998 CLINICAL PEARLS Legome • COLD, BLUE FEET

Clinical Pearls: Cold Feet

ERIC LEGOME, MD

Figure 1. The patient’s feet on presentation to the emer-gency department.

Chief Complaint. Cold, painful, bluish purple feet.

History of Present Illness. A 68-year-old manpresents with several days of increasing pain anddiscoloration in both feet. He also describes his feetas ‘‘cold.’’ The symptoms have progressed to wherehe is unable to ambulate due to the pain. He deniesany trauma. His past medical history is significantfor coronary artery disease, hypertensive cardio-myopathy, and a cerebrovascular accident. Hismedicines include nitroglycerin, losartan, atenolol,aldactone, famotidine and furosemide. Warfarinwas begun approximately three weeks prior to pre-sentation.

Physical Examination. The patient is generallywell-appearing but mildly uncomfortable due topainful feet. He is hypertensive, with a blood pres-sure of 200/100 mm Hg; the vital signs are other-wise normal. The cardiac exam reveals a regularrate and rhythm with a faint apical murmur. Theabdomen is soft without palpable masses. The feetare dusky bluish purple bilaterally, with blanching

From the Department of Emergency Medicine, MassachusettsGeneral Hospital, Harvard Medical School (EL), Boston, MA.Section editor: Lawrence B. Stack, MD, Vanderbilt UniversityMedical Center, Nashville, TN.Received September 11, 2000; revision received May 25, 2001;accepted June 27, 2001.Address for correspondence and reprints: Eric. L. Legome, MD,Massachusetts General Hospital, Department of EmergencyMedicine, Associate Residency Director, Harvard AffiliatedResidency in Emergency Medicine, Residency Office, Founders150, Boston, MA 02114. Fax: 617-724-4021; e-mail: legome.eric@mgh.harvard.edu

to slight pressure. There are dorsalis pedis andposterior tibial pulses present bilaterally. No ery-thema or edema is present. Sensation and motorfunction are intact in both feet. No other skin le-sions are present. The physical exam is otherwiseunremarkable.

Laboratory. The international normalized ratio(INR) is 2. The hematocrit is 41%, white blood cellcount 7,300/mm3, and platelet count 224/mm3.Electrolytes are all within normal limits. A sedi-mentation rate, requested due to a concern for aninflammatory vasculitis, is 12. Urinalysis is nor-mal without casts or red blood cells.

(The diagnosis, discussion, and clinical pearls appear on page1007.)

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The presentation of intussuscep-tion in anaphylactoid purpura isvariable and may be identical to thatof intestinal vasculitis, edema, ormural hematoma, and, as such, sur-gery may be unnecessary.6,13,14 Care-ful clinical monitoring with serial ul-trasound examinations is importantfor all patients with anaphylactoidpurpura accompanied with promi-nent abdominal symptoms. Not onlycan the clinician thus identify thecomplication of intussusception atan earlier time than would be thecase in the absence of such diagnos-tic vigilance, unnecessary surgerymay be avoided for patients with un-complicated intestinal vasculitis andedema.4,11,12 Therapeutic reduction ofthe affected region of the bowel withair or contrast enema is not sug-gested because the affected bowel isgenerally inflamed, hemorrhagic,and/or edematous as a result of thevasculitis, and thus the risk of per-foration is high. Further, the intus-susception is usually confined to thesmall bowel, and, as such, it is noteasily reduced by use of an enema.15

Surgery should be limited to cases ofnon-reducible intussusception and/or intestinal perforation.12

CONCLUSIONS

Intussusception in anaphylactoidpurpura typically features a hema-toma as a lead point lesion and ne-cessitates surgical reduction or re-section. When no lead point is foundon imaging studies, spontaneous re-duction of the intussusception mayoccur subsequent to the administra-tion of anti-inflammatory drugtreatment. Serial ultrasound exam-inations are useful to assess the res-olution of intestinal edema.

References

1. Choong CK, Kimble RM, Pease P,Beasley SW. Colic-colic intussusceptionin Henoch-Schonlein purpura. PediatrSurg Int. 1998; 14:173–4.2. Vinton NE. Gastrointestinal bleedingin infancy and childhood. GastroenterolClin North Am. 1994; 23(1):103–4.3. Glasier CM, Siegel MJ, McAlisterWH, Shackelford GD. Henoch-Schonleinsyndrome in children: gastrointestinalmanifestation. AJR. 1981; 136:1081–5.4. Couture A, Veyrac C, Baud C, GaliferRB, Armelin I. Evaluation of abdominalpain in Henoch-Schonlein syndrome byhigh frequency ultrasound. Pediatr Ra-diol. 1992; 22:12–7.5. Bomelburg T, Claasen U, von Len-gerke HJ. Intestinal ultrasonographic

findings in Schonlein-Henoch syndrome.Eur J Pediatr. 1991; 150:158–60.6. Martinez-Frontanilla LA, Haase GM,Ernster JA, Bailey CW. Surgical compli-cations in Henoch-Schonlein purpura. JPediatr Surg. 1984; 19:434–6.7. Lindenauer SM, Tank ES. Surgicalaspects of Henoch-Schonlein’s purpura.Surgery. 1966; 59:982–7.8. Singleton EB, Wagner ML, DuttonRV. Radiology of the Alimentary Tract inInfants and Children, second ed. Phila-delphia: W. B. Saunders, 1977.9. Franken EA. Gastrointestinal radiol-ogy in pediatrics. Hagerstown, MD: Har-per & Row, 1975.10. Ravitch MM, Welch KJ, Benson CD,Aberdeen E, Randolph JG. PediatricSurgery, third ed, vol 2. Chicago: YearBook, 1979.11. Connolly B, O’Halpin D. Sono-graphic evaluation of the abdomen inHenoch-Schonlein purpura. Clin Radiol1994; 49:320–3.12. Hu SC, Feeney MS, McNicholas M,et al. Ultrasonography to diagnose andexclude intussusception in Henoch-Schonlein purpura. Arch Dis Child. 1991;66:1065–7.13. Mir E. Surgical complications inHenoch-Schonlein purpura in childhood.Z Kinderchir. 1988; 43:391–3.14. Harvey JG, Colditz PB. Henoch-Schonlein purpura: a surgical review.Aust Paediatr J. 1984; 20:13–6.15. Martinez-Frontanilla LA, SilvermanL, Meagher DP. Intussusception inHenoch-Schonlein purpura: diagnosiswith ultrasound. J Pediatr Surg. 1988;23:375–6.

Clinical Pearls (cont. from page 998)

Diagnosis. ‘‘Purple toe syndrome.’’

Discussion.

History. Complications of coumarin anticoagu-lants include bleeding, hypersensitivity reactions,purpura, and, less commonly, skin necrosis.1 ‘‘Pur-ple toe syndrome,’’ like warfarin necrosis, is a rel-atively rare complication of coumarin therapy.

In the first report in 1961, Feder and Anerbachdescribed six male patients who developed bilat-eral purple toe and foot discoloration three to eightweeks after beginning warfarin therapy. All hadbegun anticoagulations within the preceding twomonths. Skin biopsies on four of the patientsshowed nonspecific findings without signs of necro-sis or inflammation.2 Since the original small se-ries, a handful of case reports have also reportedsimilar presentations.3—7 While early case reportsall involved male patients, later case reports haveshown a female predominance.3,4–7 ‘‘Blue toe’’ syn-drome is a term that has been used to describe

both the identical syndrome from warfarin use anddiscolored toes due to other vascular or thromboticetiologies.8

Clinical Features. The clinical picture of the ‘‘pur-ple toe’’ syndrome usually involves bilateral discol-oration of the feet with variable lower leg involve-ment. The discoloration is blue-tinged, blanches toslight pressure, and tends to fade with elevation ofthe feet. The affected distal extremity is usuallycool to the touch and moderately tender to palpa-tion. The pain has been described both as a coldsensation and as a burning sensation. Arterialpulses have been present in all patients.3,5,7,8 In theoriginal series, hand involvement preceded foot in-volvement, but this has not been reported since.2

Discontinuation of warfarin or its derivativestends to alleviate most patients’ symptoms of pain.However, the discoloration may persist.

The exact etiology of this disorder is unclear.The most plausible theory is that it is due to cho-lesterol emboli from atherosclerotic plaques causedby warfarin-induced bleeding in these plaques.5,8,9

1008 CLINICAL PEARLS Legome • COLD, BLUE FEET

Another hypothesis is the lesions are secondary todirect toxicity from the medication on the capillar-ies. This may lead to venodilatation and vascularpermeability.6–8 Biopsies have not offered any clearhistopathologic evidence of the cause in most pre-vious cases, although cholesterol embolization hasbeen seen in several patients in one series.9 Theetiology of warfarin necrosis is believed to be sec-ondary to a relative hypercoaguable state due tointerference with the endogenous anticoagulantpathways leading to microvessel thrombosis. Pa-thology has shown fibrin deposition in the smallveins and postcapillary venules with associatedhemorrhage and necrosis in the dermis and sub-cutaneous fat.5,8 Clinically, warfarin necrosis andblue toe syndrome can be differentiated by severalfactors. The usual site of occurrence is the feet inpurple toe syndrome vs the breast, thighs, and but-tocks in warfarin necrosis. The onset is later inpurple toe syndrome, i.e., three to eight weeks vsthree to six days, and the toes do not usually pro-gress to hemorrhagic blisters and necrosis in pur-ple toe syndrome.7,8

There is difficulty in interpreting the medical lit-erature when distinguishing ‘‘blue toe’’ syndromefrom ‘‘purple toe’’ syndrome. Both have been usedto describe identical types of lesions due to thesame presumed pathophysiology, i.e., emboli pre-cipitated by warfarin.10,11 Some authors have writ-ten about blue toe syndrome as an entity that mayoccur in the absence or presence of warfarin useand is due to showers of cholesterol emboli from aproximal source of atherosclerotic plaque, espe-cially after invasive vascular procedures or throm-bolysis. This has also been known as the choles-terol emboli syndrome. Others have identified theetiology of blue toe syndrome as including hyper-coaguability disorders or syndromes with periph-eral vascular pathology.8,10,12–14 As with ‘‘purple toesyndrome,’’ the patients have discolored digits buta perfused foot.

Treatment. No specific treatment has been shownto be effective or has even been suggested for thisentity other than discontinuation of warfarin. Incases where outcome was reported, discontinua-tion of the drug seemed to lead to improvement insymptoms, but the discoloration of the extremitieslasted for a variable period of time, at least severalweeks.2,3,7 As noted, blue toe syndrome due to cho-lesterol emboli from atherosclerotic plaques isprobably the same entity as purple toe syndrome,although several authors have used it to delineateother etiologies besides a complication from war-farin use. Some authors have advocated a workupfor atheromatous plaques when this presentationof discolored toes is seen. However, no specific ther-apy or intervention has been proven clearly effi-

cacious.10,12,–14,15 Small series have shown some im-provement with debridement of the plaques.14

There is a report in which the toes became gan-grenous leading to amputation, although this wasin a patient with a pre-existing severe vasculardisease.16

A reasonable approach to the patient with blueor purple toes in the emergency department set-ting is a thorough physical exam concentrating onthe vascular system, discontinuation of warfarin (ifnot essential), and consultation with a vascularsurgeon to guide further evaluation.

Clinical Pearls.

1. Patients recently started on warfarin may pre-sent with a variety of dermatologic findings, in-cluding discoloration of digits and skin necrosis.

2. Blue/purple or cyanotic-appearing digits maynot be due to acute arterial insufficiency.

3. Patients who present with a clinical picture con-sistent with ‘‘blue’’ or ‘‘purple toe’’ syndromeshould have their warfarin discontinued andshould be considered for further investigationfor atheromatous arterial plaques.

Key words. purple; blue; toe; emboli; warfarin; feet.

References

1. Hutchison TA, Shahan DR, Anderson ML (eds). DRUGDEXwSystem. Englewood, CO: MICROMEDEX, 2000.2. Feder W, Anerbach R. ‘‘Purple toes’’: an uncommon sequelaof oral warfarin drug therapy. Ann Intern Med. 1961; 55:911–7.3. Akle CA, Joiner CL. Purple toe syndrome. J R Soc Med.1981; 74:219.4. Rosling H. Purple-toe syndrome—a side effect of peroral an-ticoagulant therapy. Lakartidningen. 1983; 80:4700.5. Soisson AP, Vu KK, Brittain PC, Chamales I. An unusualcutaneous reaction to anticoagulant therapy. Milit Med. 1994;159:271–4.6. Di Cato MA. Case report: ‘‘purple toes’’ syndrome: an un-common complication of oral anticoagulant therapy. PostgradMed. 1975; 58:133–4.7. Lebsack CS, Weibert R. ‘‘Purple toes’’ syndrome. PostgradMed. 1982; 71:81–3.8. Sallah S, Thomas D, Roberts H. Warfarin and heparin-in-duced skin necrosis and the purple toe syndrome: infrequentcomplications of anticoagulant treatment. Thromb Haemost.1997; 78:785–90.9. Hyman BT, Landas SK, Ashman RF, et al. Warfarin-relatedpurple toes syndrome and cholesterol microembolization. Am JMed. 1987; 82:1233–7.10. Applebaum RM, Kronzon I. Evaluation and managementof cholesterol embolization and the blue toe syndrome. CurrOpin Cardiol. 1996; 11:533–42.11. Rauh G, Spengel FA. Blue toe syndrome after initiation oflow-dose anticoagulation. Eur J Med Res. 1998; 3:278–80.12. Wingo JP, Nix ML, Greenfield LJ, Barnes RW. The bluetoe syndrome: hemodynamics and therapeutic correlates ofoutcome. J Vasc Surg. 1986; 3:475–80.13. Karmody AM, Powers SR, Monaco VJ, Leather RP. ‘‘Bluetoe’’ syndrome. An indication for limb salvage surgery. ArchSurg. 1976; 111:1263–8.14. Bojar RM, Payne DD, Murphy RE, et al. Surgical treat-ment of systemic atheroembolism from the thoracic aorta. AnnThoracic Surg. 1996; 61:1389–93.

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15. Blackshear JL, Oldenburg WA, Cohen MD. Making the di-agnosis when the patient has ‘‘blue toes.’’ Geriatrics. 1994; 49:37–9, 43–5.

16. Bols A, Nevelsteen A, Veraeghe R. Atheromatous emboli-zation precipitated by oral anticoagulants. Int Angiol. 1994; 13:271–4.

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