Advertisement

Nonatherosclerotic PAD: Approach to Exertional Pain in the Lower Extremities

  • Ari J. Mintz
  • Ido WeinbergEmail author
Peripheral Vascular Disease (MR Jaff, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Peripheral Vascular Disease

Abstract

Atherosclerotic peripheral artery disease is the most common cause of intermittent claudication. Nonatherosclerotic peripheral artery disease is a heterogeneous collection of diseases affecting the extracoronary arteries which is not due to atherosclerosis. These diseases include, but are not limited to, popliteal artery entrapment syndrome, cystic adventitial disease, external iliac endofibrosis, and thromboangiitis obliterans. Due to its relatively low prevalence, nonatherosclerotic peripheral artery disease may be misdiagnosed leading to the mismanagement of potentially treatable conditions. The proper and timely diagnosis of these conditions is paramount to the prevention of adverse outcomes as treatments widely vary. The diagnostic approach to patients presenting with intermittent claudication must take into account both atherosclerotic as well as nonatherosclerotic causes of peripheral artery disease making the differential vital to clinical practice.

Keywords

Peripheral artery disease Intermittent claudication Nonatherosclerotic peripheral artery disease 

Notes

Compliance with Ethics Guidelines

Conflict of Interest

Ari J. Mintz and Ido Weinberg declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Selvin E, Erlinger TP. Prevalence of and risk factors for peripheral arterial disease in the United States: results from the National Health and Nutrition Examination Survey, 1999–2000. Circulation. 2004;110:738–43.PubMedCrossRefGoogle Scholar
  2. 2.
    Hirsch AT, Criqui MH, Treat-Jacobson D, Regensteiner JG, Creager MA, Olin JW, et al. Peripheral artery disease detection, awareness, and treatment in primary care. JAMA. 2001;286:1317–24.PubMedCrossRefGoogle Scholar
  3. 3.
    Diehm C, Allenberg JR, Pittrow D, Mahn M, Tepohl G, Haberl RL, et al. German Epidemiologic Trial on Ankle Brachial Index Study Group; mortality and vascular morbidity in older adults with asymptomatic versus symptomatic peripheral artery disease. Circulation. 2009;120:2053–61.PubMedCrossRefGoogle Scholar
  4. 4.
    Weinberg I, Jaff MR. Nonatherosclerotic arterial disorders of the lower extremities. Circulation. 2012;126:213–22.PubMedCrossRefGoogle Scholar
  5. 5.
    Levien LJ, Veller MG. Popliteal artery entrapment syndrome: more common than previously recognized. J Vasc Surg. 1999;30:587–98.PubMedCrossRefGoogle Scholar
  6. 6.
    di Marzo L, Cavallaro A. Popliteal vascular entrapment. World J Surg. 2005;29 Suppl 1:S43–5.PubMedCrossRefGoogle Scholar
  7. 7.
    Bouhoutos J, Daskalakis E. Muscular abnormalities affecting the popliteal vessels. Br J Surg. 1981;68:501–6.CrossRefGoogle Scholar
  8. 8.
    Pillai J. A current interpretation of popliteal vascular entrapment. J Vasc Surg. 2008;48:61S–5S.PubMedCrossRefGoogle Scholar
  9. 9.
    Causey MW, Singh N, Miller S. Intraoperative duplex and functional popliteal entrapment syndrome: strategy for effective treatment. Ann Vasc Surg. 2010;24:556–61.PubMedCrossRefGoogle Scholar
  10. 10.
    Sinha S, Houghton J, Holt PJ, Thompson MM, Loftus IM, Hinchliffe RJ. Popliteal entrapment syndrome. J Vasc Surg. 2012;55:252–262.e30.PubMedCrossRefGoogle Scholar
  11. 11.
    Angeli AA, Angeli DA, Aggeli CA, Mandrekas DP. Chronic lower leg swelling caused by isolated popliteal venous entrapment. J Vasc Surg. 2011;54:851–3.PubMedCrossRefGoogle Scholar
  12. 12.
    Korngold EC, Jaff MR. Unusual causes of intermittent claudication: popliteal artery entrapment syndrome, cystic adventitial disease, fibromuscular dysplasia, and endofibrosis. Curr Treat Options Cardiovasc Med. 2009;11:156–66.PubMedCrossRefGoogle Scholar
  13. 13.
    Akkersdijk WL, de Ruyter JW, Lapham R, Mali W, Eikelboom BC. Colour duplex ultrasonographic imaging and provocation of popliteal artery compression. Eur J Vasc Endovasc Surg. 1995;10:342–5.PubMedCrossRefGoogle Scholar
  14. 14.
    Holden A, Merrilees S, Mitchell N, et al. Magnetic resonance imaging of popliteal artery pathologies. Eur J Radiol. 2008;67:159–68.PubMedCrossRefGoogle Scholar
  15. 15.
    Marzo L, Cavallaro A, Mingoli A, Sapienza P, Tedesco M, Stipa S. Popliteal artery entrapment syndrome: the role of early diagnosis and treatment. Surgery. 1997;122:26–31.PubMedCrossRefGoogle Scholar
  16. 16.
    Tomasian A, Lai C, Finn JP, et al. Cystic adventitial disease of the popliteal artery: features on 3T cardiovascular magnetic resonance. J Cardiovasc Magn Reson. 2008;10:38.PubMedCentralPubMedCrossRefGoogle Scholar
  17. 17.
    Steffen CM, Ruddle A, Shaw JF. Adventitial cystic disease: multiple cysts causing common femoral artery occlusion. Eur J Vasc Endovasc Surg. 1995;9:118–9.PubMedCrossRefGoogle Scholar
  18. 18.
    França M, Pinto J, Machado R, et al. Case 157: bilateral adventitial cystic disease of the popliteal artery. Radiology. 2010;255(2):655–60.PubMedCrossRefGoogle Scholar
  19. 19.
    Motaganahalli RL, Pennell RC, Mantese VA, Westfall SG. Cystic adventitial disease of the popliteal artery. J Am Coll Surg. 2009;209:541.PubMedCrossRefGoogle Scholar
  20. 20.
    Cassar K, Engeset J. Cystic adventitial disease: a trap for the unwary. Eur J Vasc Endovasc Surg. 2005;29:93–6.PubMedCrossRefGoogle Scholar
  21. 21.
    Flanigan DP, Burnham SJ, Goodreau JJ, Bergan JJ. Summary of cases of adventitial cystic disease of the popliteal artery. Ann Surg. 1979;189:165–75.PubMedCentralPubMedCrossRefGoogle Scholar
  22. 22.
    Meka M, Hamrick MC, Wixon CL. Cystic adventitial disease of the popliteal artery: a potential cause of lower extremity claudication. Am Surg. 2009;75:86–9.PubMedGoogle Scholar
  23. 23.
    Rai S, Davies RS, Vohra RK. Failure of endovascular stenting for popliteal cystic disease. Ann Vasc Surg. 2009;23:410 e1–e5.PubMedCrossRefGoogle Scholar
  24. 24.
    Chevalier JM, Enon B, Walder J, et al. Endofibrosis of the external iliac artery in bicycle racers: an unrecognized pathological state. Ann Vasc Surg. 1986;1:297–303.PubMedCrossRefGoogle Scholar
  25. 25.
    Kral CA, Han DC, Edwards WD, Spittell PC, Tazelaar HD, Cherry Jr KJ. Obstructive external iliac arteriopathy in avid bicyclists: new and variable histopathologic features in four women. J Vasc Surg. 2002;36:565–70.PubMedCrossRefGoogle Scholar
  26. 26.
    Rousselet M, Saint-Andre J, L'Hoste P. Stenotic intimal thickening of the external iliac artery in competition cyclists. Hum Pathol. 1990;21:524–9.PubMedCrossRefGoogle Scholar
  27. 27.
    Taylor AJ, George KP. Exercise induced leg pain in young athletes misdiagnosed as pain of musculo-skeletal origin. Man Ther. 2001;6:48–52.PubMedCrossRefGoogle Scholar
  28. 28.
    Abraham P, Chevalier JM, Saumet JL. External iliac artery endofibrosis: a 40-year course. J Sports Med Phys Fitness. 1997;37:297–300.PubMedGoogle Scholar
  29. 29.
    Alimi YS, Accrocca F, Barthelemy P, Hartung O, Dubuc M, Boufi M. Comparison between duplex scanning and angiographic findings in the evaluation of functional iliac obstruction in top endurance athletes. Eur J Vasc Endovasc Surg. 2004;28:513–9.PubMedCrossRefGoogle Scholar
  30. 30.
    Abraham P, Leftheriotis G, Bourre Y, Chevalier JM, Saumet JL. Echography of external iliac artery endofibrosis in cyclists. Am J Sports Med. 1993;21:861–3.PubMedCrossRefGoogle Scholar
  31. 31.
    Lomis NN, Miller FJ, Whiting JH, Giuliano AW, Yoon HC. Exercise-induced external iliac artery intimal fibrosis: confirmation with intravascular ultrasound. J Vasc Interv Radiol. 2000;11:51–3.PubMedCrossRefGoogle Scholar
  32. 32.
    Maree AO, Ashequl Islam M, Snuderl M, et al. External iliac artery endofibrosis in an amateur runner: hemodynamic, angiographic, histopathological evaluation and percutaneous revascularization. Vasc Med. 2007;12:203–6.PubMedCrossRefGoogle Scholar
  33. 33.
    Slovut DP, Olin JW. Fibromuscular dysplasia. N Engl J Med. 2004;350:1862–71.PubMedCrossRefGoogle Scholar
  34. 34.
    Cragg AH, Smith TP, Thompson BH, Maroney TP, Stanson AW, Shaw GT, et al. Incidental fibromuscular dysplasia in potential renal donors: long-term clinical follow-up. Radiology. 1989;172:145–7.PubMedCrossRefGoogle Scholar
  35. 35.••
    O’Connor SC, Gornik HL. Recent developments in the understanding and management of fibromuscular dysplasia. J Am Heart Assoc. 2014;3:e001259. This paper provides an updated description on the evolving nomenclature of fibromuscular dysplasia as well as updated prevalence data from recent registries.PubMedCentralPubMedCrossRefGoogle Scholar
  36. 36.
    Harrison Jr EG, McCormack LJ. Pathologic classification of renal arterial disease in renovascular hypertension. Mayo Clin Proc. 1971;46(3):161–7.PubMedGoogle Scholar
  37. 37.
    Gray BH, Young JR, Olin JW. Miscellaneous arterial diseases. In: Young JR, Olin JW, Bartholomew JR, editors. Peripheral vascular diseases. 2nd ed. St. Louis: Mosby-Yearbook; 1996. p. 425–40.Google Scholar
  38. 38.
    Sauer L, Reilly LM, Goldstone J, Ehrenfeld WK, Hutton JE, Stoney RJ. Clinical spectrum of symptomatic external iliac fibromuscular dysplasia. J Vasc Surg. 1990;12:488–96.PubMedCrossRefGoogle Scholar
  39. 39.
    Begelman SM, Olin JW. Fibromuscular dysplasia. Curr Opin Rheumatol. 2000;12:41–7.PubMedCrossRefGoogle Scholar
  40. 40.
    Das CJ, Neyaz Z, Thapa P, Sharma S, Vashist. Fibromuscular dysplasia of the renal arteries: a radiological review. Int Urol Nephrol. 2007;39:233–8.PubMedCrossRefGoogle Scholar
  41. 41.
    Gowda MS, Loeb AL, Crouse LD, Kramer PH. Complementary roles of color-flow duplex imaging and intravascular ultrasound in the diagnosis of renal artery fibromuscular dysplasia: should renal arteriography serve as the “gold standard”? J Am Coll Cardiol. 2003;41:1305–11.PubMedCrossRefGoogle Scholar
  42. 42.
    Lassiter FD. The string-of-beads sign. Radiology. 1998;206(2):437–8.PubMedCrossRefGoogle Scholar
  43. 43.
    Pamell AP, Loose HW, Chamberlain K. Fibromuscular dysplasia of the external iliac artery: treatment by percutaneous transluminal angioplasty. Br J Radiol. 1988;61:1080–2.CrossRefGoogle Scholar
  44. 44.
    Trinquart L, Mounier-Vehier C, Sapoval M, Gagnon N, Plouin PF. Efficacy of revascularization for renal artery stenosis caused by fibromuscular dysplasia: a systematic review and meta-analysis. Hypertension. 2010;56:525–32.PubMedCrossRefGoogle Scholar
  45. 45.
    Weyand CM, Goronzy JJ. Medium- and large-vessel vasculitis. N Engl J Med. 2003;349:160–9.PubMedCrossRefGoogle Scholar
  46. 46.
    Ozen S, Ruperto N, Dillon MJ, et al. EULAR/PReS endorsed consensus criteria for the classification of childhood vasculitides. Ann Rheum Dis. 2006;65(7):936–41.PubMedCentralPubMedCrossRefGoogle Scholar
  47. 47.
    Watts R, Al-Taiar A, Mooney J, Scott D, MacGregor A. The epidemiology of Takayasu arteritis in the UK. Rheumatology. 2009;48:1008–11.PubMedCrossRefGoogle Scholar
  48. 48.
    Seko Y. Takayasu arteritis. Insights into immunopathology. Jpn Heart J. 2000;41:15–26.PubMedCrossRefGoogle Scholar
  49. 49.
    Connolly JE, Wilson SE, Lawrence PL, Fujitani RM. Middle aortic syndrome: distal thoracic and abdominal coarctation, a disorder with multiple etiologies. J Am Coll Surg. 2002;75:110–7.Google Scholar
  50. 50.
    Arend WP, Michel BA, Bloch DA, Hunder GG, Calobrese LH, Edworthy SM, et al. The American College of Rheumatology 1990 criteria for the classification of Takayasu arteritis. Arthritis Rheum. 1990;33:1129–32.PubMedCrossRefGoogle Scholar
  51. 51.
    Gonzalex-Gay MA, Vazquez-Rodriguez TR, Lopez-Diaz MJ, Miranda-Filloy JA, Gonzalex-Juanatey C, Martin J, et al. Epidemiology of giant cell arteritis and polymyalgia rheumatica. Arthritis Rheum. 2009;61:1454–61.CrossRefGoogle Scholar
  52. 52.
    Weyand CM, Goronzy JJ. Arterial wall injury in giant cell arteritis [review]. Arthritis Rheum. 1999;42:844–53.PubMedCrossRefGoogle Scholar
  53. 53.
    Kermani TA, Matteson EL, Hunder GC, Warrington KJ. Symptomatic lower extremity vasculitis in giant cell arteritis: a case series. J Rheumatol. 2009;36:2277–83.PubMedCrossRefGoogle Scholar
  54. 54.
    Hunder GG, Bloch DA, Michel BA, et al. The American College of Rheumatology 1990 criteria for the classification of giant cell arteritis. Arthritis Rheum. 1990;33:1122–8.PubMedCrossRefGoogle Scholar
  55. 55.
    Seyahi E, Yurdakul S. Behcet’s syndrome and thrombosis. Mediterr J Hematol Infect Dis. 2011;3(1), e2011026.PubMedCentralPubMedCrossRefGoogle Scholar
  56. 56.
    Yurdakul S, Yazici Y. Epidemiology of Behçet’s syndrome and regional differences in disease expression. In: Yazici Y, Yazici H, editors. Behçet’s syndrome. 1st ed. New York: Springer; 2010. p. 35–52.CrossRefGoogle Scholar
  57. 57.
    Sakane T, Takeno M, Suzuki N, Inaba G. Behcet’s disease. N Engl J Med. 1999;341:1284–91.PubMedCrossRefGoogle Scholar
  58. 58.
    International Study Group for Behçet's Disease. Criteria for diagnosis of Behçet's disease. Lancet. 1990;335(8697):1078–80.Google Scholar
  59. 59.
    Kural-Seyahi E, Fresko I, Seyahi N, et al. The long-term mortality and morbidity of Behcet syndrome: a 2-decade outcome survey of 387 patients followed at a dedicated center. Medicine (Baltimore). 2003;82:60–76. doi: 10.1097/00005792-200301000-00006.CrossRefGoogle Scholar
  60. 60.
    Fresko I, Melikoglu M, Tunc R, et al. Behcet’s syndrome: pathogenesis, clinical manifestations and treatment in vasculitis. In: Gene V, Ball S, Bridges Louis, editors. 1st edition. Oxford University Press; USA 2002.Google Scholar
  61. 61.
    Melikoglu M, Ugurlu S, Tascilar K, et al. Large vessel involvement in Behcet’s syndrome: a retrospective survey. Ann Rheum Dis. 2008;67(Suppl II):67.Google Scholar
  62. 62.
    Buckley A, Southwood T, Culham G, Nadel H, Malleson P, Petty R. The role of ultrasound in Takayasu’s arteritis. J Rheumatol. 1991;18:1073–80.PubMedGoogle Scholar
  63. 63.
    Nicoletti G, Mannarella C, Nigro A, Sacco A, Olivieri I. The “macaroni sign” of Takayasu’s arteritis. J Rheumatol. 2009;36:2042–3.PubMedCrossRefGoogle Scholar
  64. 64.
    Gotway MB, Araoz PA, Macedo TA, Stanson AW, Higgins SB, Ring EJ, et al. Imaging findings in Takayasu’s arteritis. Am J Roentgenol. 2005;184:1945–50.CrossRefGoogle Scholar
  65. 65.
    Arnaud L, Haroche K, Malek Z, Archambaud F, Gambotti L, Grimon G, et al. Is (18)F-fluorodeoxyglucose positron emission tomography scanning a reliable way to assess disease activity in Takayasu arteritis? Arthritis Rheum. 2009;60:1193–200.PubMedCrossRefGoogle Scholar
  66. 66.
    Ogino H, Matsuda H, Minatoya K, Sasaki H, Tanaka H, Matsumura Y, et al. Overview of late outcome of medical and surgical treatment for Takayasu arteritis. Circulation. 2008;118:2738–47.PubMedCrossRefGoogle Scholar
  67. 67.•
    Salvarani C, Magnani L, Catanoso M, Pipitone N, Versari A, Dardani L, et al. Tocilizumab: a novel therapy for patients with large-vessel vasculitis. Rheumatology (Oxford). 2012;51:151–6. This study described successful findings of a new treatment approach to medium and large vessel vasculitis with the anti-IL-6 receptor antibody tocilizumab.CrossRefGoogle Scholar
  68. 68.
    Pande RL, Beckman JA. Systemic vasculitides. In: Jaff MR, White CJ, editors. Vascular disease: diagnostic and therapeutic approaches. Minneapolis: Cardiotext; 2011. p. 341–63. Print.Google Scholar
  69. 69.
    Buerger L. Landmark publication from the American Journal of the Medical Sciences, ‘thrombo-angiitis obliterans: a study of the vascular lesions leading to presenile spontaneous gangrene’. 1908. Am J Med Sci. 2009;337:274.PubMedCrossRefGoogle Scholar
  70. 70.
    Combemale P, Consort T, Denis-Thelis L, et al. Cannabis arteritis. Br J Dermatol. 2005;152:166.PubMedCrossRefGoogle Scholar
  71. 71.
    Olin JW. Thromboangiitis obliterans (Buerger’s disease). N Engl J Med. 2000;343:864.PubMedCrossRefGoogle Scholar
  72. 72.
    Salimi J, Tavakkoli H, Salimzadeh A, et al. Clinical characteristics of Buerger’s disease in Iran. J Coll Phys Surg Pak. 2008;18:502.Google Scholar
  73. 73.
    Sasajima T, Kubo Y, Inaba M, Goh K, Azuma N. Role of infrainguinal bypass in Buerger’s disease: an eighteen year experience. Eur J Vasc Endovasc Surg. 1997;13:186–92.PubMedCrossRefGoogle Scholar
  74. 74.
    Piazza G, Creager MA. Thromboangiitis obliterans. Circulation. 2010;121:1858.PubMedCentralPubMedCrossRefGoogle Scholar
  75. 75.
    Fiessinger N, Schafer M. Trial of iloprost versus aspirin treatment for critical limb ischemia of thromboangiitis obliterans: the TAO study. Lancet. 1990;335:555–7.PubMedCrossRefGoogle Scholar
  76. 76.
    The European TAO Study Group. Oral iloprost in the treatment of thromboangiitis obliterans (Buerger’s disease): a double-blind, randomized, placebo-controlled trial. Eur J Vasc Endovasc Surg. 1998;15:300–7.CrossRefGoogle Scholar
  77. 77.
    Shindo S, Matsumoto H, Ogata K, Kubota K, Kojima A, Ishimoto T, et al. Arterial reconstruction in Buerger’s disease: bypass to disease free collaterals. Int Angiol. 2002;21:228–32.PubMedGoogle Scholar
  78. 78.
    Hislop M, Tierney P, O’Brien M, Mahony N. Chronic exertional compartment syndrome: the controversial “fifth” compartment of the leg. Am J Sports Med. 2003;31:770–6.PubMedGoogle Scholar
  79. 79.
    Schep G, Schmikli SL, Bender MH, Mosterd WL, Hammacher ER, Wijn PF. Recognising vascular causes of leg complaints in endurance athletes. Part 1: validation of a decision algorithm. Int J Sports Med. 2002;23:313–21.PubMedCrossRefGoogle Scholar
  80. 80.
    Perlowski AA, Jaff MR. Vascular disorders in athletes. Vasc Med. 2010;15:469–79.PubMedCrossRefGoogle Scholar
  81. 81.
    Detmer DE. Diagnosis and management of chronic compartment syndrome of the leg. Semin Orthop. 1988;3:223.Google Scholar
  82. 82.•
    Waterman BR, Liu J, Newcomb R, Schoenfeld AJ, Orr JD, Belmont PJ. Risk factors for chronic exertional compartment syndrome in a physically active military population. Am J Sports Med. 2013;41:2545–9. This study provided a large sample of participants in attempts to establish a previously unknown prevalence of chronic exertional compartment syndrome a physically active population.PubMedCrossRefGoogle Scholar
  83. 83.
    Glorioso J, Wilckens J. Exertional leg pain. In: O’Connor F, Wilder R, editors. The textbook of running medicine. New York: McGraw-Hill; 2001. p. 181–98.Google Scholar
  84. 84.
    Hutchinson M. Chronic exertional compartment syndrome. Br J Sports Med. 2011;45:952–3.PubMedCrossRefGoogle Scholar
  85. 85.
    Edwards P, Myerson MS. Exertional compartment syndrome of the leg: steps for expedient return to activity. Phys Sports Med. 1996;24:31–46.CrossRefGoogle Scholar
  86. 86.
    Detmer DE, Sharpe K, Sufit RL, Girdley FM. Chronic compartment syndrome: diagnosis, management, and outcomes. Am J Sports Med. 1985;13:162–70.PubMedCrossRefGoogle Scholar
  87. 87.
    Touliopolous S, Hershman EB. Lower leg pain. Diagnosis and treatment of compartment syndromes and other pain syndromes of the leg. Sports Med. 1999;27:193–204.PubMedCrossRefGoogle Scholar
  88. 88.
    Pedowitz RA, Hargens AR, Mubarak SJ, Gershuni DH. Modified criteria for the objective diagnosis of chronic compartment syndrome of the leg. Am J Sports Med. 1990;18:35.PubMedCrossRefGoogle Scholar
  89. 89.
    Tzortziou V, Maffulli N, Padhiar N. Diagnosis and management of chronic exertional compartment syndrome (CECS) in the United Kingdom. Clin J Sport Med. 2006;16:209.PubMedCrossRefGoogle Scholar
  90. 90.
    Rorabeck CH, Fowler PJ, Nott L. The results of fasciotomy in the management of chronic exertional compartment syndrome. Am J Sports Med. 1988;16:224.PubMedCrossRefGoogle Scholar
  91. 91.
    Styf JR, Körner LM. Chronic anterior-compartment syndrome of the leg. Results of treatment by fasciotomy. J Bone Joint Surg Am. 1986;68:1338.PubMedGoogle Scholar
  92. 92.
    van Zoest WJ, Hoogeveen AR, Scheltinga MR, et al. Chronic deep posterior compartment syndrome of the leg in athletes: postoperative results of fasciotomy. Int J Sports Med. 2008;29:419.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  1. 1.Internal MedicineLahey Hospital and Medical CenterBurlingtonUSA
  2. 2.Vascular MedicineMassachusetts General HospitalBostonUSA

Personalised recommendations