Abstract
Purpose
Autoimmune diseases are a common cause of delayed wound healing and should be considered in patients with chronic wounds who do not respond to local wound care or who fail skin grafting in the absence of infection.
Recent Findings
Epidemiologic studies have shown that, of patients with chronic wounds evaluated in specialized wound healing clinics, 20–23 % have autoimmune etiologies for their wounds including vasculitis, rheumatoid arthritis, systemic lupus erythematosus, scleroderma, pyoderma gangrenosum, and other autoimmune diseases.
Summary
In this article, autoimmune diseases known to be associated with chronic wounds and delayed wound healing are reviewed and the importance of a multidisciplinary approach for patients with chronic wounds, with involvement of rheumatology and dermatology, is highlighted. This approach allows for investigation of underlying systemic disease and improves clinical outcomes for many of these challenging patients.
Similar content being viewed by others
References
Papers of particular interest, published recently, have been highlighted as: • Of importance
Sen CK, Gordillo GM, Roy S, Kirsner R, Lambert L, Hunt TK, et al. Human skin wounds: a major and snowballing threat to public health and the economy. Wound Repair Regen. 2009;17(6):763–71.
Escandon J, Vivas AC, Tang J, Rowland KJ, Kirsner RS. High mortality in patients with chronic wounds. Wound Repair Regen. 2011;19(4):526–8.
Price P, Harding K. The impact of foot complications on health-related quality of life in patients with diabetes. J Cutan Med Surg. 2000;4(1):45–50.
Körber A, Klode J, Al-Benna S, Wax C, Schadendorf D, Steinstraesser L, et al. Etiology of chronic leg ulcers in 31,619 patients in Germany analyzed by an expert survey. JDDG: Journal der Deutschen Dermatologischen Gesellschaft. 2011;9(2):116–21.
Goslen JB. Autoimmune ulceration of the leg. Clin Dermatol. 1990;8(3–4):92–117.
Shanmugam VK, Schilling A, Germinario A, Mete M, Kim P, Steinberg J, et al. Prevalence of immune disease in patients with wounds presenting to a tertiary wound healing centre. International Wound Journal. 2011:1–9. Important article demonstrating prevalence of autoimmune disease in patients presenting to a wound clinic .
Li J, Chen J, Kirsner R. Pathophysiology of acute wound healing. Clin Dermatol. 2007;25(1):9–18.
Shanmugam V, DeMaria D, Attinger C. Lower extremity ulcers in rheumatoid arthritis: features and response to immunosuppression. Clin Rheumatol. 2011;30(6):849–53.
Oien RF, Hakansson A, Hansen BU. Leg ulcers in patients with rheumatoid arthritis—a prospective study of aetiology, wound healing and pain reduction after pinch grafting. Rheumatology. 2001;40(7):816–20.
Jebakumar AJ, Udayakumar PD, Crowson CS, Gabriel SE, Matteson EL. Occurrence and effect of lower extremity ulcer in rheumatoid arthritis—a population-based study. J Rheumatol. 2014;41(3):437–43 .Important epidemiologic study demonstrating the prevalence and morbidity of leg ulceration in patients with rheumatoid arthritis.
Makol A, Matteson EL, Warrington KJ. Rheumatoid vasculitis: an update. Curr Opin Rheumatol. 2015;27(1):63–70.
Assmann G, Pfreundschuh J, Voswinkel J. Rituximab in patients with rheumatoid arthritis and vasculitis-associated cutaneous ulcers. Clin Exp Rheumatol. 2010;28(1 Suppl 57):81–3.
Sayah A, English Iii JC. Rheumatoid arthritis: a review of the cutaneous manifestations. J Am Acad Dermatol. 2005;53(2):191–209.
Shanmugam VK, Fernandez S, Evans KK, McNish S, Banerjee A, Couch K, et al. Postoperative wound dehiscence: predictors and associations. Wound Repair and Regeneration. 2015:n/a-n/a. Important large epidemiologic study investigating predictors of post-operative wound dehiscence.
Tuffaneilli DL, Dubois EL. Cutaneous manifestations of systemic lupus erythematosus. Arch Dermatol. 1964;90:377–86.
Chia HY, Tang MB. Chronic leg ulcers in adult patients with rheumatological diseases—a 7-year retrospective review. Int Wound J. 2014;11(6):601–4.
Dabiri G, Falanga V. Connective tissue ulcers. Journal of Tissue Viability. 2013;22(4):92–102.
Sakakibara K, Matsumoto M, Motohashi S, Suzuki S. Recurrent refractory arterial thromboembolism in a patient with anti-phospholipid antibody syndrome. Intern Med. 2013;52(10):1145–6.
Manzi S, Sánchez-Guerrero J, Merrill JT, Furie R, Gladman D, Navarra SV, et al. Effects of belimumab, a B lymphocyte stimulator-specific inhibitor, on disease activity across multiple organ domains in patients with systemic lupus erythematosus: combined results from two phase III trials. Ann Rheum Dis. 2012;71(11):1833–8.
Shanmugam V, Price P, Attinger C, Steen V. Lower extremity ulcers in systemic sclerosis: features and response to therapy. Int J Rheumatol. 2010.
Hafner J, Schneider E, Burg G, Cassina PC. Management of leg ulcers in patients with rheumatoid arthritis or systemic sclerosis: the importance of concomitant arterial and venous disease. J Vasc Surg. 2001;32(2):322–9.
Deguchi J, Shigematsu K, Ota S, Kimura H, Fukayama M, Miyata T. Surgical result of critical limb ischemia due to tibial arterial occlusion in patients with systemic scleroderma. J Vasc Surg. 2009;49(4):918–23.
Braswell SF, Kostopoulos TC, Ortega-Loayza AG. Pathophysiology of pyoderma gangrenosum (PG): an updated review. J Am Acad Dermatol. 2015;73(4):691–8.
Kaur MR, Lewis HM. Severe recalcitrant pyoderma gangrenosum treated with infliximab. Br J Dermatol. 2005;153(3):689–91.
Guenova E, Teske A, Fehrenbacher B, Hoerber S, Adamczyk A, Schaller M, et al. Interleukin 23 expression in pyoderma gangrenosum and targeted therapy with ustekinumab. Arch Dermatol. 2011;147(10):1203–5.
Perniciaro CV, Winkelmann RK, Hunder GG. Cutaneous manifestations of Takayasu’s arteritis. A clinicopathologic correlation. J Am Acad Dermatol. 1987;17(6):998–1005.
Boudny C, Nievergelt H, Braathen LR, Simon D. Wegener’s granulomatosis presenting as pyoderma gangrenosum. JDDG: Journal der Deutschen Dermatologischen Gesellschaft. 2008;6(6):477–9.
Carlson JA. The histological assessment of cutaneous vasculitis. Histopathology. 56(1):3–23.
Kawakami T, Okano T, Soma Y. Rituximab therapy for deep toe ulcer with microscopic polyangiitis refractory to corticosteroids and cyclophosphamide. J Dermatol. 2014;41(2):191–2.
Patel FB, Couch KS, McNish S, Miller JD, Siegel R, Easley S, et al. A 66 year-old woman with hemoptysis. Arthritis Care Res (Hoboken). 2015.
Olin JW. Thromboangiitis obliterans (Buerger’s disease). N Engl J Med. 2000;343(12):864–9.
Sneller MC, Hu Z, Langford CA. A randomized controlled trial of rituximab following failure of antiviral therapy for hepatitis C virus-associated cryoglobulinemic vasculitis. Arthritis Rheum. 2012;64(3):835–42.
Dammacco F, Sansonno D. Therapy for hepatitis C virus-related cryoglobulinemic vasculitis. N Engl J Med. 2013;369(11):1035–45.
De Virgilio A, Greco A, Magliulo G, Gallo A, Ruoppolo G, Conte M, et al. Polyarteritis nodosa: a contemporary overview. Autoimmunity Reviews.
Raju RM, Raju SM, Zhao Y, Rubin EJ. Leveraging advances in tuberculosis diagnosis and treatment to address nontuberculous mycobacterial disease. Emerg Infect Dis. 2016;22(3):365–9.
Chan MP. Neutrophilic panniculitis: algorithmic approach to a heterogeneous group of disorders. Archives of Pathology & Laboratory Medicine. 2014;138(10):1337–43.
Koshy M, Entsuah R, Koranda A, Kraus A, Johnson R, Bellvue R, et al. Leg ulcers in patients with sickle cell disease [see comments]. Blood. 1989;74(4):1403–8.
Chaine B, Neonato M, Girot R, Aractingi S. Cutaneous adverse reactions to hydroxyurea in patients with sickle cell disease. Arch Dermatol. 2001;137(4):467–70.
Sirieix M, Debure C, Baudot N, Dubertret L, Roux M, Morel P, et al. Leg ulcers and hydroxyurea: forty-one cases. Arch Dermatol. 1999;135(7):818–20.
Best PJ, Daoud MS, Pittelkow MR, Petitt RM. Hydroxyurea-induced leg ulceration in 14 patients. Ann Intern Med. 1998;128(1):29–32.
Shanmugam VK, McNish S, Shara N, Hubley KJ, Kallakury B, Dunning DM, et al. Chronic leg ulceration associated with polycythemia vera responding to ruxolitinib (Jakafi®). The Journal of Foot and Ankle Surgery. (0).
Alavi A, Hafner J, Dutz JP, Mayer D, Sibbald RG, Criado PR, et al. Atrophie Blanche: is it associated with venous disease or livedoid vasculopathy? Adv Skin Wound Care. 2014;27(11):518–24.
Acland KM, Darvay A, Wakelin SH, Russell-Jones R. Livedoid vasculitis: a manifestation of the antiphospholipid syndrome? Br J Dermatol. 1999;140(1):131–5.
Callen JP. Livedoid vasculopathy: what it is and how the patient should be evaluated and treated. Arch Dermatol. 2006;142(11):1481–2.
Cardoso R, Gonçalo M, Tellechea O, Maia R, Borges C, Silva JAP, et al. Livedoid vasculopathy and hypercoagulability in a patient with primary Sjögren’s syndrome. Int J Dermatol. 2007;46(4):431–4.
Frances C, Barete S. Difficult management of livedoid vasculopathy. Arch Dermatol. 2004;140(8):1011.
Jorizzo JL. Livedoid vasculopathy: what is it? Arch Dermatol. 1998;134(4):491–3.
Mimouni D, Ng PP, Rencic A, Nikolskaia OV, Bernstein BD, Nousari HC. Cutaneous polyarteritis nodosa in patients presenting with atrophie blanche. Br J Dermatol. 2003;148(4):789–94.
Tran M, Becherel P, Cordel N, Piette JC, Frances C. “Idiopathic” livedoid vasculitis. Ann Dermatol Venerol. 2001;128:1003–7.
Wakelin SH, Ellis JP, Black MM. Livedoid vasculitis with anticardiolipin antibodies: improvement with danazol. Br J Dermatol. 1998;139(5):935–7.
Winkelmann R, Schroeter A, Kierland R, Ryan T. Clinical studies of livedoid vasculitis: (segmental hyalinizing vasculitis). Mayo Clin Proc. 1974;49(10):746–50.
Hairston BR, Davis M, Pittelkow MR, Ahmed I. Livedoid vasculopathy: further evidence for procoagulant pathogenesis. Arch Dermatol. 2006;142(11):1413–8.
Charabaty S, Shanmugam V. A 65-year-old man with longstanding seropositive rheumatoid arthritis and lower extremity ulceration. Arthritis Care & Research. 2009;61(9):1275–80.
Falanga V, Fine MJ, Kapoor WN. The cutaneous manifestations of cholesterol crystal embolization. Arch Dermatol. 1986;122(10):1194–8.
Weenig RH, Sewell LD, Davis MDP, McCarthy JT, Pittelkow MR. Calciphylaxis: natural history, risk factor analysis, and outcome. J Am Acad Dermatol. 2007;56(4):569–79.
Malbos S, Ureña-Torres P, Bardin T, Ea H-K. Sodium thiosulfate is effective in calcific uremic arteriolopathy complicating chronic hemodialysis. Joint Bone Spine. 2016;83(1):89–92.
Lonowski S, Martin S, Worswick S. Widespread calciphylaxis and normal renal function: no improvement with sodium thiosulfate. Dermatology online journal. 2015;21(5).
Francès C, Niang S, Laffitte E. Pelletier Fl, Costedoat N, Piette JC. Dermatologic manifestations of the antiphospholipid syndrome: two hundred consecutive cases. Arthritis & Rheumatism. 2005;52(6):1785–93.
Wiszniewski A, Bykowska K, Bilski R, Jaśkowiak W, Proniewski J. Prevalence rate for inherited thrombophilia in patients with chronic and recurrent venous leg ulceration. Wound Repair Regen. 2011;19(5):552–8.
Shanmugam VK, McNish S, Duncan J, Root B, Tassi E, Wellstein A, et al. Late failure of a split-thickness skin graft in the setting of homozygous factor V Leiden mutation: a case report and correlative animal model from the Wound Etiology and Healing (WE-HEAL) study. International Wound Journal. 2013:n/a-n/a.
Sams W. Livedo vasculitis. Therapy with pentoxifylline. Arch Dermatol. 1988;124(5):684–7.
Weishaupt C, Strölin A, Kahle B, Kreuter A, Schneider SW, Gerss J, et al. Anticoagulation with rivaroxaban for livedoid vasculopathy (RILIVA): a multicentre, single-arm, open-label, phase 2a, proof-of-concept trial. The Lancet Haematology. 3(2):e72–e9.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of Interest
Victoria Shanmugam reports grants from the National Institute of Nursing Research during the conduct of the study.
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.
Additional information
This article is part of the Topical Collection on Wound Care and Healing
Rights and permissions
About this article
Cite this article
Shanmugam, V.K. Vasculitic Diseases and Prothrombotic States Contributing to Delayed Healing in Chronic Wounds. Curr Derm Rep 5, 270–277 (2016). https://doi.org/10.1007/s13671-016-0157-2
Published:
Issue Date:
DOI: https://doi.org/10.1007/s13671-016-0157-2