Вы находитесь на странице: 1из 8

Venous Eczema and Lipodermatosclerosis

Laurel M. Morton, MD, and Tania J. Phillips, MD, FRCPC


Cutaneous changes are a common feature of chronic venous insufciency and include venous eczema and lipodermatosclerosis. This review will address the presumed pathophysiology of these conditions, their clinical ndings, and important management strategies. Semin Cutan Med Surg 32:169-176 2013 Frontline Medical Communications KEYWORDS venous eczema, lipodermatosclerosis, chronic venous insufciency

hronic venous disease is commonly encountered in both the United States and Europe.1,2 The most common disorders within this spectrum of disease include lower extremity edema, varicosities, and venous leg ulcers. The cutaneous manifestations of venous insufciency are very common and often require dermatologic expertise. This article will address venous eczema and lipodermatosclerosis (LDS), which can sometimes produce diagnostic dilemmas and treatment challenges. Venous eczema (otherwise known as gravitational eczema, varicose eczema and stasis dermatitis) affects the lower legs and ankles. The skin becomes erythematous, scaly and pruritic. There are also often associated signs of venous disease, such as varicose veins, edema, hemosiderin pigmentation, atrophie blanche, and LDS. LDS is a progressive brotic process of the dermis and subcutaneous fat associated with chronic venous insufciency (CVI), resulting in hyperpigmentation and induration of the lower leg. The presence of these cutaneous conditions is important for the classication of venous disease (Table 1). Unfortunately, there is scarce epidemiologic data regarding the prevalence of venous eczema and LDS. In fact, little data exists for chronic venous disease in general, likely because it is rarely life-threatening and has multiple denitions. However, up to 17% of men and 40% of women suffer from CVI;1 and of the 23% of Americans with varicose veins, 2 million will develop skin changes.4 The pathophysiology of cutaneous changes seen in venous disease remains unclear. It involves chronic ambulatory venous hypertension and resulting microangiopathic and inammatory changes, which lead to classic clinical and histoDepartment of Dermatology, Boston University, Massachusetts. Disclosures: The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conicts of Interest and none were reported. Correspondence: Laurel M. Morton, MD, Department of Dermatology, Boston University 1 Devonshire Place #3804, Boston, MA 02109. E-mail: Laurel.m.morton@gmail.com

pathologic ndings. The management of venous eczema and LDS requires treatment of underlying venous insufciency with consideration of other medical and surgical interventions, if appropriate.

Pathophysiology
The normal venous system consists of a high pressure deep venous system and a supercial system, linked by communicating veins. One-way valves prevent retrograde blood ow. During walking, the calf muscle pump contracts, raising the deep venous pressure, emptying the deep veins, and propelling blood towards the heart. Once the deep veins empty, the deep venous pressure falls, the valves open, and blood ows from the supercial to the deep system. CVI arises from failure of the calf muscle pump or abnormalities in the venous system, such as valve dysfunction, venous outow obstruction or a combination of these factors. In these circumstances, venous pressure fails to decrease signicantly during exercise, creating ambulatory venous hypertension.5 How these mechanical changes result in the skin signs and symptoms of venous disease is not well understood. Microangiopathic and proinammatory effects resulting from venous hypertension are thought to play a role. The microcirculatory changes resulting from CVI encompass decreased capillary counts, increased capillary diameter, permeability to proteins and erythrocytes, and increased subcutaneous uid ow.6 Increased permeability of small vessels leads to pericapillary brin cuff formation7 postulated to result in decreased oxygenation of involved skin.8,9 However, brin deposition is not conuent, which may mitigate against decreased oxygen diffusion. Fibrin may also impair tissue healing by inhibiting new collagen formation, contributing to the brosis seen in LDS. Inammatory cells may be even more important in the development of venous eczema and LDS. The white blood cell trapping theory proposes that due to decreased ow, 169

1085-5629/13/$-see front matter 2013 Frontline Medical Communications DOI: 10.12788/j.sder.0026

170
Table 1 Classication System for Chronic Venous Disease (CEAP)3 Grade Description

L.M. Morton and T.J. Phillips


Finally, it is clear that the architecture of skin must change to account for the rm induration of LDS. Expression of mRNA for matrix metalloproteinase (MMP) 1 and 2 is increased in LDS as is active MMP2. This unrestrained activity likely leads to extracellular matrix turnover18 and eventually venous ulceration.18,19 Tissue hypoxia and white cell activation may also stimulate transforming growth factor (TGF)-1 production and accelerate brosis.19

C: Clinical Manifestations No visible or palpable signs of venous C0 disease C1 Telangiectasias or reticular veins C2 Varicose veins; distinguished from reticular veins by a diameter of 3 mm or greater C3 Edema C4 Changes in skin and subcutaneous tissue secondary to chronic venous disease: 4a (pigmentation or eczema), 4b (LDS or atrophie blanche) C5 Healed venous ulcer C6 Active venous ulcer E: Etiologic Factors EC Congenital EP Primary ES Secondary (post-thrombotic) EN No venous cause identied A: Anatomic Distribution of Disease AS Supercial veins AP Perforator veins AD Deep veins AN No venous location identied P: Pathophysiologic Findings PR Reux PO Obstruction PR,O Reux and obstruction PN No venous pathophysiology identiable
Abbreviation: LDS, lipodermatosclerosis.

Clinical Findings and Disease Course


Early clinical ndings of CVI include lower extremity edema, a condition that frequently presents at the ankles, worsens towards the end of the day, and improves overnight. Although not always present, varicosities range from thin telangiectasias to submalleolar venous ares to larger tortuous vessels.20,21 Over months to years, as venous hypertension continues, distal red-brown hyperpigmentation due to extravasated erythrocytes, hemosiderin-laden macrophages, and melanin deposition occurs.22 These changes tend to be localized to the gaiter area. At this stage of the disease, xerosis and pruritus may appear and can develop into venous eczema. This very pruritic condition begins at the ankle, particularly over the medial malleolus.23,24 It is often, but not always, bilateral. It may begin as sharply demarcated erythematous papules and vesicles; however, it eventually becomes diffuse, poorly dened, and may demonstrate serous exudate and crust.23-25 It is less frequently warm to the touch compared to cellulitis.25 In venous eczema, secondary infection can occur and should be suspected when the skin barrier has broken down and other signs of impetiginization exist. Contact dermatitis is common in these patients. Inciting agents include topical antibiotics such as neomycin and bacitracin, lanolin products,26 fragrances, parabens,27 corticosteroids,28 rubber components,29 and epoxy resin.30 A thorough history should be procured and patch testing considered in patients with recalcitrant lower extremity dermatitis. Disseminated eczema (id reaction) has also been reported in the context of contact dermatitis seen in patients with chronic venous disease.23,31,32 There is a clinical continuum of LDS ranging from acute to chronic disease.33 Acute LDS presents as painful, erythematous and purple, indurated plaques conned to the lower extremity. White scale may be present and lesions are usually well-demarcated from normal skin.7,19 LDS is often warm, tender, and clinically misdiagnosed as acute cellulitis, erythema nodosum, or inammatory morphea. Two thirds of patients with LDS demonstrate abnormal venous reux and/or ejection.34 In its more chronic form, LDS is associated with a classic inverted champagne bottle appearance of the distal third of the lower leg. Skin changes are characterized by hyperpigmentation and brosis of dermal and subcutaneous tissue,19,33 which is bilateral in approximately half of the cases (Figure 1).35 This morphology was rst described as hypodermatitis sclerodermiformis by Huriez in 1955.36 Over time,

white blood cells accumulate and release toxic oxygen metabolites and proteolytic enzymes resulting in capillary damage, increased permeability, and brin cuff formation.10 A 28.6% decrease in circulating white blood cells was shown in patients with CVI.11 Histologic specimens of LDS reveal increased white blood cells in tissue.12 T lymphocytes and macrophages increase in patients with varicose veins. Patients with severe LDS also show elevated interleukin-1 and interleukin-1, important proinammatory cytokines.13 Neutrophils, mast cells and interleukin-8 are also important mediators of inammation in CVI.14,15 Neutrophils exit the circulation and transverse the endothelium to enter the dermis. The cell-adhesion molecule L-selectin aids neutrophils in this process by adhering to endothelial cells to promote rolling along blood vessel walls. After leukocyte activation, L-selectin is shed and CD11b begins to allow similar adhesion and eventual extravascular migration.16 In chronic venous disease, plasma L-selectin increases and L-selectin decreases on the surface of circulating neutrophils. Venous hypertension possibly leads to this neutrophil activation and migration into tissue with subsequent decreased presence in circulation.16 Others have demonstrated increased adhesion molecules ICAM-1 and VCAM-1 in inamed liposclerotic skin.17

Venous eczema and lipodermatosclerosis


theories regarding its etiology have varied. Huriez and colleagues suspected cellulitis in the setting of venous insufciency.36 Many years later, acid-fast microorganisms were thought to be an inciting factor.37 Today, most authors agree that LDS is either exclusive to, or highly associated with, venous insufciency.20 The lower extremities are most often involved though it has been documented in other dependent locations. One interesting report describes a 54-year-old female with congestive heart failure demonstrating clinical and histologic ndings supportive for LDS in a pendulous abdomen.38 Risks factors for the development of LDS include female gender, elevated body mass index, and deep venous incompetence. One retrospective study of 97 LDS patients showed that 87% were women and 67% had deep venous incompetence while the mean body mass index was 34.3.35

171

Pathology
In CVI, the dermis may demonstrate lobulated, thick-walled small blood vessels in the papillary and reticular dermis, extravasated erythrocytes, hemosiderin-laden macrophages, lymphohistiocytic inltrates, and brosis (Figure 2).39,40 Venous eczema also demonstrates parakeratosis, epithelial hyperkeratosis, and dermal edema, which can be pronounced in the papillary dermis. Fibrosis is variable and a mononuclear cell inammatory inltrate is somewhat inconspicuous.41 These changes may be mild in acute LDS and more prominent in chronic disease.39,40 In LDS, the pathology lies in the subcutaneous tissue and broadly includes fat necrosis, a lymphohistiocytic inltrate, and septal brosis.40 Acute lesions demonstrate focally ex-

Figure 2 Histopathologic changes of chronic venous insufciency at low power showing lobules of small blood vessels, hemorrhage and hemosiderin.

travasated erythrocytes, ischemic necrosis in fat lobules with hyalinized fat, a sparse inammatory inltrate, and mild septal brosis. Lipomembranous fat necrosis and microcysts may only be seen in limited areas.40 As lesions progress, inammation is more prominent as is septal brosis and obliteration of fat lobules. Cyst-like cavities occur within the adipose tissue and pseudocysts more often possess the classic lipomembranous scalloped, feathered lining. Foamy macrophages and lipogranulomas may also occur.40 Moth-eatenappearing elastic bers, resembling those in pseudoxanthoma elasticum, may be present and help differentiate LDS from other brosing entities (Figure 3).39

Figure 1 An example of bilateral chronic lipodermatosclerosis demonstrating hyperpigmented and indurated plaques at the lower, medial legs.

Figure 3 Lipodermatosclerosis histopathology at low power showing deep-seated brosis and fat degeneration with microand macrocysts.

172

L.M. Morton and T.J. Phillips

Differential Diagnosis and Diagnostic Measures


It is important to differentiate venous eczema and LDS from other dermatologic conditions of the lower extremities. For the experienced clinician, these entities are most frequently diagnosed by physical examination.33,42 The differential diagnosis for venous eczema includes other papulosquamous conditions such as nummular eczema and psoriasis. These conditions usually affect additional body sites with nail changes or joint complaints in the case of psoriasis. Xerosis and eczema craquele can resemble venous eczema but are frequently more diffuse and generally improve with emollients and topical steroids alone. Venous eczema is commonly misdiagnosed as cellulitis.43,44 Both entities can present with pitting edema, erythema, serous drainage, and even desquamation. However, cellulitis is usually unilateral, tender, and may be associated with systemic symptoms such as a fever. Venous eczema is commonly bilateral and tends to be itchy, nontender, and more chronic.44 Perhaps the most challenging condition to rule out is allergic contact dermatitis since this may be seen in conjunction with venous eczema, which is characterized by a decreased skin barrier that may increase the rate of sensitization.45 In cases where allergy is suspected, patch testing is a valuable diagnostic tool.46 Irritant contact dermatitis should also be considered and the patient closely questioned about topical applications to the skin. Acute LDS is also frequently misdiagnosed as cellulitis as it presents with a very tender, well-circumscribed red plaque; however it does not improve with antibiotics. LDS may be confused with other panniculitidies such as erythema nodosum (usually presenting with multiple red tender nodules on the shins), thrombophlebitis (presenting as redness and tenderness along the course of the vein, usually accompanied by swelling), and brosing conditions such as inammatory morphea (presenting with indurated round or oval plaques which may be red to purple on initial presentation).19,47 LDS can be seen as a secondary diagnosis in patients with connective tissue disease; it should be considered prior to the use of immunosuppressants in these patients with lower extremity brosis.48 A rare but interesting case of sarcoidosis masquerading as LDS was reported where ulcerated plaques, morpheaform lesions, and lower extremity edema closely mimicked ndings of CVI.49 Biopsy should be avoided in patients with LDS since up to 50% of biopsy sites fail to heal33 and may become chronic ulcers. Furthermore, the histologic changes are not specic to this entity.50 Duplex ultrasound should be performed to conrm the suspected diagnosis of venous insufciency51,52 and can specically identify incompetent veins.53 Ultrasound indentometry may be a useful way to quantify brosis in LDS54 and the durometer can be used to assess skin hardness. It has been reported that magnetic resonance imaging can be used in the diagnosis of LDS, showing characteristic though not pathognomonic brosclerotic septa and a honeycomb pattern in the subcutaneous tissue.42

Treatment Options
Management of venous eczema and LDS must address underlying venous insufciency, primarily by compression therapy. Venous eczema may also be treated with topical interventions typically used for eczematous skin disease. There are several useful adjunctive measures for LDS in Table 2.

Compression Therapy
Compression is a mainstay of treatment for CVI. A 2012 Cochrane Database review, including 48 randomized controlled trials, veried that compression increases venous ulcer healing rates compared to no compression. Furthermore, multi-component compression containing an elastic bandage is more effective than compression without an elastic component.55 Given that venous eczema and LDS also improve with compression, this should be the rst-line treatment recommendation for patients. In one study of 150 patients, graduated compression alone effectively reduced the skin changes seen in LDS.56 In particular, below-the-knee, opentoe, graded compression is ideal.33 Pressure at 20-30 mm Hg may be sufcient for less severe cases; however, patients with any history of ulcer disease should employ 30-40 mm Hg.4 It is important to note that up to two thirds of patients may be nonadherent in the use of compression stockings for reasons including a binding sensation, presumed ineffectiveness, the sensation that they are too hot to wear, limb soreness, poor cosmesis, contact dermatitis, pruritus, and cost.57 Prior to attempting more aggressive interventions, clinicians should attempt to elicit an honest report from patients regarding their compliance with compression. While not ideal,58 even 10-15 mm Hg pressure may improve symptoms of venous insufciency.59 In one small study of 11 patients, ultrasound revealed that compression from 18-26 mm Hg is sufcient to decrease dermal edema in LDS patients.58 Compression wraps rather than stockings should be utilized in patients with open venous leg ulcers.19 Other simple interventions focus on lifestyle changes such as weight loss, increased leg elevation, and increased exercise to improve calf muscle pump function.4,52

Topical Interventions for Dermatitis


In addition to treating underlying venous insufciency with compression, venous eczema is managed topically with emollients and immunomodulators, including corticosteroids60 and calcineurin-inhibitors. There is scant data to support this approach. In one study of 19 patients with stasis dermatitis, betamethasone valerate 0.12% foam led to improvement in erythema compared to vehicle alone.61 Dissemond et al also reported one case of dermatitis treated twice daily for 5 days with topical 0.1% tacrolimus that resulted in complete healing.60 For severe venous eczema, a short course of oral corticosteroids can be helpful. In 2012, Maroo et al suggested treating venous eczema with a combination of oral doxycycline and topical tacrolimus. The authors cite the anticollagenase, anti-inammatory and immunomodulatory effects of doxycycline and the T-cell

Venous eczema and lipodermatosclerosis


Table 2 Treatment Recommendations for Lipodermatosclerosis Treatment Compression Recommended Dosing 30-40 mm Hg graduated compression (20-30 mm Hg may be effective in patients without history of venous leg ulcer) Stanozolol 2-5 mg by mouth twice daily Danazol 100-200 mg by mouth twice daily Oxandralone 100 mg by mouth twice daily Adverse Effects Limb soreness Contact dermatitis Pruritus Edema and hypertension Abnormal liver function tests Lipid abnormalities Virilization Dysmenorrhea Exacerbation of prostatic hypertrophy Peliosis hepatitis Hepatocellular carcinoma Monitoring

173

Prior to initiation, rule out arterial disease by palpating for pulses; ABI Blood pressure, liver function tests, lipid panel, prostatespecic antigen, complete blood count and renal function tests at baseline Blood pressure monitoring weekly for up to one month and then every 3-4 weeks Liver function tests every 3-4 weeks Uncontrolled hypertension, congestive heart failure, history of prostate adenocarcinoma and benign prostatic hypertrophy are contraindications

Anabolic Agents

Pentoxifylline

400-800 mg by mouth 3 times daily

Intralesional Triamcinolone Topical Capsaicin

5-10 mg/ml intradermal (dose varies based on area of involvement) 0.075% cream

Nausea Dizziness Heartburn Vomiting Pain with injection Cutaneous atrophy and dyspigmentation Burning sensation and/or pain Dermatitis

Abbreviation: ABI, ankle brachial index.

inhibitory effects of tacrolimus as important mechanisms for disease modication. Of 15 patients that completed the study with CVI, 13 showed improvement with 6 patients achieving 0-15% improvement of the involved area, 6 patients achieving 15-35% improvement, and one patient achieving greater than 35% improvement. The study showed statistically signicant improvement in pain, edema, erythema, pigmentation, pruritus, and exudate.62

Anabolic Agents for Lipodermatosclerosis


If tolerated, compression should be used to treat LDS. It is important to remember that patients with LDS often do not tolerate compression due to extreme skin tenderness. In addition to compression therapy, multiple publications have supported the use of stanozolol, an anabolic steroid with brinolytic properties.19 In a 6-month trial with 23 patients, Burnand et al showed an increased rate of LDS healing (based on involved area) with stanozolol 5 mg twice daily with compression compared to placebo with compression.63 In 1991, McMullin and colleagues showed similar results in a larger double-blind randomized controlled trial with 60 patients. After 6 months, those treated with graduated compression stockings (30-40 mm Hg) plus stanozolol 5 mg twice daily showed a 28% reduction of the involved area compared to a 14% reduction in patients treated with com-

pression alone.64 The authors postulated that perivascular brin deposition in LDS created local hypoxia and eventually ulceration.64 They also suggested that stanozolol may improve oxygenation due to its brinolytic properties; however, transcutaneous oxygen measurements were not affected.64 Lower doses of 2 mg twice daily may also be successful in acute LDS with decreased pain in 3 weeks and decreased induration at 8-10 weeks.33 Stanozolol might even be considered as monotherapy when patients absolutely cannot tolerate compression due to pain. In an open trial of 17 patients, stanozolol 2 mg twice daily alone reduced dermal thickness (as measured by high resolution ultrasound) and pain after 8 weeks and all participants tolerated compression at the end of treatment.65 Stanozolol has reversible anabolic and androgenic effects,66 including sodium retention with edema and hypertension, hirsuitism, acne, liver function, lipid abnormalities, and dysmenorrhea. Patients on this medication should have their blood pressure closely monitored and undergo liver function tests every 3-4 weeks. If the latter become elevated, the dose should be reduced.19 This intervention is best avoided in patients with uncontrolled hypertension or congestive heart failure.33 Danazol, a weak androgen with brinolytic properties used for endometriosis and acquired angioedema, has been

174 reported in several cases to improve pain and induration of LDS at doses between 200 mg-400 mg (in divided twice daily dosing).67,68 However, the virilizing side effects can be marked.67 Unfortunately, manufacturers in the United States no longer distribute danazol due to its abuse among weight lifters.19 Oxandrolone, another anabolic agent with less androgenicity, has also been used. Because it undergoes less metabolism by the liver compared to the aforementioned agents, Segal and colleagues chose this medication in a patient with LDS and elevated liver enzymes. After 2 weeks of 100mg twice daily dosing, the patient experienced pain reduction and subjective softening of the skin.66

L.M. Morton and T.J. Phillips


for 8 minutes 3 times weekly for 4-8 weeks. Patients also used compression stockings. A durometer was used to measure skin hardness; erythema was monitored by a reectance erythema meter. This intervention improved pain and tenderness within 2 weeks. A total of 10 of 13 legs showed a reduction in hardness (averaging 60%) and 7 of 9 legs showed decreased erythema. No adverse events were reported.74 There is little evidence for this modality; however, it is certainly a safe intervention in recalcitrant disease and in patients unable to proceed with other therapeutic options.

Surgical Intervention
The best published data supporting venous ablation in CVI more specically references venous leg ulcers. The 2004 ESCHAR study evaluated 500 patients with active or recently healed venous leg ulcers. Patients were randomly assigned to receive ablative supercial vein surgery with compression or compression alone. Data revealed that 24-week healing rates were similar between groups. Ulcer recurrence at 12 months was signicantly reduced in the patients that also received surgery (12% vs 28%). For this reason, patients with documented supercial venous disease and a history of leg ulcers are generally referred for ablative surgery.75 Many studies of surgical intervention for venous insufciency do not provide specic descriptions regarding improvement of LDS. In patients treated with saphenofemoral junction ligation and ultrasound-guided foam sclerotherapy, Figueiredo et al reported improved venous clinical severity scores, taking LDS into account.76

Pentoxifylline
An alternative for patients who cannot tolerate or safely take stanozolol is pentoxifylline, a demethylxanthine derivative that increases red blood cell exibility, alters broblast physiology, and stimulates brinolysis. Pentoxifylline is generally given in doses of 400 mg 3 times daily. A 2012 Cochrane Database review states that this agent improves venous ulcer healing when combined with compression or when used alone.69 A retrospective study published in 2012 supported the use of pentoxifylline 1200 mg daily in combination with hydroxychloroquine in dosages up to 6.5 mg/kg/day in the treatment of LDS. Without compression, 13 of 30 patients experienced complete remission of pain, edema resolution occurred in 14 of 15 patients, and erythema resolution occurred in 24 of 28 patients. Induration was signicantly improved in 17 patients.70 For difcult cases, the dose of pentoxifylline may be increased to 800 mg 3 times daily. Side effects include nausea, dizziness, heartburn, and occasional vomiting.

Conclusion
Cutaneous disease is frequent in CVI. It is imperative that clinicians identify conditions such as venous eczema and LDS, differentiating them from similar appearing disorders with a thorough history and physical exam. While the most important aspect of management is compression therapy, this spectrum of disease offers an exciting avenue for further research since much of the literature to date focuses on the management of venous leg ulcers rather than venous eczema and LDS.

Other Nonsurgical Interventions


Campbell and Miller have shown that intralesional triamcinolone at concentrations of 5-10 mg/ml effectively improves pain, edema, induration, and erythema of LDS.71 In their study of 28 patients, compression was also utilized and multiple treatments were required for lasting improvement.71 Intralesional therapy with platelet-rich plasma was used to treat a 76 year old man with LDS who failed multiple interventions including compression, anabolic steroids, pentoxifylline, antibiotics, nonsteroidal anti-inammatory drugs, and surgery. He was given autologous platelet-rich plasma subcutaneously at 2-week intervals. Five treatments resulted in decreased pain, hyperpigmentation, induration, and eventual epithelialization of an associated leg ulcer. Platelet-richplasma may work by stimulating adipose tissue regeneration and angiogenesis.72 Topical capsaicin, frequently employed to treat localized pruritus, improved LDS in 2 patients who failed more conventional therapy. The topical 0.075% capsaicin cream was used for 3 weeks and the authors postulate that the cream may have brinolytic and antithrombotic effects.73 The least-invasive intervention utilized for LDS is ultrasound. In 2009, Damian et al reported 11 patients with longstanding LDS treated with 3 MHz of continuous ultrasound

Acknowledgements
Thank you to Dr. Daniel Miller and Dr. Meera Mahalingam at Skin Pathology Laboratory at Boston University Medical Center for assisting with the acquisition of histopathologic images.

References
1. Beebe-Dimmer JL, Pfeifer JR, Engle JS, Schottenfeld D. The epidemiology of chronic venous insufciency and varicose veins. Ann Epidemiol. 2005;15(3):175-184. 2. Fowkes FG, Evans CJ, Lee AJ. Prevalence and risk factors of chronic venous insufciency. Angiology. 2001;52(Suppl 1):S5-S15. 3. Eklf B, Rutherford RB, Bergan JJ, et al. Revision of the CEAP classication for chronic venous disorders: consensus statement. J Vasc Surg. 2004;40(6):1248-1252. 4. Hamdan A. Management of varicose veins and venous insufciency. JAMA. 2012;308(24):2612-2621.

Venous eczema and lipodermatosclerosis


5. Raffetto JD. Dermal pathology, cellular biology, and inammation in chronic venous disease. Thromb Res. 2009;123(Suppl 4):S66-S71. 6. Jnger M, Steins A, Hahn M, Hfner HM. Microcirculatory dysfunction in chronic venous insufciency (CVI). Microcirculation. 2000;7(6 Pt 2):S3-S12. 7. Burnand KG, Whimster I, Naidoo A, Browse NL. Pericapillary brin in the ulcer-bearing skin of the leg: the cause of lipodermatosclerosis and venous ulceration. Br Med J (Clin Res Ed). 1982;285(6348):1071-1072. 8. Mani R, White JE, Barrett DF, Weaver PW. Tissue oxygenation, venous ulcers and brin cuffs. J R Soc Med. 1989;82(6):345-346. 9. Falanga V, Moosa HH, Nemeth AJ, Alstadt SP, Eaglstein WH. Dermal pericapillary brin in venous disease and venous ulceration. Arch Dermatol. 1987;123(5):620-623. 10. Coleridge Smith PD, Thomas P, Scurr JH, Dormandy JA. Causes of venous ulceration: a new hypothesis. Br Med J (Clin Res Ed) 1988; 296(6638):1726-1727. 11. Thomas PR, Nash GB, Dormandy JA. White cell accumulation in dependent legs of patients with venous hypertension: a possible mechanism for trophic changes in the skin. Br Med J (Clin Res Ed). 1988; 296(6638):1693-1695. 12. Scott HJ, Coleridge Smith PD, Scurr JH. Histological study of white blood cells and their association with lipodermatosclerosis and venous ulceration. Br J Surg. 1991;78(2):210-211. 13. Wilkinson LS, Bunker C, Edwards JC, Scurr JH, Smith PD. Leukocytes: Their role in the etiopathogenesis of skin damage in venous disease. J Vasc Surg. 1993;17(4):669-675. 14. Nicolaides AN. Chronic venous disease and the leukocyte-endothelium interaction: from symptoms to ulceration. Angiology. 2005;56(Suppl 1):S11-S19. 15. Zhang L, Zhang BG, Zhang JW, Zhang H. Immune function of erythrocytes in patients with chronic venous insufciency of the lower extremities. Chin Med J (Engl). 2007;120(24):2224-2228. 16. Saharay M, Shields DA, Porter JB, Scurr JH, Coleridge Smith PD. Leukocyte activity in the microcirculation of the leg in patients with chronic venous disease. J Vasc Surg. 1997;26(2):265-273. 17. Weyl A, Vanscheidt W, Weiss JM, Peschen M, Schopf E, Simon J. Expression of the adhesion molecules ICAM-1, VCAM-1, and E-selectin and their ligands VLA-4 and LFA-1 in chronic venous leg ulcers. J Am Acad Dermatol. 1996;34(3):418-423. 18. Herouy Y, May AE, Pornschlegel G, et al. Lipodermatosclerosis is characterized by elevated expression and activation of matrix metalloproteinases: implications for venous ulcer formation. J Invest Dermatol. 1998; 111(5):822-827. 19. Miteva M, Romanelli P, Kirsner RS. Lipodermatosclerosis. Dermatol Ther. 2010;23(4):375-388. 20. Valencia IC, Falabella A, Kirsner RS, Eaglstein WH. Chronic venous insufciency and venous leg ulceration. J Am Acad Dermatol. 2001; 44(3):401-421; quiz 422-424. 21. Ramelet AA. European Dermatology Forum: skin diseases in Europe. Skin diseases with a high public health impact: chronic venous insufciency. Eur J Dermatol. 2008;18(2):211-213. 22. Phillips TJ, Dover JS. Leg ulcers. J Am Acad Dermatol. 1991;25(6 Pt 1):965-987. 23. Reider N, Fritsch PO. Other eczematous eruptions. In: Bolognia JL, Jorizzo JL, Schaffer JV, eds. Rapini RP, ed. Dermatology. Vol I. 3rd ed. Elsevier Saunders; 2012:219-232. 24. Na CR, Wang S, Kirsner RS, Federman DG. Elderly adults and skin disorders: common problems for nondermatologists. South Med J. 2012; 105(11):600-606. 25. Hirschmann JV, Raugi GJ. Lower limb cellulitis and its mimics: part II. Conditions that simulate lower limb cellulitis. J Am Acad Dermatol. 2012;67(2):177. e171-e179; quiz 185-176. 26. Wilson CL, Cameron J, Powell SM, Cherry G, Ryan TJ. High incidence of contact dermatitis in leg-ulcer patientsimplications for management. Clin Exp Dermatol. 1991;16(4):250-253. 27. Angelini G, Rantuccio F, Meneghini CL. Contact dermatitis in patients with leg ulcers. Contact Dermatitis. 1975;1(2):81-87. 28. de Groot AC, van Ginkel CJ, Bruynzeel DP. Contact allergy for corticosteroids [in Dutch]. Ned Tijdschr Geneeskd. 1997;141(32):1559-1562.

175
29. Gooptu C, Powell SM. The problems of rubber hypersensitivity (Types I and IV) in chronic leg ulcer and stasis eczema patients. Contact Dermatitis. 1999;41(2):89-93. 30. Shupp DL, Winkelmann RK. The role of patch testing in stasis dermatitis. Cutis. 1988;42(6):528-530. 31. Watson WW. Widespread dermatitis after topical treatment of chronic leg ulcers and stasis dermatitis. CMAJ. 1988;139(2):103. 32. Hogan DJ. Widespread dermatitis after topical treatment of chronic leg ulcers and stasis dermatitis. CMAJ. 1988;138(4):336-338. 33. Kirsner RS, Pardes JB, Eaglstein WH, Falanga V. The clinical spectrum of lipodermatosclerosis. J Am Acad Dermatol. 1993;28(4):623-627. 34. Greenberg AS, Hasan A, Montalvo BM, Falabella A, Falanga V. Acute lipodermatosclerosis is associated with venous insufciency. J Am Acad Dermatol. 1996;35(4):566-568. 35. Bruce AJ, Bennett DD, Lohse CM, Rooke TW, Davis MD. Lipodermatosclerosis: review of cases evaluated at Mayo Clinic. J Am Acad Dermatol. 2002;46(2):187-192. 36. Huriez, Lagache, Desmons, Pelce. Leg ulcers and trophic disorders of venous origin; data from the study of one thousand hospitalized patients with ulcers [in French]. Rev Prat. 1955;5(26):2703-2721. 37. Cantwell AR Jr, Kelso DW, Rowe L. Hypodermitis sclerodermiformis and unusual acid-fast bacteria. Arch Dermatol. 1979;115(4):449-452. 38. Bull RH, Mortimer PS. Acute lipodermatosclerosis in a pendulous abdomen. Clin Exp Dermatol. 1993;18(2):164-166. 39. Walsh SN, Santa Cruz DJ. Lipodermatosclerosis: a clinicopathological study of 25 cases. J Am Acad Dermatol. 2010;62(6):1005-1012. 40. Huang TM, Lee JY. Lipodermatosclerosis: a clinicopathologic study of 17 cases and differential diagnosis from erythema nodosum. J Cutan Pathol. 2009;36(4):453-460. 41. Hunt SJ SCD, Barnhill RL. Vascular tumors. In: Barnhill R, ed. Textbook of Dermatopathology. 2nd ed. New York, New York: McGraw-Hill; 2004: 821-870. 42. Chan CC, Yang CY, Chu CY. Magnetic resonance imaging as a diagnostic tool for extensive lipodermatosclerosis. J Am Acad Dermatol. 2008; 58(3):525-527. 43. Bailey E, Kroshinsky D. Cellulitis: diagnosis and management. Dermatol Ther. 2011;24(2):229-239. 44. Keller EC, Tomecki KJ, Alraies MC. Distinguishing cellulitis from its mimics. Cleve Clin J Med. 2012;79(8):547-552. 45. Prakash AV, Davis MD. Contact dermatitis in older adults: a review of the literature. Am J Clin Dermatol. 2010;11(6):373-381. 46. Nedorost ST, Stevens SR. Diagnosis and treatment of allergic skin disorders in the elderly. Drugs Aging. 2001;18(11):827-835. 47. Fallahzadeh MK, Khalesi M, Namazi MR. Lipodermatosclerosis: a commonly misdiagnosed complication of chronic venous insufciency. Scientic World Journal. 2010;10:576-577. zes F, Pontes Vilas Boas Freitas A, 48. Dias Gonzalez F, Pedreira Magalh Castro Lima Filho H, Santiago MB. Lipodermatosclerosis in patients with diffuse connective tissue diseases. Eur J Intern Med. 2006;17(4): 288-289. 49. Huang CL, Mutasim DF. Sarcoidosis mimicking lipodermatosclerosis. Cutis. 2005;75(6):322-324. 50. Heymann WR. Lipodermatosclerosis. J Am Acad Dermatol. 2009;60(6): 1022-1023. 51. Cina A, Pedicelli A, Di Stasi C, et al. Color-Doppler sonography in chronic venous insufciency: what the radiologist should know. Curr Probl Diagn Radiol. 2005;34(2):51-62. 52. Gloviczki P, Comerota AJ, Dalsing MC, et al. The care of patients with varicose veins and associated chronic venous diseases: clinical practice guidelines of the Society for Vascular Surgery and the American Venous Forum. J Vasc Surg. 2011;53(5 Suppl):2S-48S. 53. Egeblad K, Baekgaard N. Chronic venous insufciency. Results of duplex scanning of 205 lower extremities with varices: 106 not previously operated and 99 previously operated for varicose veins [in Danish]. Ugeskr Laeger. 2003;165(31):3016-3018. 54. Geyer MJ, Brienza DM, Chib V, Wang J. Quantifying brosis in venous disease: mechanical properties of lipodermatosclerotic and healthy tissue. Adv Skin Wound Care. 2004;17(3):131-142.

176
55. OMeara S, Cullum N, Nelson EA, Dumville JC. Compression for venous leg ulcers. Cochrane Database Syst Rev. 2012;11:CD000265. 56. Vandongen YK, Stacey MC. Graduated compression stockings reduce lipodermatosclerosis and ulcer recurrence. Phlebology. 2000(15):33-37. 57. Raju S, Hollis K, Neglen P. Use of compression stockings in chronic venous disease: patient compliance and efcacy. Ann Vasc Surg. 2007; 21(6):790-795. 58. Gniadecka M, Karlsmark T, Bertram A. Removal of dermal edema with class I and II compression stockings in patients with lipodermatosclerosis. J Am Acad Dermatol. 1998;39(6):966-970. 59. Benigni JP, Sadoun S, Allaert FA, Vin F. Efcacy of Class 1 elastic compression stockings in the early stages of chronic venous disease. A comparative study. Int Angiol. 2003;22(4):383-392. 60. Dissemond J, Knab J, Lehnen M, Franckson T, Goos M. Successful treatment of stasis dermatitis with topical tacrolimus. Vasa. 2004;33(4): 260-262. 61. Weiss SC, Nguyen J, Chon S, Kimball AB. A randomized controlled clinical trial assessing the effect of betamethasone valerate 0.12% foam on the short-term treatment of stasis dermatitis. J Drugs Dermatol. 2005; 4(3):339-345. 62. Maroo N, Choudhury S, Sen S, Chatterjee S. Oral doxycycline with topical tacrolimus for treatment of stasis dermatitis due to chronic venous insufciency: a pilot study. Indian J Pharmacol. 2012;44(1):111113. 63. Burnand K, Clemenson G, Morland M, Jarrett PE, Browse NL. Venous lipodermatosclerosis: treatment by brinolytic enhancement and elastic compression. Br Med J. 1980;280(6206):7-11. 64. McMullin GM, Watkin GT, Coleridge Smith PD, Scurr JH. Efcacy of brinolytic enhancement with stanozolol in the treatment of venous insufciency. Aust N Z J Surg. 1991;61(4):306-309. 65. Vesic S, Vukovic J, Medenica LJ, Pavlovic MD. Acute lipodermatosclerosis: an open clinical trial of stanozolol in patients unable to sustain compression therapy. Dermatol Online J. 2008;14(2):1.

L.M. Morton and T.J. Phillips


66. Segal S, Cooper J, Bolognia J. Treatment of lipodermatosclerosis with oxandrolone in a patient with stanozolol-induced hepatotoxicity. J Am Acad Dermatol. 2000;43(3):558-559. 67. Hafner C, Wimmershoff M, Landthaler M, Vogt T. Lipodermatosclerosis: successful treatment with danazol. Acta Derm Venereol. 2005;85(4): 365-366. 68. Hammerman S MI, Falanga V. An acute case of lipodermatosclerosis successfully treated with danazol. J Am Acad Dermatol. 2012;66(4 Supp. 1):AB42. 69. Jull AB, Arroll B, Parag V, Waters J. Pentoxifylline for treating venous leg ulcers. Cochrane Database Syst Rev. 2012;12:CD001733. 70. Choonhakarn C, Chaowattanapanit S. Lipodermatosclerosis: improvement noted with hydroxychloroquine and pentoxifylline. J Am Acad Dermatol. 2012;66(6):1013-1014. 71. Campbell LB, Miller OF 3rd. Intralesional triamcinolone in the management of lipodermatosclerosis. J Am Acad Dermatol. 2006;55(1):166168. 72. Jeong KH, Shin MK, Kim NI. Refractory lipodermatosclerosis treated with intralesional platelet-rich plasma. J Am Acad Dermatol. 2011;65(5): e157-e158. 73. Yosipovitch G, Mengesha Y, Facliaru D, David M. Topical capsaicin for the treatment of acute lipodermatosclerosis and lobular panniculitis. J Dermatolog Treat. 2005;16(3):178-180. 74. Damian DL, Yiasemides E, Gupta S, Armour K. Ultrasound therapy for lipodermatosclerosis. Arch Dermatol. Mar 2009;145(3):330-332. 75. Barwell JR, Davies CE, Deacon J, et al. Comparison of surgery and compression with compression alone in chronic venous ulceration (ESCHAR study): randomised controlled trial. Lancet. 2004;363(9424): 1854-1859. 76. Figueiredo M, de Araujo SP, Figueiredo MF. Late follow-up of saphenofemoral junction ligation combined with ultrasound-guided foam sclerotherapy in patients with venous ulcers. Ann Vasc Surg. 2012;26(7): 977-981.