- Email: [email protected]
Seasonal and Latitudinal Impact of Polymorphic Light Eruption on Quality of Life
LETTERS TO THE EDITOR
See related commentary on page 1431
Seasonal and Latitudinal Impact of Polymorphic Light Eruption on Quality of Life Journal of Investigative Dermatology (2006) 126,1648–1651. doi:10.1038/sj.jid.5700306; published online 20 April 2006
TO THE EDITOR Polymorphic light eruption (PLE) is a recurring photosensitivity condition characterized by eruption of non-scarring pruritic papules and/or blisters and/or plaques on sun-exposed skin sites. Estimated to affect 11–21% of European and North American populations (Morison and Stern, 1982; Ros and Wennersten, 1986; Pao et al., 1994), this solar-induced disorder potentially disrupts the occupation, leisure activities, and family life of many people. The negative impact of skin disease on the general well-being of patients has been measured using validated quality of life (QOL) tools including the Dermatology Life Quality Index (DLQI; Lewis and Finlay, 2004). These facilitate comparisons with other skin diseases, assist therapeutic risk–benefit evaluation, and may be utilized in resource allocation. In this study, we employed the DLQI, a questionnaire relating to patients’ recall of the impact of their disorder in the previous week. Our aim was to examine the impact of PLE on QOL, assessing influence of season and latitude. There are anecdotal reports that patients are most affected by their PLE at the onset of spring, and conversely that they are more affected in summer, when ambient UVR levels are higher. Although it may be speculated that patients living at lower latitudes, that is, with higher ambient UVR, might suffer more, it is also conceivable that those at higher latitudes with more pronounced seasonality, and consequently less skin photoadaptation, may experience a greater impact.
To examine for any latitudinal variation, we studied subjects residing across the most southerly to the most northerly countries of Europe. These comprised 237 adult PLE patients attending hospital dermatology departments in Athens, Greece (37.981N), Besanc¸on, France (47.241N), Leiden, The Netherlands (52.161N), Manchester, UK (53.481N), and Turku, Finland (60.461N). Ambient UVR levels were monitored at these locations during assessment weeks. Participants completed the DLQI in four consecutive seasons, that is, for the first weeks of April, July, October, and January in 2003–2004. Additionally, the relationship between QOL and clinical severity was examined using a PLE severity score (PLESS). Diagnostic inclusion and exclusion criteria (Table 1) and PLESS (Table 2) are shown, and detailed methodology is presented in Supplementary Material (Materials and Methods, References). A response rate of 69–81% was seen over the four seasons (Table S1a). Mean age was 43.3 years (range 18–74), with four female:one male; further characteristics of participants are shown in Table S1b. DLQI scores showed a strong seasonal pattern (Figure 1a), with mean7SE of 3.3370.3, 5.9470.4, 2.5970.3, and 1.3670.2 for April, July, October, and January, respectively, all countries combined (Kruskal– Wallis H; w2 ¼ 112.81, Po0.001). Significant differences were seen: January vs April, January vs July, April vs July, and July vs October (z44.64, Po0.001). The DLQI correlated with global visual analogue score for life quality in all seasons (r ¼ 0.73–0.86, Po0.01; Figure S1). The same seasonal pattern in impairment of QOL was seen in all countries
Abbreviations: DLQI, Dermatology Life Quality Index; IQR, interquartile range; PLE, polymorphic light eruption; PLESS, PLE severity score; QOL, quality of life
1648 Journal of Investigative Dermatology (2006), Volume 126
(Figure 1b). Differences occurred in DLQI scores between Manchester and Athens (z ¼ 4.06, Po0.001) in April, and Manchester and Leiden (z ¼ 2.64, Po0.01) in July. No relationship was found between DLQI and age, or sex, whereas a greater impairment of QOL associated with PLE was found in skin phototype I. Differences in DLQI scores occurred between skin type 1 and 2 (z ¼ 2.20, P ¼ 0.03) and 1 and 3 (z ¼ 2.72, Po0.01) in April, between 1 and 2 (z ¼ 2.40, P ¼ 0.02) and 1 and 3 (z ¼ 3.02, Po0.01) in July, and between skin type 1 and all other skin types in October (z42.61, Po0.01). A seasonal pattern of ambient UVR levels (July4April4October4January) was confirmed, with highest total and maximum UVR levels across the seasons in Athens, followed by Besanc¸on, whereas those for the other three countries were similar and lower (Figure 2 and Figure S2, respectively). Within season, no positive association was found between DLQI and total or maximum ambient UVR levels. However, there was a small positive correlation between impairment of QOL of PLE and increasing latitude in springtime (r ¼ 0.25, Po0.01), with no significant relationship in summer. Interestingly, we also found that impairment of QOL in springtime, but not summer, correlated with PLE clinical severity. The PLESS was obtained for 165 of the participating patients. The mean7SD five-item PLESS was as follows: Athens 4.6771.76, Besanc¸on 4.5572.18, Leiden 5.9471.97, Manchester 4.871.99, and Turku 4.957 2.03. The DLQI correlated with the five-item PLESS in April, October, and January (r ¼ 0.41, 0.22, and 0.27, respectively, Po0.05). The same & 2006 The Society for Investigative Dermatology
TC Ling et al. Impact of PLE on QOL
Table 1. Diagnostic inclusion and exclusion criteria for PLE Inclusion criteria Rash occurs following sun exposure Rash occurs mainly on photoexposed skin Rash is recurrent Rash is pruritic Lesions are papules and/or vesicles and/or plaques Rash heals without scarring Exclusion criteria Known coexistent photosensitivity disorder Rash with eczematous features ENA antibody positive Markedly low MED to UVB or UVA Histology (if performed) incompatible with PLE PLE, polymorphic light eruption.
Table 2. PLESS Clinical characteristics
Score
1. How many months of the year are you affected?
0 (up to 1 month) 1 (1–3 months) 2 (4–6 months) 3 (more than 6 months)
2. Is your face included?
0 (never) 1 (sometimes) 2 (always)
3. Visual analogue score for severity of itching
0 (VAS 1–3)
0
10
1 (VAS 4–6)
0=no itch
10=worst imaginable itch
2 (VAS 7–10)
4. How long does your rash take to resolve?
0 (up to 1 week ) 1 (1–2 weeks) 2 (more than 2 weeks)
5. Which treatments have you previously received?
0 (creams/antihistamines only) 1 (phototherapy/systemic steroids) 2 (systemic immunosuppression)
6. Provocation threshold (UVA challenge)
0 (not provoked) 1 (provoked after three challenges) 2 (provoked after two challenges) 3 (provoked after one challenge)
Total PLESS Maximum five-point score (without UVA challenge)
11
Maximum six-point score
14
PLESS, PLE severity score.
correlations were apparent when the six-item score, that is, including rash provocation threshold, was analyzed for the 113 patients undergoing this test
(r ¼ 0.40, 0.24, and 0.30 respectively, Po0.05). In summary, this study has revealed a significant seasonal pattern in life
quality reduction in PLE, reflecting the cycle in ambient UVR levels. The summer, as opposed to the spring, is seen to be the season of maximal impairment, regardless of latitude, with a mean DLQI of 5.94 indicating a moderate effect on patient’s life (Hongbo et al., 2005). Within season, there is an absence of any strong relationships between DLQI and latitude or UVR level, and weak correlations seen could be owing to confounding factors. A positive correlation was observed between life quality impairment and increasing latitude, rather than UVR level, in April. This may indicate that springtime QOL is influenced to a greater degree by the more abrupt seasonal change in ambient UVR that occurs in northern Europe than absolute UVR level. Sufferers may be relatively unprepared in spring, whereas protective behavioral factors and skin photoadaptation may operate by summer. The finding that DLQI–PLESS correlation was highest in springtime, with no significant relationship in summer, may again reflect the greater influence of behavioral or other factors in the summer. Two centers, Manchester and Leiden, provide an interesting comparison as they lie at similar latitudes and had similar ambient UVR levels during assessment weeks. Despite this, the DLQI was consistently lower in Leiden than Manchester, reaching a statistically significant difference in summer. The higher proportion of skin phototype I PLE patients in Manchester might exert an influence (Table S1b), although PLESS scores were equivalent at the centers. A range of psychosocial factors can influence the impact of dermatological disorders on QOL (Wittkowski et al., 2004) and the recent finding of high levels of psychological distress in PLE sufferers in northwest England may be pertinent (Ling et al., 2004). PLE causes significant seasonal impact on QOL throughout Europe. Latitude and clinical severity appear to exert an influence in springtime; loss of these relationships in summer suggests that other, yet undetermined, behavioral and/or psychological factors may be operating. www.jidonline.org 1649
TC Ling et al. Impact of PLE on QOL
CONFLICT OF INTEREST
30
The authors state no conflicts of interest.
ACKNOWLEDGMENTS The European Union Framework V Programme, project no. QLK4-CT01-0015, financed this collaborative research. We are grateful to Leena Koulu (Turku, Finland) and Brigitte Faivre (Besanc¸on, France) for assistance with acquisition of QOL data. We thank Peter Gorts (RIVM, The Netherlands), Kostas Eleftheratos (Athens, Greece), Andy Pearson (Leeds, UK), and Anders Lindfors (Turku, Finland) for assistance with acquisition of solar data.
DLQI
20
10
0 April
July
October
January
Figure 1. Seasonal impact of PLE on QOL. Participating patients (n ¼ 237) completed DLQI questionnaires relating to the impact of their PLE on their QOL on four occasions, in the first weeks of April, July, October, and January in 2003–2004. All patients had consulted a hospital dermatology department, where their diagnosis of PLE was confirmed according to diagnostic inclusion and exclusion criteria (Table 1). The combined results for five European locations (Athens, Greece; Besanc¸on, France; Leiden, The Netherlands; Manchester, UK; Turku, Finland) are presented. Data are median, interquartile range (IQR), and outliers, where o represents a data point 1.5–3 IQR and * represents a data point 43 IQR. The whiskers represent a data point in the 25th and 75th centiles 71.5 IQR.
a
30 Athens Besancon
25
Leiden Manchester
20 DLQI
Turku
15
10
Tsui C. Ling1, Helen L. Richards2, Artiena S. Janssens3, Lina Anastassopoulou4, Christina Antoniou4, Francois Aubin5, Thomas L. Diepgen6, Rosemary Fazakerley1,7, Frank R. de Gruijl3, Christer T. Jansen8, Stan Pavel3, Andrew Smedley7, Alexander J Stratigos4, Ann R. Webb7, Neil K. Gibbs1 and Lesley E. Rhodes1 1 Dermatological Sciences, University of Manchester, Manchester, UK; 2Clinical Psychology, University of Manchester, Manchester, UK; 3Department of Dermatology, University of Leiden, Leiden, The Netherlands; 4 Department of Dermatology, University Hospital of Athens, Athens, Greece; 5 Department of Dermatology, Universite´ de Franche Comte´, Besanc¸on, France; 6 Department of Clinical Social Medicine and Epidemiology, University of Heidelberg, Heidelberg, Germany; 7School of Earth Atmospheric and Environmental Sciences, University of Manchester, Manchester, UK and 8Department of Dermatology, University of Turku, Turku, Finland. E-mail: [email protected]
5
SUPPLEMENTARY MATERIAL
0 April
Total ambient UVR (J/m2)
b
July
October
45,000
January Athens
40,000
Besancon
35,000
Leiden
30,000
Manchester
25,000
Turku
20,000 15,000
Table S1. Summary of sequence variants in the desmoplakin gene in the patient with striate palmoplantar keratoderma, WH, and cardiomyopathy compared to reference wild-type sequence (GenBank accession number M77830). Figure S1. Immunofluorescence showing the distribution of Dp, plakoglobin, and keratin 1 in the skin of the patient compared to normal sitematched skin.
REFERENCES
10,000 5,000 0 April
July
October
January
Figure 2. Influence of latitude on QOL in PLE. (a) Patients completed DLQI questionnaires at five centers in four seasons in 2003–2004 (methods as in Figure 1). The individual locations are shown: Athens, Greece (37.981N); Besanc¸on, France (47.241N); Leiden, The Netherlands (52.161N); Manchester, UK (53.481N); Turku, Finland (60.461N). Data are presented as median and IQR, and the whiskers represent a data point in the 25th and 75th centiles 71.5 IQR. (b) Total ambient UVR levels were obtained at each location for all QOL assessment weeks, using UV measurements obtained from local instruments. For further details, see Supplementary material. Data are expressed as total daily erythemal UVR doses (J/m2).
1650 Journal of Investigative Dermatology (2006), Volume 126
Hongbo Y, Thomas CL, Harrison MA, Salek MS, Finlay AY (2005) Translating the science of quality of life into practice: what do dermatology life quality index scores mean? J Investig Dermatol 125:659–64 Lewis V, Finlay AY (2004) 10 years experience of the Dermatology Life Quality Index (DLQI). J Investig Dermatol Symp Proc 9:169–80 Ling TC, Richards HL, Huber K, Brownrigg M, Brooke RCC, Gibbs NK et al. (2004) Psychological distress in polymorphic light erup-
EE Norgett et al. Early Death from Cardiomyopathy
tion. Br J Dermatol 151(Suppl 68):104 (abstract) Morison WL, Stern RS (1982) Polymorphous light eruption: a common reaction uncommonly recognized. Acta Derm Venereol (Stockh) 62:237–40
Pao C, Norris PG, Corbett M, Hawk JLM (1994) Polymorphic light eruption: prevalence in Australia and England. Br J Dermatol 130:62–4 Ros AM, Wennersten G (1986) Current aspects of polymorphous light eruption in Sweden. Photodermatology 3:298–302
Wittkowski A, Richards HL, Griffiths CE, Main CJ (2004) The impact of psychological and clinical factors on quality of life in individuals with atopic dermatitis. J Psychosom Res 57:195–200
Early Death from Cardiomyopathy in a Family with Autosomal Dominant Striate Palmoplantar Keratoderma and Woolly Hair Associated with a Novel Insertion Mutation in Desmoplakin Journal of Investigative Dermatology (2006) 126, 1651–1654. doi:10.1038/sj.jid.5700291; published online 20 April 2006
TO THE EDITOR Desmosomes are major cell adhesion junctions, particularly abundant in the epidermis and the heart where absolute strength and rigidity of the tissue during mechanical stress is of vital importance. Desmoplakin (Dp) is the most abundant protein of the desmosome. We have previously shown that the Dp mutation 7901delG, which causes a frameshift and subsequent truncation of the protein with partial loss of the keratinbinding domain, has been found to be the underlying cause of an autosomal recessive syndrome presenting as dilated left ventricular cardiomyopathy, woolly hair, and striate palmoplantar keratoderma (Norgett et al., 2000). Subsequently, other Dp mutations have been described associated with cardiac and cutaneous syndromes (Alcalai et al., 2003; Uzumcu et al., 2006). Other Dp mutations have been reported associated either with nonsyndromic striate palmoplantar keratoderma (Armstrong et al., 1999; Whittock et al., 1999) or with nonsyndromic arrthymogenic right ventricular cardiomyopathy (Rampazzo et al., 2002). Here, we describe the identification of a novel dominant Dp mutation associated with striate palmoplantar keratoderma, woolly hair, and cardiomyopathy. The patient first presented aged 3 years with hyperkeratosis and fissuring
of the skin on her palms and soles (Figure 1). The hyperkeratosis on her feet extended over the Achilles tendon and she was also noted to have woolly unmanageable hair. Of note, her father apparently had a similar phenotype and died suddenly a month after her birth
from arrthymogenic right ventricular dysplasia. No other known family members were affected. On examination at age 14, she had psoriasiform hyperkeratosis of the knees, elbows, and shins with prominence around hair follicles. She had a striate keratoderma
a
b
c
d
Figure 1. Skin and hair phenotypes of patient. Clinical pictures showing the striated keratoderma on (a) palm and (b) sole of the patient and (c, d) the woolly hair phenotype.
Abbreviations: Dp, Desmoplakin
www.jidonline.org 1651
See related commentary on page 1431
Seasonal and Latitudinal Impact of Polymorphic Light Eruption on Quality of Life Journal of Investigative Dermatology (2006) 126,1648–1651. doi:10.1038/sj.jid.5700306; published online 20 April 2006
TO THE EDITOR Polymorphic light eruption (PLE) is a recurring photosensitivity condition characterized by eruption of non-scarring pruritic papules and/or blisters and/or plaques on sun-exposed skin sites. Estimated to affect 11–21% of European and North American populations (Morison and Stern, 1982; Ros and Wennersten, 1986; Pao et al., 1994), this solar-induced disorder potentially disrupts the occupation, leisure activities, and family life of many people. The negative impact of skin disease on the general well-being of patients has been measured using validated quality of life (QOL) tools including the Dermatology Life Quality Index (DLQI; Lewis and Finlay, 2004). These facilitate comparisons with other skin diseases, assist therapeutic risk–benefit evaluation, and may be utilized in resource allocation. In this study, we employed the DLQI, a questionnaire relating to patients’ recall of the impact of their disorder in the previous week. Our aim was to examine the impact of PLE on QOL, assessing influence of season and latitude. There are anecdotal reports that patients are most affected by their PLE at the onset of spring, and conversely that they are more affected in summer, when ambient UVR levels are higher. Although it may be speculated that patients living at lower latitudes, that is, with higher ambient UVR, might suffer more, it is also conceivable that those at higher latitudes with more pronounced seasonality, and consequently less skin photoadaptation, may experience a greater impact.
To examine for any latitudinal variation, we studied subjects residing across the most southerly to the most northerly countries of Europe. These comprised 237 adult PLE patients attending hospital dermatology departments in Athens, Greece (37.981N), Besanc¸on, France (47.241N), Leiden, The Netherlands (52.161N), Manchester, UK (53.481N), and Turku, Finland (60.461N). Ambient UVR levels were monitored at these locations during assessment weeks. Participants completed the DLQI in four consecutive seasons, that is, for the first weeks of April, July, October, and January in 2003–2004. Additionally, the relationship between QOL and clinical severity was examined using a PLE severity score (PLESS). Diagnostic inclusion and exclusion criteria (Table 1) and PLESS (Table 2) are shown, and detailed methodology is presented in Supplementary Material (Materials and Methods, References). A response rate of 69–81% was seen over the four seasons (Table S1a). Mean age was 43.3 years (range 18–74), with four female:one male; further characteristics of participants are shown in Table S1b. DLQI scores showed a strong seasonal pattern (Figure 1a), with mean7SE of 3.3370.3, 5.9470.4, 2.5970.3, and 1.3670.2 for April, July, October, and January, respectively, all countries combined (Kruskal– Wallis H; w2 ¼ 112.81, Po0.001). Significant differences were seen: January vs April, January vs July, April vs July, and July vs October (z44.64, Po0.001). The DLQI correlated with global visual analogue score for life quality in all seasons (r ¼ 0.73–0.86, Po0.01; Figure S1). The same seasonal pattern in impairment of QOL was seen in all countries
Abbreviations: DLQI, Dermatology Life Quality Index; IQR, interquartile range; PLE, polymorphic light eruption; PLESS, PLE severity score; QOL, quality of life
1648 Journal of Investigative Dermatology (2006), Volume 126
(Figure 1b). Differences occurred in DLQI scores between Manchester and Athens (z ¼ 4.06, Po0.001) in April, and Manchester and Leiden (z ¼ 2.64, Po0.01) in July. No relationship was found between DLQI and age, or sex, whereas a greater impairment of QOL associated with PLE was found in skin phototype I. Differences in DLQI scores occurred between skin type 1 and 2 (z ¼ 2.20, P ¼ 0.03) and 1 and 3 (z ¼ 2.72, Po0.01) in April, between 1 and 2 (z ¼ 2.40, P ¼ 0.02) and 1 and 3 (z ¼ 3.02, Po0.01) in July, and between skin type 1 and all other skin types in October (z42.61, Po0.01). A seasonal pattern of ambient UVR levels (July4April4October4January) was confirmed, with highest total and maximum UVR levels across the seasons in Athens, followed by Besanc¸on, whereas those for the other three countries were similar and lower (Figure 2 and Figure S2, respectively). Within season, no positive association was found between DLQI and total or maximum ambient UVR levels. However, there was a small positive correlation between impairment of QOL of PLE and increasing latitude in springtime (r ¼ 0.25, Po0.01), with no significant relationship in summer. Interestingly, we also found that impairment of QOL in springtime, but not summer, correlated with PLE clinical severity. The PLESS was obtained for 165 of the participating patients. The mean7SD five-item PLESS was as follows: Athens 4.6771.76, Besanc¸on 4.5572.18, Leiden 5.9471.97, Manchester 4.871.99, and Turku 4.957 2.03. The DLQI correlated with the five-item PLESS in April, October, and January (r ¼ 0.41, 0.22, and 0.27, respectively, Po0.05). The same & 2006 The Society for Investigative Dermatology
TC Ling et al. Impact of PLE on QOL
Table 1. Diagnostic inclusion and exclusion criteria for PLE Inclusion criteria Rash occurs following sun exposure Rash occurs mainly on photoexposed skin Rash is recurrent Rash is pruritic Lesions are papules and/or vesicles and/or plaques Rash heals without scarring Exclusion criteria Known coexistent photosensitivity disorder Rash with eczematous features ENA antibody positive Markedly low MED to UVB or UVA Histology (if performed) incompatible with PLE PLE, polymorphic light eruption.
Table 2. PLESS Clinical characteristics
Score
1. How many months of the year are you affected?
0 (up to 1 month) 1 (1–3 months) 2 (4–6 months) 3 (more than 6 months)
2. Is your face included?
0 (never) 1 (sometimes) 2 (always)
3. Visual analogue score for severity of itching
0 (VAS 1–3)
0
10
1 (VAS 4–6)
0=no itch
10=worst imaginable itch
2 (VAS 7–10)
4. How long does your rash take to resolve?
0 (up to 1 week ) 1 (1–2 weeks) 2 (more than 2 weeks)
5. Which treatments have you previously received?
0 (creams/antihistamines only) 1 (phototherapy/systemic steroids) 2 (systemic immunosuppression)
6. Provocation threshold (UVA challenge)
0 (not provoked) 1 (provoked after three challenges) 2 (provoked after two challenges) 3 (provoked after one challenge)
Total PLESS Maximum five-point score (without UVA challenge)
11
Maximum six-point score
14
PLESS, PLE severity score.
correlations were apparent when the six-item score, that is, including rash provocation threshold, was analyzed for the 113 patients undergoing this test
(r ¼ 0.40, 0.24, and 0.30 respectively, Po0.05). In summary, this study has revealed a significant seasonal pattern in life
quality reduction in PLE, reflecting the cycle in ambient UVR levels. The summer, as opposed to the spring, is seen to be the season of maximal impairment, regardless of latitude, with a mean DLQI of 5.94 indicating a moderate effect on patient’s life (Hongbo et al., 2005). Within season, there is an absence of any strong relationships between DLQI and latitude or UVR level, and weak correlations seen could be owing to confounding factors. A positive correlation was observed between life quality impairment and increasing latitude, rather than UVR level, in April. This may indicate that springtime QOL is influenced to a greater degree by the more abrupt seasonal change in ambient UVR that occurs in northern Europe than absolute UVR level. Sufferers may be relatively unprepared in spring, whereas protective behavioral factors and skin photoadaptation may operate by summer. The finding that DLQI–PLESS correlation was highest in springtime, with no significant relationship in summer, may again reflect the greater influence of behavioral or other factors in the summer. Two centers, Manchester and Leiden, provide an interesting comparison as they lie at similar latitudes and had similar ambient UVR levels during assessment weeks. Despite this, the DLQI was consistently lower in Leiden than Manchester, reaching a statistically significant difference in summer. The higher proportion of skin phototype I PLE patients in Manchester might exert an influence (Table S1b), although PLESS scores were equivalent at the centers. A range of psychosocial factors can influence the impact of dermatological disorders on QOL (Wittkowski et al., 2004) and the recent finding of high levels of psychological distress in PLE sufferers in northwest England may be pertinent (Ling et al., 2004). PLE causes significant seasonal impact on QOL throughout Europe. Latitude and clinical severity appear to exert an influence in springtime; loss of these relationships in summer suggests that other, yet undetermined, behavioral and/or psychological factors may be operating. www.jidonline.org 1649
TC Ling et al. Impact of PLE on QOL
CONFLICT OF INTEREST
30
The authors state no conflicts of interest.
ACKNOWLEDGMENTS The European Union Framework V Programme, project no. QLK4-CT01-0015, financed this collaborative research. We are grateful to Leena Koulu (Turku, Finland) and Brigitte Faivre (Besanc¸on, France) for assistance with acquisition of QOL data. We thank Peter Gorts (RIVM, The Netherlands), Kostas Eleftheratos (Athens, Greece), Andy Pearson (Leeds, UK), and Anders Lindfors (Turku, Finland) for assistance with acquisition of solar data.
DLQI
20
10
0 April
July
October
January
Figure 1. Seasonal impact of PLE on QOL. Participating patients (n ¼ 237) completed DLQI questionnaires relating to the impact of their PLE on their QOL on four occasions, in the first weeks of April, July, October, and January in 2003–2004. All patients had consulted a hospital dermatology department, where their diagnosis of PLE was confirmed according to diagnostic inclusion and exclusion criteria (Table 1). The combined results for five European locations (Athens, Greece; Besanc¸on, France; Leiden, The Netherlands; Manchester, UK; Turku, Finland) are presented. Data are median, interquartile range (IQR), and outliers, where o represents a data point 1.5–3 IQR and * represents a data point 43 IQR. The whiskers represent a data point in the 25th and 75th centiles 71.5 IQR.
a
30 Athens Besancon
25
Leiden Manchester
20 DLQI
Turku
15
10
Tsui C. Ling1, Helen L. Richards2, Artiena S. Janssens3, Lina Anastassopoulou4, Christina Antoniou4, Francois Aubin5, Thomas L. Diepgen6, Rosemary Fazakerley1,7, Frank R. de Gruijl3, Christer T. Jansen8, Stan Pavel3, Andrew Smedley7, Alexander J Stratigos4, Ann R. Webb7, Neil K. Gibbs1 and Lesley E. Rhodes1 1 Dermatological Sciences, University of Manchester, Manchester, UK; 2Clinical Psychology, University of Manchester, Manchester, UK; 3Department of Dermatology, University of Leiden, Leiden, The Netherlands; 4 Department of Dermatology, University Hospital of Athens, Athens, Greece; 5 Department of Dermatology, Universite´ de Franche Comte´, Besanc¸on, France; 6 Department of Clinical Social Medicine and Epidemiology, University of Heidelberg, Heidelberg, Germany; 7School of Earth Atmospheric and Environmental Sciences, University of Manchester, Manchester, UK and 8Department of Dermatology, University of Turku, Turku, Finland. E-mail: [email protected]
5
SUPPLEMENTARY MATERIAL
0 April
Total ambient UVR (J/m2)
b
July
October
45,000
January Athens
40,000
Besancon
35,000
Leiden
30,000
Manchester
25,000
Turku
20,000 15,000
Table S1. Summary of sequence variants in the desmoplakin gene in the patient with striate palmoplantar keratoderma, WH, and cardiomyopathy compared to reference wild-type sequence (GenBank accession number M77830). Figure S1. Immunofluorescence showing the distribution of Dp, plakoglobin, and keratin 1 in the skin of the patient compared to normal sitematched skin.
REFERENCES
10,000 5,000 0 April
July
October
January
Figure 2. Influence of latitude on QOL in PLE. (a) Patients completed DLQI questionnaires at five centers in four seasons in 2003–2004 (methods as in Figure 1). The individual locations are shown: Athens, Greece (37.981N); Besanc¸on, France (47.241N); Leiden, The Netherlands (52.161N); Manchester, UK (53.481N); Turku, Finland (60.461N). Data are presented as median and IQR, and the whiskers represent a data point in the 25th and 75th centiles 71.5 IQR. (b) Total ambient UVR levels were obtained at each location for all QOL assessment weeks, using UV measurements obtained from local instruments. For further details, see Supplementary material. Data are expressed as total daily erythemal UVR doses (J/m2).
1650 Journal of Investigative Dermatology (2006), Volume 126
Hongbo Y, Thomas CL, Harrison MA, Salek MS, Finlay AY (2005) Translating the science of quality of life into practice: what do dermatology life quality index scores mean? J Investig Dermatol 125:659–64 Lewis V, Finlay AY (2004) 10 years experience of the Dermatology Life Quality Index (DLQI). J Investig Dermatol Symp Proc 9:169–80 Ling TC, Richards HL, Huber K, Brownrigg M, Brooke RCC, Gibbs NK et al. (2004) Psychological distress in polymorphic light erup-
EE Norgett et al. Early Death from Cardiomyopathy
tion. Br J Dermatol 151(Suppl 68):104 (abstract) Morison WL, Stern RS (1982) Polymorphous light eruption: a common reaction uncommonly recognized. Acta Derm Venereol (Stockh) 62:237–40
Pao C, Norris PG, Corbett M, Hawk JLM (1994) Polymorphic light eruption: prevalence in Australia and England. Br J Dermatol 130:62–4 Ros AM, Wennersten G (1986) Current aspects of polymorphous light eruption in Sweden. Photodermatology 3:298–302
Wittkowski A, Richards HL, Griffiths CE, Main CJ (2004) The impact of psychological and clinical factors on quality of life in individuals with atopic dermatitis. J Psychosom Res 57:195–200
Early Death from Cardiomyopathy in a Family with Autosomal Dominant Striate Palmoplantar Keratoderma and Woolly Hair Associated with a Novel Insertion Mutation in Desmoplakin Journal of Investigative Dermatology (2006) 126, 1651–1654. doi:10.1038/sj.jid.5700291; published online 20 April 2006
TO THE EDITOR Desmosomes are major cell adhesion junctions, particularly abundant in the epidermis and the heart where absolute strength and rigidity of the tissue during mechanical stress is of vital importance. Desmoplakin (Dp) is the most abundant protein of the desmosome. We have previously shown that the Dp mutation 7901delG, which causes a frameshift and subsequent truncation of the protein with partial loss of the keratinbinding domain, has been found to be the underlying cause of an autosomal recessive syndrome presenting as dilated left ventricular cardiomyopathy, woolly hair, and striate palmoplantar keratoderma (Norgett et al., 2000). Subsequently, other Dp mutations have been described associated with cardiac and cutaneous syndromes (Alcalai et al., 2003; Uzumcu et al., 2006). Other Dp mutations have been reported associated either with nonsyndromic striate palmoplantar keratoderma (Armstrong et al., 1999; Whittock et al., 1999) or with nonsyndromic arrthymogenic right ventricular cardiomyopathy (Rampazzo et al., 2002). Here, we describe the identification of a novel dominant Dp mutation associated with striate palmoplantar keratoderma, woolly hair, and cardiomyopathy. The patient first presented aged 3 years with hyperkeratosis and fissuring
of the skin on her palms and soles (Figure 1). The hyperkeratosis on her feet extended over the Achilles tendon and she was also noted to have woolly unmanageable hair. Of note, her father apparently had a similar phenotype and died suddenly a month after her birth
from arrthymogenic right ventricular dysplasia. No other known family members were affected. On examination at age 14, she had psoriasiform hyperkeratosis of the knees, elbows, and shins with prominence around hair follicles. She had a striate keratoderma
a
b
c
d
Figure 1. Skin and hair phenotypes of patient. Clinical pictures showing the striated keratoderma on (a) palm and (b) sole of the patient and (c, d) the woolly hair phenotype.
Abbreviations: Dp, Desmoplakin
www.jidonline.org 1651