Uncommon leg ulcers in the lower extremityNicos Labropoulos, PhD, DIC, RVT,a,b Danielle Manalo, MD,a Nima P. Patel, MD,b

Jay Tiongson, MD,a Landon Pryor, MD,a and Athanasios D. Giannoukas, MD,c Maywood, Ill; Newark, NJ;and Larissa, Greece

Objective: To determine the prevalence of uncommon ulcers, unrelated to venous or arterial etiology, in patientspresenting to vascular clinics.Methods: This was a multicenter prospective study of consecutive patients presenting with lower extremity ulceration. Thesettings were university hospital outpatient centers and venous clinics. A total of 799 limbs in 710 patients with leg ulcerswere evaluated. Patients with venous ulcer disease and with evidence of arterial disease with an ankle-brachial index lessthan 0.7 were excluded from the study. Out of 710 patients, 17 patients with a total of 21 limbs fit the criteria forinclusion. All limbs included in this study underwent physical examination, ankle-brachial index measurements, duplexultrasonography, and skin biopsies.Results: The mean age of patients with uncommon ulcers was 65.6 years, and the mean duration was 5.5 years. A total of2.1% of all leg ulcers seen were due to uncommon etiology unrelated to venous or arterial pathology. Most of these ulcerswere located in the medial lower calf (n � 19). In six patients with ulcers, the histology did not reveal any specific cause;five had a neoplasia, three had chronic inflammation, two had sickle cell disease, two had vasculitis, one had rheumatoidarthritis, one had pyoderma gangrenosum, and one had ulcer due to hydroxyurea.Conclusions: The prevalence of leg ulcers unrelated to arterial and venous disease that presented with signs and symptomsof chronic venous disease was 2.1%. Their etiology is variable, most often including vasculitis, neoplasia, metabolicdisorders, infection, and other rare causes. Early identification of uncommon ulcers may facilitate timely and appropriate

management. (J Vasc Surg 2007;45:568-73.)

Chronic leg ulceration is a common condition withlimited epidemiologic data. Some studies report prevalencerates between 0.18% and 2% of the European population1,2

and up to 5% of the population over 65 years of age.1 Theoverwhelming majority of leg ulcers are of venous origin,cited in the literature from anywhere between 45% and 90%of all leg ulcers.1,2 The second most common cause of legulcers is arterial occlusive disease, followed by neuropathiculcers. Interpretation of these data has been complicated bythe recent shift toward arterial and mixed ulcers, likelybecause of the aging population and improved detection ofarterial disease.1 The high prevalence of risk factors foratherosclerotic occlusion, especially in Western popula-tions, also contributes to the increasing incidence of ulcer-ation.2 Proper identification of the etiology of leg ulcers isimperative for appropriate management, because incorrecttreatment may cause significant harm.2

Venous ulcers are classically located in the gaiter areawith the appearance of an irregular border, fibrinous debris,extensive granulations, and weeping; the surrounding skinmay demonstrate edema, hemosiderin pigmentation, hy-

From the Department of Surgery, Loyola University Medical Center, May-wood,a the Department of Surgery, University of Medicine and Dentistryof New Jersey, Newark,b and the Department of Surgery, University ofThessaly, Larissa.c

Competition of interest: none.Additional material for this article may be found online at www.jvascsurg.org.Reprint requests: Nicos Labropoulos, PhD, Department of Surgery, Vascu-

lar Laboratory, University of Medicine and Dentistry of New Jersey, 150Bergen St, Room D-447, Newark, NJ 07101-1709 (e-mail: nlabrop@yahoo.com).

0741-5214/$32.00Copyright © 2007 by The Society for Vascular Surgery.

doi:10.1016/j.jvs.2006.11.012

568

perkeratosis, atrophie blanche, or cellulitis.1,2 Some ulcersthat appear to be venous are of other etiologies. Carcino-matous growth can be masked as a deteriorating leg ulcer.3

Case reports have described livedoid vasculitis or calciphy-laxis in patients who were otherwise expected to havevenous ulcers.4,5 However, information on ulcers withuncommon etiologies is lacking. Therefore, this study wasperformed to determine the prevalence of these ulcers inpatients presenting to a vascular clinic.

METHODS

A total of 710 patients and 799 limbs with leg ulcersfrom various centers were evaluated. Patients with legulcers of nonvenous etiology and nonarterial ischemic dis-ease were included in the study. They were selected fromconsecutive patients with leg ulcers (class 6 according to theCEAP classification6) attending a venous clinic. The ulcerswere associated with signs and symptoms of chronic venousdisease. These included pain, swelling, burning sensation,itching, heaviness, restless limb, skin discoloration, andlipodermatosclerosis. They were located on the medialmalleolus, lateral malleolus, or calf. Patients with foot ul-cers were not included in the study. Appreciable arterialdisease that may have contributed to the ulcer formationwas eliminated by including only those patients with anankle-brachial index of greater than 0.7. These patientswere also excluded from the multicenter study and there-fore were not available for this study. Patients with footulcers were unlikely to have venous disease and were ex-cluded as well.

Duplex ultrasonography was used to investigate the veinsin the lower extremity from groin to ankle. The femoropop-

liteal veins; deep calf veins; great saphenous veins, small saphe-

dial; n

JOURNAL OF VASCULAR SURGERYVolume 45, Number 3 Labropoulos et al 569

nous veins, and their tributaries; nonsaphenous veins; andperforating veins were evaluated in all limbs. Reflux was con-sidered to be present when the retrograde flow lasted longerthan 1 second in the femoropopliteal veins and more than0.5 seconds in the superficial and deep calf veins. Evidenceof thrombosis was documented by the noncompressibilityof the vein, visualization of the thrombus, filling defects oncolor mode, intraluminal webs, recanalized intraluminalchannels, and wall thickening. Limbs with reflux or ob-struction were excluded.

The physical examination, the ankle-brachial index,and the ultrasound investigation were performed by spe-cialists in vascular medicine or vascular surgery. The partic-ipating centers had at least 3 years of experience in exam-ining patients with chronic venous disease. All limbs thatwere included in this study underwent skin biopsies. A3-mm punch biopsy or incisional biopsy provides a full-thickness tissue sample with minimal scarring.7 The datawere inserted in a customized Microsoft Access database(Microsoft Corp, Redmond, Wash).

RESULTS

Out of 799 patients with leg ulcers, 17 patients with 21ulcerated limbs were included in the study (Table I). Fourpatients had bilateral ulcers. The mean age was 65.6 years(SD, 15.2 years), and the mean duration of the ulcers was5.5 years. The location of the ulcers was predominately onthe medial aspect of the lower calf (n � 19): one waslocated in the anterolateral and one in the posterior aspectof the calf. Three patients demonstrated venous reflux byduplex ultrasonography. Two of them underwent strippingof the great saphenous vein and stab avulsions of thevaricosities. The third patient had injection sclerotherapy of

Table I. Characteristics of the ulcers found on 21 patients

Sex Age (y) Limb Location on calf Duration (y)

M 63 L u-l/med 3R u-l/med 3

F 72 L l/med 5R l/med 5

F 52 L m-l/med 4M 73 R l/med 8M 54 R l/ant-lt 2M 68 L m/post 1M 79 L l/med 16F 76 R l/med 18F 73 R l/med 15F 64 L m-l/med 3

R m-l/med 3M 71 L l/med 4F 82 R m-l/med 7F 73 R l/med 14M 78 L m/med 2

59 L l/med 0.17M 17 R l/med 0.33M L l/med 0.25F 62 R l/med 0.75

ABI, Ankle-brachial index; u, upper calf; m, mid calf; l, lower calf; med, me

a calf tributary. The deep veins were normal in all three

patients, and no other venous abnormality was found.Despite of the successful treatment for the reflux, the ulcersstill persisted. The third patient had also an ankle-brachialindex of 0.7, which decreased to 0.58 after exercise. He hada significant stenosis in the superficial femoral and poplitealarteries. Both lesions were successfully treated with percu-taneous transluminal angioplasty, and the ankle-brachialindex increased to 0.92. The ulcer was reduced in size afterthe arterial and venous treatment but never healed. None ofthe patients had trauma, deep venous thrombosis, superfi-cial venous thrombosis, congestive heart failure, chronicrenal failure, hepatic failure, diabetes mellitus, or depen-dency.

The size of the ulcer varied. The largest diameterranged from 2 to 14 cm. The ulcers had characteristics of achronic wound. Most of them were highly inflamed andhad necrotic tissue and hyperproliferation in the sur-rounding skin. On closer inspection, there were differentcharacteristics in many ulcers, but this information wasnot systemically collected. When the patients were foundnot to have arterial or venous disease, they were sent to adermatologist and had a skin biopsy.

Three patients were being treated with antibiotics forcellulitis with concurrent lymphedema. Two other pa-tients were also being treated with antibiotics. These twopatients were given antibiotics by their referring physi-cians but were not shown to have an infection. Obesitywas not an exclusion factor, and two of our patients withundetermined pathology were obese, with a body massindex of 34 and 39 kg/m2.

Pathology was identified in 15 limbs of 13 patients(Table II). Two patients had no histologic analysis becausethe biopsy specimens were lost in the pathology depart-

Duplex ABI Medication Pathology

nl abx Undeterminednl abx Undeterminednl Vasculitisnl Vasculitisnl abx Chronic inflammationnl abx Chronic inflammationnl abx Chronic inflammationnl Kaposi sarcomanl Carcinoma

ous reflux nl Squamous cell carcinomaous reflux nl Squamous cell carcinoma

nl Undeterminednl Undeterminednl No histologynl abx No histologynl Basal cell carcinomanl Pyoderma gangrenosumnl Hydroxyureanl Sickle cellnl Sickle cell

d reflux 0.7 Rheumatoid arthritis

l, normal; abx, antibiotics; post, posterior; ant-lt, anterior lateral.

nlnlnlnlnlnlnlnl

VenVennlnlnlnlnlnlnlnlnlMil

ment and the patients refused to have another biopsy

JOURNAL OF VASCULAR SURGERYMarch 2007570 Labropoulos et al

performed. Two of the four patients with bilateral ulcershad undetermined pathology despite histologic study. Twopatients with venous reflux had a histologic diagnosis ofsquamous cell carcinoma (SCC). One patient each hadulcer pathology that revealed Kaposi sarcoma, carcinoma,basal cell carcinoma (BCC), pyoderma gangrenosum, andhydroxyurea. The patient with the Kaposi sarcoma wasimmunosuppressed. Histologic diagnoses were obtained intwo patients with bilateral ulcers. One patient had nonspe-cific vasculitis; the other had pathology that confirmedsickle cell anemia.

One patient with a combination of mild reflux and anankle brachial index of 0.7 had an ulcer etiology of rheu-matoid arthritis. Three patients with cellulitis receivingantibiotic therapy had pathology consistent with chronicinflammation.

DISCUSSION

The differential diagnosis for leg ulcers is extensive.Fortunately, most of the conditions are rare and exist inthe literature as small case series or case reports. Themost common etiologies of leg ulcers can be groupedinto venous, arterial, or neuropathic ulcers. In our study,uncommon leg ulcers accounted for 2.1% of all legulcers. Appendix II (online only) includes the results froma literature search for case reports of uncommon leg ulcersin adults. Clearly, our study has underestimated the preva-lence of uncommon leg ulcers because many of thosepatients do not go to vascular clinics. This was also becausein this study, only ulcers that had a venous appearance andlocation were included. Furthermore, the rest of the pa-tients who had venous etiology and arterial disease did nothave a biopsy performed. Therefore, other patients fromthe same pool were missed.

One patient in our study had pyoderma gangrenosumlocated on the medial aspect of the mid calf. It is anuncommon but impressive ulcer of unknown etiology. Fifty

Table II. Pathology results

Pathology Limbs No. Patients

Undetermined 5 3No histology available* 1 1Chronic inflammation 3 3SCC 2 2Kaposi sarcoma 1 1Carcinoma 1 1BCC 1 1Sickle cell anemia 2 1Vasculitis 2 1Pyoderma gangrenosum 1 1Hydroxyurea 1 1RA 1 1Total 21 16% of uncommon ulcers out of

total leg ulcers 1.3% 2.1%

SCC, Squamous cell carcinoma; BCC, basal cell carcinoma.*The histology specimen was lost, and the biopsy was not repeated.

percent of cases are associated with chronic disease, and the

other 50% are considered idiopathic.8 Lesions are mostcommonly found on the lower legs, but they may occuranywhere on the skin.9 Usually they begin as painful pus-tules, with rapid development of necrosis and ulceration.Fully established lesions show single or multiple ulcers withwell-defined, raised, purple, serpiginous, and underminedborders.7 There are also several variants, and this can makethe diagnosis difficult. Investigations including skin biopsyshould be undertaken to rule out other etiologies.7 Theinitial goals of treatment are to address any underlyingdisorders and provide adequate wound care. Systemic treat-ment with corticosteroids followed by cyclosporine orother immunomodulatory agents has been successful intreating pyoderma gangrenosum.2

Leg ulcers are a common complication in patients withhomozygous sickle cell disease and those with associated�-thalassemia, with prevalence rates from 8% to 10% ofpatients aged 10 to 50 years.10 Contributing factors toulcer formation include vessel obstruction by sickled cells,increased venous and capillary pressure, secondary bacterialinfection, and decreased oxygen-carrying capacity of theblood.9 The medial malleoli are the most common site ofleg ulceration in sickle cell disease and in other chronichemolytic anemias, suggesting perhaps that stasis may playa role in leg ulceration associated with chronic hemolyticanemia. These ulcers are often bilateral, persistent, andrecurrent. This was illustrated in the patient in our studywith bilateral ulcers on the medial aspect of the lowercalves. Depending on the extent of the lesions, treatmentmodalities may include bed rest, debridement, wet-to-drysaline dressings, blood transfusions, and topical antibiot-ics.11 Skin grafts and myocutaneous flaps may be requiredfor extensive ulcers.

Rheumatoid arthritis and Felty syndrome are com-monly associated with leg ulcers. Studies report that 9% to10% of patients with rheumatoid arthritis12,13 and approx-imately 25% of patients with Felty syndrome have legulcers. The etiologies of these ulcers are frequently multi-factorial. Concurrent venous or arterial disease is oftencontributory, as seen in our study with one patient who hadrheumatoid arthritis with concurrent mild venous refluxand an ankle-brachial index of 0.7. Other causes includevasculitis, diabetes, deformities, trauma, or pressure fromill-fitting shoes.2 Occasionally the cause is uncertain. Oienet al12 reviewed 20 cases of leg ulcers in patients withrheumatoid arthritis and reported 1 patient with a leg ulcerof undetermined etiology. No further discussion was maderegarding this finding. This nonvenous, nonarterial ulcerlikely represents a less common ulcer similar to those seenin our study. Two patients had undetermined pathologydespite histologic study.

Leg ulcers have been documented as a rare complica-tion of long-term hydroxyurea treatment in patients under-going therapy for myeloproliferative disorders.14 Thesepainful, persistent ulcers may not manifest until after aduration of 2 to 15 years of treatment.2 Usually located onthe malleoli, the ulcer appears fibrous, with atrophic peri-

ulcerous skin. Twenty-four case reports were found in the

JOURNAL OF VASCULAR SURGERYVolume 45, Number 3 Labropoulos et al 571

literature between 1996 and June 2004. One multicenterretrospective study of 41 cases of leg ulceration duringhydroxyurea therapy noted that 80% of the ulcers com-pletely recovered after discontinuation of the drug; the resthad improvement and reduction in ulcer size.15 One pa-tient in our study had a hydroxyurea ulcer on the medialaspect of the lower calf for 2 months. The duration ofhydroxyurea therapy was 3 years. After the discontinuationof the drug, the ulcer was healed.

Calciphylaxis is a rare condition that can develop as acomplication of secondary hyperparathyroidism, whichmost commonly occurs in patients with end-stage renaldisease. Up to 4% of patients receiving renal dialysis mayshow signs of calciphylaxis.16 It is characterized by exces-sive calcium deposition in the skin, soft tissues, and arteries.Patients may present with a range of skin manifestations,from painful subcutaneous nodules to nonhealing extrem-ity ulcers and gangrene.17 The exact pathogenesis remainsuncertain. Ischemic necrosis preferentially affects cutane-ous vessels of the trunk and limb girdle. There is often rapidonset, with large, painful plaques that evolve into full-thickness necrosis and gangrene, similar to that seen withwarfarin-associated necrosis.7 Treatment includes localwound care, correction of the calcium/phosphorus ratio,and surgical evaluation for possible arterial revasculariza-tion and parathyroidectomy.16

Five patients had ulcers of neoplastic origin. Two pa-tients with venous reflux presented with ulcer etiologies ofSCC. As mentioned previously, stasis ulcers are likely todegenerate into malignancy.3 The ulcers may often bepainless, appear hypertrophic or hemorrhagic with irregularborders, and exhibit a slow progressive growth. The dura-tion of each ulcer with SCC in our study was 18 and 15years. One epidemiologic study noted an increase in theincidence of SCC in venous ulcers.18 It is the second mostcommon form of skin cancer and often arises on sun-exposed areas of middle-aged and elderly individuals of faircomplexion. It can also occur on non–sun-exposed areassuch as the genitals and mucous membranes. It is interest-ing to note that SCC is the most common type of skincancer in African Americans, often involving skin that is notchronically sun-exposed.17 The ulcers with SCC in ourstudy were in the gaiter area, a location consistent withvenous ulcers.

BCC is the most common type of skin cancer, typicallyarising on areas of chronic sun exposure, especially the headand neck. However, 8% of BCC arises on the lower extrem-ity.19 It may appear as a chronic ulcer refractory to treat-ment or may even appear as a benign ulcer with adequategranulation tissue, without the classic rolled pearly borderor surface telangiectasia. One patient in our study had ahistologic diagnosis of BCC. He had an ulcer that waslocated in the lower calf/malleolus. Most lesions of bothSCC and BCC can be treated with various surgical modal-ities, including cryosurgery, electrodesiccation and curet-tage, excision, and Mohs surgery.20

A variety of other atypical causes, as well as idiopathic or

unknown causes of leg ulcerations, have been reported.21

For instance, vasculitis is a known condition that causesulcerations.22 Scott et al23 diagnosed leg ulcers in 38% ofpatients with systemic rheumatoid vasculitis. Both limbs inone patient in our series were diagnosed with vasculitisby ulcer biopsy, and this was the likely cause for persis-tence. The diagnosis of vasculitis as the causative agentfor an ulcer is difficult, given the low yield associatedwith ulcer edge biopsies.24 Furthermore, microbial col-onization of the ulcer per se can cause a histologicpicture of bacterial necrotizing vasculitis. Ulcers in fourlimbs in our patient population were not attributable toany of the known causes. The patients had a normalduplex scan and biopsy of the ulcer.

Three patients with cellulitis and lymphedema hadchronic inflammation on the biopsy sample. Probably thesepatients do not need to have a biopsy, but it is difficult tomake such a recommendation because the sample is sosmall. These patients had no other vascular disease.Usually patients with lymphedema and ulceration havearterial or venous disease or cancer.25,26 The prevalenceof lymphedema alone in a large prospective study was2.5% (17/689).27

An ulcer that fails to heal after 3 to 4 months of woundcare should be biopsied. The biopsy should be performedof the ulcer edge for a diagnosis and to rule out malignancy.If a biopsy is intended to determine an uncommon cause ofulceration, including vasculitis, both the edge of the ulcerand the ulcer bed should be sampled.28 Punch biopsies(3-4 mm) or a wedge or a rectangular biopsy using a scalpelwill harvest sufficient tissue for histologic analysis. If malig-nancy is suspected, several biopsies should be obtainedfrom the wound bed by using either a shave or punchmethod. If an atypical wound infection is considered, abiopsy for tissue culture should be performed.29 A total oftwo patients with four limbs in our study had pathologyreports showing undetermined pathology. If an unusual legulcer is present and the biopsy is not helpful, more specifictests should be part of the workup. For example, cryo-globulins may be associated with hepatitis C and leg ulcer-ation. Therefore, hepatitis C serologies and serum levelsof cryoglobulins may be helpful in making the diagno-sis.30 It is important to keep in mind that there arenumerous staining techniques available to detect vascu-lar pathology, micro-organisms, malignancies, dermato-logic disorders, or storage diseases. The pathologistshould receive detailed information about the clinicalproblem and the potential differential diagnoses.2 In ourcase, an extensive battery of tests was performed, but allresults were nondiagnostic.

In general, though, we recommend arterial and venoustesting before any other test because the prevalence ofvascular disease has been shown to be very high in manyclinical and epidemiologic studies. Also, many ulcers havemixed etiology, and arterial and venous testing can demon-strate the vascular pathology that may contribute to the

ulcer formation.

JOURNAL OF VASCULAR SURGERYMarch 2007572 Labropoulos et al

CONCLUSION

Extremely rare ulcers of numerous etiologies exist onlyas case reports scattered throughout the literature. Wefound uncommon leg ulcers in 17 patients out of 710patients evaluated for leg ulcers. Vasculitic, bacterial, viral,metabolic, and neoplastic ulcers have been described insingle case reports or small case series. Such ulcers and thoserefractory to initial treatment necessitate referral for furtherevaluation. As mentioned previously, biopsies are not al-ways confirmatory. However, identification of these pa-tients in the setting of a vascular clinic may provide moreaccurate data on the prevalence and etiology of uncommonleg ulcers. More importantly, it may facilitate the earlieridentification neoplastic ulcers.31-88

AUTHOR CONTRIBUTIONS

Conception and design: NLAnalysis and interpretation: NL, JT, LP, ADGWriting the article: NL, DM, NPP, JT, LP, ADGCritical revision of the article: NL, DM, NPP, JT, LP, ADGFinal approval of the article: NL, DM, NPP, JT, LP, ADGStatistical analysis: NLOverall responsibility: NL

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Submitted Aug 11, 2006; accepted Nov 1, 2006.

Additional material for this article may be found onlineat www.jvascsurg.org.

APPENDIX I: PARTICIPATING CENTERSNicos Labropoulos, Danielle Manalo, Jay Tiongson,

Landon Pryor, Luis Leon, and Apostolos K. Tassiopoulos,Loyola University Medical Center, Maywood, Ill; NimaPatel and Peter J. Pappas, University of Medicine andDentistry of New Jersey, Newark, NJ; Berndt Arfvidsson,Bo Eklof, and Robert Kistner, Straub Foundation, Hono-lulu, Hawaii; Kostas Delis and Andrew N. Nicolaides, StMary’s Hospital, Imperial College, London, UK; DimitrisTsantillas, Praxis für Gef. Chirurgie and Phlebologie, Augs-burg, Germany; Paolo Zamboni, University of Ferrara,Ferrara, Italy; Athanasios D. Giannoukas, University ofThessaly, Larissa, Greece; Carmen L. Porto, State Univer-sity of Rio de Janeiro, Rio de Janeiro, Brazil; Fanilda S.Barros, Angiolab, Vitoria, Brasil; and Carlos A. Engelhornand Ana L. Engelhorn, Pontificia Universidade Catolica do

Parana, Curitiba, Brasil.

JOURNAL OF VASCULAR SURGERYMarch 2007573.e1 Labropoulos et al

APPENDIX II, Online only.

Case reports of nonvenous, nonarterial ulcers in adults, 1966 to July 2006

References Condition Most common location Morphology Comments

31-33 Pyoderma gangrenosum Lower legs but canappear anywhere onskin

Well-defined, raised, purple, serpiginous,undermined border; rapiddevelopment of necrosis and ulceration

9, 34, 35 Sickle cell anemia Medial malleoli; oftenbilateral

New ulcers are painful, inflammation mayarise on old scar; may be purulent,have poor granulation tissue, and benonhealing if �10 cm

Can occur spontaneouslyor as a result of localtrauma

36-38 Rheumatoid arthritis, Feltysyndrome

May occur in unusuallocations

Smooth, undulating, irregular“geographic” shape; can be associatedwith livedo reticularis and palpablepurpura

Often multifactorial,including concurrentvenous or arterialdisease, vasculitis,diabetes, deformities,trauma, or pressure

13, 39-44 Hydroxyurea Malleoli Painful, persistent; fibrous-appearing withatrophic periulcerous skin

1, 45-48 Calciphylaxis Trunk and limb girdle Painful subcutaneous nodules tononhealing extremity ulcers andgangrene.

Associated with chronicrenal failure

49, 50 Osteomyelitis Foot Several types: nonhealing superficial ulcerwith thickened, sclerosed bone coveredpartly by a thin layer of epithelium;deep ulcer, where base consists ofexcavated bone; or multiple sinuses;sclerotic bone changes and periostealthickening seen by radiography

17, 51-54 Squamous cell carcinoma When mucosal surfacesare excluded, themost commonlocation is the lowerextremity

May be hypertrophic or hemorrhagic;irregular borders; lymphadenopathy;often painless; slow progressive growth

The most common typeof skin cancer inblacks; predisposingfactors are burn scarsand chronic infection

18, 55-57 Basal cell carcinoma 8% of basal cellcarcinomas arise onthe lower extremity

Chronic ulcer refractory to treatment;may appear benign (ie, healthygranulation tissue, no rolled pearlyborder or surface telangiectasia)

1, 58, 59 Necrobiosis lipoidica(diabeticorum)

Anterior lower limb Oval or irregular reddish brown plaquewith central atrophy and translucenttelangiectasias

60, 61 Thalassemia Medial malleoli Chronic, nonpainful; shallow withirregular shape; surrounding skin mayhave no erythema orhyperpigmentation

Higher prevalence of legulcers in sickle cellanemia and thatassociated with alphathalassemia

62, 63 Scleroderma Lower limb Ischemic skin lesions varying form digitalpitting scars to wide ulcers

Concurrent arterial orvenous disease iscommon—a commoncomplication ofsquamous cellcarcinoma and poorlyresponsive to commonpharmacologictreatments

64-66 Prolidase deficiency Thigh and lower leg Skin fragility with leg ulceration andcharacteristic pitting and scarring;telangiectasias, purpura, lymphedemacan also be present; histology isnonspecific

Hereditary conditiondiagnosed inchildhood

7, 67, 68 Livedo reticularis Lower legs, feet, ankles Fishnet-like skin mottling; color changesfrom reddish blue to deep bluemottling upon cold exposure; canprogress to hemorrhagic blisters andpunched-out ulcers; can heal withatrophie blanche

Nonspecific clinicalreaction associatedwith a variety ofconditions

JOURNAL OF VASCULAR SURGERYVolume 45, Number 3 Labropoulos et al 573.e2

APPENDIX II, Online only. Continued.

References Condition Most common location Morphology Comments

69 Purpura Lower legs and feet Purpura often preceded by a burningsensation or pain localized to theaffected skin areas associated withedema; often followed by ulcerationsafter exposure to severe cold leading toscar formation and brownishpigmentation

Associated with essentialcryoglobulinemia oressentialcryofibrinogenemia

70, 71 Polyarteritis nodosa Ankle, lower leg May present with atrophie blanche72, 73 Leprosy Legs and arms Posttraumatic with secondary infection or

erythema necroticans: angular inflamedlesions that slough to leave deep ulcers

74, 75 Sarcoidosis Cutaneous involvementin approximately 25%of cases; ulcerativelesions are rare butusually occur on thelegs

Small, usually 1-2 cm, frequently resolvewith systemic corticosteroid therapy

76 Livedo vasculitis Lower extremities Focal purpura proceeding to configurate,stellate, infarctive ulcers covered withdark adherent eschar surrounded by aborder of inflammation; can heal withatrophie blanche

77-80 Other anemias Variable81 Erythema induratum of

BazinPosterior aspect of

lower third of calvesPersistent and recurrent nodules that

often ulcerate in cold weather; lowercalves may plump with erythrocyanoticcirculation and follicularhyperkeratosis; ulcers are irregular andshallow with bluish tense borders;usually heal spontaneously withinseveral months, leaving atrophichyperpigmented areas; histologicallyappears as a tuberculoid granulomawith or without caseation and mayinvolve subcutaneous vessels or fat

Significant number ofpatients may have apast or present historyof tuberculosis

82, 83 Behçet disease Oral and genital; rarelyon the legs

May have features of thrombosis and/orvasculitis

84, 85 Panniculitis Variable Variable Case reports revealedthat panniculitis was amanifestation ofsubcutaneous tophus,B-cell lymphoma,calciphylaxis, andCandida albicans

86, 87 Erythema elevatum diutinum(necrotizing vasculitis)

Legs Large erythematous ulcerated nodules;purpuric eruptions surrounded bywarm erythematous skin;depigmentation at site of old healedulcer; histologically a form ofleukocytoclastic vasculitis characterizedby an abundant infiltrate of neutrophils

84, 88 Diphtheria Legs Chronic, nonhealing, slow growing;covered with purulent membranesurrounded by necrotic zone