Alessandro Giunta e Sergio ChimentiClinica Dermatologica - Università di Roma Tor Vergata

The burden of psoriasis: le comorbidità

Consulente, relatore, board member o investigator per Abbott, Abbvie, Novartis, PfizerConflitti di interesse

Per comorbidità si intende una o più condizioni morbose che insorgono in associazione con una data malattia di base, spesso in relazione a meccanismi patogenetici comuni

Al contrario delle sindromi, in cui i sintomi sono in genere sincroni o comunque in stretta correlazione temporale, le comorbidità sono indipendenti dal punto di vista temporale dalla patologia di base

Definizione di comorbidità

Comorbidità e psoriasi

La prima descrizione di una comorbidità nella psoriasi è opera di Alibert che, nel 1818, osservò che i pazienti affetti da psoriasi frequentemente soffrivano di una artropatia infiammatoria

Questo avvenne solo 10 anni dopo la classificazione della psoriasi come una entità distinta da parte di Willan

Willan R. On Cutaneous Diseases. London, 1808

Alibert JL. Précis Théorique et Pratique sur les Maladies de la Peau, Vol. 1. Caille et Ravier, Paris, 1818

Malattia Trattamento

Paziente

Le comorbidità nella psoriasi

Malattia Trattamento

Paziente

Le comorbidità nella psoriasi

Comorbidità e psoriasiMalattie endocrino-metabolicheA. Diabete mellito e insulino-resistenzaB. DislipidemiaC. ObesitàD. Sindrome metabolicaApparato cardiocircolatorioE. Scompenso cardiacoF. Infarto del miocardioG. Ipertensione arteriosaApparato gastrointestinaleA. Morbo di ChronB. CeliachiaMalattie psichiatricheMaltattie dell’apparato visivoMalattie dell’apparato renale

Comorbidità e psoriasiMalattie endocrino-metabolicheA. Diabete mellito e insulino-resistenzaB. DislipidemiaC. ObesitàD. Sindrome metabolicaApparato cardiocircolatorioE. Scompenso cardiacoF. Infarto del miocardioG. Ipertensione arteriosaApparato gastrointestinaleA. Morbo di ChronB. CeliachiaMalattie psichiatricheMaltattie dell’apparato visivoMalattie dell’apparato renale

Psoriasi e morbo di ChronGut, 1968, 9, 17-21

Diseases associated with ulcerative colitis andCrohn's disease

BARBARA HAMMER, PAMELA ASHURST, AND J. NAISH

From the Department ofGastroenterology, Frenchay Hospital, Bristol

The causes of both ulcerative colitis and Crohn'sdisease remain unknown, but a number of cluespoint towards a relationship between these twodiseases and a possible genetic background forboth. The studies of Evans and Acheson (1965) andof Wigley and Maclaurin (1962), preceded by thoseof Houghton and Naish (1958), indicate that theprevalence of ulcerative colitis in people of pre-dominantly British stock is approximately 1 per 1,000population, whereas the prevalence of Crohn'sdisease is approximately 1 per 8,000. The evidencefrom the North Island of New Zealand (Wigley andMaclaurin, 1962) is that those of Maori stock whoare living the same urban or rural life as those ofEuropean stock have a very much decreased risk ofcontracting ulcerative colitis. In fact, the disease inMaoris is excessively rare. It is almost certain thatthe disease is equally rare amongst the Chinese andJapanese, but in countries where the chronicdysenteries are the commonest inflammatory boweldisorder it will probably be some years beforereliable epidemiological studies can be made of theprevalence of such diseases as colitis and Crohn'sdisease.

In the meantime the epidemiological evidence fromBritain (Evans and Acheson, 1965) and from theU.S.A. points to a definite genetic susceptibility toboth ulcerative colitis and Crohn's disease (Kirsnerand Spencer, 1963; Sherlock, Bell, Steinberg, andAlmy, 1963). In various studies of populationsculled through hospital records, the most inform-ative of which is that of Evans and Acheson (1965)in which the hospital statistics were related to thepopulation at risk (Oxfordshire, England), it hasbeen shown that some 5% of colitics and 8% ofsufferers from Crohn's disease have a first-degreerelative suffering from the same disease. Further-more, a significant number of colitics have nearrelatives suffering from Crohn's disease and viceversa. The increased liability of the Jewish popu-lation to contract colitis and Crohn's disease hasbeen noted in many publications (Acheson, 1960;Birnbaum, Groen, and Kallner, 1960).

There are other interesting links between ulcer-ative colitis and Crohn's disease on the one handand ankylosing spondylitis (Acheson, 1960; Mc-Bride, King, Baikie, Crean, and Sircus, 1963) andautoimmune hepatitis (Holdsworth, Hall, Dawson,and Sherlock, 1965) on the other. Since either dis-ease may precede the development of the other, andsince the prevalence of the linked disease is oftenhigher than can be accounted for by chance in thefirst degree relatives of propositi, it is reasonable toassume that there may be a weak genetic pre-disposition to the development of one or more ofthese diseases with environmental stress deter-mining the onset and expression.

In an attempt to find out more about the questionof familial susceptibility we have ascertained theprevalence of certain diseases, some of which arethought to be of an allergic or autoclastic nature, ina group of patients suffering from ulcerative coli-tis, a group of patients suffering from Crohn'sdisease, and in their first degree relatives.

METHODS AND MATERIAL

The case records of 242 patients suffering from ulcerativecolitis and 45 patients suffering from Crohn's diseasewere first scrutinized. All these patients had been underthe care of one of us (J.M.N.) at Frenchay Hospital orSouthmead Hospital, Bristol, during the years 1952 to1965 inclusive. All of the patients with Crohn's diseasewere interviewed and the criteria of diagnosis criticallyreviewed. Diagnosis was based on histological data in allbut a few of these cases and in these few the radiologicaland clinical findings were unequivocally those of Crohn'sdisease. Cases of Crohn's disease of the colon wereincluded. Of the 242 patients with ulcerative colitis, 48were rejected either because they were dead, because thecriteria for diagnosis (radiological, sigmoidoscopic,histological, and haematological) were incomplete, orbecause they could not be traced. This left 198 patientsavailable for analysis. Of these 97 were interviewed and101 replied to a postal questionnaire. The questions putto these patients were as follows: any personal history ofconstitutional eczema (not dermatitis), psoriasis, hayfever, asthma, polyarthritis, any thyroid disease? Any

17

group.bmj.com on February 8, 2014 - Published by gut.bmj.comDownloaded from

A. Nel 1973, Verbov in uno studio prospettico sulle patologie dermatologiche di 142 pazienti affetti da IBD, osservò una prevalenza della psoriasi del 5% nel Morbo di Crohn e del 7,5% nella rettocolite ulcerosa

B. Per quanto interessanti, I suoi risultati erano difficili da interpretare, essendo la psoriasi una patologia di comune osservazione nella popolazione generale

C. Più recentemente, una possibile patogenesi comune delle due patologie è stata suggerita dalla vicinanza sul cromosoma 6q21 del gene CARD-15 e del locus di suscettibilità PSORS8

Psoriasi e morbo di Chron

Verbov J. Transactions of the St.John's Hospital Dermatological Society. 1973

A. Borgiani P, Vallo L, D'Apice MR, Giardina E, Pucci S, Capon F, Nistico S, Chimenti S, Pallone F, Novelli G. Exclusion of CARD15/NOD2 as a candidate susceptibility gene to psoriasis in the Italian population. Eur J Dermatol. 2002 Nov-Dec;12(6):540-2

B. Giardina E, Novelli G, Costanzo A, Nistico S, Bulli C, Sinibaldi C, Sorgi ML, Chimenti S, Pallone F, Taccari E, Borgiani P. Psoriatic arthritis and CARD15 gene polymorphisms: no evidence for association in the Italian population. J Invest Dermatol. 2004 May;122(5):1106-7

C. Jenisch S, Hampe J, Elder JT, Nair R, Stuart P, Voorhees JJ, Schreiber S, Kabelitz D, Christophers E, Weichenthal M. CARD15 mutations in patients with plaque-type psoriasis and psoriatic arthritis: lack of association. Arch Dermatol Res. 2006 Mar;297(9):409-11

D. Lascorz J, Burkhardt H, Huffmeier U, Bohm B, Schurmeyer-Horst F, Lohmann J, Stander M, Wendler J, Kelsch R, Baumann C, Kuster W, Traupe H, Reis A. Lack of genetic association of the three more common polymorphisms of CARD15 with psoriatic arthritis and psoriasis in a German cohort. Ann Rheum Dis. 2005 Jun;64(6):951-4.

CARD-15, MC e PsO

Psoriasi e IBDs

0%5%

10%15%20%

Morbo di Chron Rettocolite ulcerosa

9,19%9,39%

Prevalenza della psoriasi (%)

Comorbidità e psoriasiMalattie endocrino-metabolicheA. Diabete mellito e insulino-resistenzaB. DislipidemiaC. ObesitàD. Sindrome metabolicaApparato cardiocircolatorioE. Scompenso cardiacoF. Infarto del miocardioG. Ipertensione arteriosaApparato gastrointestinaleA. Morbo di ChronB. CeliachiaMalattie psichiatricheMaltattie dell’apparato visivoMalattie dell’apparato renale

Per sindrome metabolica si intende uno stato fisiopatologico che identifica un sottogruppo di pazienti con un aumentato rischio di patologia cardiovascolare e diabete mellito di tipo 2

La Sindrome Metabolica

In pazienti senza altri fattori di rischio cardiovascolare o diabete, la sindrome metabolica comportava un rischio:A. da 1,5 a 2 volte maggiore per lo sviluppo di coronaropatia

B. di circa 2 volte maggiore per l’ictus ischemico

C. di circa 3 volte per lo sviluppo di diabete mellito di tipo 2

Huang PL. A comprehensive definition for metabolic syndrome. Dis Model Mech 2009 May-Jun; 2 (5-6): 231-237.

McNeill AM, Rosamond WD, Girman CJ, Hill Golden S, Schmidt MI, East HE, Ballantyne CM, Heiss G. The metabolic syndrome and 11-year of risk incident cardiovascular disease in the atherosclerosis risk in communities study. Diabetes Care 2005; 28: 385-390.

Ford ES. Risks for all-cause mortality, cardiovascular disease, and diabetes associated with the metabolic syndrome: a summary of the evidence. Diabetes Care 2005; 28: 1769-1778

NCEP-ATP III (2005)

Si può correttamente porre diagnosi di sindrome metabolica, se si riscontrano tre o più dei seguenti criteri:A. Circonferenza vita > 102 cm (uomini) o > 88 cm (donne);

B. PA sistolica > 130 mmHg o PA diastolica > 85 mmHg o in trattamento farmacologico

C. Trigliceridemia ≥ 150 mg/dl o in trattamento farmacologico

D. HDL < 40 mg/dl (uomini) o < 50 mg/dl (donne) o in trattamento farmacologico

E. Glicemia a digiuno ≥ 100 mg/dl o in trattamento farmacologico

National Cholesterol Education Program Adult Treatment Panel III

Tra le varie componenti della sindrome metabolica, l’associazione tra psoriasi e obesità è quella maggiormente

documentata

Psoriasi e Obesità

Tra le varie componenti della sindrome metabolica, l’associazione tra psoriasi e obesità è quella maggiormente

documentata

Psoriasi e Obesità

Nurses’ Health Study II A. Studio prospettico longitudinale su 78.626 donne statunitensi

per un periodo di 14 anniB. Relazione tra vari indici di adiposità (BMI, circonferenza della

vita, circonferenza dei fianchi e Waist-to-Hip Ratio) e l’incidenza di psoriasi

C. Limiti dello studio: autodeterminazione delle misure antropometriche e diagnosi dermatologica non necessariamente confermata da visita specialistica

Prima evidenza prospettica che l’obesità possa favorire lo sviluppo della psoriasi

Hamminga EA, van der Lely AJ, Neumann HA, Thio HB. Chronic inflammation in psoriasis and obesity: implications for therapy. Med Hypoth 2006; 67: 768-773

Obesità e risposta terapeutica

61 pazienti obesi con psoriasi in un trial clinico randomizzato doppio ciecoA. Introduzione di una dieta ipocalorica con perdita di pesoB. Trattamento con ciclosporina a basse dosiMaggiore efficacia del farmaco

Gisondi P, Del Giglio M, Di Francesco V, Zamboni M, Girolomoni G. Weight loss improves the response of obese patients with moderate-to-severe chronic plaque psoriasis to low-dose cyclosporine therapy: a

randomized, controlled, investigator-blinded clinical trial. Arch Dermatol 2010; 146 (5): 544-546

Obesità e terapie biologicheSignificativo aumento di peso e di BMI nei pazienti trattati con anti-TNF-α rispetto al gruppo di controllo, con un incremento ponderale medio a 48 settimane pari a 2,18 kg per ETA, 1,53 kg per IFX e 2,57 kg per ADAA. l’aumento di peso e del BMI non influisca negativamente sulla

efficacia della terapia biologicaB. Nessuna alterazione significativa del profilo dei lipidi plasmatici

(trigliceridi, colesterolo totale, HDL e LDL)

Saraceno R, Schipani C, Mazzotta A, Esposito M, Di Renzo L, De Lorenzo A, Chimenti S. Effect of anti-tumor necrosis factor-alpha therapies on body mass index in patients with psoriasis. Pharmacol Res 2008; 57:

290-295

Diversi studi osservazionali, con differenti modalità, hanno dimostrato una maggiore prevalenza dell’insulino-resistenza

(o diabete) nei pazienti con psoriasi rispetto alla popolazione sana

Psoriasi e insulino-resistenza

Cohen AD, Gilutz H, Henkin Y, Zahger D, Shapiro J, Bonneh DY, Vardy DA. Psoriasis and the Metabolic Syndrome. Acta Derm Venereol 2007; 87: 506-509

Neimann AL, Shin DB, Wang X, Margolis DJ, Troxel AB, Gelfand JM. Prevalence of cardiovascular risk factors in patients with psoriasis. J Am Acad Dermatol 2006;55: 829-835

Sommer DM, Jenish S, Suchan M, Cristophers E, Weichenthal M. Increased prevalence of the metabolic syndrome in patients with moderate to severe psoriasis. Arch Dermatol Res 2006; 298: 321-328

Shapiro J, Cohen AD, David M, Hodak E, Chodik G, Viner A, Kremer E, Heymann A. The association between psoriasis, diabetes mellitus, and atherosclerosis in Israel: a case-control study. J Am Acad Dermatol 2007; 56 (4): 629-634

Cohen AD, Dreiher J, Shapiro Y, Vidavsky L, Vardy DA, Davidovici B, Meyerovitch J. Psoriasis and diabetes: a population-based cross-sectional study. J Eur Acad Dermatol Venereol 2008; 22: 585-589

A. Correlazione significativa tra gravità della psoriasi, secrezione insulinica e livelli sierici di resistina, un’adipochina implicata nella patogenesi dell’insulino-resistenza .(1) L’obesità (e l’iperproduzione di resistina) contribuisce notevolmente a questa condizione

B. Tuttavia, anche i pazienti psoriasici non obesi mostrano una tendenza verso lo sviluppo di insulino-resistenza (2)

C. Inoltre, i parametri indicativi di insulino-resistenza (Homeostasis Model Assesment for Insulin Resistance, HOMA-IR, e il Fasting Insulin Resistance Index, FIRI) così come la glicemia e l’insulinemia a digiuno erano significativamente più elevati nei pazienti psoriatici rispetto ai controlli, e ancor più nei pazienti con psoriasi di tipo II rispetto al tipo I

Psoriasi e insulino-resistenza

(1) Boehncke S, Thaci D, Beschmann H, Ludwig RJ, Ackermann H, Badenhoop K, Boehncke WH. Psoriasis patients show signs of insulin resistance. Br J Dermatol 2007; 157 (6): 1249-1251

(2) Ucak S, Ekmekci TR, Basat O, Koslu A, Altuntas Y. Comparison of various insulin sensitivity indices in psoriasis patients and their relationship with type of psoriasis. J Eur Acad Dermatol Venereol 2006; 20: 517-522

Non Alcholic Fatty Liver Disease (NAFLD)Epatomegalia lieve-moderata dovuta ad accumulo diffuso di grassi neutri (trigliceridi) negli epatociti

A. Attualmente considerata come una manifestazione epatica della sindrome metabolica

B. Causa più comune di elevazione dei livelli di transaminasiC. Forma più diffusa di patologia epatica nei paesi più

industrializzati, colpendo circa un terzo della popolazione generale

Rivera R, Vanaclocha F. Nonalcoholic fatty liver disease and psoriasis. Actas Dermosifiliogr. 2010; 101 (8): 657-658

Gisondi P, Targher G, Zoppini G, Girolomoni G. Non-alcoholic fatty liver disease in patients with chronic plaque psoriasis. Journal of Hepatology 2009; 51: 758-764

Prevalenza della SM nei pazienti psoriasici

Nisa N, Qazi MA. Prevalence of metabolic syndrome in patients with psoriasis. Indian J Dermatol Venereol Leprol 2010; 76 (6): 662-665

Mebazaa A, El Asmi M, Zidi W, Zayani Y, Cheikh Rouhou R, El Ounifi S, Kanoun F, Mokni M, Osman AB, Feki M, Slimane H, Mebazaa A, Kaabachi N. Metabolic syndrome in Tunisian psoriatic patients: prevalence and determinants. J Eur Acad Dermatol Venereol 2010

Takahashi H, Takahashi I, Honma M, Ishida-Yamamoto A, Iizuka H. Prevalence of metabolic sindrome in Japanese psoriasis patients. J Dermatol Sci 2010 ;57 (2):143-4

Li F, Jin HZ, Wang BX. Prevalence of metabolic syndrome in psoriasis inpatients in Peking Union Medical College Hospital. Acta Acad Med Sin 2010. 32 (5): 583- 585

USA

India

Tunisia

Giappone

Cina

0 10 20 30 40

38,1

24,4

35,5

38

40

Identikit del paziente con SM

Ahdout J, Kim J, Chiu M. Modifiable metabolic syndrome-associated lifestyle factors in psoriasis patients. J Am Acad Dermatol 2009; 60: AB169

Miele L, De Simone C, Cefalo C, Vallone S, Bussoletti C, Forgione A, Gabrieli ML, Vero V, Di Stasi C, D’Agostino M, Amerio P, Gasbarrini G, Grieco A. Prevalence of nonalcoholic fatty liver disease (NADFL) and metabolic syndrome in patients with psoriasis. Digestive and Liver Disease 2008; 40: S179

A. sesso maschileB. età > 50 anni C. BMI > 25 D. psoriasi moderato-severa (PASI > 10) E. malattia di lungo corso F. esordio della malattia in età giovanile.

- Comorbidità Cardiovascolari -

Wu Y, et al. J Drugs Dermatol. 2008;7(4):373-7.

Types of costs Odds Ratio and 95% CI OR 95% CI P

Diabetes 1.42 1.10-1.84 <0.01

Hypertension 1.49 1.23-1.80 <0.01

High Cholesterol 1.35 1.11-1.63 <0.01

Congestive Heart Failure 1.19 0.69-2.06 NS

0 3 2 1

10

Rel

ativ

e ri

sk

(95%

con

fiden

ce in

terv

als)

1.0

0.5 80!

Mild psoriasis Severe psoriasis

Age (years)

70!60!50!40!30!20!

- Psoriasi e Infarto del Miocardio -

Adjusted relative risk is shown on a log scaleGelfand JM, et al. JAMA. 2006;296:1735-41.

THERAPEUTICSBJD

British Journal of Dermatology

Survival rate of antitumour necrosis factor-a treatments forpsoriasis in routine dermatological practice: a multicentreobservational studyM. Esposito,1 P. Gisondi,2 N. Cassano,3 G. Ferrucci,4 M. Del Giglio,2 F. Loconsole,3 A. Giunta,1 G.A. Vena,3

S. Chimenti1 and G. Girolomoni2

1Department of Dermatology, University of Rome Tor Vergata, Viale Oxford 81 – 00133, Rome, Italy2Section of Dermatology and Venereology, Department of Medicine, University of Verona, Verona, Italy3Unit of Dermatology and Venereology, Department of Biomedical Sciences and Human Oncology, University of Bari, Bari, Italy4Informa s.r.l., Rome, Italy

CorrespondenceMaria Esposito.E-mail: espositomaria@virgilio.it

Accepted for publication30 April 2013

Funding sourcesThis work was supported by an unrestricted grantfrom Pfizer.

Conflicts of interestSee Appendix for details.

DOI 10.1111/bjd.12422

Summary

Background Adherence is an overall marker of treatment success, and it depends onmultiple factors including efficacy and safety. Despite the wide use of tumournecrosis factor (TNF)-a blockers in the treatment of plaque-type psoriasis, fewdata regarding treatment adherence in routine clinical practice are available.Objectives To estimate the long-term survival rate of anti-TNF-a therapy in acohort of patients with psoriasis in routine clinical practice; to evaluate the rea-sons for and predictors of treatment discontinuation.Methods The Outcome and Survival rate Concerning Anti-TNF Routine treatment(OSCAR) study was based on a retrospective analysis to estimate the long-termsurvival rate of the first anti-TNF-a treatment in patients with psoriasis, fromthree Italian academic referral centres. Adult patients (n = 650) with plaque pso-riasis treated with a first course of adalimumab, etanercept or infliximab for! 3 months were included.Results Global adherence to anti-TNF-a treatments after 28!9 " 15!4 months(867 " 462 days) of observation was 72!6%. Etanercept showed a longer sur-vival (mean 51!4 months, 1565 days; P < 0!001) compared with infliximab(36!8 months, 1120 days) and adalimumab (34!7 months, 1056 days). Treat-ment discontinuation due to primary and secondary inefficacy was observed in5!2% and 14!5% of patients, respectively, whereas discontinuation due to adverseevents was reported in 29 subjects (4!5%). Independent predictors of treatmentwithdrawal were female gender [hazards ratio (HR) 1!3], treatment with ada-limumab or infliximab compared with etanercept (HR 2!7 and 1!7, respectively),and the concomitant use of traditional systemic treatment, as a rescue therapy,compared with monotherapy (HR 1!9).Conclusions Overall survival of anti-TNF-a agents in psoriasis is elevated, with drugdiscontinuation mostly due to inefficacy. Etanercept showed a longer adherencecompared with adalimumab and infliximab.

What’s already known about this topic?

• Very few studies have analysed long-term efficacy and safety of antitumour necrosisfactor (anti-TNF)-a agents in plaque psoriasis.

• Treatment adherence is an overall marker of treatment success, and it depends onmultiple factors including efficacy, safety, patients’ satisfaction and dermatologists’confidence with the treatment.

• Survival rate is a standardized method for estimating treatment adherence.

© 2013 British Association of Dermatologists666 British Journal of Dermatology (2013) 169, pp666–672

0,2%

5,7% 8,8%

11,8%

21,7%

36,2%

Proportion of patients (%)

Chron Disease Cardiac disorders Diabetes Liver disorders Dislipidemia Hypertension

- Comorbidità e Biologici: esperienza personale -

Coexistence of symptomatic PsA (diagnosed by CASPAR criteria) was observed in 381 subjects (58.6%), without differences among the 3 drugs

Observed patients (n): 650

E-Mail karger@karger.comwww.karger.com/drm

Original Paper

Dermatology 2012;225:312–319 DOI: 10.1159/000345623

Efficacy and Safety of Subcutaneous Anti-Tumor Necrosis Factor-Alpha Agents, Etanercept and Adalimumab, in Elderly Patients Affected by Psoriasis and Psoriatic Arthritis: An Observational Long-Term Study

Maria Esposito a Alessandro Giunta a Annamaria Mazzotta a Arianna Zangrilli a Graziella Babino a Mauro Bavetta a Roberto Perricone b Sergio Chimenti a Maria Sole Chimenti b

Departments of a Dermatology and b Rheumatology, University of Rome ‘Tor Vergata’, Rome , Italy

PASI50 was 91.80 and 82.14% at week 156 with etanercept and adalimumab treatment, respectively, while the propor-tion of patients achieving PASI75 was 83.61 and 71.43% at week 156 when treated with etanercept and adalimumab, respectively. The mean DAS44-ESR score decreased from 5.80 to 0.89 and from 3.43 to 1.44 at week 156 and the mean Pain-VAS score decreased from 75.10 to 3.15 and from 71.30 to 18.26 at week 156 with etanercept and adalimumab treat-ment, respectively. Both treatment adherence and safety profile were good. Conclusions: Our study demonstrates that subcutaneous anti-TNF- ! agents are appropriate in the long-term management of elderly patients.

Copyright © 2012 S. Karger AG, Basel

Introduction

Psoriasis (Pso) and psoriatic arthritis (PsA) are chron-ic and disabling inflammatory diseases, characterized by an unpredictable course involving relapses. Pso affects 2–3% of the world’s population with a negative impact on the quality of life [1–3] . Long-term management of these

Key Words Adalimumab ! Anti-TNF-alpha ! Elderly ! Etanercept ! Psoriasis

Abstract Background: In elderly patients the management of psoria-sis is challenging due to contraindications and a higher risk of side effects. Objective: Our retrospective study aimed to evaluate the long-term efficacy and safety profile of subcu-taneous anti-tumor necrosis factor (anti-TNF) agents in el-derly psoriatic patients. Methods: The study included 89 pa-tients (aged 6 65 years) with plaque-type psoriasis and pso-riatic arthritis treated with the subcutaneous anti-TNF- ! agents etanercept or adalimumab as monotherapy for a long-term continuous period. Results: Efficacy results were consistent and stable over long-term observation, as ex-pressed by mean Psoriasis Area and Severity Index (PASI) score variation, percentage of patients achieving PASI50and PASI75 and by the improvement of articular indices, pain visual analogue scale (Pain-VAS) and 44-Joint Disease Activ-ity Score (DAS44-ESR). The proportion of patients achieving

Received: May 24, 2012 Accepted after revision: October 29, 2012 Published online: December 28, 2012

Maria Esposito, MD Department of Dermatology, University of Rome ‘Tor Vergata’ Viale Oxford, 81 IT–00133 Roma (Italy) E-Mail espositomaria   @   virgilio.it

© 2012 S. Karger AG, Basel1018–8665/12/2254–0312$38.00/0

Comorbidities observed in adalimumab and etanercept treated patients. They have been classified in 6 groups: (i) cardiovascular, including mainly hypertension (40 patients) or history of acute myocardial infarction (9 patients); (ii) metabolic, patients with type II diabetes and hypercholesterolemia; (iii) chronic renal insufficiency; (iv) infective: latent tuberculosis (2 patients; etanercept group)

and chronic hepatitis C virus infection patients (4 patients; 2 etanercept and 2 adalimumab group); (v) respiratory chronic insufficiency: all patients have been heavy smokers (>15 cigarettes daily); (vi) other, including hyperthyroidism (2 patients,

etanercept group) and hypothyroidism (4 patients; 1 etanercept and 3 adalimumab group).

- Elderly patients: esperienza personale -

Comorbidity Adalimumab Etanercept Total

Cardiovascular 67.86 49.18 55.05

Metabolic 37.71 34.42 34.83

Chronic renal insufficiency - 11.47 7.86

Infective 7.14 6.56 6.74

Respiratory chronic insufficiency - 4.92 3.37

Other 10.71 4.92 6.74

a"

Comorbidità e psoriasiMalattie endocrino-metabolicheA. Diabete mellito e insulino-resistenzaB. DislipidemiaC. ObesitàD. Sindrome metabolicaApparato cardiocircolatorioE. Scompenso cardiacoF. Infarto del miocardioG. Ipertensione arteriosaApparato gastrointestinaleA. Morbo di ChronB. CeliachiaMalattie psichiatricheMaltattie dell’apparato visivoMalattie dell’apparato renale

Malattia Trattamento

Paziente

Le comorbidità nella psoriasi

- Psoriasi e QoL -Ph

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Healthy adults

Dermatitis

Cancer

Depression

Hypertension

Arthritis

Myocardial infarction

Chronic lung disease

Type 2 diabetes

Psoriasis

Congestive heart failure

60

50

40

30

55

47 45 45 44 43 43 42 42 41

35

Rapp SR et al. J Am Acad Dermatol. 1999; 41:401.

60

50

40

30

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Healthy adults

53

Hypertension

52

Type 2 diabetes

52

Myocardial infarction

52

Congestive heart failure

50

Cancer

49

Arthritis

49

Dermatitis

46

Psoriasis

46

Chronic lung disease

45

Depression

35

- Psoriasi e QoL -

Rapp SR et al. J Am Acad Dermatol. 1999; 41:401.

Fax +41 61 306 12 34E-Mail karger@karger.chwww.karger.com

Clinical and Laboratory Investigations

Dermatology 2006;212:123–127 DOI: 10.1159/000090652

An Italian Study on Psoriasis and Depression

Maria Esposito a Rosita Saraceno

a Alessandro Giunta a Mara Maccarone

b Sergio Chimenti

a

a Department of Dermatology, Tor Vergata University of Rome, Rome , and b

ADIPSO Italia – Associazione per la Difesa degli Psoriasici, Italy

Conclusion: Our results are consistent with previous studies showing that psoriasis is associated with pro-found psychological morbidity, in particular with depres-sion in a large number of patients. It is important to con-sider this association in the overall management of psoriasis.

Copyright © 2006 S. Karger AG, Basel

Psoriasis is a chronic skin disease affecting 1–2% of the population [1] . Psoriasis is characterized by hyper-proliferation of epidermis resulting in thick, red, scaly lesions [2] . Itchiness, skin fl aking, swelling, redness, pain and other manifestations frequently accompany the le-sions, and the arthritic complications of the disease can cause pain and lead to loss of mobility and even disabil-ity [3] . Psoriatic outbreaks are often unpredictable, and psoriasis can have an enormous physical, functional and psychological impact on a patient’s quality of life. It is not surprising that psoriasis is associated with signifi cant so-cial and economic problems [3–11] .

To assess the severity of disease it is necessary to use an index that takes into account both the physical and psy-chological status of the patient [12–15] . The validated in-dexes most frequently used in clinical practice to measure the severity of psoriasis in terms of physical involvement are the Body Surface Area index [16] , the Psoriasis Area and Severity Index (PASI) [17] and the Self-Administered PASI [18] . Some of the tools for evaluation of the psycho-

Key Words Psoriasis ! Psychological disorders ! Depression ! Italian population

Abstract Background: Psoriasis is often associated with the risk of physical disability, social discomfort and psychologi-cal disorders. Objectives: The aim of this study was to investigate the prevalence of depressive symptomatol-ogy among Italian patients with psoriasis vulgaris, in or-der to better evaluate the disease severity in this patient population. Methods: Five thousand Italian patients with psoriasis were mailed the Center for Epidemiological Studies-Depression Scale (CES-D) questionnaire, a 20-item instrument developed to perform epidemiological studies of depressive symptomatology in the general population. Questionnaires with responses to 16 or more items were considered evaluable. Results: We received evaluable questionnaires from 2,391 patients, including 1,528 men (63.9%) and 863 women (36.1%). Depressive symptomatology was observed in 1,482/2,391 patients (62% overall; females, 63%; males, 61%). Men ! 40 years of age were signifi cantly more likely to report depressive symptoms than were men 6 40 years of age (67 vs. 58%, respectively; p = 0.002). Depressive symptomatology was more prevalent in psoriatic patients with only pri-mary or secondary education than in psoriatic patients with higher education (51 vs. 32%, respectively; p ! 0.02).

Received: October 1, 2004 Accepted: June 16, 2005

Sergio ChimentiDepartment of Dermatology, Tor Vergata University of RomePoliclinico Tor Vergata, viale Oxford 81IT–00133 Rome (Italy)Tel. +39 06 2090 2743, Fax +39 06 2090 2742, E-Mail chimenti@dermatologica.it

© 2006 S. Karger AG, Basel1018–8665/06/2122–0123$23.50/0

Accessible online at:www.karger.com/drm

- Psoriasi, fumo e alcol -

A. Cigarette smoking and the use of tranquilizers, sleeping medications, and antidepressants are statistically correlatedwith impaired psoriasis-related quality of life 1

B. Alcohol intake is increased in psoriasis patients (2–3-fold) and alcohol misuse is related to a higher incidence and greater severity of psoriasis 2

C. The prevalence of smoking is increased in psoriasis comparedto a non-psoriasis population (37% vs 13%) 3

D. Increased intensity of smoking is associated with a 2-fold increased risk of severe psoriasis 4

1. Davidsson S, et al. In J Dermatol. 2005;44:378-83. 2. Farber EM, Nall L. Cutis. 1994;53:21-7. 3. Herron MD, et al. Arch Dermatol. 2005;141:1527-34. 4. Fortes C, et al. Arch Dermatol. 2005;141:1580-4.

Psoriasi e comorbidità

A. Obesità (~2-fold) 1,2

B. Fumo di sigaretta (~2-fold) 1

C. Diabete (~1.5-fold) 2

D. Ipertensione (~2-fold)2

E. Scompenso cardiaco (~2-fold) 2

F. Infarto del miocardio (pso lieve: ~1.5-fold; pso severa: ~7-fold) 3

G. Aumentata mortalità cardiovascolare (~1.5-fold) 4

H. Depressione (5.5% ideazioni suicide) 5

I. Mortalità (pso severa: ~1.5 fold) 6

1. Herron MD, et al. Arch Dermatol. 2005; 141:1527-34. 2. Henseler T, et al. J Am Acad Dermatol. 1995;32:982-6. 3. Gelfand JM, et al. JAMA. 2006; 296:1735-41. 4. Mallbris L, et al. Eur J Epidemiol.

2004;19:225-30. 5. Gupta MA, Gupta AK. Br J Dermatol. 1998;139:846-50. 6. Gelfand JM, et al. Arch Dermatol. 2007; 143:1493-9.

PSORIASI

PSORIASI

Malattie cardiovascolari

Diabete e sindrome metabolica

Depressione e disturbi del comportamento

Malattie infiammatorie croniche intestinali

Alessandro Giunta e Sergio ChimentiClinica Dermatologica - Università di Roma Tor Vergata

The burden of psoriasis: le comorbidità