Differential Diagnosis: Vasculitis, Rheumatoid Arthritis, Behçet’s Disease, and Thromboembolism

  • Benjamin Chaigne
  • Loïc Guillevin


Although systemic sclerosis is the main systemic cause of digital ulcers, other inflammatory and non-inflammatory conditions are associated with digital ischemia and necrosis. Herein, we review the causes of digital ulcers and distal gangrene, other than systemic sclerosis. Digital ulcers and necrosis arise from three potential mechanisms: vascular inflammation, thrombosis, and vascular spasms. Occurrence and management of digital ulcer in systemic necrotizing vasculitides, rheumatoid arthritis, and Behçet’s disease are specifically addressed. In these three diseases, digital ulcers and distal necrosis are rare and severe manifestations, reflecting vascular injury requiring appropriate management and combining symptomatic and local treatments, immunosuppressants, and biological therapy. Other etiologies and treatments of digital ulcerations, e.g., antiphospholipid syndrome, thromboangiitis obliterans, vascular embolism, or Raynaud’s phenomenon, are also described.


Digital ulcer Vasculitis Rheumatoid arthritis Behçet’s disease Thromboembolism Antiphospholipid syndrome Ergotism Raynaud’s syndrome 


  1. 1.
    Nitsche A. Raynaud, digital ulcers and calcinosis in scleroderma. Reumatol Clin. 2012;8(5):270–7.PubMedCrossRefGoogle Scholar
  2. 2.
    Lega JC, Seror R, Fassier T, Aumaître O, Quere I, Pourrat J, et al. Characteristics, prognosis, and outcomes of cutaneous ischemia and gangrene in systemic necrotizing vasculitides: a retrospective multicenter study. Semin Arthritis Rheum. 2014;43(5):681–8.PubMedCrossRefGoogle Scholar
  3. 3.
    Francès C, Dû LT, Piette JC, Saada V, Boisnic S, Wechsler B, et al. Wegener’s granulomatosis. Dermatological manifestations in 75 cases with clinicopathologic correlation. Arch Dermatol. 1994;130(7):861–7.PubMedCrossRefGoogle Scholar
  4. 4.
    Daoud MS, Gibson LE, DeRemee RA, Specks U, el-Azhary RA, Su WP. Cutaneous Wegener’s granulomatosis: clinical, histopathologic, and immunopathologic features of thirty patients. J Am Acad Dermatol. 1994;31(4):605–12.PubMedCrossRefGoogle Scholar
  5. 5.
    Hu CH, O’Loughlin S, Winkelmann RK. Cutaneous manifestations of Wegener granulomatosis. Arch Dermatol. 1977;113(2):175–82.PubMedCrossRefGoogle Scholar
  6. 6.
    Aymard B, Bigard MA, Thompson H, Schmutz JL, Finet JF, Borrelly J. Perianal ulcer: an unusual presentation of Wegener’s granulomatosis. Report of a case. Dis Colon Rectum. 1990;33(5):427–30.PubMedCrossRefGoogle Scholar
  7. 7.
    Choi SW, Lew S, Cho SD, Cha HJ, Eum EA, Jung HC, et al. Cutaneous polyarteritis nodosa presented with digital gangrene: a case report. J Korean Med Sci. 2006;21(2):371–3.PubMedPubMedCentralCrossRefGoogle Scholar
  8. 8.
    Reed WB, Jensen AK, Konwaler BE, Hunter D. The cutaneous manifestations in Wegener’s granulomatosis. Acta Derm Venereol. 1963;43:250–64.PubMedGoogle Scholar
  9. 9.
    Otani Y, Anzai S, Shibuya H, Fujiwara S, Takayasu S, Asada Y, et al. Churg–Strauss syndrome (CSS) manifested as necrosis of fingers and toes and liver infarction. J Dermatol. 2003;30(11):810–5.PubMedCrossRefGoogle Scholar
  10. 10.
    Shimbo J, Miwa A, Aoki K. Cryofibrinogenemia associated with polyarteritis nodosa. Clin Rheumatol. 2006;25(4):562–3.PubMedCrossRefPubMedCentralGoogle Scholar
  11. 11.
    Zulian F, Corona F, Gerloni V, Falcini F, Buoncompagni A, Scarazatti M, et al. Safety and efficacy of iloprost for the treatment of ischaemic digits in paediatric connective tissue diseases. Rheumatology (Oxford). 2004;43(2):229–33.CrossRefGoogle Scholar
  12. 12.
    Guillevin L, Durand-Gasselin B, Cevallos R, Gayraud M, Lhote F, Callard P, et al. Microscopic polyangiitis: clinical and laboratory findings in eighty-five patients. Arthritis Rheum. 1999;42(3):421–30.PubMedCrossRefGoogle Scholar
  13. 13.
    Comarmond C, Pagnoux C, Khellaf M, Cordier J-F, Hamidou M, Viallard J-F, et al. Eosinophilic granulomatosis with polyangiitis (Churg–Strauss): clinical characteristics and long-term follow-up of the 383 patients enrolled in the French Vasculitis Study Group cohort. Arthritis Rheum. 2013;65(1):270–81.PubMedCrossRefGoogle Scholar
  14. 14.
    Pagnoux C, Seror R, Henegar C, Mahr A, Cohen P, Le Guern V, et al. Clinical features and outcomes in 348 patients with polyarteritis nodosa: a systematic retrospective study of patients diagnosed between 1963 and 2005 and entered into the French Vasculitis Study Group Database. Arthritis Rheum. 2010;62(2):616–26.PubMedCrossRefGoogle Scholar
  15. 15.
    Kejriwal R, Lim TM, Kumar S. Wegener’s granulomatosis and acute upper limb digital ischemia. Int J Rheum Dis. 2008;11(2):185–7.CrossRefGoogle Scholar
  16. 16.
    Bessias N, Moulakakis KG, Lioupis C, Bakogiannis K, Sfyroeras G, Kakaletri K, et al. Wegener’s granulomatosis presenting during pregnancy with acute limb ischemia. J Vasc Surg. 2005 Oct;42(4):800–4.PubMedCrossRefGoogle Scholar
  17. 17.
    Ferenczi K, Chang T, Camouse M, Han R, Stern R, Willis J, et al. A case of Churg–Strauss syndrome associated with antiphospholipid antibodies. J Am Acad Dermatol. 2007;56(4):701–4.PubMedCrossRefGoogle Scholar
  18. 18.
    Pagnoux C, Chironi G, Simon A, Guillevin L. Atherosclerosis in ANCA-associated vasculitides. Ann N Y Acad Sci. 2007;1107:11–21.PubMedCrossRefGoogle Scholar
  19. 19.
    Raza K, Thambyrajah J, Townend JN, Exley AR, Hortas C, Filer A, et al. Suppression of inflammation in primary systemic vasculitis restores vascular endothelial function: lessons for atherosclerotic disease? Circulation. 2000;102(13):1470–2.PubMedCrossRefGoogle Scholar
  20. 20.
    Guillevin L, Lhote F, Gayraud M, Cohen P, Jarrousse B, Lortholary O, et al. Prognostic factors in polyarteritis nodosa and Churg–Strauss syndrome. A prospective study in 342 patients. Medicine (Baltimore). 1996;75(1):17–28.CrossRefGoogle Scholar
  21. 21.
    Guillevin L, Pagnoux C, Seror R, Mahr A, Mouthon L, Le Toumelin P. The Five-Factor Score revisited: assessment of prognoses of systemic necrotizing vasculitides based on the French Vasculitis Study Group (FVSG) cohort. Medicine (Baltimore). 2011;90(1):19–27.CrossRefGoogle Scholar
  22. 22.
    Leung A, Sung CB, Kothari G, Mack C, Fong C. Utilisation of plasma exchange in the treatment of digital infarcts in Wegener’s granulomatosis. Int J Rheum Dis. 2010;13(4):e59–61.PubMedCrossRefPubMedCentralGoogle Scholar
  23. 23.
    Maia M, Brandão P, Monteiro P, Barreto P, Brandão D, Ferreira J, et al. Upper limb ischemia in a patient with Wegener’s granulomatosis. Interact Cardiovasc Thorac Surg. 2008;7(6):1137–40.PubMedCrossRefPubMedCentralGoogle Scholar
  24. 24.
    Genta MS, Genta RM, Gabay C. Systemic rheumatoid vasculitis: a review. Semin Arthritis Rheum. 2006;36(2):88–98.PubMedCrossRefPubMedCentralGoogle Scholar
  25. 25.
    Gorman JD, David-Vaudey E, Pai M, Lum RF, Criswell LA. Particular HLA-DRB1 shared epitope genotypes are strongly associated with rheumatoid vasculitis. Arthritis Rheum. 2004;50(11):3476–84.PubMedCrossRefPubMedCentralGoogle Scholar
  26. 26.
    Turesson C, Schaid DJ, Weyand CM, Jacobsson LT, Goronzy JJ, Petersson IF, et al. Association of HLA-C3 and smoking with vasculitis in patients with rheumatoid arthritis. Arthritis Rheum. 2006;54(9):2776–83.PubMedCrossRefPubMedCentralGoogle Scholar
  27. 27.
    Puéchal X, Said G. Necrotizing vasculitis of the peripheral nervous system: nonsystemic or clinically undetectable? Arthritis Rheum. 1999;42(4):824–5.PubMedCrossRefPubMedCentralGoogle Scholar
  28. 28.
    Puéchal X, Gottenberg JE, Berthelot JM, Gossec L, Meyer O, Morel J, et al. Rituximab therapy for systemic vasculitis associated with rheumatoid arthritis: results from the AutoImmunity and Rituximab Registry. Arthritis Care Res (Hoboken). 2012;64(3):331–9.CrossRefGoogle Scholar
  29. 29.
    Voskuyl A, Hazes J, Zwinderman A, Paleolog E, van der Meer FJM, Daha M, et al. Diagnostic strategy for the assessment of rheumatoid vasculitis. Ann Rheum Dis. 2003;62(5):407–13.PubMedPubMedCentralCrossRefGoogle Scholar
  30. 30.
    Hasegawa M, Nagai Y, Sogabe Y, Hattori T, Inoue C, Okada E, et al. Clinical analysis of leg ulcers and gangrene in rheumatoid arthritis. J Dermatol. 2013;40(12):949–54.PubMedCrossRefGoogle Scholar
  31. 31.
    Soyfoo MS, Couturier B, Cogan E. Cryofibrinogenaemia with vasculitis: a new overlap syndrome causing severe leg ulcers and digital necrosis in rheumatoid arthritis? Rheumatology. 2010;49(12):2455–7.PubMedCrossRefGoogle Scholar
  32. 32.
    Puéchal X, Miceli-Richard C, Mejjad O, Lafforgue P, Marcelli C, Solau-Gervais E, et al. Anti-tumour necrosis factor treatment in patients with refractory systemic vasculitis associated with rheumatoid arthritis. Ann Rheum Dis. 2008;67(6):880–4.PubMedCrossRefGoogle Scholar
  33. 33.
    Bartels CM, Bridges AJ. Rheumatoid vasculitis: vanishing menace or target for new treatments? Curr Rheumatol Rep. 2010;12(6):414–9.PubMedPubMedCentralCrossRefGoogle Scholar
  34. 34.
    Criteria for diagnosis of Behçet’s disease. International Study Group for Behçet’s Disease. Lancet. 1990;335(8697):1078–80.Google Scholar
  35. 35.
    Alpsoy E, Zouboulis CC, Ehrlich GE. Mucocutaneous lesions of Behçet’s disease. Yonsei Med J. 2007;48(4):573–85.PubMedPubMedCentralCrossRefGoogle Scholar
  36. 36.
    Travis SP, Czajkowski M, McGovern DP, Watson RG, Bell AL. Treatment of intestinal Behçet’s syndrome with chimeric tumour necrosis factor alpha antibody. Gut. 2001;49(5):725–8.PubMedPubMedCentralCrossRefGoogle Scholar
  37. 37.
    Gera C, Jose W, Malhotra N, Malhotra V, Dhanoa J. Radial artery occlusion, a rare presentation of Behçet’s disease. J Assoc Physicians India. 2008;56:643–4.PubMedPubMedCentralGoogle Scholar
  38. 38.
    Ateş A, Karaaslan Y, Aşlar ZÖ. A case of Behçet’s disease associated with necrotizing small vessel vasculitis. Rheumatol Int. 2006;27(1):91–3.PubMedCrossRefPubMedCentralGoogle Scholar
  39. 39.
    Cantini F, Salvarani C, Niccoli L, Senesi C, Truglia MC, Padula A, et al. Behçet’s disease with unusual cutaneous lesions. J Rheumatol. 1998;25(12):2469–72.PubMedPubMedCentralGoogle Scholar
  40. 40.
    Yurtkuran M, Yurtkuran M, Alp A, Sivrioglu K, Dilek K, Tamgaç F, et al. Hand involvement in Behçet’s disease. Joint Bone Spine. 2006;73(6):679–83.PubMedCrossRefPubMedCentralGoogle Scholar
  41. 41.
    Movasat A, Shahram F, Carreira PE, Nadji A, Akhlaghi M, Naderi N, et al. Nail fold capillaroscopy in Behçet’s disease, analysis of 128 patients. Clin Rheumatol. 2009;28(5):603–5.PubMedCrossRefPubMedCentralGoogle Scholar
  42. 42.
    Chen KR, Kawahara Y, Miyakawa S, Nishikawa T. Cutaneous vasculitis in Behçet’s disease: a clinical and histopathologic study of 20 patients. J Am Acad Dermatol. 1997;36(5 Pt 1):689–96.PubMedCrossRefPubMedCentralGoogle Scholar
  43. 43.
    Hatemi G, Silman A, Bang D, Bodaghi B, Chamberlain AM, Gul A, et al. EULAR recommendations for the management of Behçet disease. Ann Rheum Dis. 2008;67(12):1656–62.PubMedCrossRefPubMedCentralGoogle Scholar
  44. 44.
    Yurdakul S, Mat C, Tüzün Y, Ozyazgan Y, Hamuryudan V, Uysal O, et al. A double-blind trial of colchicine in Behçet’s syndrome. Arthritis Rheum. 2001;44(11):2686–92.PubMedCrossRefPubMedCentralGoogle Scholar
  45. 45.
    Alibaz-Oner F, Karadeniz A, Ylmaz S, Balkarl A, Kimyon G, Yazc A, et al. Behçet disease with vascular involvement: effects of different therapeutic regimens on the incidence of new relapses. Medicine (Baltimore). 2015;94(6):e494.CrossRefGoogle Scholar
  46. 46.
    Küçükşahin O, Ateş A, Okoh AK, Kulahcioglu E, Turgay M, Kınıklı G. Treatment resistant severe digital ischemia associated with antiphospholipid syndrome in a male patient with systemic sclerosis. Case Rep Rheumatol. 2014;2014:291382.PubMedPubMedCentralGoogle Scholar
  47. 47.
    Crome CR, Rajagopalan S, Kuhan G, Fluck N. Antiphospholipid syndrome presenting with acute digital ischaemia, avascular necrosis of the femoral head and superior mesenteric artery thrombus. BMJ Case Rep. 2012;2012:bcr2012006731.PubMedPubMedCentralCrossRefGoogle Scholar
  48. 48.
    Jou IM, Liu MF, Chao SC. Widespread cutaneous necrosis associated with antiphospholipid syndrome. Clin Rheumatol. 1996;15(4):394–8.PubMedCrossRefGoogle Scholar
  49. 49.
    Hai A, Aslam M, Ashraf TH. Symmetrical peripheral gangrene: a rare presentation of antiphospholipid syndrome. Intern Emerg Med. 2012;7(Suppl 1):S71–3.PubMedCrossRefGoogle Scholar
  50. 50.
    Cervera R, Piette J-C, Font J, Khamashta MA, Shoenfeld Y, Camps MT, et al. Antiphospholipid syndrome: clinical and immunologic manifestations and patterns of disease expression in a cohort of 1,000 patients. Arthritis Rheum. 2002;46(4):1019–27.PubMedCrossRefPubMedCentralGoogle Scholar
  51. 51.
    Francès C, Niang S, Laffitte E, Le Pelletier F, Costedoat N, Piette JC. Dermatologic manifestations of the antiphospholipid syndrome: two hundred consecutive cases. Arthritis Rheum. 2005;52(6):1785–93.PubMedCrossRefPubMedCentralGoogle Scholar
  52. 52.
    Wollina U, Verma SB. Acute digital gangrene in a newborn. Arch Dermatol. 2007;143(1):121–2.PubMedCrossRefPubMedCentralGoogle Scholar
  53. 53.
    Grossman A, Gafter-Gvili A, Green H, Ben Aharon I, Stemmer SM, Molad Y, et al. Severe digital ischemia – a presenting symptom of malignancy-associated antiphospholipid syndrome. Lupus. 2008;17(3):206–9.PubMedCrossRefPubMedCentralGoogle Scholar
  54. 54.
    Méchinaud-Lacroix F, Jehan P, Debré MA, Prieur AM, Sizun J, Harousseau JL. Thrombotic manifestations and acute distal ischemia in primary antiphospholipid syndrome in children. Arch Fr Pediatr. 1992;49(Suppl 1):257–9.PubMedPubMedCentralGoogle Scholar
  55. 55.
    Rezende SM, Franco R. Multiple peripheral artery occlusions in antiphospholipid syndrome. Am J Hematol. 2007;82(6):498.PubMedCrossRefPubMedCentralGoogle Scholar
  56. 56.
    Bouaziz JD, Barete S, Le Pelletier F, Amoura Z, Piette JC, Francès C. Cutaneous lesions of the digits in systemic lupus erythematosus: 50 cases. Lupus. 2007;16(3):163–7.PubMedCrossRefPubMedCentralGoogle Scholar
  57. 57.
    Vayssairat M, Abuaf N, Deschamps A, Baudot N, Gaitz JP, Chakkour K, et al. Nail fold capillary microscopy in patients with anticardiolipin antibodies: a case–control study. Dermatology (Basel). 1997;194(1):36–40.CrossRefGoogle Scholar
  58. 58.
    Candela M, Pansoni A, De Carolis ST, Pomponio G, Corvetta A, Gabrielli A, et al. Nail fold capillary microscopy in patients with antiphospholipid syndrome. Recenti Prog Med. 1998;89(9):444–9.PubMedGoogle Scholar
  59. 59.
    Szodoray P, Hajas A, Toth L, Szakall S, Nakken B, Soltesz P, et al. The beneficial effect of plasmapheresis in mixed connective tissue disease with coexisting antiphospholipid syndrome. Lupus. 2014;23(10):1079–84.PubMedCrossRefPubMedCentralGoogle Scholar
  60. 60.
    Asherson RA, Cervera R, Klumb E, Stojanovic L, Sarzi-Puttini P, Yinh J, et al. Amputation of digits or limbs in patients with antiphospholipid syndrome. Semin Arthritis Rheum. 2008;38(2):124–31.PubMedCrossRefGoogle Scholar
  61. 61.
    Jelušić M, Starčević K, Vidović M, Dobrota S, Potočki K, Banfić L, et al. Familial antiphospholipid syndrome presenting as bivessel arterial occlusion in a 17-year-old girl. Rheumatol Int. 2013;33(5):1359–62.PubMedCrossRefGoogle Scholar
  62. 62.
    Francès C, Tribout B, Boisnic S, Drouet L, Piette AM, Piette JC, et al. Cutaneous necrosis associated with the lupus anticoagulant. Dermatologica. 1989;178(4):194–201.PubMedCrossRefGoogle Scholar
  63. 63.
    Zahavi J, Charach G, Schafer R, Toeg A, Zahavi M. Ischaemic necrotic toes associated with antiphospholipid syndrome and treated with iloprost. Lancet. 1993;342(8875):862.PubMedCrossRefPubMedCentralGoogle Scholar
  64. 64.
    Cohen H, Doré CJ, Clawson S, Hunt BJ, Isenberg D, Khamashta M, et al. Rivaroxaban in antiphospholipid syndrome (RAPS) protocol: a prospective, randomized controlled phase II/III clinical trial of rivaroxaban versus warfarin in patients with thrombotic antiphospholipid syndrome, with or without SLE. Lupus. 2015;24(10):1087–94.PubMedPubMedCentralCrossRefGoogle Scholar
  65. 65.
    Dargon PT, Landry GJ. Buerger’s disease. Ann Vasc Surg. 2012;26(6):871–80.PubMedCrossRefPubMedCentralGoogle Scholar
  66. 66.
    Klein-Weigel PF, Richter JG. Thromboangiitis obliterans (Buerger’s disease). Vasa. 2014 Sep;43(5):337–46.PubMedCrossRefPubMedCentralGoogle Scholar
  67. 67.
    Rosencrance G, Thistlewaite T. Images in clinical medicine. Thromboangiitis obliterans. N Engl J Med. 1996;334(14):891.PubMedCrossRefPubMedCentralGoogle Scholar
  68. 68.
    Sims JR, Hanson EL. Images in clinical medicine. Thromboangiitis obliterans (Buerger’s disease). N Engl J Med. 1998;339(10):672.PubMedCrossRefPubMedCentralGoogle Scholar
  69. 69.
    Ohta T, Ishibashi H, Sugimoto I, Iwata H, Kawanishi J, Yamada T, et al. The clinical course of Buerger’s disease. Ann Vasc Dis. 2008;1(2):85–90.PubMedPubMedCentralCrossRefGoogle Scholar
  70. 70.
    Fiessinger JN, Schäfer M. Trial of iloprost versus aspirin treatment for critical limb ischaemia of thromboangiitis obliterans. TAO Study Lancet. 1990;335(8689):555–7.PubMedCrossRefGoogle Scholar
  71. 71.
    Bozkurt AK, Cengiz K, Arslan C, Mine DY, Oner S, Deniz DB, et al. A stable prostacyclin analogue (iloprost) in the treatment of Buerger’s disease: a prospective analysis of 150 patients. Ann Thorac Cardiovasc Surg. 2013;19(2):120–5.PubMedCrossRefGoogle Scholar
  72. 72.
    De Haro J, Acin F, Bleda S, Varela C, Esparza L. Treatment of thromboangiitis obliterans (Buerger’s disease) with bosentan. BMC Cardiovasc Disord. 2012;12:5.PubMedPubMedCentralCrossRefGoogle Scholar
  73. 73.
    Gaines PA, Swarbrick MJ, Lopez AJ, Cleveland T, Beard J, Buckenham TM, et al. The endovascular management of blue finger syndrome. Eur J Vasc Endovasc Surg. 1999;17(2):106–10.PubMedCrossRefGoogle Scholar
  74. 74.
    Haesler P, Hoffmann U, Meyer VE, Bollinger A. Cutaneous micro167embolisms in aneurysm of the distal ulnar artery. Vasa. 1994;23(2):–70.Google Scholar
  75. 75.
    Bansal RC, Pauls GL, Shankel SW. Blue digit syndrome: transesophageal echocardiographic identification of thoracic aortic plaque-related thrombi and successful outcome with warfarin. J Am Soc Echocardiogr. 1993;6(3 Pt 1):319–23.PubMedCrossRefGoogle Scholar
  76. 76.
    Lacombe M. Digital microembolism after thrombosis of an arteriovenous fistula. Presse Méd. 1989;18(31):1525.PubMedGoogle Scholar
  77. 77.
    Cardani R, Pileggi A, Ricordi C, Gomez C, Baidal DA, Ponte GG, et al. Allosensitization of islet allograft recipients. Transplantation. 2007;84(11):1413–27.PubMedCrossRefGoogle Scholar
  78. 78.
    Acar P, Emmerich J, Acar C, Capron L, Fiessinger JN. Staphylococcus aureus endocarditis: an unusual clinical picture. Rev Méd Interne. 1993;14(7):733–6.PubMedCrossRefGoogle Scholar
  79. 79.
    Chanudet X, Clément R, Brunetti G, Ollivier JP, Bauduceau B, Celton H, et al. Digital microembolism disclosing intracardiac thrombosis. Ann Cardiol Angeiol (Paris). 1986;35(2):107–10.Google Scholar
  80. 80.
    Poppe H, Poppe LM, Bühler C, Machann W, Solymosi L, Dlaske H, et al. Painful cyanotic discoloration of the distal phalanges IV and V of the left hand in a 53-year-old female smoker. J Dtsch Dermatol Ges. 2013;11(9):887–91.PubMedGoogle Scholar
  81. 81.
    Maverakis E, Patel F, Kronenberg DG, Chung L, Fiorentino D, Allanore Y, et al. International consensus criteria for the diagnosis of Raynaud’s phenomenon. J Autoimmun. 2014;48–49:60–5.PubMedPubMedCentralCrossRefGoogle Scholar
  82. 82.
    CEDEF. Item 327—Raynaud phenomenon. Ann Dermatol Venereol. 2012;139(11 Suppl):A223–6.Google Scholar
  83. 83.
    Senel S, Zorlu P, Dogan B, Acar M. Successfully treated fingertip necrosis in an infant with primary Raynaud phenomenon. Indian J Pediatr. 2014;81(12):1399–400.PubMedCrossRefGoogle Scholar
  84. 84.
    Uygur S, Tuncer S. Partial fingertip necrosis following a digital surgical procedure in a patient with primary Raynaud’s phenomenon. Int Wound J. 2014;11(6):581–2.PubMedCrossRefGoogle Scholar
  85. 85.
    Landry GJ, Edwards JM, McLafferty RB, Taylor LM, Porter JM. Long-term outcome of Raynaud’s syndrome in a prospectively analyzed patient cohort. J Vasc Surg. 1996;23(1):76–85; discussion 85–86PubMedCrossRefGoogle Scholar
  86. 86.
    Valdovinos ST, Landry GJ. Raynaud syndrome. Tech Vasc Interv Radiol. 2014;17(4):241–6.PubMedCrossRefGoogle Scholar
  87. 87.
    Marr JS, Malloy CD. An epidemiologic analysis of the ten plagues of Egypt. Caduceus. 1996;12(1):7–24.PubMedGoogle Scholar
  88. 88.
    Craig AM, Klotz JL, Duringer JM. Cases of ergotism in livestock and associated ergot alkaloid concentrations in feed. Front Chem. 2015;3:8. Available from: Scholar
  89. 89.
    Liaudet L. Severe ergotism associated with interaction between ritonavir and ergotamine. BMJ. 1999;318(7186):771.PubMedPubMedCentralCrossRefGoogle Scholar
  90. 90.
    Ayarragaray JEF. Ergotism: a change of perspective. Ann Vasc Surg. 2014;28(1):265–8.PubMedCrossRefPubMedCentralGoogle Scholar
  91. 91.
    Acle S, Roca F, Vacarezza M, Álvarez RA. Ergotism secondary to ergotamine-ritonavir association. Report of three cases. Rev Med Chil. 2011;139(12):1597–600.PubMedCrossRefPubMedCentralGoogle Scholar
  92. 92.
    Brancaccio G, Celoria GM, Falco E. Ergotism. J Vasc Surg. 2008;48(3):754.PubMedCrossRefPubMedCentralGoogle Scholar
  93. 93.
    Musikatavorn K, Suteparuk S. Ergotism unresponsive to multiple therapeutic modalities, including sodium nitroprusside, resulting in limb loss. Clin Toxicol (Phila). 2008;46(2):157–8.CrossRefGoogle Scholar
  94. 94.
    Piquemal R, Emmerich J, Guilmot JL, Fiessinger JN. Successful treatment of ergotism with Iloprost – a case report. Angiology. 1998;49(6):493–7.PubMedCrossRefPubMedCentralGoogle Scholar
  95. 95.
    Schmutz J-L, Barbaud A, Trechot P. Pseudoporphyria and coxib. Ann Dermatol Venereol. 2006;133(2):213.PubMedCrossRefPubMedCentralGoogle Scholar
  96. 96.
    Turnbull N, Callan M, Staughton RCD. Diclofenac-induced pseudoporphyria; an under-recognized condition? Clin Exp Dermatol. 2014;39(3):348–50.PubMedCrossRefPubMedCentralGoogle Scholar
  97. 97.
    Cron RQ, Finkel TH. Nabumetone induced pseudoporphyria in childhood. J Rheumatol. 2000;27(7):1817–8.PubMedPubMedCentralGoogle Scholar
  98. 98.
    Maerker JM, Harm A, Foeldvari I, Höger PH. Naproxen-induced pseudoporphyria. Hautarzt. 2001;52(11):1026–9.PubMedCrossRefPubMedCentralGoogle Scholar
  99. 99.
    Roche M, Daly P, Crowley V, Darby C, Barnes L. A case of porphyria cutanea tarda resulting in digital amputation and improved by anastrozole. Clin Exp Dermatol. 2007;32(3):327–8.PubMedCrossRefPubMedCentralGoogle Scholar
  100. 100.
    Prendiville JS, Crow YJ. Blue (or purple) toes: chilblains or chilblain lupus-like lesions are a manifestation of Aicardi–Goutières syndrome and familial chilblain lupus. J Am Acad Dermatol. 2009;61(4):727–8.PubMedCrossRefPubMedCentralGoogle Scholar
  101. 101.
    Lee-Kirsch MA, Gong M, Schulz H, Rüschendorf F, Stein A, Pfeiffer C, et al. Familial chilblain lupus, a monogenic form of cutaneous lupus erythematosus, maps to chromosome 3p. Am J Hum Genet. 2006;79(4):731–7.PubMedPubMedCentralCrossRefGoogle Scholar
  102. 102.
    Perdan-Pirkmajer K, Praprotnik S, Tomšič M. Digital ulcers as the first manifestation of carpal tunnel syndrome. Rheumatol Int. 2011;31(5):685–6.PubMedCrossRefPubMedCentralGoogle Scholar
  103. 103.
    Simonnet N, Marcantoni N, Simonnet L, Griffon C, Chakfe N, Wertheimer J, et al. Puffy hand in long-term intravenous drug users. J Mal Vasc. 2004;29(4):201–4.PubMedCrossRefPubMedCentralGoogle Scholar
  104. 104.
    Cowan NC, Kane P, Karani J. Case report: metallic mercury embolism – deliberate self-injection. Clin Radiol. 1992;46(5):357–8.PubMedCrossRefPubMedCentralGoogle Scholar
  105. 105.
    Johnson-Arbor K. Images in clinical medicine. Digital frostbite. N Engl J Med. 2014;370(2):e3.PubMedCrossRefPubMedCentralGoogle Scholar
  106. 106.
    Ashokkumar GK, Madhu R, Shaji M, Singh BR. Bilateral symmetrical digital gangrene of upper and lower limbs due to purpura fulminans caused by Streptococcus pyogenes: a rare entity. Indian J Crit Care Med. 2015;19(5):290–1.PubMedPubMedCentralCrossRefGoogle Scholar
  107. 107.
    Alves JV, Matos DM, Furtado CM, Fernandes Bártolo EA. Bacillary angiomatosis presenting as a digital ulcer. Indian J Dermatol Venereol Leprol. 2015;81(4):398–400.PubMedCrossRefPubMedCentralGoogle Scholar
  108. 108.
    Akhtar N, Begum M, Saleh AA, Paul HK, Uddin MJ, Chowdhury AQ. Cutaneous sporotrichosis. Mymensingh Med J. 2010;19(3):458–61.PubMedPubMedCentralGoogle Scholar
  109. 109.
    Chaabane H, Turki H. Images in clinical medicine. Cutaneous leishmaniasis with a paronychia-like lesion. N Engl J Med. 2014;371(18):1736.PubMedCrossRefPubMedCentralGoogle Scholar
  110. 110.
    Bouchentouf R, Benjelloun A, Aitbenasser MA. Digital ulcers revealing lung carcinoma. Rev Pneumol Clin. 2012;68(6):367–9.PubMedCrossRefGoogle Scholar
  111. 111.
    Allen D, Robinson D, Mittoo S. Paraneoplastic Raynaud’s phenomenon in a breast cancer survivor. Rheumatol Int. 2010;30(6):789–92.PubMedCrossRefGoogle Scholar
  112. 112.
    Pronk WG, Baars JP, De Jong PC, Westermann AM. Some unusual paraneoplastic syndromes. Case 2. Digital ulceration as a paraneoplastic syndrome in ovarian cancer. J Clin Oncol. 2003;21(13):2620–2.PubMedCrossRefGoogle Scholar
  113. 113.
    Ohtsuka T, Yamakage A, Yamazaki S. Digital ulcers and necroses: novel manifestations of angiocentric lymphoma. Br J Dermatol. 2000;142(5):1013–6.PubMedCrossRefGoogle Scholar
  114. 114.
    Field J, Lane IF. Carcinoma of the lung presenting with digital ischaemia. Thorax. 1986;41(7):573–4.PubMedPubMedCentralCrossRefGoogle Scholar
  115. 115.
    Hladunewich M, Sawka C, Fam A, Franssen E. Raynaud’s phenomenon and digital gangrene as a consequence of treatment for Kaposi’s sarcoma. J Rheumatol. 1997;24(12):2371–5.PubMedGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Benjamin Chaigne
    • 1
  • Loïc Guillevin
    • 1
  1. 1.National Referral Center for Rare Systemic Autoimmune Diseases, Department of Internal Medicine, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris (APHP), Université Paris DescartesParisFrance

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