Hand eczema classification: a cross-sectional, multicentre study of the aetiology and morphology of hand eczema

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1 CONTACT DERMATITIS AND ALLERGY BJD British Journal of Dermatology Hand eczema classification: a cross-sectional, multicentre study of the aetiology and morphology of hand eczema T.L. Diepgen, K.E. Andersen,* F.M. Brandao, M. Bruze,à D.P. Bruynzeel, P. Frosch, M. Gonçalo,** A. Goossens, C.J. Le Coz,àà T. Rustemeyer, I.R. White and T Agner *** on behalf of the European Environmental and Contact Dermatitis Research Group 1 Department of Social Medicine, Occupational and Environmental Dermatology, University Hospital Heidelberg, Thibautstr. 3, Heidelberg, Germany *Department of Dermatology, Odense University Hospital, Odense, Denmark Department of Dermatology, Hospital Garcia de Orta, Almanda, Portugal àdepartment of Occupational and Environmental Dermatology, Malmö University Hospital and Lund University, Lund, Sweden Department of Dermatology, Free University Hospital, Amsterdam, the Netherlands Department of Dermatology, Klinikum Dortmund and University of Witten Herdecke, Dortmund, Germany **Department of Dermatology, University Hospital, Coimbra, Portugal Department of Dermatology, University Hospital, K. U. Leuven, Leuven, Belgium ààdepartment of Dermatology, University Hospital, Strasbourg, France Department of Cutaneous Allergy, St Thomas Hospital, London, U.K. Department of Dermatology, University of Copenhagen, Gentofte Hospital, Copenhagen, Denmark ***Department of Dermatology, University of Copenhagen, Roskilde Hospital, Copenhagen, Denmark Summary Correspondence Thomas L. Diepgen. thomas.diepgen@med.uni-heidelberg.de Accepted for publication 8 August 2008 Key words classification, hand eczema, subdiagnosis Conflicts of interest None declared. 1 European Environmental and Contact Dermatitis Research Group: e05eecdrg/index_ger.html DOI /j x Background Hand eczema is a long-lasting disease with a high prevalence in the background population. The disease has severe, negative effects on quality of life and sometimes on social status. Epidemiological studies have identified risk factors for onset and prognosis, but treatment of the disease is rarely evidence based, and a classification system for different subdiagnoses of hand eczema is not agreed upon. Randomized controlled trials investigating the treatment of hand eczema are called for. For this, as well as for clinical purposes, a generally accepted classification system for hand eczema is needed. Objectives The present study attempts to characterize subdiagnoses of hand eczema with respect to basic demographics, medical history and morphology. Methods Clinical data from 416 patients with hand eczema from 10 European patch test clinics were assessed. Results A classification system for hand eczema is proposed. Conclusions It is suggested that this classification be used in clinical work and in clinical trials. Hand eczema is a common disease with a point prevalence in the background population of 9Æ7% 1 and an incidence rate reported to be 5Æ5 8Æ8 per 1000 person-years. 2,3 Epidemiological studies have identified risk factors influencing development and prognosis, 4 7 and measures for the prevention of hand eczema have been successfully introduced. 8,9 With respect to hand eczema treatment, however, validated randomized controlled trials are lacking, 10 and treatments are often used without differentiation between hand eczema subdiagnoses Few clinical studies have identified hand eczema subtypes. 14,15 Classification of the subdiagnoses of hand eczema is needed in the clinical situation and even more in clinical trials. Several classification systems have been suggested, most of them including both morphological and aetiological parameters in the classification. 16 The present study collected data on demography, medical history and morphology, and related these data to different hand eczema subdiagnoses. A future perspective is to decide on a generally accepted classification of hand eczema. Materials and methods The study was designed as a cross-sectional multicentre study, and was performed within the European Environmental and Contact Dermatitis Research Group (EECDRG: net/content/e05eecdrg/index_ger.html) from September

2 354 Hand eczema classification, T.L. Diepgen et al. to August Patients with hand eczema referred to one of the 10 participating patch test clinics in Europe were invited to participate. A medical history, including information about atopy, psoriasis, domestic and occupational s, frequency of eruptions and sick leave, was recorded. The clinical examination included evaluation of hand eczema severity by use of a scoring system (Hand Eczema Severity Index, HECSI 17 ). The HECSI includes scoring of erythema, infiltration, vesicles, fissures, scaling and oedema (score from 0 to 3), as well as a scoring of the affected area (fingertips, fingers, palms, dorsal hand and wrist, score from 0 to 4), and was performed by the doctor. All participants were patch tested with the European Standard Series. Additional patch tests and prick tests, aimed at specific patients and according to the tradition of the clinics, were added. On the basis of these observations, a diagnosis was made. The diagnostic options, based on clinical practice and decided after discussion in the EECDRG group, were: allergic contact dermatitis (ACD), irritant contact dermatitis (ICD), atopic hand eczema (AHE), discoid hand eczema, vesicular hand eczema and hyperkeratotic hand eczema. The diagnoses ACD and ICD were used only when relevant allergic or irritant s were assessed. More than one diagnosis could be provided for each patient. Statistics Data are presented as median values and interquartile range (IQR); in addition, mean ± SD values are given. Pearson s v 2 test was used to test the hypothesis of no association of columns and rows in data sheets. P <0Æ05 was considered as statistically significant. For the comparison of continuous measurements (i.e. age, HECSI score) between groups nonparametric tests were used (Mann Whitney U-test and Kruskal Wallis test). Results Medical history In total, 416 patients from the 10 participating clinics were included in the study. Each clinic provided from 27 (min) to 50 (max) patients for the study. The median age was 39 years (range 18 78); participants were 252 women and 164 men, gender ratio 1Æ54. The female preponderance was most pronounced in the young age groups (Fig. 1); 17Æ5% had a family history of atopic dermatitis (AD), and 23Æ5% reported a personal history of AD, ranging from 12% to 28% between the centres. Sixteen (3Æ8%) reported a personal history of psoriasis. Contact sensitization was found in 262 patients (63Æ0%), who had a positive reaction to one or more of the patchtested allergens. A contact allergy of relevance for the current eczema was found in 120 patients, allocated to either the ACD or the ACD ICD diagnostic subgroups (see below). Two hundred and sixty-one were prick tested, and type 1 allergy was found in 90 (34Æ5%). Fig 1. Distribution of hand eczema in relation to age (years) (n = 416 participants included). Female preponderance was most pronounced in the young age groups. Persistent eruptions were reported by 270 (64Æ9%), 102 (24Æ5%) reported eruptions more than four times per year, and 42 (10Æ1%) reported eruptions less frequently than four times per year. One hundred and eighteen (28Æ4%) reported sick leave due to hand eczema, and 51 (12Æ3%) reported sick leave for more than five consecutive weeks. Of all cases, 51Æ7% were reported as occupational (OHE). The median duration for the disease was 39 years (mean ± SD 40Æ1 ±13Æ6) in total and 41 years (mean ± SD 40Æ2 ±12Æ5) for those patients with OHE. Diagnosis A diagnosis was available in 396 patients, while a final diagnosis was not obtained in 20 patients. The seven most frequently used subdiagnoses or combinations of subdiagnoses were ACD, ACD ICD, ICD, AHE, AHE ICD, vesicular hand eczema and hyperkeratotic hand eczema, and these diagnoses were made in 319 patients (80Æ6%). The frequency and percentage for patients included in these subdiagnoses and for the 77 not included are given in Table 1. The distribution of subdiagnoses of hand eczema in relation to gender is given in Figure 2. ICD was found to affect women significantly more frequently than the other subdiagnoses (P <0Æ05). In the ACD and vesicular subdiagnostic groups there was a predominance of men (Fig. 2). Different diagnoses in relation to age groups are shown in Figure 3, with statistically significant variation in age distribution between the subdiagnostic groups (Kruskal Wallis test, P <0Æ0001). The youngest age was found for patients with AHE (median age 28 years, IQR 23 36) and the highest for patients with hyperkeratotic eczema (median age 52 years, IQR 48 58). The distribution of diagnoses of hand eczema in relation to contact sensitization, personal history of AD and occupational cause is illustrated in Figure 4. Contact sensitization was, as per definition, found in all patients who had a diagnosis of ACD, but contact sensitization was also diagnosed in patients with all other subdiagnoses. OHE was naturally reported more

3 Hand eczema classification, T.L. Diepgen et al. 355 Table 1 Subdiagnoses given for the 319 patients included in the diagnostic subgroups, and for 77 patients not included in the diagnostic subgroups Frequency Percentage ACD 60 15Æ2 ACD ICD 60 15Æ2 ICD 85 21Æ5 AHE 23 5Æ8 AHE ICD 31 7Æ8 Vesicular 37 9Æ3 Hyperkeratotic 21 5Æ3 Total 319 patients in the seven most frequent subdiagnostic groups ACD AHE 9 2Æ3 ACD AHE protein contact 1 0Æ3 dermatitis ACD AHE vesicular eczema 1 0Æ3 ACD hyperkeratotic eczema 2 0Æ5 ACD ICD AHE 6 1Æ5 ACD ICD AHE hyperkeratotic 1 0Æ3 eczema ACD ICD AHE vesicular eczema 1 0Æ3 ACD ICD AHE vesicular 1 0Æ3 eczema hyperkeratotic eczema ACD ICD hyperkeratotic eczema 4 1Æ0 ACD vesicular eczema 1 0Æ3 hyperkeratotic eczema AHE hyperkeratotic eczema 1 0Æ3 AHE vesicular eczema 8 2Æ0 AHE vesicular eczema 1 0Æ3 hyperkeratotic eczema Discoid eczema 3 0Æ8 Discoid eczema other diagnosis 1 0Æ3 ICD AHE vesicular eczema 1 0Æ3 ICD discoid eczema 4 1Æ0 ICD hyperkeratotic eczema 9 2Æ3 ICD vesicular eczema 15 3Æ8 ICD vesicular eczema discoid 1 0Æ3 eczema Other diagnosis 6 1Æ5 Total 77 patients outside the seven most frequent diagnostic subgroups ACD, allergic contact dermatitis; ICD, irritant contact dermatitis; AHE, atopic hand eczema. frequently in the exogenous diagnostic groups (ACD and ICD), but OHE was also reported in patients with vesicular and hyperkeratotic eczema. Three patients with AHE were reported to the authorities as having OHE, as this can be done also by people other than the dermatologist (by the general practitioner or in some countries also by the patient himself herself). With respect to psoriasis no significant difference in distribution between the subdiagnostic groups was found. Only one patient with hyperkeratotic eczema reported psoriasis. Similarly, the frequency of sick leave and eruptions did not differ between the subdiagnostic groups. Only 10 cases of discoid eczema were diagnosed, in five cases in combination with ICD (Table 1). Fig 2. Gender in relation to subdiagnoses (n = 319 patients). ACD, allergic contact dermatitis; ICD, irritant contact dermatitis; AHE, atopic hand eczema. ICD was found to affect women significantly more frequently than the other subdiagnoses (v 2 test, P <0Æ05). Age ACD (allergic contact dermatitis) ACD ICD (allergic and irritant) ICD (irritant contact dermatitis) AHE (atopic hand eczema) AHE and ICD (atopic hand eczema) Morphology/hand eczema severity index The HECSI score, representing affected area on the hands as well as severity of symptoms, is shown for different subdiagnoses of hand eczema in Figure 5. The median HECSI score was 18 (IQR 8 40): 21 (IQR 10 53) for men and 14Æ5 (IQR 6 30) for women. The highest scores were found in the ACD and hyperkeratotic subdiagnostic groups, and the lowest score Vesicular Hyperkeratotic dermatitis Fig 3. Age in relation to subdiagnoses (n = 319 patients). ACD, allergic contact dermatitis; ICD, irritant contact dermatitis; AHE, atopic hand eczema. A statistically significant difference was found in age distribution between the diagnostic subgroups (P < 0Æ0001). The youngest age was found for patients with AHE and the highest for patients with hyperkeratotic eczema. The plot shows mean (), median (horizontal line), interquartile range (box) and range of values (whiskers).

4 356 Hand eczema classification, T.L. Diepgen et al. Details on morphology are given in Table 3. Erythema and scaling were the most frequent clinical symptoms for most subdiagnoses, except for hyperkeratotic hand eczema where infiltration was more dominating than erythema. Discussion Fig 4. Percentage of patients with contact sensitization, personal history of atopic dermatitis or reported occupational eczema given for the different subdiagnostic groups (n = 319). ACD, allergic contact dermatitis; ICD, irritant contact dermatitis; AHE, atopic hand eczema. HECSI-score ACD (allergic contact dermatitis) ACD ICD (allergic and irritant) ICD (irritant contact dermatitis) AHE (atopic hand eczema) AHE and ICD (atopic hand eczema) in the ICD subdiagnostic group (Kruskal Wallis test, P <0Æ05). The affected area location of eczema on the hands for the different subdiagnoses is shown in Table 2. Fingers were the most affected areas, except for the vesicular and hyperkeratotic types where palms were the most affected areas. The wrist was the least affected area. The back of the hands was more frequently affected for AHE and combined AHE and ICD. In AHE the fingertips were rarely affected. Vesicular Hyperkeratotic dermatitis Fig 5. Hand Eczema Severity Index (HECSI) score in relation to subdiagnoses (n = 319). ACD, allergic contact dermatitis; ICD, irritant contact dermatitis; AHE, atopic hand eczema. The highest scores were found in ACD and hyperkeratotic subdiagnostic groups, and the lowest score in the ICD subdiagnostic group (P < 0Æ05). Plot shows mean (), median (horizontal line), interquartile range (box) and range of values (whiskers). This study attempted to characterize different subdiagnoses of hand eczema with respect to basic demographics, medical history and morphology. Participants, obtained from 10 European dermatological clinics, represented a typical hand eczema population with respect to age, gender and previous history of AD. 1,18 A predominance of women only in the young age groups has previously been reported. 19 Contact sensitization was found in 63% of the population, which is higher than reported in studies of patients with hand eczema recruited from the background population, 20,21 but is in agreement with findings in patents with recognized OHE, where the frequency of contact sensitization was reported to be 65% and 48% in women and men, respectively. 18 The high frequency of contact sensitization is naturally also related to extensive testing of the patients, which is performed in the participating dermatological clinics the more you test the more you find. Frequency of eruptions and sick leave are indicators of eczema severity, and the fact that 65% had persistent eruptions and 28% had had sick leave due to hand eczema shows that the material comprises relatively severe cases. The median HECSI score was below the values in patients with chronic hand eczema evaluated in the original HECSI paper, 17,22 but higher than values from a hand eczema population recruited from the background population, 23 supporting the impression that this population was relatively severely affected. On the basis of the clinical data from the 416 patients, seven subdiagnoses or combined subdiagnoses were chosen, and are recommended for use as a classification system for hand eczema. The diagnoses comprised the seven most frequent subdiagnoses made. Distribution of subdiagnoses shows ICD to be the most frequent diagnosis, comprising more than 25% of the patients, with ACD and AHE as the second and third most frequent. This agrees with previous reports. 18,22,23 The observation that ICD was the significantly most frequent subdiagnosis in women could be due to domestic wet work as a contributing factor to this subdiagnosis, and that this is traditionally a burden to female skin. The finding that ACD was related to more severe hand eczema as compared with ICD, when assessed by HECSI, contradicts recent findings in patients with OHE where ICD was found to be related to severe eczema. 18,23 The observation that AHE was more frequent in younger age groups, with hyperkeratotic eczema having preponderance in the older age groups, is in agreement with the general perception of these subdiagnoses. With respect to discoid eczema this subdiagnosis was used as the only diagnosis for only four cases, and the distribution and morphology for these cases were close to AHE, so it is suggested that this subdiagnosis should not be used. A brief

5 Hand eczema classification, T.L. Diepgen et al. 357 Table 2 Median values (and interquartile range) for Hand Eczema Severity Index score (score affected area) obtained from each region on the hands from the different subgroups of eczema Location ACD ACD ICD ICD AHE AHE ICD Vesicular Hyperkeratotic Total Fingertip 2 (0 6Æ5) 1 (0 6) 1 (0 4) 0 (0 4) 0 (0 2) 1 (0 5) 1 (0 7) 1 (0 4) Finger 5 (2 9) 4 (2 6) 4 (2 6) 5 (3 7) 3 (2 6) 5 (2 8) 4 (2 6) 4 (2 7) Palm 3Æ5 (0 8) 1 (0 4) 1 (0 5) 3 (0 7) 0 (0 1) 6 (1 8) 5 (0 8) 2 (0 6) Dorsal hand 1 (0 4) 0 (0 3) 0 (0 2) 0 (0 4) 1 (0 5) 0 (0 2) 0 (0 1) 0 (0 3) Wrist 0 (0 2) 0 (0 1) 0 (0 0) 0 (0 0) 0 (0 2) 0 (0 0) 0 (0 0) 0 (0 0) ACD, allergic contact dermatitis; ICD, irritant contact dermatitis; AHE, atopic hand eczema. Fingers are the most affected area for all diagnostic types, except for the vesicular and hyperkeratotic types where palms are the most affected areas. Table 3 Median values (and interquartile range) for Hand Eczema Severity Index score obtained from the different clinical symptoms from different subgroups of eczema Morphology ACD ACD ICD ICD AHE AHE ICD Vesicular Hyperkeratotic Total Erythema 3Æ5 (2 6) 3 (1Æ5 4) 3 (1 4) 3 (2 5) 2 (1 4) 3 (1 5) 2 (0 4) 3 (1 4) Infiltration 2Æ5 (1 6) 2 (0 4) 2 (0 3) 4 (2 4) 1 (0 4) 2 (1 4) 3 (2 4) 2 (1 4) Vesicles 1 (0 4) 0Æ5 (0 2) 0 (0 2) 0 (0 1) 0 (0 0) 3 (2 4) 0 (0 0) 0 (0 2) Fissures 2 (0 3) 2 (0 3) 0 (0 2) 2 (0 3) 0 (0 1) 1 (0 3) 3 (1 4) 1 (0 3) Scaling 3 (2 5) 3 (1 5) 2 (1 4) 3 (2 5) 2 (1 4) 3 (1 5) 3 (2 5) 3 (1 5) Oedema 0 (0 2) 0 (0 1) 0 (0 1) 0 (0 0) 0 (0 1) 0 (0 2) 0 (0 0) 0 (0 1) ACD, allergic contact dermatitis; ICD, irritant contact dermatitis; AHE, atopic hand eczema. Table 4 Characteristics for the various subdiagnostic groups Demographics Medical history Most frequent clinical signs Most frequent locations Definition ACD ACD ICD ICD AHE (endogenous) AHE ICD Vesicular (endogenous) Hyperkeratotic (endogenous) Predominance of men Most frequent diagnosis for women Affects young age groups Predominance of men Affects older age groups Relevant contact allergy; highest HECSI Relevant contact allergy and relevant irritant Relevant irritant ; lowest HECSI Atopic dermatitis Atopic dermatitis and relevant irritant High HECSI Erythema, scaling, infiltration Erythema, scaling, infiltration Erythema, scaling, infiltration Infiltration, erythema, scaling Erythema, scaling Vesicles, erythema, scaling Infiltration, fissures, scaling Finger, palm, fingertip Finger, fingertip palm Finger, fingertip palm Finger, palm Finger, dorsal hand Palm, finger Palm, finger Relevant contact allergy Relevant contact sensitization and relevant irritant Relevant irritant Atopic skin disease Atopic skin disease and relevant irritant Vesicular morphology and no relevant contact sensitization, no relevant irritant, no atopic disease Hyperkeratotic morphology in the palms and no relevant contact sensitization, no relevant irritant, no atopic disease ACD, allergic contact dermatitis; ICD, irritant contact dermatitis; AHE, atopic hand eczema; HECSI, Hand Eczema Severity Index. overview of demographics, medical history, clinical signs and location of eczema is given in Table 4. However, it is still important to remember that there is no simple translation from morphology to subdiagnoses of hand eczema, and that a full diagnostic examination, including patch testing, for all patients with hand eczema needs to be carried out. 13 Analysis

6 358 Hand eczema classification, T.L. Diepgen et al. of variation of diagnoses between clinics was not possible due to the low number of cases included. However, the variation was considerable, emphasizing the need for further clinical studies to improve the classification of hand eczema. In conclusion, a classification system for hand eczema is proposed, and a characterization of the different subdiagnoses is attempted. Until now agreement on a classification system for hand eczema has been lacking. This is a major disadvantage for communication between different clinics and it is especially a drawback in clinical trials. It is suggested that in future the classification presented in Table 4 be used. References 1 Meding B, Järvholm B. Hand eczema in Swedish adults: changes in prevalence between 1983 and J Invest Dermatol 2002; 118: Meding B, Swanbeck G. Predictive factors for hand eczema. Contact Dermatitis 1990; 23: Lerbaek A, Kyvik KO, Ravn H et al. Incidence of hand eczema in a population-based twin cohort: genetic and environmental risk factors. Br J Dermatol 2007; 157: Cvetkovski RS, Zachariae R, Jensen H et al. Prognosis of occupational hand eczema: a follow-up study. Arch Dermatol 2006; 142: Meding B, Wrangsjö K, Järvholm B. Fifteen-year follow-up of hand eczema: persistence and consequences. Br J Dermatol 2005; 152: Weisshaar E, Radulescu M, Bock M et al. Educational and dermatological aspects of secondary individual prevention in healthcare workers. Contact Dermatitis 2006; 54: Apfelbacher CJ, Radulescu M, Diepgen TL, Funke U. Occurrence and prognosis of hand eczema in the car industry: results from the PACO follow-up study (PACO II). Contact Dermatitis 2008; 58: Held E, Mygind K, Wolff C et al. Prevention of work-related skin problems: an intervention study in wet work employees. Occup Environ Med 2002; 59: Weisshaar E, Radulescu M, Soder S et al. Secondary individual prevention of occupational skin diseases in health care workers, cleaners and kitchen employees: aims, experiences and descriptive results. Int Arch Occup Environ Health 2007; 80: van Coevorden AM, Coenraads PJ, Svensson A et al. Overview of studies of treatments for hand eczema the EDEN hand eczema survey. Br J Dermatol 2004; 151: Veien NK, Menné T. Treatment of hand eczema. Skin Therapy Lett 2003; 8: Diepgen TL, Svensson A, Coenraads PJ. Therapy of hand eczema. What can we learn from the published clinical studies? Hautarzt 2005; 56: Diepgen TL, Agner T, Aberer W et al. Management of chronic hand eczema. Contact Dermatitis 2007; 57: Cronin E. Clinical patterns of hand eczema in women. Contact Dermatitis 1985; 13: Thestrup-Pedersen K, Andersen KE, Menné T, Veien NK. Treatment of hyperkeratotic dermatitis of the palms (eczema keratoticum) with oral acitretin. A single-blind placebo-controlled study. Acta Derm Venereol (Stockh) 2001; 81: Agner T. Hand eczema. In: Contact Dermatitis (Frosch PJ, Menné T, Lepoittevin J-P, eds), 4th edn. Berlin: Springer-Verlag, 2006; Held E, Skoet R, Johansen JD, Agner T. The hand eczema severity index (HECSI): a scoring system for clinical assessment of hand eczema. A study of inter- and intraobserver reliability. Br J Dermatol 2005; 152: Skoet R, Olsen J, Mathiesen B et al. A survey of occupational hand eczema in Denmark. Contact Dermatitis 2004; 51: Meding B, Järvholm B. Incidence of hand eczema a populationbased retrospective study. J Invest Dermatol 2004; 122: Meding B, Wrangsjö K, Järvholm B. Fifteen-year follow-up of hand eczema: predictive factors. J Invest Dermatol 2005; 124: Nielsen NH, Linneberg A, Menné T et al. The association between contact allergy and hand eczema in 2 cross-sectional surveys 8 years apart. Contact Dermatitis 2002; 47: Lerbaek A, Kyvik KO, Ravn H et al. Clinical characteristics and consequences of hand eczema an 8-year follow-up study of a population-based twin cohort. Contact Dermatitis 2008; 58: Jungbauer FH, van der Vleuten P, Grotoff JV, Coenraads JP. Irritant hand dermatitis: severity of disease, occupational to skin irritants and preventive measures 5 years after initial diagnosis. Contact Dermatitis 2004; 50: