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Acute and Recurrent Cellulitis

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Acute and Recurrent Cellulitis MATTI KARPPELIN Acute and Recurrent Cellulitis ACADEMIC DISSERTATION To be presented, with the permission of the Board of the School of Medicine of the University of Tampere, for public discussion in the Small Auditorium of Building M, Pirkanmaa Hospital District, Teiskontie 35, Tampere, on May 8th, 2015, at 12 o’clock. UNIVERSITY OF TAMPERE MATTI KARPPELIN Acute and Recurrent Cellulitis Acta Universitatis Tamperensis 2048 Tampere University Press Tampere 2015 ACADEMIC DISSERTATION University of Tampere, School of Medicine Tampere University Hospital, Department of Internal Diseases Finland Supervised by Reviewed by Docent Jaana Syrjänen Docent Anu Kantele University of Tampere University of Helsinki Finland Finland Docent Olli Meurman University of Turku Finland The originality of this thesis has been checked using the Turnitin OriginalityCheck service in accordance with the quality management system of the University of Tampere. Copyright ©2015 Tampere University Press and the author Cover design by Mikko Reinikka Distributor: [email protected] https://verkkokauppa.juvenes.fi Acta Universitatis Tamperensis 2048 Acta Electronica Universitatis Tamperensis 1538 ISBN 978-951-44-9783-4 (print) ISBN 978-951-44-9784-1 (pdf) ISSN-L 1455-1616 ISSN 1456-954X ISSN 1455-1616 http://tampub.uta.fi Suomen Yliopistopaino Oy – Juvenes Print Tampere 2015 441 729 Painotuote CONTENTS LIST OF ORIGINAL PUBLICATIONS .............................................................. 6 ABBREVIATIONS .............................................................................................. 7 ABSTRACT .......................................................................................................... 8 TIIVISTELMÄ ................................................................................................... 10 1. INTRODUCTION ......................................................................................... 12 2. REVIEW OF THE LITERATURE ............................................................... 15 2.1 Cellulitis and erysipelas .......................................................................... 15 2.1.1 Definition of cellulitis .................................................................. 15 2.1.2 Clinical characteristics of cellulitis .............................................. 17 2.1.2.1 Diagnosis and differential diagnosis of cellulitis ............. 17 2.1.2.2 Recurrent cellulitis ........................................................... 23 2.1.2.3 Treatment of cellulitis ...................................................... 25 2.1.2.4 Prevention of recurrent cellulitis ...................................... 28 2.1.3 Epidemiology of cellulitis ............................................................ 31 2.1.3.1 Historical overview on the epidemiology of cellulitis ............................................................................ 31 2.1.3.2 Incidence of cellulitis ....................................................... 33 2.1.3.3 Clinical risk factors for cellulitis ...................................... 34 2.1.3.4 Clinical risk factors for recurrent cellulitis ...................... 36 2.1.4 Aetiology and pathogenesis of, and genetic susceptibility to cellulitis ........................................................................................ 42 2.1.4.1 Bacteriology of cellulitis .................................................. 42 2.1.4.2 Serology in cellulitis ........................................................ 45 2.1.4.3 Pathogenesis of cellulitis .................................................. 47 2.1.4.4 Genetic susceptibility to cellulitis .................................... 48 2.2 Inflammatory markers in bacterial infections ......................................... 50 2.2.1 C-reactive protein ......................................................................... 50 2.2.2 Pentraxin-3 ................................................................................... 52 3. AIMS OF THE STUDY ................................................................................ 54 4. SUBJECTS AND METHODS ...................................................................... 55 4.1 Overview of the study ............................................................................. 55 4.2 Clinical material 1, acute cellulitis and five year follow-up (studies I-IV) .......................................................................................... 56 4.2.1 Patients and case definition .......................................................... 56 4.2.2 Patients' household members ....................................................... 56 4.2.3 Controls ........................................................................................ 57 4.2.4 Study protocol .............................................................................. 57 4.2.4.1 Clinical examination ........................................................ 57 4.2.4.2 Patient sample collection ................................................. 57 4.2.4.3 Sample collection from control subjects .......................... 58 4.2.4.4 Sample collection from household members ................... 58 4.3 Clinical material 2, recurrent cellulitis (study V).................................... 60 4.3.1 Patients and case definition .......................................................... 60 4.3.2 Controls and study protocol ......................................................... 61 4.4 Bacteriological methods .......................................................................... 61 4.4.1 Bacterial cultures .......................................................................... 61 4.4.2 Identification and characterisation of isolates .............................. 62 4.4.2.1 T-serotyping ..................................................................... 62 4.4.2.2 emm-typing ...................................................................... 62 4.5 Serological methods ................................................................................ 63 4.6 Inflammatory markers ............................................................................. 64 4.6.1 C-reactive protein assays and leukocyte count ............................. 64 4.6.2 Pentraxin-3 determinations ........................................................... 64 4.7 Statistical methods .................................................................................. 64 4.8 Ethical considerations ............................................................................. 65 5. RESULTS ...................................................................................................... 66 5.1 Characteristics of the study material ....................................................... 66 5.1.1 Clinical material 1, acute cellulitis and five year follow-up ........ 66 5.1.2 Clinical material 2, recurrent cellulitis ......................................... 68 5.2 Clinical risk factors ................................................................................. 69 5.2.1 Clinical risk factors for acute cellulitis (clinical material 1) ........ 69 5.2.2 Clinical risk factors for recurrent cellulitis (clinical materials 1 and 2) ......................................................................... 69 5.2.2.1 Clinical material 1, five year follow-up (study IV) ......... 69 5.2.2.2 Clinical material 2, recurrent cellulitis (study V) ............ 72 5.3 Bacterial findings in acute cellulitis (study II) ........................................ 74 4 5.4 Serological findings in acute and recurrent cellulitis (study III)............. 78 5.4.1 Streptococcal serology ................................................................. 78 5.4.2 ASTA serology ............................................................................. 80 5.5 Antibiotic treatment choices in relation to serological and bacterial findings ................................................................................................... 81 5.6 Seasonal variation in acute cellulitis (study II) ....................................... 81 5.7 C-reactive protein and pentraxin-3 in acute bacterial non- necrotising cellulitis (studies I and IV) .................................................. 82 5.7.1 C-reactive protein in acute bacterial non-necrotising cellulitis ........................................................................................ 82 5.7.2 Pentraxin-3 in acute cellulitis ....................................................... 85 5.7.3 C-reactive protein and pentraxin-3 as predictors of cellulitis recurrence ..................................................................................... 88 6. DISCUSSION ................................................................................................ 90 6.1 Clinical risk factors for acute cellulitis and recurrent cellulitis .............. 90 6.1.1 Clinical risk factors for acute cellulitis (study I) .......................... 90 6.1.2 Clinical risk factors for recurrent cellulitis (studies I, IV, V) ...... 91 6.1.2.1 Previous cellulitis ............................................................. 91 6.1.2.2 Obesity ............................................................................. 92 6.1.2.3 Traumatic wound ............................................................. 93 6.1.2.4 Diabetes ............................................................................ 93 6.1.2.5 Age ..................................................................................
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