University of Groningen
Hand eczema
Oosterhaven, Jart
DOI:
10.33612/diss.98242014
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Oosterhaven, J. (2019). Hand eczema: impact, treatment and outcome measures. https://doi.org/10.33612/diss.98242014
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Hand Eczema
Impact, Treatment and Outcome Measures
ISBN
978-94-034-1949-7 (printed version) 978-94-034-1948-0 (e-version)
© 2019, J.A.F. Oosterhaven, Groningen, The Netherlands
All rights reserved. No part of this thesis may be reproduced or transmitted in any form or by any means without prior permission from the author.
Financial support for the publication of this thesis was provided by:
Almirall, BAP Medical, DermaCura, Eurocept Homecare, Galderma, La Roche Posay, LEO Pharma, Researchfonds Dermatologie, Rijksuniversiteit Groningen, Stichting Milieu en Arbeidsdermatologie, Universitair Medisch Centrum Groningen, Vereniging voor Mensen met Constitutioneel Eczeem.
The study in chapter 9 was supported by Stichting Milieu en Arbeidsdermatologie. Cover design: Evelien Jagtman, https://evelienjagtman.com
Layout: Jart Oosterhaven
HAND ECZEMA
Impact, Treatment and Outcome Measures
PhD thesis
to obtain the degree of PhD at the
University of Groningen
on the authority of the
Rector Magnificus prof. C. Wijmenga
and in accordance with
the decision by the College of Deans.
This thesis will be defended in public on
Wednesday 16 October 2019 at 12.45 hours
by
Jan Ate Franke Oosterhaven
born on 18 November 1987
Supervisors
Dr. M.L.A. Schuttelaar
Prof. P.J. Coenraads
Assessment Committee
Prof. T. Agner
Prof. M. Fartasch
Prof. S.A. Reijneveld
Drs. F.B. Poelmann
Dr. J.H. Koetje
Chapter 1 General introduction 8
Section I – Impact
Chapter 2 Systematic review of cost-of-illness studies in hand eczema 22
Chapter 3 Presenteeism in a Dutch hand eczema population – 40 a cross-sectional survey
Section II – Treatment
Chapter 4 Study protocol: efficacy of oral alitretinoin versus oral 70 cyclosporine A in patients with severe recurrent vesicular
hand eczema (ALICsA). A randomized prospective open-label trial with blinded outcome assessment.
Chapter 5 Azathioprine treatment and drug survival in patients with 92 chronic hand eczema – results from daily practice
Chapter 6 Dupilumab treatment of very severe refractory atopic hand 98 eczema
Chapter 7 The effect of dupilumab on hand eczema in patients with 102 atopic dermatitis – an observational study
Section III – Outcome measures
Chapter 8 Guideline for translation and national validation of the 122 Quality Of Life in Hand Eczema Questionnaire (QOLHEQ)
Chapter 9 Validation of the Dutch QOLHEQ 156
Chapter 10 Cross-cultural validation of the QOLHEQ 206
Chapter 11 Interpretability of the QOLHEQ 256
Chapter 12 Responsiveness and interpretability of the Hand Eczema 298
Severity Index
Chapter 13 General discussion and future perspectives 318
Chapter 14 Appendices 328
Summary 330
Samenvatting (Dutch summary) 332
Dankwoord (Acknowledgements) 334
List of publications 338
Chapter 1
General introduction
Parts of this introduction were published before in:
Schuttelaar MLA, Oosterhaven JAF, Christoffers WA, et al. (2019).
Evidence-Based Management of Hand Eczema. In SM John et al. (Eds.),
Kanerva’s Occupational Dermatology. Springer Nature Switzerland AG.
GENERAL INTRODUCTION
This thesis consists of studies performed within the ‘Expert Center for Eczematous and Occupational Dermatoses’ at the department of Dermatology, University Medical Center Groningen, in the Netherlands. The overarching topic of this thesis is hand eczema. This general introduction gives a concise overview of hand eczema, leading up to the aims that this thesis is based on. These aims concern three areas relevant to hand eczema, which will be given special consideration in this introduction: impact, treatment, and outcome measures. More in depth introduction will be provided in the related chapters.
EPIDEMIOLOGY
Hand eczema is a common disease with a 1-year prevalence of at least 9.1% in the general population, including mild as well as severe cases. This was mostly measured in Scandinavian countries, showing an average 1-year prevalence of 6.4% in men and 10.5% in women in a systematic review from 2010. In the same review an incidence of 5.5 cases per 1000 person-years was found (9.6 in women, 4.0 in men). Self-reported hand eczema in women peaks at a young age, especially between 19 and 29 years, and decreases with age, while in men the incidence rate increases gradually with age.1,2 The higher prevalence in women is most likely explained by a difference in exposure, at home as well as occupationally, and not so much by a difference in susceptibility between the sexes.1,3 The pathogenesis of hand eczema is still largely unknown. According to a twin study, external factors explain up to 59% (confidence interval (CI) 47-72) of why an individual develops hand eczema.4 This means that around 40% of internal factors should explain why one individual is more prone to develop the disease than someone else.
There are several risk factors that are often associated with hand eczema: atopic dermatitis (AD) in childhood5, persistent/severe AD6,7, low age of onset of hand eczema8, contact allergies5,8, wet work9, and occupation10–12. Whether the use of tobacco is a risk factor for hand eczema is still subject of debate, but recent studies do seem to point in the direction of an association.13–18 Notable factors that were not associated with hand eczema in several studies are, for adolescents, asthma, rhinoconjunctivitis, specific IgE, and a parental history of allergy-related disease; and, for adults, body weight, alcohol consumption, lower educational level and stress.6,14,19 Conversely, other studies did find an association between incident as well as persistent hand eczema and generalized xerosis, food allergy, hay fever, asthma, lower educational level, stress (all self-reported) and obesity.2,5,18,20,21 Filaggrin gene (FLG) null-mutations seem not directly associated with incident hand eczema, although such mutations do strongly predict persistent hand eczema in individuals with AD.5,22 Clearly, much concerning the interplay between hand eczema and various possible risk factors still needs further elucidation.
DIAGNOSIS
To date, hand eczema is still a clinical diagnosis. The term eczema (in the literature often interchangeably used with the term dermatitis) is a general term used to describe an inflammation of skin in which, for hand eczema, a combination of erythema, scaling, fissures, erosions, infiltration, vesicles, hyperkeratosis, oedema and/or lichenification can be seen (see Figure 1). Hand eczema is called chronic when it lasts for more than three months or relapses twice or more in one year.23
1
classificationofhandeczema
No consensus has yet been reached on the classification of hand eczema. This is mostly because the disease is multifactorial, involving endogenous and exogenous factors. Known exogenous factors causing hand eczema are allergens and irritants, while the disease-inducing potential of these factors is largely based on a person’s susceptibility to them.24 Predisposing endogenous characteristics are, however, still largely unknown. It must be emphasized that hand eczema in general cannot simply be depicted as ‘atopic dermatitis localized on the hands’. Although it is often associated with AD, there are numerous patients who present themselves with isolated hand eczema, while having no history of (or currently active) AD. Patients may have a contact allergy as underlying cause of the hand eczema, which is why every patient with hand eczema should be tested for allergies with patch tests (epicutanous allergy testing).23,25 There are, however, many patients negative to patch testing. Such patients often have a contact dermatitis caused by irritant substances in the environment, which is the most common cause of hand eczema1,26, but they may also have a type of endogenous hand eczema which cannot clearly be attributed to exogenous causes. In these patients we currently rely on morphological descriptions for classification until we learn more about the underlying triggers of disease.
One way of classifying the disease is from a clinical point of view. Menné et al. proposed a classification based on hand eczema morphology as seen in daily practice27, with types of hand eczema that may be distinguishable, but can overlap and also change during the course of the disease:
• Chronic fissured hand eczema • Recurrent vesicular hand eczema • Hyperkeratotic palmar eczema • Pulpitis
• Interdigital eczema • Nummular hand eczema
Because a clear link between morphology and etiology is still not found and because knowledge about etiology is important for proper management of hand eczema, Menné et al. also put forward a separate etiological classification. This was later updated26 and resulted in a combined morphological/etiological classification (Table 1).
This table might give the impression that multiple items are mutually exclusive by definition, while in clinical practice they are often seen in conjunction. This again reflects the multifactorial nature of hand eczema. In daily practice more than one etiological diagnosis is often given. The combination of ICD and ACD is common, as is the combination of ICD and AHE.
It is clear that more knowledge is needed about what actually happens in the skin of hand eczema patients and whether a difference in function of (epi)dermal components could be linked to morphology. Until then, the definitions mentioned above can be used to classify hand eczema.
1
Table 1 Subgroups of hand eczema and definitions by Agner et al.26Subgroup of hand eczema Defined as
Irritant contact dermatitis (ICD)
A documented exposure of the hands to an irritant, which is quantitatively likely to cause contact dermatitis.
No relevant contact allergy (no current exposure to allergens to which the patient has reacted positive in patch test).
An example of a well-defined irritant exposure likely to cause contact dermatitis is wet-work: wet hands or wearing of gloves for 2 h, or more than 20 hand washes daily. Relevance of the irritant exposure may be defined as either suspected or certified.
Allergic contact dermatitis (ACD)
Positive patch test reaction to the topical exposure to an allergen or a cross-reacting allergen, and a relevant – either documented or suspected – current exposure to this allergen on the hands.
Relevance may be defined as either suspected or certified
Atopic hand eczema (AHE) Hand eczema in a patient with a medical history of atopic eczema, previous or current, according to the UK criteria.
No documented irritant exposure likely to cause ICD Protein contact dermatitis /
Contact urticaria (PCD/CU)
Hand eczema in patients exposed to proteins (food, latex and other biological material) with a positive prick test, or proven specific IgE, to suspected items. A considerable part of patients with PCD/CU will have atopic symptoms as well Vesicular endogenous hand
eczema
Recurrent hand eczema with vesicular eruptions. No relevant contact allergy, and no documented irritant exposure likely to cause dermatitis, and no personal history of atopic dermatitis
Hyperkeratotic endogenous hand eczema
Chronic eczema with hyperkeratosis in the palms of the hands, or pulpitis, and no vesicles or pustules.
No documented irritant exposure to the involved skin areas, likely to cause ICD
Unclassified Eczema which does not fit into any of the above-mentioned subgroups
MEASURING HAND ECZEMA SEVERITY
The management of hand eczema depends for a great deal on the severity of the disease. Severity can be estimated in part by determining the impact of the disease (see ‘Impact’). However, the work-up of hand eczema should also always include an assessment of the morphological (clinical) severity to enable monitoring over time and quantification of treatment or prevention efforts in clinical studies as well as in daily practice.28 Various instruments to assess clinical hand eczema severity have been developed that incorporate different hallmark signs of eczema (e.g. erythema, scaling, edema, papules, vesicles) and often also the extent of the disease. Unfortunately, most of these instruments have not been validated properly.29
Two instruments, which have been partly validated for use (only in Caucasian individuals), are currently often used:
• the ‘Photographic guide for the severity of hand eczema’ (‘Photoguide’), which functions as an image guided Physicians Global Assessment. The hand eczema severity is scored by the treating physician on a 5-point visual scale (clear, almost clear, moderate, severe, very severe) depicting 4 images representative for each of the severity grades.30 This instrument has also successfully been tested for use by patients to rate their own hand eczema severity.31
• the Hand Eczema Severity Index (HECSI), which is a continuous scale from 0-360 points that takes morphological signs (erythema, infiltration/papulation, vesicles, fissures, squamae, edema), location and extent into account.32
capture all subtypes in its images (like the severity of an isolated pulpitis), while HECSI has quite a large inter-observer variability, possibly owing to the lack of guidance on how the locations of the hand are defined and how to exactly score severity of the different signs. Also, responsiveness (sensitivity-to-change) and interpretability of the HECSI have not been studied. The best instrument to assess severity of hand eczema has not yet been established and might not yet exist. In this thesis, the Photographic guide and HECSI are applied in various chapters and the HECSI is studied in more detail.
IMPACT
Hand eczema can have large impact on patients. The disease can severely affect patients financially, occupationally and psychosocially.
Regarding financial impact, several studies have been published that assess the cost-of-illness of hand eczema.33–38 In this thesis, these studies are systematically reviewed to obtain an estimation of how high the financial burden of hand eczema is, for patients as well as for society.
Occupationally, hand eczema can lead to sickness presenteeism and absenteeism from work11,39,40. Many people with a chronic disease like hand eczema will often still attend work, while they should have stayed at home (presenteeism). These people will frequently be less productive and are prone to absenteeism in the long term. This holds true for many chronic conditions and is also relevant in eczema.41 For hand eczema, this has only been studied once, in a group of Dutch healthcare workers with generally mild disease.42 Frequent flares and more severe hand eczema are risk factors for a poor long-term prognosis. This might eventually lead to loss of job and problems getting a new job.40 This particularly applies to women, probably because they are more often employed in a wet-work occupation.3,43,44
When focusing on psychosocial consequences, it is known that depression and anxiety are correlated with hand eczema.45–47 In a large European multicenter study on the relation between depression/anxiety (measured using the Hospital Anxiety and Depression Scale) and 13 dermatological conditions, the strength of the correlation with hand eczema was in the top 3, along with psoriasis and ulcus cruris.48
Another way to measure the psychosocial impact of a disease is to look at quality of life impairment. This can be done using generic (non-specific) or skin-specific measurement instruments, but these may fail to grasp the real impact that a specific medical problem have on a patient. Because of this, disease-specific instruments are increasingly developed.49 Currently, the only disease-specific measurement instrument to assess quality of life in hand eczema is the Quality Of Life in Hand Eczema Questionnaire (QOLHEQ). The QOLHEQ consists of 30 questions, covering four subdomains: symptoms, emotions, functioning and treatment/ prevention. The questionnaire was validated in a German and Japanese population.50,51 It can aid clinicians in determining an individual approach to optimize the care for a hand eczema patient, for example by supplying educational or psychological interventions in patients that score particularly high on specific subscales. Furthermore, it offers the opportunity to measure disease-specific quality of life as a Patient Reported Outcome (PRO) in clinical studies on hand eczema. The QOLHEQ has not been validated for use in a Dutch population. Also, it is not yet known how QOLHEQ scores should be compared across countries and how values should be interpreted.
TREATMENT
1
on the diagnosis, prevention and treatment of hand eczema.23 Furthermore, a Cochrane review was performed on the available literature concerning the treatment of hand eczema.52 From these publications it becomes apparent that the cornerstone of treatment is topical therapy with emollients, corticosteroids and calcineurin inhibitors. The retinoid alitretinoin is recommended as second line therapy, as several large trials have proven its effectiveness.53–59 This effectiveness was mainly seen in hyperkeratotic and chronic fissured hand eczema and less in the recurrent vesicular subtype. A large trial is currently being performed in the United Kingdom to compare psoralen ultraviolet A (PUVA) to alitretinoin to add to the positioning of ultraviolet irradiation therapy in treatment strategies for hand eczema.60 The most used third line treatments are cyclosporine A, azathioprine, methotrexate and acitretin. For these drugs, studies in hand eczema patients are scarce. There is a need for well-designed randomized controlled trials (RCTs) and particularly for head-to-head trials, comparing the various systemic treatments. Also, the potential use of emerging treatments in the form of biopharmaceuticals (biologicals) for atopic dermatitis61,62 should be explored for hand eczema patients.
OUTCOME MEASURES
In quantitative science measurement plays a key role. It is vital to know what you are measuring and even more so that the instrument that you are using actually measures what you want it to measure. This is increasingly acknowledged and large initiatives have been started to improve measurement in medicine (also termed ‘clinimetrics’). The COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) initiative is an international group of experts aiming to “improve the quality of studies on measurement properties by developing methodology and practical tools for assessing measurement properties, and call for standardization of outcomes and outcome measurement instruments by developing core outcome sets (COS)”.63 This group provides guidance on how measurement properties of instruments should be assessed. We applied this to the field of existing outcome measurement instruments in hand eczema to assess whether meaningful measurements can be/are currently performed in hand eczema and to add a sense of how particular scores should be interpreted. Several chapters in this thesis use the COSMIN methodology.64
AIMS AND OUTLINE OF THE THESIS
In this thesis we aim to study various elements of the impact and treatment of hand eczema (section I and II). Furthermore, a large part of this thesis concerns validity and interpretability of outcome measurement instruments used in studies with hand eczema patients (section III).
Section I of this thesis explores the impact of hand eczema on financial and occupational
aspects of a patient’s life. Chapter 2 is a systematic review on cost-of-illness in hand eczema in which the available literature is summarized and analyzed. In chapter 3, the phenomenon ‘presenteeism’ (attending work while sick) is studied in hand eczema patients, providing a sense of how hand eczema affects patients in their work.
In Section II of this thesis we focus on how improvement can be gained regarding the systemic treatment for severe hand eczema. It comprises four chapters with studies on various drugs. In chapter 4, we describe a protocol for a clinical trial in which alitretinoin is compared with cyclosporine-A for the treatment of severe recurrent vesicular hand eczema.
Chapter 5 consists of a retrospective cross-sectional cohort study in which we report the effect
of azathioprine on patients treated at our center since the beginning of the millennium. In
chapters 6 and 7, the effect of the biological agent dupilumab, an interleukin 4 and 13 inhibitor,
Finally, Section III contains several chapters in which two outcome measures used in hand eczema studies take center stage. Chapter 8 is a guideline explaining how validation of a quality of life measurement can be performed. The Quality Of Life in Hand Eczema Questionnaire (QOLHEQ) is taken as an example, paving the way for chapter 9-11 in which multiple stages of this validation process are described. In chapter 9, validation data of the Dutch version of the QOLHEQ is reported, demonstrating its validity in a Dutch population. The QOLHEQ is also internationally validated to assess comparability between several countries worldwide.
Chapter 10 consists of a report on this cross-cultural validation study and in chapter 11 we
describe how scores obtained with the QOLHEQ should be interpreted when comparing international values. Finally, in chapter 12, we turn to the Hand Eczema Severity Index (HECSI) and present a study on the interpretability of this severity measurement instrument for hand eczema patients, which can be used in daily practice as well as in clinical studies.
1
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48. Dalgard FJ, Gieler U, Tomas-Aragones L, et al. The psychological burden of skin diseases: a cross-sectional multicenter study among dermatological out-patients in 13 European countries. J Invest Dermatol. 2015;135(4):984-991.
49. Prinsen CAC, de Korte J, Augustin M, et al. Measurement of health-related quality of life in dermatological research and practice: outcome of the EADV Taskforce on Quality of Life. J Eur Acad Dermatology Venereol. 2013;27(10):n/a-n/a.
50. Ofenloch RF, Weisshaar E, Dumke AK, Molin S, Diepgen TL, Apfelbacher C. The Quality of Life in Hand Eczema Questionnaire (QOLHEQ): validation of the German version of a new disease-specific measure of quality of life for patients with hand eczema. Br J Dermatol. 2014;171(2):304-312.
51. Minamoto K, Diepgen TL, Sato K, et al. Quality of Life in Hand Eczema Questionnaire: Validation of the Japanese version of a disease-specific measure of quality of life for hand eczema patients. J Dermatol. 2018;45(11):1301-1305.
52. Christoffers WA, Coenraads P-J, Svensson Å, et al. Interventions for hand eczema. Cochrane Database Syst Rev. 2019;4:CD004055.
53. Ruzicka T, Larsen FG, Galewicz D, et al. Oral alitretinoin (9-cis-retinoic acid) therapy for chronic hand dermatitis in patients refractory to standard therapy: results of a randomized, double-blind, placebo-controlled, multicenter trial. Arch Dermatol. 2004;140(12):1453-1459.
54. Ruzicka T, Lynde CW, Jemec GB, et al. Efficacy and safety of oral alitretinoin (9-cis retinoic acid) in patients with severe chronic hand eczema refractory to topical corticosteroids: results of a randomized, double-blind, placebo-controlled, multicentre trial. Br J Dermatol. 2008;158(4):808-817.
55. Bissonnette R, Worm M, Gerlach B, et al. Successful retreatment with alitretinoin in patients with relapsed chronic hand eczema. Br J Dermatol. 2010;162(2):420-426.
56. Fowler JF, Graff O, Hamedani AG. A phase 3, randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of alitretinoin (BAL4079) in the treatment of severe chronic hand eczema refractory to potent topical corticosteroid therapy. J Drugs Dermatol. 2014;13(10):1198-1204.
57. Diepgen TL, Pfarr E, Zimmermann T. Efficacy and tolerability of alitretinoin for chronic hand eczema under daily practice conditions: results of the TOCCATA open study comprising 680 patients. Acta Derm Venereol. 2012;92(3):251-255.
58. Thaçi D, Augustin M, Westermayer B, Kamps A, Hennig M. Effectiveness of alitretinoin in severe chronic hand eczema: PASSION, a real-world observational study. J Dermatolog Treat. 2016;27(6):577-583.
59. Augustin M, Thaçi D, Kamps A. Impact on quality of life of alitretinoin in severe chronic hand eczema: FUGETTA real-world study. JDDG J der Dtsch Dermatologischen Gesellschaft. 2016;14(12):1261-1270.
60. ALPHA: ALitretinoin versus PUVA in severe chronic HAnd eczema trial. Available at: https://ctru.leeds.ac.uk/ alpha/.
61. Boguniewicz M. Biologic Therapy for Atopic Dermatitis: Moving Beyond the Practice Parameter and Guidelines. J allergy Clin Immunol Pract. 2017;5(6):1477-1487.
62. Lee GR, Maarouf M, Hendricks AK, Lee DE, Shi VY. Current and emerging therapies for hand eczema. Dermatol
Ther. February 2019:e12840.
63. COSMIN. About the COSMIN initiative. Available at: https://www.cosmin.nl/about/.
64. de Vet HCW, Terwee CB, Mokkink LB, Knol DL. Measurement in Medicine. 1st ed. New York: Cambridge University Press; 2011.
SECTION I
IMPACT
Chapter 2
Systematic review of cost-of-illness
studies in hand eczema
K Politiek
1& JAF Oosterhaven
1,
KM Vermeulen, MLA Schuttelaar
1
Both authors contributed equally
SUMMARY
The individual burden of disease in hand eczema patients is considerable. However, little is known about the socio-economic impact of this disease. The aims of this review were to evaluate the literature on cost-of-illness in hand eczema, and to compose a checklist for future use. The literature was retrieved from the MEDLINE and EMBASE databases up to October 2015. Quality evaluation was based on seven relevant items in cost-of-illness studies. Cost data (direct and indirect) were extracted and converted into euros (price level 2014) by use of the Dutch Consumer Price Index. Six articles were included. The mean annual total cost per patient ranged from €1311 to €9792 (direct cost per patient, €521 to €3722; and indirect cost per patient, €100 to €6846). Occupational hand eczema patients showed indirect costs up to 70% of total costs, mainly because of absenteeism. A large diversity in hand eczema severity was found between studies. The socio-economic burden of hand eczema is considerable, especially for more severe and/or occupational hand eczema. Absenteeism from paid work leads to a high total cost-of-illness, although disregard of presenteeism often leads to underestimation of indirect costs. Differences in included cost components, the occupational status of patients and hand eczema severity make international comparison difficult. A checklist was added to standardize the approach to cost-of-illness studies in hand eczema.
2
INTRODUCTION
Hand eczema is a common condition in the general population, with a 1-year prevalence of up to 10%.1 It is a persistent and often relapsing disease.2 Hand eczema can have far-reaching personal consequences, and may have a drastic impact on the lives of those affected. In patients with chronic hand eczema, the long-term prognosis is poor, involving low health-related quality of life and negative occupational consequences.3,4 Furthermore, chronic hand eczema, especially of occupational origin, frequently results in productivity loss, owing to presenteeism (i.e. ‘working while sick’), absenteeism, or even job loss.5,6
Cost-of-illness studies identify and measure all of the costs of a disease, and generate a monetary estimate of the total burden of a particular disease. These studies are important for identifying benefits that would be obtained with prevention of the disease or with more effective treatment. Several cost-of-illness studies have been performed for hand eczema. These studies are valuable, because they give an insight into the factors that contribute to high costs incurred by this often disabling disease. The first objective of this study is to present a systematic review of these cost-of-illness studies in hand eczema. The quality of included studies is evaluated, and differences between studies are identified. On the basis of this review, our second objective is to compose a checklist for future cost-of-illness studies in hand eczema to increase standardized reporting across countries, in order to enhance comparability.
METHODS
We performed this review in accordance with relevant standards from the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines.7
A comprehensive literature search in the electronic databases MEDLINE (via PubMed) and EMBASE was conducted to identify published studies on cost-of-illness in hand eczema up to October 2015. A detailed search strategy is presented in Appendix 1. We checked reference lists to identify additional studies. All cost studies that estimated healthcare and/or non-healthcare costs associated with hand eczema were included. Studies with a model-based cost analysis were excluded. Only studies published in English were reviewed. All results in this review were based on published data; authors were not contacted for additional information or missing data.
A data extraction sheet was developed to standardize the items to be extracted. The identified studies were independently evaluated and reviewed by three authors (K.P., J.O., and K.V.). Differences in opinion were resolved by discussion until a consensus was reached. For each selected study, information regarding study design, population (e.g. age, sex, occupational status, and hand eczema severity) and cost estimates was extracted. In cost-of-illness studies, four cost components can be distinguished:
• Direct medical costs, which are healthcare-related expenses, for example costs of visits, hospital admission, diagnostics and treatment;
• Direct non-medical costs, which are directly associated with hand eczema but are not medical in nature, such as transport costs;
• Indirect costs, which include productivity losses related to morbidity;
• Intangible costs, which refer to psychological problems, pain, discomfort, anxiety and suffering, usually assessed by the use of quality of life measures. These costs are often omitted from cost-of-illness studies, because of the difficulty of quantifying them in monetary terms.8–10
The outcomes of primary interest for this review were direct (medical and non-medical), indirect, and total costs of hand eczema.
The quality of the studies was evaluated on the basis of seven relevant elements in cost-of-illness studies. Reviewers in the field of rheumatology composed a concise list of elements (based on expert literature) to evaluate cost-of-illness studies, because formal international guidelines for quality analyses of such studies are lacking.11–13 The following elements were evaluated:
1) Clear perspective of the study, which includes a description of which costs are relevant according to the purpose of the study. The most commonly used approach is the societal perspective, wherein all costs are relevant, irrespective of who pays for them. 2) Clearly stated study population, which includes a description of the source of patient
recruitment, and the sociodemographic and disease characteristics of patients. 3) All relevant direct costs and their data sources should be included and explained in
detail.
4) All relevant indirect costs and their data sources should be included and explained in detail.
5) Incremental costs. These are most often used to refer to the difference in cost and/ or effect between two or more interventions being compared in an evaluation. This is, however, often more applicable to cost-effectiveness studies and less to cost-of-illness studies, except when a comparison is made with a disease-free population. 6) Discounting, which should be applied to direct and indirect costs that are collected
during a time period of > 1 year.
7) A sensitivity analysis. Cost-of-illness studies rely on estimates with varying degrees of uncertainty. By creating a set of scenarios, the investigator takes uncertain (often estimated) factors into account, and thus determines a range of possible values of the real cost-of-illness.
Cost estimates were indexed to the price level of 2014 by the use of the Dutch Consumer Price Index (http://cbs.nl). Prices were all converted into euros, according to the 2014 exchange rate (http://www.x-rates.com).
RESULTS
LITERATURE SEARCH
Our database search identified 221 studies in MEDLINE and 219 studies in EMBASE. After identification and removal of duplicates, the titles and abstracts were carefully analyzed. Thirteen studies were identified for full-text analysis. From these, seven studies were excluded, which ultimately resulted in the inclusion of six studies in this review (Figure 1). The oldest identified study was published in 2006, and the most recent study in 2013.
CHARACTERISTICS OF INCLUDED STUDIES
Methods and patient characteristics of the reviewed studies are summarized in Table 1. Five of six studies were conducted in Europe: three in Germany, one in The Netherlands, and one in Italy. One study was conducted in the United States. An important difference between studies was the variation in severity of hand eczema. Some studies included only severe hand eczema patients,14 whereas other studies included patients with different disease severities.15 Another important difference concerned the percentage of employed patients in the studied populations, and their reported days of sick leave. This ranged from an average of 7 to 76 days per year, with high average numbers of sick days (absenteeism) being reported by two German studies on occupational hand eczema.16,17
2
Database search MEDLINE: n = 221
EMBASE: n = 219
Records after identification and removal of duplicates
n = 321
Records screened for relevance by title and
abstract n = 322
Records excluded:
- Hand eczema not main subject: n = 228 - No hand eczema cost study: n = 69 - No economic assessment: n = 1 - Design article: n = 2
- Abstract for poster or presentation: n =9 Records obtained from
reference lists n = 1
Full-text articles assessed for eligibility
n = 13
Records excluded: - No economic assessment: n = 3
- Cost-effectiveness model-based study: n = 3 - Language not English: n = 1
Studies included in review n = 6
Figure 1 Flowchart of data inclusion.
The methodology to estimate cost-of-illness regarding the data collection on healthcare consumption also varied among the included studies. One study used medical claims,18 but most studies used medical charts in combination with questionnaires that focused mainly on sick leave and non-medical direct costs. For calculating indirect costs, the human capital approach was used in most studies. Only Van Gils et al. used the friction cost method.19 COSTS OF HAND ECZEMA
Table 2 shows an overview of the reported annual cost-of-illness; when reported, this is broken down by cost components and hand eczema severity. Although the included cost components were reasonably similar between studies, variable costs were found. The mean annual direct cost per patient ranged from €521 to €3722. The mean annual indirect cost per patient ranged from €100 to €6846. The mean total annual cost per patient ranged from €1311 to €9792.
Table 1
. Char
ac
ter
istics of included studies
First author , Public ation y ear , Coun tr y A ugustin, 2011, German y 15 Cor tesi, 2013, Italy 14 D iep gen, 2013, A cta Derm G erman y 17 D iep gen, 2013, C on tac t Derma titis G erman y 16 Fo wler , 2006, USA 18 G ils v an, 2013, Nether lands 19 Popula tion char ac teristics: numb er , age (y ears), % male n = 223, 45.7, 43.9 n = 104, 44.5, 39.4 SHI: n = 223 OHI: n = 87 45.7, 46.5 n = 151, 44.9, 64.9 n = 507, 45.7, 40.7 IC: n = 101 UC: n = 95 43.0, 50.5 Inclusion crit eria Adult pa tien ts with clinically diag nosed
CHE and insur
ed b y SHI. No adequa te response t o a t
least one ther
ap y att empt with t opical st er oids (II-IV ) in the last 4 w eeks . Initial diag nosis > 12 mon ths pr evious . Pa tien t tr ea ted in relev an t c en ter on a con tinuous basis in last 12 mon ths . Sev er e CHE pa tien ts fr om t er tiar y r ef er ral cen ters . Elig ible pa tien ts had t o iden tify with cr iter ia similar t o the study of Ruzick a et al . fr om 2008. 26 SHI pa tien ts w er e included as descr ibed in A ugustin et al . fr om 24 der ma tology pr ac tic es and clinics acr oss G er man y 15. OHI pa tien ts w er e recruit ed fr om t w o OHI cen ters . T hese pa tien ts had CHE tha t w as c onsider ed to be r ela ted t o w or k or oc cupa tional exposur e and their tr ea tmen t c osts w er e reimbursed b y the OHI. O ccupa tional hand ecz ema, diag nosed in a specializ ed hand ecz ema clinic (Univ ersit y Clinic Heidelber g). T he OHI confir
med the diag
nosis and r ef er red the pa tien ts for t er tiar y individual pr ev en tion. Adult pa tien ts (≥ 18 y ear). Diag nosed with
CHE using a postal questionnair
e with
questions based on a clinical algor
ithm (see appendic es of this publica tion). Pa tien ts ≥ 16 y ears , moder at e t o sev er e CHE , > 3 mon ths . Pa tien ts with mild hand der ma titis on sick lea ve fr om w or k
because of their der
ma titis or pa tien ts tha t sc or ed a t least 4 poin ts on a VAS f or per ceiv ed bur den
of disease in the last 3 mon
ths bef or e baseline , w er e also elig ible f or inclusion. Se verit y sc or e hand ecz ema PGA, phot og raphic guide PGA, phot og raphic guide and m TLSS PGA, phot og raphic guide and m TLSS
PGA and OHSI
Sev er ity sc or e not per for med Phot og raphic guide and HECSI Hand ecz ema se verit y a t time of inclusion Clear : n = 1, A lmost clear : n = 27, M ild: n = 54, M oder at e: n = 107, Sev er e: n = 31 Sev er e: n = 104 Clear/almost clear : n = 45, Mild: n = 74, Moder at e: n = 140, Sev er e: n = 51
Clear/almost clear/mild: n = 58, Moder
at e/sev er e: n = 93 Hand ecz ema sev er ity not specified Hand ecz ema sev er ity not specified CHE: Chr onic Hand E cz ema; FCM: F ric tion C ost M ethod; HCM: Human C apital M ethod; HECSI: The Hand E cz ema S ev er ity I nde x; NR: Not R epor ted; OHI: O ccupa tional Health I nsur anc
e; OHSI: Osnabrück Hand ecz
ema S ev er ity I nde x; PGA: P hy sician Global A ssessmen t; m TLSS: modified Total L esion S ympt om S cor e; SHI: S ta tut or y Health Insur anc e; V AS: V isual A nalog Scale .
2
Table 1
. Char
ac
ter
istics of included studies
First author , Public ation y ear , Coun tr y A ugustin, 2011, German y 15 Cor tesi, 2013, Italy 14 D iep gen, 2013, A cta Derm G erman y 17 D iep gen, 2013, C on tac t Derma titis G erman y 16 Fo wler , 2006, USA 18 G ils v an, 2013, Nether lands 19 Popula tion char ac teristics: numb er , age (y ears), % male n = 223, 45.7, 43.9 n = 104, 44.5, 39.4 SHI: n = 223 OHI: n = 87 45.7, 46.5 n = 151, 44.9, 64.9 n = 507, 45.7, 40.7 IC: n = 101 UC: n = 95 43.0, 50.5 Inclusion crit eria Adult pa tien ts with clinically diag nosed
CHE and insur
ed b y SHI. No adequa te response t o a t
least one ther
ap y att empt with t opical st er oids (II-IV ) in the last 4 w eeks . Initial diag nosis > 12 mon ths pr evious . Pa tien t tr ea ted in relev an t c en ter on a con tinuous basis in last 12 mon ths . Sev er e CHE pa tien ts fr om t er tiar y r ef er ral cen ters . Elig ible pa tien ts had t o iden tify with cr iter ia similar t o the study of Ruzick a et al . fr om 2008. 26 SHI pa tien ts w er e included as descr ibed in A ugustin et al . fr om 24 der ma tology pr ac tic es and clinics acr oss G er man y 15. OHI pa tien ts w er e recruit ed fr om t w o OHI cen ters . T hese pa tien ts had CHE tha t w as c onsider ed to be r ela ted t o w or k or oc cupa tional exposur e and their tr ea tmen t c osts w er e reimbursed b y the OHI. O ccupa tional hand ecz ema, diag nosed in a specializ ed hand ecz ema clinic (Univ ersit y Clinic Heidelber g). T he OHI confir
med the diag
nosis and r ef er red the pa tien ts for t er tiar y individual pr ev en tion. Adult pa tien ts (≥ 18 y ear). Diag nosed with
CHE using a postal questionnair
e with
questions based on a clinical algor
ithm (see appendic es of this publica tion). Pa tien ts ≥ 16 y ears , moder at e t o sev er e CHE , > 3 mon ths . Pa tien ts with mild hand der ma titis on sick lea ve fr om w or k
because of their der
ma titis or pa tien ts tha t sc or ed a t least 4 poin ts on a VAS f or per ceiv ed bur den
of disease in the last 3 mon
ths bef or e baseline , w er e also elig ible f or inclusion. Se verit y sc or e hand ecz ema PGA, phot og raphic guide PGA, phot og raphic guide and m TLSS PGA, phot og raphic guide and m TLSS
PGA and OHSI
Sev er ity sc or e not per for med Phot og raphic guide and HECSI Hand ecz ema se verit y a t time of inclusion Clear : n = 1, A lmost clear : n = 27, M ild: n = 54, M oder at e: n = 107, Sev er e: n = 31 Sev er e: n = 104 Clear/almost clear : n = 45, Mild: n = 74, Moder at e: n = 140, Sev er e: n = 51
Clear/almost clear/mild: n = 58, Moder
at e/sev er e: n = 93 Hand ecz ema sev er ity not specified Hand ecz ema sev er ity not specified CHE: Chr onic Hand E cz ema; FCM: F ric tion C ost M ethod; HCM: Human C apital M ethod; HECSI: The Hand E cz ema S ev er ity I nde x; NR: Not R epor ted; OHI: O ccupa tional Health I nsur anc
e; OHSI: Osnabrück Hand ecz
ema S ev er ity I nde x; PGA: P hy sician Global A ssessmen t; m TLSS: modified Total L esion S ympt om S cor e; SHI: S ta tut or y Health Insur anc e; V AS: V isual A nalog Scale . First author , Public ation y ear , Coun tr y A ugustin, 2011, German y 15 Cor tesi, 2013, Italy 14 D iep gen, 2013, A cta Derm G erman y 17 D iep gen, 2013, C on tac t Derma titis G erman y 16 Fo wler , 2006, USA 18 G ils v an, 2013, Nether lands 19 M ean disease dur ation (y ears) 9.3 6.7 8.2 NR NR NR Emplo yed (%) 65.8 61.5 73.5 (SHI) / 100 ( OHI) 100 NR NR Pa tien ts with a t least 1 da y absenc e fr om w or k (%), (measur ed p erio d) 33.9 (12 mon ths) 45.3 (1 mon th) 33.9 (SHI)/62.7 ( OHI) (12 mon ths) 62.9 (12 mon ths) NR NR Sick da ys p er w or king pa tien t (mean), (measur ed perio d) 7.2 (12 mon ths) 4.9 (1 mon th) 47.2 (12 mon ths) 76.4 (12 mon ths) NR NR Typ e of analy sis Cost -out come discr iption Cost -out come discr iption Cost -out come discr iption Cost -out come discr iption Cost -out come discr iption Cost -eff ec tiv eness and c ost -utilit y Perio d of da ta collec tion 2008 2009 and 2010 2008 A pr il 2006 t o A pr il 2007 M ar ch 2001 t o No vember 2003 July 2008 t o No vember 2010 D ur ation of study 1 y ear 8 w eeks 1 y ear 1 y ear 33 mon ths 1 y ear M etho d of c ost da ta collec tion Q uestionnair e and retr ospec tiv e char t review s Q uestionnair e and retr ospec tiv e char t review s Q uestionnair e and retr ospec tiv e char t review s Retr ospec tiv e char t review s and pa tien t in ter view
Health plan paid amoun
t and pa tien t copa ymen t Pr ospec tiv e questionnair es and retr ospec tiv e char t review s Rep or ted indir ec t costs HCM HCM HCM HCM HCM FCM Valuta Eu ro Eu ro Eu ro Eu ro D ollar Eu ro CHE: Chr onic Hand E cz ema; FCM: F ric tion C ost M ethod; HCM: Human C apital M ethod; HECSI: The Hand E cz ema S ev er ity I nde x; NR: Not R epor ted; OHI: O ccupa tional Health I nsur anc
e; OHSI: Osnabrück Hand ecz
ema S ev er ity I nde x; PGA: P hy sician Global A ssessmen t; m TLSS: modified Total L esion S ympt om S cor e; SHI: S ta tut or y Health Insur anc e; V AS: V isual A nalog Scale . Table 1 Con tinued
Augustin, 201115 Almost cleara, n = 9 Moderate HEa,n = 39 Severe HEa, n = 39 Very severe HEa, n = 14 All types of HE severity, n = 223 Direct costs Medical
Visits (GP, SC, other, phone) 89 116 118 147 119
Hospital admission 126c 235c 470c 1140c 441c Outpatient rehabilitation – – – – – Diagnostics √ √ √ √ 274 UV irradiation 177 258 329 519 315 Medication 358 362 643 827 412 Emollients √ √ √ √ 122 OTC medicines – – – – – Visits other – – – – – Non-medical Out-of-pocket costs √ √ √ √ 256 Transport – – – – –
Total direct cost (/patient/year) 1211 1383 2199 3228 1939
Indirect costs
Production losses (presenteeism) – – – – –
Absenteeism from paid work 100 347 364 1054 430
Total indirect cost (/patient/year) 100 347 364 1054 430
Total cost (/patient/year) 1311 1730 2563 4282 2369
All prices in mean euros (€)/year. A hyphen (–) means that this cost item was not included in this study as such. HE: Hand Eczema; GP: General Practioner; IC: Integrated Care; OHI: Occupational Health Insurance;
OTC: Over-The-Counter; SC: Secondary Care; SHI: Statutory Health Insurance; UC: Usual Care.
Note: cost components with checkmarks (√) are included in total costs. If reported by authors as being merged with other cost components, this is specified below.
a Augustin et al. reported four ways of depicting hand eczema severity. We chose to show prices based on the
maximum hand eczema severity in the past 12 months as measured by the photographic guide. In our opinion, this is the best available option to retrospectively link costs to severity.
b This was reported as ‘outpatient services’. The components of these ‘services’ were not specified. c Hospital costs included both hospital admission and daycare
d This was reported as ‘inpatient rehabilitation’. Whether this is the same as the inpatient treatment (including daycare)
of Augustin et al. is unclear.
e Outpatient rehabilitation was reported as ‘outpatient services’. It included costs of PUVA/UVB therapy,
but other components of these ‘services’ were not specified.
f UV irradiation was included in emollients and this was called ‘non-pharmological therapy’. g Emollients were included in medication.
h Emollients were included in over-the-counter medicines. Over-the-counter medicines were excluded from total costs. i These were not further specified. The authors report that there might be some overlap between out-of-pocket
expenses and complementary therapies (visits other).
j Out-of-pocket costs included at least: ‘Products and instruments such as gloves or gauze bandages, vacuum cleaners
Cortesi, 201314 Diepgen, 2013 (Acta Derm)17 Diepgen, 2013 (Contact Dermatitis)16 Fowler, 200618 Gils van, 201319 Severe HE,
n = 104 All types of HE severity, n = 310 All types of HE severity, n = 151 All types of HE severity, n = 140 All types of HE severity, n = 196 Direct costs Medical
Visits (GP, SC, other, phone) 522 √ √ 2105b √
Hospital admission 857 √ 1253d 674 – Outpatient rehabilitation – – 773e – – Diagnostics 250 √ 294 – √ UV irradiation √ f √ √ e – – Medication 232 √ 167 943 √ Emollients 238 √ √ g √ h √ OTC medicines – – – 166h – Visits other – – 225i – – Non-medical Out-of-pocket costs 346j √ 235 – – Transport 553 – √ – –
Total direct cost (/patient/year) 2997 3682 OHI 1939 SHI 2945 3722 1039 IC521 UC
Indirect costs
Production losses (presenteeism) √ – – – –
Absenteeism from paid work √ √ 6846 – √
Total indirect cost (/patient/year) 2329 3808 OHI 430 SHI 6846 – 1191 UC2883 IC
Total cost (/patient/year) 5326 7490 OHI 2369 SHI 9792 3722 1712 UC3922 IC
2
Augustin, 201115 Almost cleara, n = 9 Moderate HEa,n = 39 Severe HEa, n = 39 Very severe HEa, n = 14 All types of HE severity, n = 223 Direct costs MedicalVisits (GP, SC, other, phone) 89 116 118 147 119
Hospital admission 126c 235c 470c 1140c 441c Outpatient rehabilitation – – – – – Diagnostics √ √ √ √ 274 UV irradiation 177 258 329 519 315 Medication 358 362 643 827 412 Emollients √ √ √ √ 122 OTC medicines – – – – – Visits other – – – – – Non-medical Out-of-pocket costs √ √ √ √ 256 Transport – – – – –
Total direct cost (/patient/year) 1211 1383 2199 3228 1939
Indirect costs
Production losses (presenteeism) – – – – –
Absenteeism from paid work 100 347 364 1054 430
Total indirect cost (/patient/year) 100 347 364 1054 430
Total cost (/patient/year) 1311 1730 2563 4282 2369
All prices in mean euros (€)/year. A hyphen (–) means that this cost item was not included in this study as such. HE: Hand Eczema; GP: General Practioner; IC: Integrated Care; OHI: Occupational Health Insurance;
OTC: Over-The-Counter; SC: Secondary Care; SHI: Statutory Health Insurance; UC: Usual Care.
Note: cost components with checkmarks (√) are included in total costs. If reported by authors as being merged with other cost components, this is specified below.
a Augustin et al. reported four ways of depicting hand eczema severity. We chose to show prices based on the
maximum hand eczema severity in the past 12 months as measured by the photographic guide. In our opinion, this is the best available option to retrospectively link costs to severity.
b This was reported as ‘outpatient services’. The components of these ‘services’ were not specified. c Hospital costs included both hospital admission and daycare
d This was reported as ‘inpatient rehabilitation’. Whether this is the same as the inpatient treatment (including daycare)
of Augustin et al. is unclear.
e Outpatient rehabilitation was reported as ‘outpatient services’. It included costs of PUVA/UVB therapy,
but other components of these ‘services’ were not specified.
f UV irradiation was included in emollients and this was called ‘non-pharmological therapy’. g Emollients were included in medication.
h Emollients were included in over-the-counter medicines. Over-the-counter medicines were excluded from total costs. i These were not further specified. The authors report that there might be some overlap between out-of-pocket
expenses and complementary therapies (visits other).
j Out-of-pocket costs included at least: ‘Products and instruments such as gloves or gauze bandages, vacuum cleaners
Cortesi, 201314 Diepgen, 2013 (Acta Derm)17 Diepgen, 2013 (Contact Dermatitis)16 Fowler, 200618 Gils van, 201319 Severe HE,
n = 104 All types of HE severity, n = 310 All types of HE severity, n = 151 All types of HE severity, n = 140 All types of HE severity, n = 196 Direct costs Medical
Visits (GP, SC, other, phone) 522 √ √ 2105b √
Hospital admission 857 √ 1253d 674 – Outpatient rehabilitation – – 773e – – Diagnostics 250 √ 294 – √ UV irradiation √ f √ √ e – – Medication 232 √ 167 943 √ Emollients 238 √ √ g √ h √ OTC medicines – – – 166h – Visits other – – 225i – – Non-medical Out-of-pocket costs 346j √ 235 – – Transport 553 – √ – –
Total direct cost (/patient/year) 2997 3682 OHI 1939 SHI 2945 3722 1039 IC521 UC
Indirect costs
Production losses (presenteeism) √ – – – –
Absenteeism from paid work √ √ 6846 – √
Total indirect cost (/patient/year) 2329 3808 OHI 430 SHI 6846 – 1191 UC2883 IC
Total cost (/patient/year) 5326 7490 OHI 2369 SHI 9792 3722 1712 UC3922 IC
Table 2 Continued
Costs are higher with more severe hand eczema. This is mainly because of the use of more expensive treatment and the higher incidence of hospitalization in this group. The latter represents the most substantial cost item in direct costs.14–16 Wide variation can be found in mean medication cost, ranging from €167 to €943 per patient per year, in proportion to hand eczema severity.
In studies evaluating costs of occupational hand eczema, high indirect costs are reported. In the study of Diepgen et al., all patients had occupation-related hand eczema, and only tertiary referral patients were included. These patients were all at risk of losing their job, and had high rates of absenteeism. This resulted in the highest indirect and total costs of all included studies. Although indirect costs amounted up to 70% of the total costs, direct costs were also high. Cost items that contributed highly to direct costs were hospital admission, utilized by 26% of the patients in the last 12 months, and outpatient services, which also included the costs of psoralen and ultraviolet (UV) A (PUVA)/UVB therapy. Usually, the patients had 12 visits to the dermatologist a year, because this monthly frequency is typical for the special report (‘Hautarztbericht’) requested by the statutory work insurance provider in
occupation-related cases in Germany.16
Fowler et al. did not collect direct non-medical and indirect costs at all, and this, by definition, results in a substantial underestimation of the total cost-of-illness.18 Presenteeism (leading to productivity loss during work) was only included by Cortesi et al., who measured it with a short version of the Health and Labour Questionnaire (SF-HLQ). The authors found that 65% of the included patients with severe hand eczema reported loss of productivity at work, with an average of 10.1 days per patient per month.14 All studies included assessments of health-related quality of life; however, no intangible costs were given. Augustin et al. claim to report intangible costs, although they actually only report outcome measures in their natural units (Dermatology Life Quality Index (DLQI)/Skindex scores); no translation to costs was made.15
In two evaluated studies, only total direct and indirect costs were shown, and no details about cost components were reported.17,19 Owing to this lack of insight into the division of the total costs, split data could not be shown in Table 2. Finally, two studies reported missing data on costs, which obviously also results in an underestimation of the true costs.18,19
QUALITY EVALUATION
All studies were critically evaluated on the basis of seven elements (Table 3). The first element, the perspective of the study, was well described. All studies determined costs from a societal perspective. The population (second element) was not clearly described in three studies. Cortesi
et al. showed, in their clinical characteristics, a range of Physician Global Assessment scores
(from clear to severe) for included patients, scored at the moment of inclusion. However, in the inclusion criteria of the study, only severe hand eczema patients are described.14 Diepgen et al. characterized their study population according to a ‘special report’ (‘Hautarztbericht’), which cannot be understood by the international reader without further information.16 The hand eczema population in the study of Fowler et al. was included by the use of a well-described postal self-assessment questionnaire. However, this questionnaire had an 85% sensitivity and 95% specificity score, which could lead to an inclusion bias. Moreover, hand eczema severity could not be specified on the basis of this questionnaire.18
Relevant direct and indirect medical cost components (third and fourth element) were not described and/or explained in detail in all studies. Fowler et al. did not collect non-medical direct and indirect costs at all.18 Van Gils et al. and, particularly, Diepgen et al. included more direct cost components, but did not provide a detailed explanation or breakdown of these costs.17,19 All studies included absenteeism, but only Cortesi et al. measured presenteeism.14 Discounting (fifth element) was not applicable in any of the included studies, except for the study by Fowler
et al. In this study, patients were observed over a period of > 1 year. Here, discounting should
have been applied.18 Incremental costs (sixth element) were only calculated in the study by van Gils et al. and Fowler et al. Additionally, van Gils et al. performed one sensitivity analysis (seventh element); they compared costs of productivity losses calculated with the friction cost method to productivity losses calculated with the human capital method.19 We scored this element as partly fulfilled, because the sensitivity analysis was conducted with only one element. For a solid conclusion, a broader variation in underlying assumptions and estimations is needed.
DISCUSSION
The purpose of our study was to give an overview of cost-of-illness studies that are performed for hand eczema. It is surprising that, despite the high socio-economic burden of hand eczema,
