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Pathogenesis & Treatment Hidradenitis Suppurativa Hidradenitis Hidradenitis suppurativa s uppurativa: Pathogenesis & t re atmen t Hessel van der Zee Pathogenesis and t reatment H.H.van der Z e e ISBn: 978-90-73436-97-8 Hidradenitis Suppurativa: Pathogenesis and Treatment Hessel BW.indd 1 11-Oct-11 10:36:28 AM Financial support for printing of this thesis was generously provided by Merck Sharp & Dohme BV Pfi zer BV Janssen-Cilag BV Smith & Nephew BV ABBOTT BV Astellas Pharma BV Medi Nederland BV Galderma SA LEO Pharma BV Novartis Pharma BV Oldekamp Medisch BV KCI Medical BV Fagron BV Laservision Instruments BV MT-Diagnostics Netherlands BV BD Biosciences Louis Widmer Nederland Clean Air Techniek BV La Roche-Posay Mölnlycke Health Care Glaxo Smith Kline Beiersdorf NV Yo medical BV ISBN: 978-90-73436-97-8 Layout and printing: Optima Grafi sche Communicatie, Rotterdam, The Netherlands Copyright © H.H. van der Zee No part of this thesis may be reproduced or transmitted in any form of by any means, electronic or mechanically, including photocopying, recording or any information storage and retrieval system, without the permission in writing of the author, or when appropriate, of the publishers of the publications. Hessel BW.indd 2 11-Oct-11 10:36:29 AM Hidradenitis Suppurativa: Pathogenesis and Treatment Hidradenitis Suppurativa: Pathogenese en behandeling Proefschrift ter verkrijging van de graad van doctor aan de Erasmus Universiteit Rotterdam, op gezag van de Rector Magnifi cus Prof.dr. H.G. Schmidt en volgens besluit van het College voor Promoties. De openbare verdediging zal plaatsvinden op woensdag 7 december 2011 om 11:30 uur door Hindrik Hessel van der Zee geboren te Leiderdorp Hessel BW.indd 3 11-Oct-11 10:36:29 AM PROMOTIECOMMISSIE Promotoren: Prof. dr. E.P. Prens Prof. dr. J.D. Laman Prof. dr. R. Benner Overige leden: Prof. dr. S.E.R. Hovius Dr. J.R. Mekkes Prof. dr. H.A.M. Neumann Copromotor: Dr. J. Boer Hessel BW.indd 4 11-Oct-11 10:36:29 AM Contents Chapter 1 General introduction and aims Parts of this chapter are in press in 7 Eur J Pharmacology, and are submitted for publication. Chapter 2 Clinical aspects of hidradenitis suppurativa Chapter 2.1 Depression in hidradenitis suppurativa. Submitted for publication. 39 Chapter 2.2 Hidradenitis suppurativa and infl ammatory bowel disease, are they 49 associated? Results of a pilot study. Br J Dermatol 2010;162:195-7. Chapter 2.3 Hidradenitis suppurativa-like lesions induced by wearing a leg 57 prosthesis: evidence for mechanical stress as pathogenic factor in hidradenitis suppurativa. Submitted for publication. Chapter 3 Pathomechanisms in hidradenitis suppurativa Chapter 3.1 Elevated levels of TNF-α, IL-1β and IL-10 in hidradenitis suppurativa 67 skin; A rationale for targeting TNF-α and IL-1β. Br J Dermatol 2011;164:1292-8. Chapter 3.2 Adalimumab (anti-TNF-α) treatment of hidradenitis suppurativa 81 ameliorates skin infl ammation: an in situ and ex vivo study. Submitted for publication. Chapter 3.3 Alterations in leucocyte subsets and histomorphology in normal 97 appearing perilesional skin, early, and chronic hidradenitis suppurativa lesions. Br J Dermatol in press. Chapter 4 Treatment of hidradenitis suppurativa Chapter 4.1 The eff ect of combined treatment with oral clindamycin and oral 117 rifampicin in patients with hidradenitis suppurativa. Dermatology 2009;219:143-7. Chapter 4.2 Deroofi ng: a tissue-saving surgical technique for the treatment 127 of mild to moderate hidradenitis suppurativa lesions. J Am Acad Dermatol 2010;63:475-80. Chapter 4.3 Colchicine lacks effi cacy in hidradenitis suppurativa. Dermatology in 139 press. Chapter 5 Summary of results and general discussion Parts of this chapter 147 are in press in Eur J Pharmacology, and are submitted for publication. 5 Hessel BW.indd 5 11-Oct-11 10:36:29 AM Contents Chapter 6 Samenvatting 175 Abbreviations 181 Dankwoord 183 Curriculum vitae 187 Publications 189 PhD portfolio 191 Color section 193 6 Hessel BW.indd 6 11-Oct-11 10:36:29 AM 1 G eneral introduction and aims Parts of this chapter are in press in Eur J Pharmacol- ogy, and are submitted for publication. Hessel BW.indd 7 11-Oct-11 10:36:29 AM Hessel BW.indd 8 11-Oct-11 10:36:29 AM General introduction and aims GENERAL INTRODUCTION Hidradenitis suppurativa (HS), also known as acne inversa, is an infl ammatory, debilitating follicular skin disease with natural fl are ups. It usually presents after puberty with painful, deep-seated, infl amed lesions in the inverse areas of the body, most commonly the axillary, inguinal and anogenital regions (Figure 1). HS is not a rare disease since estimated prevalence 1 rates range between 1% and 4%1,2 in European countries. HS prevalence rates in other parts of the world are unknown. The historic fi gure and founder of communism Karl Marx is thought to have been a HS suff erer3. Generally, HS develops almost always after puberty, usually in the second decade of life at a median age of 20 years4. Women are more frequently aff ected than men with a sex ratio of 3:11,4. In a study of 302 HS patients the most frequently aff ected area was the inguinofemoral area in 90%, hereafter, the axillary region in 69%, perineal/perianal involvement in 37%, buttocks in 27% and the breasts in 18% of cases4. Due to its frequent Figure 1. Prototypical hidradenitis suppurativa Axillary HS in a man (source Dept. Dermatology, Erasmus MC). (See also Color section, p. 193.) 9 Hessel BW.indd 9 11-Oct-11 10:36:29 AM Hessel BW.indd 10 and nameditHS glands sweat by many characterized ammationofareas withinfl thesymptoms associated Verneuil surgeon In butatvery1854,theFrench pace. time, slow pathogenesis changedover onHS Concepts andadenmeaningglands. meaningsweat hidros, theGreek from is derived and ammation’ gland infl sweat ‘pussing suppurativameans hidradenitis translated, Literally Historical perspective andnomenclature fox den disease. ca,and stulanssignifi fi pyoderma disease, Verneuil’s ectopic acne, acne inversa, hidradenitissuppurativa, terms usingthesearch peryear (www.pubmed.org) Number ofhitsinPubmed 2. Figure thereported of7years by meantimetilldiagnosis illustrated whichisindirectly notfamiliarwiththedisease, are physicians many However, urologists. and gynaecologists plasticsurgeons, surgeons, such asgeneralpractitioners, dermatologists, avariety by ofmedicalspecialists seenorbeingtreated patientswithHSare occurrence, 1 Chapter 10 associated with frequent and long-term sickleave andlong-term withfrequent associated HSis withisotretinoin. infruitlesstreatment resulted hasfrequently latter The acne vulgaris. andtheassumptionthatHSisanectopicbacterial variantof infectionoftheapocrineglands, the axilla and saw HS like lesions develop, supporting the concept that obstructed sweat supporting thatobstructed sweat theconcept HS likelesionsdevelop, the axillaandsaw fi thatthisdevastatingdiseaseis This indicates 2). year (Figure cpublicationseach of scientifi numbers theincreasing by illustrated ofresearch, attractive topic amore and hasbecome attention, gained more HShasgradually inthelastdecade, patients withHS.Fortunately, unmetmedicalneedin isalarge there Consequently, oftherapy. rationalimprovement for littlebasis thepathomechanismsofdisease and hence insightsinto novel yielded few sofarhas research The limited neglected disease. relatively cally ic impact, HSisascientifi especially on the buttocks ofmen especially onthebuttocks reported HSlesions, ammation,hasbeen inchronic infl persistent by triggered carcinoma, socio-economic ofthelife-threatening squamouscell thedevelopment impact. Furthermore # publications attention. more nally receiving Despite its common occurrence, its profound eff ect anditssocio-econom- onquality oflife eff itsprofound occurrence, itscommon Despite 20 40 60 80 0 1947 1948 1949 Number ofpublicationsonHSisincreasing 1950 1951 1952 1953 1954 8 . In 1955, Shelly and Cahn experimentally obstructed the sweat glands in . In glandsin experimentally obstructed 1955,ShellyandCahn thesweat 1955 1956 1957 1958 1959 1960 1961 1962 1963 1964 1965 1966 1967 7 1968 . 1969 1970 1971 1972 1973 1974 1975 1976 1977 1978 1979 6 1980 , suggestingasubstantialunderestimated 1981 1982 1983 1984 1985 1986 1987 5 1988 thatHSisa , themisconception 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 11-Oct-11 10:36:30AM General introduction and aims Box 1. The follicular occlusion tetrad Acne conglobata Dissecting cellulitis of the scalp Hidradenitis suppurativa Pilonidal sinus 1 ducts result in HS9. With plugging as the primary pathogenic mechanism, HS was classifi ed with three other follicular occlusion diseases in the follicular occlusion tetrad10. The follicular occlusion tetrad consists of acne conglobata, dissecting cellulitis of the scalp or perifolliculitis capitis et suff odiens, pilonidal sinus and hidradenitis suppurativa (Box 1). Acne conglobata is a form of acne vulgaris characterized by severe, eruptive nodulocystic acne without systemic manifestations (Figure 3). Dissecting cellulitis of the scalp is characterized by scarring alope- cia with suppurating nodules and fi stulas (Figure 4) and pilonidal sinus is characterized by infl ammatory nodules and fi stulas caused by ingrown hairs, usually in the gluteal cleft (Figure 5). It is unknown how often these diseases co-occur and what their pathogenic interrelations are. With plugging of the acrosyringium as the suspected primary event, Plewig and Steger introduced the name acne inversa in 198911. But it was not until 1990 that Yu and Cook, in a small histological
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