psoriasis: is the impairment to a patient’s life cumulative?medf.nsu.ru/files/Влияние...

DOI: 10.1111/j.1468-3083.2010.03705.x JEADV

CPD PAPER

Psoriasis: is the impairment to a patient’s life cumulative?

AB Kimball,†,* U Gieler,ffi D Linder,§ F Sampogna,– RB Warren,** M Augustin†† † ffi Department of Dermatology, Harvard Medical School, Boston, MA, USA Department of Psychosomatic Medicine and Psychotherapy, Justus-Liebig-University Giessen, Giessen, Germany §Dermatology University Clinic, Padua, Italy –Istituto Dermopatico dell’Immacolata IDI-IRCCS, Rome, Italy **Dermatological Sciences, the University of Manchester, Manchester Academic Health Sciences Centre, Salford Royal Foundation Trust, Manchester, UK ††CVderm – German Center for Health Services Research in Dermatology, University Clinics of Hamburg, Hamburg, Germany *Correspondence: Dr AB Kimball. E-mail: [email protected]

Abstract Psoriasis is associated with significant physical and psychological burden affecting all facets of a patient’s life – relationships, social activities, work and emotional wellbeing. The cumulative effect of this disability may be self- perpetuating social disconnection and failure to achieve a ‘full life potential’ in some patients. Health-related quality of life studies have quantified the burden of psoriasis providing predominantly cross-sectional data and point-in-time images of patients’ lives rather than assessing the possible cumulative disability over a patient’s lifetime. However, social and economic outcomes indicate there are likely negative impacts that accumulate over time. To capture the cumulative effect of psoriasis and its associated co-morbidities and stigma over a patient’s life course, we propose the concept of ‘Cumulative Life Course Impairment’ (CLCI). CLCI results from an interaction between (A) the burden of stigmatization, and physical and psychological co-morbidities and (B) coping strategies and external factors. Several key aspects of the

CLCI concept are supported by data similar to that used in health-related quality of life assessments. Future research should focus on (i) establishing key components of CLCI and determining the mechanisms of impairment through longitudinal or retrospective case–control studies, and (ii) assessing factors that put patients at increased risk of developing CLCI. In the future, this concept may lead to a better understanding of the overall impact of psoriasis, help identify more vulnerable patients, and facilitate more appropriate treatment decisions or earlier referrals. To our knowledge, this is a first attempt to apply and develop concepts from ‘Life Course Epidemiology’ to psoriasis research. Received: 29 January 2010; Accepted: 23 March 2010

Keywords coping strategies, Cumulative Life Course Impairment, physical co-morbidities, psoriasis, psychological co-morbidities, stigma

Conflict of interest None declared.

Funding sources The research and development of this manuscript was supported by funding from Abbott Laboratories.

Introduction Psoriasis is a chronic, inflammatory, immune-mediated, skin disease, affecting approximately 1–3% of the population worldwide.1 The pathophysiology of psoriasis is complex, involving components of the innate and adaptive immune systems, genetics and the environment. This interplay of factors results in an increase in antigen presentation, and the activation of T-helper cell type 1 (TH1) and the more recently identified T-helper cell type 17 (TH17), resulting in what we recognize as typical cutaneous pla-

ques of psoriasis.2,3 As a systemic inflammatory disease,4 psoriasis is associated with several serious physical co-morbidities, including psoriatic arthritis, cardiovascular disease, metabolic syndrome (ischaemic heart disease, hypertension, non-alcoholic fatty liver disease, diabetes and obesity), Crohn’s disease and other immune- related conditions (Table 1).5–16 Although psoriasis may initially occur at any time throughout a person’s life, onset can often occur early in childhood, and may be associated with co-morbidities at a young age.17,18 It is commonly

JEADV 2010, 24, 989–1004 ª 2010 The Authors Journal compilation ª 2010 European Academy of Dermatology and Venereology

990 Kimball et al.

Table 1 Co-morbidities in patients with psoriasis

Physical co-morbidities Psoriatic arthritis5,7,8 Crohn’s disease†5,7 Coronary heart disease6,11 Stroke6,16 Metabolic syndrome (ischaemic heart disease, hypertension, non-alcoholic fatty liver disease, diabetes and obesity)†9,10,12–15

Psychological co-morbidities Depression20,36,37,43,77 Anxiety43,44 Suicide ideation43,78 Alexithymia79

†Psoriasis is associated with pleiotropic susceptibility loci identified in type II diabetes and Crohn’s disease.80

associated with chronic inflammatory processes and concomitant diseases. Physical co-morbidities, such as psoriatic arthritis, Cro- hn’s disease and metabolic syndrome (Table 1), are associated with the presence of psoriasis and occur more frequently in psoriatic patients than in the general population, with subsequent effects on morbidity and mortality.25 The relationship between psoriasis and co-morbidities is linked to the underlying chronic inflammatory nature of psoriasis itself,4 whereby increased levels of proinflammatory factors central to psoriasis pathogenesis interact with molecular mechanisms involved in other conditions (e.g. the dysregulation of metabolic function).26 Both independently and through the inflammatory process, physical co-morbidities add to the cumulative impairment over a patient’s lifetime potentially contributing to the worsening of psoriasis and enhancing, as a consequence, poor psychological and social outcomes.

Stigma recognized that the stigma associated with visible skin lesions, cre- ates a strong psychological burden affecting multiple facets of a patient’s life including relationships, social activities, work and emotional wellbeing.19,20 Furthermore, difficulties in coping with life circumstances and key life events may worsen the psychological, social and physical effects of psoriasis. Thus, patients with poorly managed psoriasis may follow a different or diminished life course compared with what they might have expected had they not had the condition. Several health-related quality-of-life (HRQoL) studies have quantified the burden of psoriasis on a patient’s life, producing cross-sectional data in the domains of physical, psychological, social and economic functioning.21–24 However, the cross-sectional data gained in HRQoL surveys typi- cally provide point-in-time snapshot perspectives or short-term responses to therapy and do not assess possible additive and ⁄ or cumulative physical, psychological and social damage over time. Thus, there are gaps in our understanding of the various factors that interact to cause long-term impairment. In this article, we propose a new term, ‘Cumulative Life Course Impairment’ (CLCI), intended to capture the overall effect of psoriasis over a patient’s life course, considering the associated clinical and psychological implications that result in an altered or impaired life potential. CLCI will be defined on the basis of the currently available evidence that psoriasis has a cumulative impact on a patient’s life course, which is not detected by the measure of HRQoL at a specific time point. The concept of CLCI presented in this article, along with the currently available evidence to support it, is the result of a steering committee of international experts in the fields of dermatology, psychology and psychometric medicine.

Stigmatization in psoriasis has been reported in prospective cross- sectional surveys or case–control studies, the majority of which have employed validated questionnaires for data collection (Table 2).20,27–31 Results from these studies show that, because of the visibility of psoriatic lesions, patients with psoriasis commonly experience social stigmatization and overt public rejection, such as being asked to leave public places.27 It has been reported that these experiences are more common with psoriasis than with other skin conditions.28 These rejection experiences not only lead to feelings of being stigmatized, but also result in greater sensitivity to the attitudes of others and further anticipation of rejection,27 which is also more evident in psoriasis than in other dermatological disorders.32,33 Recent data have shown that patients with psoriasis have an automatic vigilance for threat.30 Either overt rejection or feelings of stigmatization can have a profound effect on self-confidence, self-image and sense of wellbeing.20 Feelings of embarrassment, shame or lack of self-confidence can result in avoidance of public places or situations where skin is exposed, thus reducing social and even employment opportunities and inhibiting relationships with others.20,34 In particular, sexual relationships can be impaired, and problems can exist even after large improvements in, or complete clearance of, disease.35 Overall, these data provide good evidence for both real and perceived stigmatization in patients with psoriasis, and suggest that this can alter patients’ self-perception, self-confidence and thus behaviour. The long-term impact of these feelings or avoidance behaviours has yet to be explored; however, it is plausible that it may contribute to an impairment of a patient’s life course.

Psychological co-morbidities The evidence

Physical co-morbidities The physical aspects of psoriasis, such as symptoms, especially itching, caused by the disease, are important components of the disease burden on a patient’s life. Moreover, psoriasis is often

Data evaluating the effects of psoriasis on mental wellbeing have been generated in prospective, cross-sectional, epidemiological phone or internet surveys, prospective clinical surveys, and large (n = 581–5687) retrospective studies (Table 2).12,20,36–42 Patient records and questionnaires, many of which are well recognized


Cumulative life course impairment in psoriasis 991

Table 2 Evidence for Cumulative Life Course Impairment

Reference

Finlay & Coles (1995)58

Study type

Survey of patients admitted for in-patient care (1992–1993)

Patients

369 patients with severe psoriasis

Assessment tool

Questionnaire: 6 questions on history; 15 questions comprising PDI; question comparing skin disease to other conditions; 4 questions to determine value placed on skin condition

Evidence

Of 150 patients currently working, 59.3% had lost a mean of 26 days from work during the preceding year because of their psoriasis. Of the 180 patients not working, 33.9% attributed this to their psoriasis.

Participants had missed 6.6% (±15.4%) of their working time within the past 4 weeks because of health problems. Mean productivity loss because of presenteeism of 7.6% (±9.1%).

3–5% of patients reported that psoriasis prevented them from getting a job.

1.3% of 79 patients not working, were out of work because of their psoriasis. 3.9% of respondents changed their job because of their psoriasis 24.3% of patients had a reduction in their earning capacity because of their psoriasis. 4.4% had gone into early retirement because of their psoriasis. Moderate-to-severe psoriasis resulted in a mean annual productivity loss of € 1310. 57 patients (31.0%) reported inactive periods resulting from sick leave because of their psoriasis, the average duration of which was 46.4 days (range: 1–90 days). The mean number of sick leave days was 14.1 days.

Social and economic outcomes

Schmitt & Ford (2006)59

Cross-sectional study of adults recruited via the internet (2005, USA)

WLQ; DLQI; SAPASI201 patients aged ‡18 years with self-reported psoriasis

Krueger et al. (2001)19 Mail survey followed by a telephone survey of patients with severe psoriasis (1998)

Sohn et al. (2006)61 Retrospective analysis of cost- of-illness study

502 patients with severe psoriasis

4-page self-administered questionnaire (reflects patients perceptions and experiences)

Assessment of direct and indirect costs; PASI; PBSA; PGA; SF-36 (German); DLQI (German)

184 out-patients


992 Kimball et al.

Table 2 Continued

Reference Horn et al. (2007) 60

Study type Six surveys of NPF database (2003–2005)

Patients Assessment tool Evidence Probability of low income (<$30 000) was significantly greater among patients with severe disease than those with mild disease (P = 0.0002). Patients with severe disease had lower probability of working full time than patients with mild psoriasis (ns). Significantly more patients with severe psoriasis (17%) vs. mild (6%) disease reported that psoriasis was the reason for not working (P = 0.01).

The ratio of divorced ⁄ married in patients with psoriasis was 1335 ⁄ 12 619 (10.6%), n = 22 828. The negative impact on relationships was similar to that in other chronic conditions.

35.5–71.3% of patients (depending on the questionnaire used) reported having sexual problems related to their psoriasis.

70% of respondents stated that the treatment of their relative or partner resulted in them having to spend extra time on housework. 57% described psychological pressures (anxiety, being upset and being worried about the patient’s future). 55% described social disruption attributable to lack of social confidence either because of embarrassment or because of the time required for care duties. 44% described limitations to holiday plans, sport and leisure activities, and evenings out. 37% described limitations on their daily activities such as shopping, work and time spent with other family members. 37% felt that their close relationships had deteriorated.

601 patients with psoriasis Information was obtained who responded to income on household income, employment status, reasonquestions for not working, and negative effect of psoriasis on the job

Frangos & Kimball (2008)62

Survey of the RPDR 22 828 patients with psoriasis

Assessed divorced ⁄ marriage ratio

Sampogna et al. (2007)35

Prospective study in a dermatological hospital (2000–2002)

936 patients with psoriasis Questionnaires and items concerning sexual life: Skindex-29 item 29; DLQI item 9; IPSO item 6; PASI; SAPASI; GHQ-12

63 relatives and partners of patients with psoriasis

Qualitative interviews or postal questions; PASI; DLQI; PDI

Eghlileb et al. (2007)63

Postal and interview survey



Table 2 Continued

Reference Stigma Ginsburg & Link (1993)27

Prospective exploratory study

100 patients; moderate-to- severe psoriasis (75% of patients); hospitalized, clinic out-patient, private out-patient

Questionnaire: elicit feelings of stigmatization, demographic data, data on patient’s psoriasis

99 patients reported a total of 50 experiences of clear rejection as a result of their disease; 19% of cases occurred at the gym, hairdressers or pool. Overt rejection or feelings of stigmatization were associated with disrupted work experience, psychiatric help-seeking behaviour and alcoholism (P < 0.01).

Patients reported significantly more experiences of stigmatization (e.g. refusal, retreat, self-esteem, rejection and concealment) than the control group (MANOVA, P < 0.05).

82.9% of patients at least often felt the need to hide their psoriasis. 74.3% of patients felt that their self-confidence was at least often affected by their psoriasis. 82.9% would often or always avoid activities like swimming and sports because of their psoriasis. 35.3% were often or always inhibited in their sexual relationships because of their psoriasis.

Patients were asked to rate 10 emotional factors with respect to their psoriasis. They were most likely to feel self-conscious (weighted average score of 4.4 out of 10) or embarrassed (3.8 ⁄ 10) by their disease.

Psoriasis patients have automatic vigilance for threat (looking for negative cues of observation linked only to psoriasis presentation). Psoriasis patients are tolerized (i.e. reduced brain blood flow) to fear ⁄ disgust stimuli; this is a protective mechanism.

Study type Patients Assessment tool Evidence

Vardy et al. (2002)28 Prospective case–control study

100 patients with psoriasis Questionnaire: experiences vs. 100 patients with mixed of stigmatization; HRQoL (WHOQOL-Bref); PASIskin conditions (matched for age, sex and education; control group)

Weiss et al. (2002)20 Prospective study in patients already in a randomized, double-blind, placebo-controlled trial

35 eligible sequential patients with psoriasis

Self-administered questionnaire: SWLS; EQ- 5D; SF-36; PASI

Koo (1996)29 Population-based epidemiological study (USA, 1991, 1992–1993)

General mail survey: 50 000 sent out; 33 411 returned (response rate, 67%;); telephone survey of patients with psoriasis (n = 616); follow-up mail survey (n = 505 completed)

Questionnaire: 22 psychosocial factors rated on a scale of 1 to 10 by patients. Patients assessed their own disease severity

Griffiths et al. (2008)30 Case–control study 40 patients with psoriasis; Psychometric 40 controls (13 each in the questionnaires and stoop MRI component)words; MRI brain scans


994 Kimball et al.

Table 2 Continued

Reference Schmid-Ott et al. (2005)31

Study type 1-year prospective follow-up

Patients 347 patients with psoriasis

Assessment tool PASI, SPASI, QES

Evidence Improvement in skin condition did not correlate with feeling less stigmatized in women over 1 year, suggesting a considerable influence of other psychological variables such as coping skills

Psychological co-morbidity Lynde et al. (2009)36 500 patients withNationwide telephone

moderate-to-severesurvey (SKIN, 2007, Canada); 5093 households psoriasis contacted

17% of psoriasis patientsQuestions modelled after those of the 2001 National reported having depression. Psoriasis Foundation’s Benchmark Survey on Psoriasis and Psoriatic Arthritis

Skindex 16; DLQI; Self-reported disease severity;

Self-administered questionnaire: SWLS; EQ-5D; SF-36; PASI

CRSD; self-rated indices of psoriasis severity

30% of psoriasis patients reported having depression. 22% of psoriasis patients reported having anxiety.

8 patients (22.9%) stated that they had been previously diagnosed with depression.

9.7% of patients reported a wish to be dead. 5.5% reported active suicidal ideation. Death wish and suicidal ideation were associated with higher depression scores (P < 0.0001) and higher patient self-ratings of psoriasis severity (P < 0.05).

Over one-quarter of the psoriatic patients were heavy drinkers. 25 patients with psoriasis (19%) drank more than 50 units ⁄ week; five showed features of dependency.

1918 deaths were observed in contrast to the 1211 deaths expected on the basis of the national mortality rates. Excess mortality was high for all causes of death directly related to alcohol; the SMR for men was 4.46 (95% CI, 3.60–5.45); for women, 5.60 (95% CI, 2.98–8.65).

Waters et al. (2009)37 Internet survey (Psoriasis1006 self-identified Patient Study Project, 2008) psoriasis patients

Weiss et al. (2002)20 Prospective study in patients already in a randomized, double-blind, placebo-controlled trial

35 eligible sequential patients with psoriasis

Gupta & Schork (1993)38 217 patients withSurvey of consecutive psoriasispatients attending Dept. Dermatology, University of Michigan

Higgins et al. (1993)39 Survey (Kings College Hospital)

130 patients with psoriasis Information on smoking history and drinkingControl groups (222 patients attending general habits obtained skin clinic; 42 patients with atopic eczema)

Poikolainen et al. (1999)40

Retrospective survey of patient records (1973–1984)

3132 men and 2555 women admitted to inpatient treatment with psoriasis as the principal diagnosis

Deaths were identified and underlying causes determined based on official death certificates coded according to the Finnish modification of the International Classification of Diseases, Eighth Revision and Ninth Revision and obtained from Statistics Finland

Sommer et al. (2006)12 Retrospective cohort study (Germany)

581 hospitalized patients with chronic plaque psoriasis

Data recorded on patient’s Increased alcohol chartsconsumption was seen twice as frequently in patients with moderate-to- severe psoriasis than in hospital-based controls.



Table 2 Continued

Reference Kirby et al. (2008) 41

Study type Prospective study of patients attending a psoriasis specialty outpatient clinic

Patients 95 patients with psoriasis

Assessment tool PDI, HADS, PSWQ, HSS, MAST

Evidence 17–30% of patients had difficulties with alcohol. 13% and 18% of patients believed they had a current or past drinking problem, respectively. There was a correlation between levels of anxiety ⁄ depression and weekly alcohol consumption (r = 0.29, P < 0.01 and r = 0.24, P = 0.03, respectively). Patients who believed that they had an alcohol problem had higher levels of anxiety (P = 0.03), depression (P < 0.01) and psoriasis-associated disability (P = 0.04).

Prevalence of psoriasis was 15%. Tobin et al. (2009)81 Survey of consecutive patients for hepatology outpatient clinics

Prospective study of patients attending outpatient clinics

100 patients with proven alcoholic liver disease

Questionnaire assessing history of psoriasis; full skin examination and PASI where relevant

GHQ-12 Sampogna et al. (2004)42

Patients with skin conditions including 936 patients with psoriasis

General mail survey: 50 000 sent out; 33 411 returned (response rate, 67%); telephone survey of patients with psoriasis (n = 616); follow-up mail survey (n = 505 completed)

72 patients with psoriasis

48% of patients had probable depression or anxiety.

Coping Koo (1996)29 Population-based

epidemiological study (USA, 1991, 1992–1993)

Questionnaire: 22 psychosocial factors rated on a scale of 1 to 10 by patients; Patients assessed their own disease severity

Patients commonly felt helpless because of their disease (weighted score of 3.9 out of 10).

Fortune et al. (2004)82

Prospective study evaluating patients before and after PUVA therapy

PDI; PLSI; HADS; PSWQ; Illness Perception Questionnaire; COPE; PASI

Medical management of disease significantly reduced disease- related disability (mean difference ± SEM: 8.01 ± 1.05, P = 0.01) and stress (mean difference ± SEM: 4.47 ± 0.92, P = 0.015).

The personality trait neuroticism was associated with the following coping strategies: an increased use of hostile reaction, escapist fantasy, self-blame, sedation, withdrawal, wishful thinking, passivity and indecisiveness (P < 0.05 to P < 0.001). Extraversion was associated with rational action, positive thinking, substitution and restraint (P < 0.05 to P < 0.001). Open individuals use humour and closed individuals use faith when dealing with stress (P < 0.01 to P < 0.001).

McCrae & Costa (2006)68

Two studies in a community sample

Adults without psoriasis (n = 255 and 151)

Study 1: Checklist of life events Study 2: Questionnaire: coping with harm and loss; coping with threat; coping with challenge


996 Kimball et al.

Table 2 Continued

Reference Hill & Kennedy (2002) 73

Study type Patients Assessment tool PDI; PLSI; HADS; COPE scale

Evidence Maladaptive coping strategies (venting emotions and mental disengagement) were significantly associated with subjective disability and psychological distress, accounting for a greater proportion of variance than age, gender or duration of disease.

89 people withCross-sectional postal psoriasissurvey of hospital outpatients and patients in a support group

Scharloo et al. (2000)69 Longitudinal study (two measures one year apart)

69 patients with psoriasis

Initial higher levels ofMedical perceptions perceived control andquestionnaire; SF-20; HADS; Utrecht Coping List; curability of illness, and more perceived symptomsBody Surface Scores were associated with greater future utilization of outpatient services. Higher initial use of coping characterized by the expression of emotions was associated with a lower number of different prescribed therapies. Initial high scores on the perception that the disease has disabling consequences were associated with more negative perceived health 1 year later. High scores on passive coping were associated with worse physical functioning at 12 months. There was strong correlation between passive coping and avoidant coping (r = 0.54, P < 0.001).

PASI, questionnaires (perceptions of how well patient was dealing with their illness, life quality, sense of coherence, and critical life events)

Patients with a low sense of cohesion suffered their first relapse 3.5 months after therapy, whereas patients with a high sense of cohesion had a first relapse after 10 months.

Kupfer et al. (2003)70 Ward-based rehabilitation study and follow-up postal questionnaires

72 patients

COPE, coping orientation of problem experience; CRSD, Carroll rating scale for depression; DLQI, Dermatology Life Quality Index; EQ-5D, Euro-QoL 5D; GHQ-12, General Health Questionnaire 12; HADS, Hospital Anxiety Depression Scale; HRQoL, health-related quality of life; HSS, health screening survey revised; IPSO, Impact of Psoriasis on Quality of Life Questionnaire; MANOVA, multivariate analysis of variance; MAST, Michigan alcohol screening test; MRI, magnetic resonance imaging; NPF, National Psoriasis Foundation; ns, not significant; PASI, Psoriasis Assessment Severity Index; PBSA, psoriatic body surface area; PDI, Psoriasis Disability Index; PGA, physician’s global assessment; PLSI, Psoriasis Life Stress Inventory; PSWQ, Penn State Worry Questionnaire; PUVA, psoralen plus ultraviolet A; QES, Questionnaire on experience with skin complaints; RPDR, Research Patient Database Registry; SAPASI, self-administered PASI; SEM, standard error of the mean; SF-36, Medical Outcomes Study Short Form 36; SMR, standardized mortality ratio; SWLS, satisfaction with life scale; WHOQOL-Bref, World health Organisation Quality of Life; WLQ, Work Limitations Questionnaire.

and have been previously validated, were used in data collection. Results show that patients with psoriasis have increased rates of depression, which occurs in up to 30% of patients irrespective of disease severity,20,36,37 anxiety, reported in over one-third of patients,43,44 and suicide ideation, evident in up to 10% of patients.38 Furthermore, the incidence of both depression and

anxiety increase with increasing disease severity, with, for example, almost half of those with moderate-to-severe disease reporting depression related to their psoriasis.20,36,37 Furthermore, there is increasing evidence that the inflammatory processes may be directly linked to some psychological conditions, such as major depression, with patients exhibiting increased



peripheral blood inflammatory biomarkers, which are known to access the brain and interact with pathophysiological pathways involved in depression.45 Conversely, increased psychological distress may trigger or further aggravate the manifestation of psoriasis through disturbances in the dynamic equilibrium established between the nervous, endocrine and immune systems.46–50 Recent work has shown that acute experimental social stress is associated with a reduction in frequency of epidermal Langerhans cells, which is accompanied by altered expression of cutaneous neuropeptides, supporting the concept of a connection between the brain and the skin (brain-skin axis).48 Psychological distress in patients with psoriasis may also lead to behavioural changes, such as increased social phobia, alcoholism and non-adherence to treatment,51 some of which may further exacerbate skin disease or even increase the risk of death.40 In particular, there is good evidence for a higher incidence of alcoholism in patients with psoriasis than in the general public, which is known to increase in relation to the severity of disease.12,39,40,52 Problems with alcohol have been further correlated with the presence of anxiety and depression in psoriatic patients.41 This may be a result of emotional reactions, whereby patients with psoriasis seem to have a lower anger reaction than healthy controls.53 In summary, we have good evidence for a high prevalence of psychological co-morbidities in patients with psoriasis. Neverthe- less, there are no longitudinal data tracking the long-term impact of these co-morbidities.

Life course epidemiology: Cumulative Life Course Impairment and modulating factors

For decades, Life Course Research has been predominantly a sub- ject of studies for sociology and related fields.54 Nevertheless, recently the study of health and health impairment over the life course has appeared as an emerging topic54 and articles on life course epidemiology, especially with regard to chronic diseases, are increasingly being published.55,56 To the authors’ best knowledge, however, no specific research has been performed on life course of psoriasis patients. As we have shown, we have evidence, predominantly from cross-sectional studies, indicating that patients with psoriasis are vulnerable to stigmatization and are at increased risk for psychological co-morbidities. However, without longitudinal data we currently cannot empirically demonstrate the cumulative impairment associated with these factors over a patient’s lifetime. How- ever, patient cases, such as the personal experience of Ray Jobling having lived with psoriasis for 50 years, provide some information about the long-term effects of disease.57 In addition, evidence of social and economic outcomes is sug- gestive of a cumulative negative impact over time. Economically, patients with psoriasis can have difficulties gaining and retaining paid employment or working to their full potential, which may limit their lifetime earning potential19,58–61 and can result in socie- tal cost associated with productivity loss.61 In one study in the

United States, data from the National Psoriasis Foundation database demonstrated that the probability of a low income (<US$30 000) was significantly greater among patients with severe disease than among those with mild psoriasis (P = 0.0002).60 However, the effects of psoriasis on income may vary from country-to-country. It must also be conceded that low income may lead to behaviours (such as unhealthy alimentary habits and poor com- pliance) that further exacerbate disease and poor socioeconomic outcomes. In addition, at the social level, psoriasis affects close relationships causing psychological pressures and disrupting family social activities, potentially resulting in higher divorce rates.62,63 The negative impact of psoriasis on relationships is similar to that of other chronic conditions,62 with relatives of patients reporting social disruption (55%), limitations to holiday plans and leisure activities (44%), and deterioration of close relationships (37%).63 We propose the concept of CLCI to indicate the cumulative life-long effects of physical co-morbidities, stigma and psychological co-morbidities, and the economic and social consequences, which have the potential to place each psoriasis patient at risk of not living their life to their full potential. It is important to recognize at risk patients and to assess or measure their risk of a dam- aged life course (although more work is required to define these measures). The core components of CLCI are summarized in Table 3. CLCI is the result of stigmatization, and physical and psychological co-morbidities, together with coping strategies and external factors, such as social support, that appear to have a potential moderating effect. In patients with ineffective coping strategies and limited social support even a small burden may be overwhelming, resulting in significant impairment. This effect may be less exaggerated in patients with highly effective coping strategies and strong social support networks, even if the burden of severity is large. The interaction of key interpersonal aspects in CLCI, such as coping strategies in relation to physical co-morbidities, stigmatization and psychological co-morbidities is schemati- cally represented in Fig. 1. Support for the role of coping as one of the key moderating components in CLCI can be found in the literature for chronic illness, which suggests that outcomes are influenced by patients’ individual coping styles (i.e. how they confront their illness)64,65 along with their beliefs about: (i) the labels and symptoms describing their illness (identity); (ii) aetiology (causes); (iii) the effects and outcome of illness (consequences); (iv) the duration of disease (timelines); and (v) how they can control or recover from illness (controllability ⁄ cure).64–67 This effect is further influenced by a person’s personality.68 In patients with psoriasis, Scharloo et al. demonstrated that coping strategies and illness perceptions accounted for the observed variance in health outcomes, with patients with higher levels of perceived control and curability of illness and greater expression of emotion having better health outcomes over the course of a year than those engaging in passive and avoidant coping behaviours (Table 2).69 In addition, in a 1-year follow-up study, Kupfer et al. demonstrated that the time


998 Kimball et al.

Table 3 Core components of Cumulative Life Course Impairment

Physical co-morbidities

Psoriatic arthritis

Cardiovascular disease

Metabolic syndrome (ischaemic heart disease, hypertension, diabetes, obesity)

Crohn’s disease

Other immune-related conditions

Stigma

Skin damage (perception) Overt public rejection Other rejecting behaviours

Psychological co-morbidities Anxiety

Social phobia

Depression

Social support

Family

Friends

Colleagues

Coping

Maladaptive coping (continued avoidance) Limited activity (skin damage) Mental disengagement

Self-image

Body image Self-confidence

Suicide ideation

Alexithymia Addiction (smoking, alcohol)

Patient support groups

Healthcare professionals

Denial Minimization Sense of coherence Helplessness Family factors

Less vulnerable to CLCI More vulnerable to CLCI

Psychological co-morbidities

Stigma

Coping Physicalco-morbidities co- morbidities

Psychological Co pin

g Stigma

Physical co-morbidities

Personality Personality

Figure 1 Interaction of key intrapersonal components that make patients more or less vulnerable to Cumulative Life Course Impairment.

to relapse despite treatment was longer in psoriasis patients who had a high sense of coherence than in those with a low sense of cohesion.70 Furthermore, cognitive-behavioural therapy in addition to standard treatment has been shown to modify patient’s perceptions of illness and reduce psychological distress, thereby improving disease severity.71,72 Further evidence that maladaptive coping strategies can increase distress and disability was presented by Hill & Kennedy, who examined the role of coping strategies in 89 patients with psoriasis in a cross-sectional postal survey. They found that maladaptive coping strategies, in particular venting emotions and mental disengagement, were significantly associated with subjective disability and psychological distress, accounting for a greater proportion of the variance than age, gender or duration of disease (Table 2).73 However, coping strategies that work in the short term may be counterproductive over the long term.68 For example, avoidance of certain social situations may alleviate immediate distress and

anxiety but if continued can result in social disconnection. Avoid- ance can also lead to decreased adherence to therapy allowing psoriasis severity to worsen.30 Moreover, throughout a person’s lifetime, the cumulative demands that psoriasis places on that individual may potentially exhaust their coping mechanisms, resulting in significant impairment. Thus, how a patient copes with psoriasis at any time point, along with their social environment, are likely key factors in determining outcomes. The interaction between the various components will change throughout an individual’s life putting a person more or less at risk of cumulative impairment. Thus, at some time points a patient may perform well (e.g. at year 10 on Fig. 2), whereas at others s ⁄ he may be performing poorly (e.g. at year 6 on Fig. 2). To accurately assess a patient’s long-term or cumulative impairment we must assess each of the key contributors, e.g. the nature of their stigmatization and physical and psychological co- morbidities, along with the impact of their coping strategies and



140 Physical co-morbidity

120

100

CLCI score

Psychological co-morbidity Stigma Total CLCI score

Point at which person is at risk of CLCI

80

60

40

20

1 2 3 4 5 Years

6 7 8 9 10

Figure 2 Hypothetical impairment over a patient’s life course.

external factors (e.g. support networks), over time (represented by the bars on Fig. 2). The overall effect on a patients’ life course is cumulative and might be visualized by an accumulation of the yearly impact of each of these components (as shown by the line in Fig. 2). Thus, even at a timepoint when an individual is performing well (according to individual component measures), putting them at less risk of CLCI at that point, she ⁄ he may still have significant life course impairment as a result of the cumulative impact of past events.

Discussion Currently available assessments of the impact of psoriasis on patients are designed to provide a point-in-time measure [e.g. last week for Dermatology Life Quality Index (DLQI)]. There is interest in developing a concept and a tool that may help physicians understand the impact over a longer period of time and to identify features of patients particularly at risk of developing CLCI (provided of course that such features exist). The assessment of a patient’s CLCI would require a prospective longitudinal assessment in newly diagnosed patients, together with a retrospective historical record of disease, psychological state, and key life events. Several key aspects of the CLCI concept are currently supported by data that have been used to support the argument for reduced HRQoL in patients with psoriasis (Table 2). These data are largely from retrospective cross-sectional studies, that vary considerably in terms of study design, patient numbers investigated (n = 35 to approximately n = 23 000), and data collection methods (non- validated vs. validated generic or disease-specific instruments). Although there is well-established support for key components of CLCI, such as stigmatization, and physical and psychological co- morbidities, longitudinal data supporting the existence and cumulative nature of psoriasis-originated life course impairment, including the ongoing interaction between components, are not currently

available. A systematic review of the literature with predetermined inclusion and exclusion criteria is required to critically evaluate the available data and determine the precise data gaps that currently exist. We suggest that there is probably also a need to develop and validate a new assessment tool (such as a ‘course of life’ questionnaire for psoriasis patients), most likely starting from existing tools, to meaningfully assess CLCI. Analogous research has been performed and published for vitiligo, cancer and atopic dermatitis using a validated ‘course of life’ questionnaire, in which achieve- ment of developmental milestones is assessed retrospectively.74 Future research into CLCI should be focused on establishing key components of CLCI and determining the mechanisms of impairment through longitudinal studies or retrospective case– control studies, along with the development of tools to assess factors that put patients more at risk of developing CLCI. As a first step, we need to identify individuals whose life has been impaired and understand the key contributors to this impairment. Once this has been established, we can begin to assess patients effectively for cumulative life impairment and its key components, which might include, for example, prolonged periods of stigmatization or reduced coping ability. A mathematical modelling approach, analogous to the one used to describe the concept of allostatic load as a cumulative biological risk,75 may be worth considering. Research can here be performed in two ways. (1) One may con- sider the cumulative psychological and physical ‘load’ derived from the ongoing chronic inflammatory disease and attempt to infer the risk for a ‘crippled’ life course. (2) It may be interesting to investigate whether ongoing ‘stress’ and other psychological and possibly metabolic burdens accumulated over time may not facilitate the onset of psoriasis. Indeed, at least for another inflammatory disease – adult onset arthritis – a cumulative effect of stress factors leading to a cumulative ‘allostatic load’ seems to influence the risk of contracting the disease later in life.76


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In conclusion, the model of CLCI strives to incorporate the multifactorial dimensions of psoriasis into a comprehensive model to describe the cumulative disease-related impairment experienced by patients throughout their lifetime. This model could support physicians in better understanding the true impact of psoriasis, potentially help the identification of key patients who may be more vulnerable to this impact, and allow physicians to make more appropriate treatment decisions earlier in the course of disease and potentially prevent the progression of CLCI. Although the key components of the concept are supported by cross- sectional data, further longitudinal research is required to prove how CLCI occurs and how this might be reduced with appropriate interventions.

Acknowledgements The concept presented in this review was derived from discus- sions held during meetings of the CLCI Steering Committee, which was comprised of the following international experts: Dr Lucia Tomas Aragones, Dr Jose Manuel Carrascosa, Prof. John de Korte, Dr Marta Ferran, Dr Fukuchi, Prof. Gregor Jemec, Marita Kosmadaki, Ms Susan Maguire, Prof. Mamitaro ˜Ohtsuki, Ms Liz Parrish, Dr Javier Pedraz Munoz, Dr Franco- ise Poot, Ms Sandra Ros, Dr Jacek Szepietowski, Prof. Anna Zalewska-Janowska. We thank Susan Cheer, PhD, who provided writing assistance on this manuscript. Financial support for writing assistance was supplied by Abbott Laboratories.



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Information on authors

Alexa Boer Kimball, MD, MPH, is an Associate Professor at Harvard Medical School, and Vice Chair of the Department of Dermatology and Director of the Clinical Unit for Research Trials in Skin, Massachusetts General Hospital. She is well recognized for her work on psoriasis, physician workforce economics and outcomes research, which is widely published in peer reviewed journals.

Uwe Gieler, MD, is a Professor and Chair of Psychosomatic Medicine and Psychotherapy at the Justus- Liebig-University of Giessen, Germany. He is also Chair of the Consultation-Liaison Service at the Clinic of Psychosomatic Medicine and Psychotherapy in Germany, and Chair of the Atopic Dermatitis Educa- ¨tion Academy, Hessen-Thuringen, among other appointments. His interests are in the fields of psycho- dermatology, including the effects of psoriasis.

Dennis Linder, MD, MSc, studied Mathematics at the Swiss Federal Institute of Technology and Medi- cine at the Innsbruck Medical University where he received specialist training in Dermatology. He lec- tures at the University of Padua Medical School. He has contributed chapters to dermatological textbooks and has authored several articles for peer-reviewed dermatology journals. He is Vice-President of the International Society of Biopsychosocial Medicine, Secretary General of the European Society for Dermatology and Psychiatry (ESDaP), and Secretary General of the Italian Society for Psychosomatic Dermatology.

Francesca Sampogna, PhD, obtained a Masters degree in Genetic Epidemiology at the University Paris ¨Sud of Paris; and a PhD in Oral Public Health at the University of Malmo, Sweden. She has been working for 10 years in dermatoepidemiology, with a particular interest in psoriasis. Her main areas of interest are: quality of life, psychosocial and psychosomatic aspects of disease, methodology in outcomes research, patient satisfaction and the patient-provider relationship.


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Richard Warren, MD, is a Clinical Senior Lecturer and Honorary Consultant Dermatologist in Manches- ter, UK. He graduated from Liverpool University with a first class honours degree in Pharmacology and gained his Medical degree, with honours, one year later. His work in Dermatology has focussed on phar- macogenetics (forming the basis of his PhD thesis), the genetic susceptibility of psoriasis, biological therapies and their use in psoriasis and, more recently, co-morbidities of psoriasis.

Matthias Augustin, MD, is Professor for Health Economics and Quality of Life Research and Head of the Outpatient Clinic for Chronic Wounds, Department of Dermatology, University Clinics of Hamburg, Germany. He is also Director of the Institute for Health Services Research in Dermatology and Nursing and Chair of the Center for Dermatological Research. His research interests are in the field of health economics and outcomes research and dermatology, on which he has published more than 200 articles.


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