RSS-Feed abonnieren
PDF herunterladen
DOI: 10.1160/TH15-04-0309
Increased risk of venous thromboembolism in patients with bullous pemphigoid
The INVENTEP (INcidence of VENous ThromboEmbolism in bullous Pemphigoid) studyFinancial support:This work was supported by “Ricerca corrente”, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, Milano, Italy. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Publikationsverlauf
Received:
15. April 2015
Accepted after major revision:
19. Juni 2015
Publikationsdatum:
22. November 2017 (online)
Summary
Activation of blood coagulation has been demonstrated in bullous pemphigoid (BP), a rare autoimmune blistering disease, potentially leading to a prothrombotic state. In order to evaluate the incidence of venous thromboembolism (VTE) in BP, a cohort study was carried out on 432 BP patients (59 % females; median age 76 years, interquartile range [IQR]: 68–82). At diagnosis, autoimmune bullous skin disorder intensity score (ABSIS) was calculated. VTE incidence was standardised with rates of the general population. Multivariable Cox proportional hazard model was used to estimate the hazard ratio of VTE according to ABSIS and concomitant risk factors. During a median follow-up of 4.2 years, 31 objectively-diagnosed VTE events were recorded. The incidence rate of VTE (per 1000 patient-years) was 17.2 overall (95 % confidence interval [CI]: 11.1–23.2), 56.7 (95 %CI: 33.0–80.4) during acute phase (22 VTE) and 6.3 (95 %CI: 2.8–11.3) during remission (9 VTE). The standardised incidence ratio was 4.06 (95 %CI: 2.73–5.65), higher during the acute phase (14.86, 95 %CI: 9.20–21.88) than during remission (1.48, 0.66–2.63). The adjusted hazard ratio of VTE was 2.74 (95 %CI: 1.07–7.04) for ABSIS > 48 vs ABSIS < 28, and 2.56 (95 %CI: 1.00–6.70) in patients with [uni2265] 2 concomitant risk factors. In conclusion, BP patients have a 15-fold increased VTE risk during acute phase, proportional to disease severity and heightened by concomitant risk factors.
§ Drs Cugno and Marzano contributed equally to this article
* INVENTEP Study Group: Paolo Fabbri7, Aurora Parodi11, Carlo Crosti2, Giovanna Zambruno4 , Ornella De Pità4, Emiliano Antiga7, Federico Bardazzi10, Michelangelo La Placa10, Elena Marra5, Marta B. Brumana8, Giorgio Pasolini6, Annalisa Vascellaro6, Ivana Zacconi12
-
References
- 1 Yancey KB. The pathophysiology of autoimmune blistering diseases. J Clin Invest 2005; 115: 825-828.
- 2 Langan SM, Smeeth L, Hubbard R. et al. Bullous pemphigoid and pemphigus vulgaris–incidence and mortality in the UK: population based cohort study. Br Med J 2008; 337: a180.
- 3 Roujeau JC, Lok C, Bastuji-Garin S. et al. High risk of death in elderly patients with extensive bullous pemphigoid. Arch Dermatol 1998; 134: 465-469.
- 4 Marazza G, Pham HC, Schärer L. et al. Autoimmune bullous disease Swiss study group. Incidence of bullous pemphigoid and pemphigus in Switzerland: a 2-year prospective study. Br J Dermatol 2009; 161: 861-868.
- 5 Hertl M, Eming R, Veldman C. T cell control in autoimmune bullous skin disorders. J Clin Invest 2006; 116: 1159-1166.
- 6 Marzano AV, Tedeschi A, Fanoni D. et al. Activation of blood coagulation in bullous pemphigoid: role of eosinophils, and local and systemic implications. Br J Dermatol 2009; 160: 266-272.
- 7 Marzano AV, Tedeschi A, Spinelli D. et al. Coagulation activation in autoimmune bullous diseases. Clin Exp Immunol 2009; 158: 31-36.
- 8 Cugno M, Tedeschi A, Asero R. et al. Skin autoimmunity and blood coagulation. Autoimmunity 2010; 43: 189-194.
- 9 Cugno M, Tedeschi A, Crosti C. et al. Activation of blood coagulation in auto-immune skin disorders. Exp Rev Clin Immunol 2009; 05: 605-613.
- 10 Marzano AV, Tedeschi A, Berti E. et al. Activation of coagulation in bullous pemphigoid and other eosinophil-related inflammatory skin diseases. Clin Exp Immunol 2011; 165: 44-50.
- 11 Marzano AV, Tedeschi A, Polloni I. et al. Prothrombotic state and impaired fibrinolysis in bullous pemphigoid, the most frequent autoimmune blistering disease. Clin Exp Immunol 2013; 171: 76-81.
- 12 Rosendaal FR, Van Hylckama Vlieg A, Doggen CJ. Venous thrombosis in the elderly. J Thromb Haemost 2007; 05 (Suppl. 01) 310-317.
- 13 Joly P, Benichou J, Lok C. et al. Prediction of survival for patients with bullous pemphigoid: a prospective study. Arch Dermatol 2005; 141: 691-698.
- 14 Yang YW, Chen YH, Xirasagar S. et al. Increased risk of stroke in patients with bullous pemphigoid: a population-based follow-up study. Stroke 2011; 42: 319-323.
- 15 Langan SM, Hubbard R, Fleming K. et al. A population-based study of acute medical conditions associated with bullous pemphigoid. Br J Dermatol 2009; 161: 1149-1152.
- 16 Pfutze M, Niedermeier A, Hertl M. et al. Introducing a novel autoimmune bullous skin disorder intensity score (ABSIS) in pemphigus. Eur J Dermatol 2007; 17: 4-11.
- 17 Naess IA, Christiansen SC, Romundstad P. et al. Incidence and mortality of venous thrombosis: a population-based study. J Thromb Haemost 2007; 05: 692-699.
- 18 Levi M. The coagulant response in sepsis and inflammation. Hamostaseologie 2010; 30: 10-16.
- 19 Ingegnoli F, Fantini F, Favalli EG. et al. Inflammatory and prothrombotic biomarkers in patients with rheumatoid arthritis: effects of tumor necrosis factor-alpha blockade. J Autoimmun 2008; 31: 175-179.
- 20 Ingegnoli F, Fantini F, Griffini S. et al. Anti-tumor necrosis factor alpha therapy normalizes fibrinolysis impairment in patients with active rheumatoid arthritis. Clin Exp Rheumatol 2010; 28: 254-257.
- 21 Irving PM, Pasi KJ, Rampton DS. Thrombosis and inflammatory bowel disease. Clin Gastroenterol Hepatol 2005; 03: 617-628.
- 22 Ogbogu PU, Rosing DR, Horne 3rd MK. Cardiovascular manifestations of hypereosinophilic syndromes. Immunol Allergy Clin North Am 2007; 27: 457-475.
- 23 Levi M, van der Poll T. Two-way interactions between inflammation and coagulation. Trends Cardiovasc Med 2005; 15: 254-259.
- 24 Garcia JG, Siflinger-Birnboim A, Bizios R. et al. Thrombin-induced increase in albumin permeability across the endothelium. J Cell Physiol 1986; 128: 96-104.
- 25 DeMichele MA, Moon DG, Fenton JW. 2nd, et al. Thrombin’s enzymatic activity increases permeability of endothelial cell monolayers. J Appl Physiol 1990; 69: 1599-1606.
- 26 Hull RD, Schellong SM, Tapson VF. et al. for the EXCLAIM study. Extended-duration venous thromboembolism prophylaxis in acutely ill medical patients with recently reduced mobility. Ann Intern Med 2010; 153: 8-18.
- 27 Oger E. for the EPI-GETBO Study Group. Incidence of venous thromboembolism: a community-based study in Western France. Thromb Haemost 2000; 83: 657-660.
- 28 Johannesdottir SA, Horváth-Puhó E, Dekkers OM. et al. Use of glucocorticoids and risk of venous thromboembolism. A nationwide population-based case-control study. J Am Med Assoc Intern Med 2013; 173: 743-752.