan sulphate (Cacipliq20Õ ). Int Wound J, Epub ahead of print 5 April 2013. DOI: 10.1111/iwj.12074.

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