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026 Hidradenitis suppurativa prevalence and disease associations using the Clinical Practice Research Datalink
Clinical Outcomes | ABSTRACTS 025
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Neurofibromatosis type 1 related breast cancer: Increased risk, exceptional histopathological characteristics and poor survival S Peltonen1, E Uusitalo2, R Kallionpa¨a¨2, S Kurki3, R Matti4 and J Peltonen2 1 Dept. of Dermatol., Univ. of Turku and Turku Univ. Hosp., Turku, Finland, 2 Dept. of Cell Biol. and Anatomy, Univ. of Turku, Turku, Finland, 3 Auria Biobank, Univ. of Turku and Turku Univ. Hosp., Turku, Finland and 4 Finnish Cancer Registry, Helsinki, Finland Neurofibromatosis type 1 (NF1) is an autosomal dominant tumor predisposition syndrome with an incidence as high as 1/2000. We have recently shown that the incidence of breast cancer in NF1 women <40 years is 11 times higher than that of normal population. The aim of the current study was to further analyze the NF1-associated breast cancer in terms of histopathology, clinical characteristics and survival. A population based cohort of 1404 NF1 patients (20,248 person-years of follow-up) was cross-referenced with the Finnish Cancer Registry. A total of 31 NF1 breast cancers were diagnosed during 1987-2013. The estimated lifetime risk for breast cancer in NF1 women was 18.0%. Archival tissue specimens were obtained from 26 invasive breast cancers of female NF1 patients. Age and sex matched breast cancer control data was used to further study the breast cancer survival and the tumor characteristics. In this analysis, NF1 breast cancer patients had significantly worse survival (p¼0.001) and the NF1 breast cancers were more commonly associated with unfavorable prognostic factors such as estrogen receptor and progesterone receptor negativity and HER2amplification. However, these characteristics did not solely explain the poor survival of the NF1 breast cancer since a further analysis with a control group matched by age, sex and estrogen receptor status still revealed a worse survival in the NF1 group (p¼0.022). Analysis of the TCGA dataset showed that NF1 mutations and deletions were associated with similar characteristics in the breast cancers of the general population as those observed in breast cancers of NF1 patients. The results are in accordance to previous findings showing that NF1 gene is one of the driver genes of breast cancer. The results also emphasize a need for follow-up of NF1 patients.
Hidradenitis suppurativa prevalence and disease associations using the Clinical Practice Research Datalink JR Ingram1, S Jenkins-Jones2, D Knipe3, C Morgan2 and V Piguet1 1 Cardiff University, Cardiff, United Kingdom, 2 Pharmatelligence, Cardiff, United Kingdom and 3 Bristol University, Bristol, United Kingdom The European prevalence of hidradenitis suppurativa (HS) remains highly uncertain, with estimates ranging from 0.05% to 4%; our study was designed to determine HS prevalence more accurately and to investigate disease associations. The Clinical Practice Research Datalink (CPRD), a primary care database of 12 million UK residents, was analysed to determine the prevalence of documented HS cases. To identify undiagnosed ‘proxy’ cases, algorithms were created to detect multiple skin boils in flexural sites. Proxy cases were validated in a subgroup of patients by sending questionnaires to their general practitioners (GPs), requesting confirmation of at least five skin boils on separate occasions in flexural sites. A case-control study compared disease associations between documented HS cases, proxy patients and age and gender-matched controls, one control matched to each case. In 2013, there were 23,353 documented HS cases from a total of 4,364,308 research-standard patient records. Read code algorithms identified a further 68,890 proxy HS patients. Diagnostic accuracy of each algorithm was established from 80 GP questionnaires, reducing the number of validated proxy patients to 13,016. Therefore overall HS point prevalence for 30 June 2013 was 0.84% (95% CI 0.83, 0.85%). Average incidence rate from 2003 to 2013 was 37.9 per 100,000 person-years (95% CI 37.4, 38.5). In documented HS cases, the female: male ratio was 3:1 and odds ratios (ORs) for current smoker, ex-smoker and obesity (BMI>30) were 3.61 (95% CI 3.44, 3.79), 1.93 (1.81, 2.05) and 3.29 (3.14, 3.45). ORs for disease associations were as follows: Crohn’s disease 2.65 (95% CI 1.89, 3.72), ulcerative colitis 1.24 (0.79, 1.94), acne 1.77 (1.66, 1.88), depression 1.69 (1.62, 1.77), polycystic ovary syndrome (PCOS) 1.19 (0.96, 1.49), hyperlipidaemia 1.79 (1.59, 2.02). In summary, using CPRD, the UK prevalence of HS is 0.84% and HS is associated with smoking, obesity, Crohn’s disease, acne, depression and hyperlipidaemia, but not ulcerative colitis or PCOS.
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Association of atopic dermatitis with cardiometabolic diseases and risk factor M Standl1, E Rodrı´guez2, H Baurecht2, A Peters1, J Schmitt3 and S Weidinger2 1 Institute of Epidemiology, Helmholtz Zentrum Mu¨ncheneGerman Research Center for Environmental Health, Neuherberg, Germany, 2 Department of Dermatology, Allergology and Venereology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany and 3 Center for Evidence-Based Healthcare, University Hospital Carl Gustav Carus, Technical University Dresden, Dresden, Germany Atopic dermatitis (AD) has been recently reported to increase the risk for cardiovascular diseases in adults, as well as related risk factors in children. These findings were mainly reported for US populations. Therefore, in the present analysis, we aim to investigate the association of AD with cardiometabolic diseases and related risk factors using data of three German cohorts of children and adults: a prospective analysis using data of 1925696 subjects of the cohort of German National Health Insurance beneficiaries, a cross-sectional analysis of 2990 individuals of the KORA F4 cohort and a longitudinal analysis of 3665 participants of the 10 and 15 year follow-ups of the GINIplus and LISAplus birth cohort studies. None of the adjusted regression models yielded significant associations of AD with any of the tested cardiometabolic diseases or related risk factors. In a sensitivity analysis of the German National Health Insurance beneficiaries, after further adjustment for health care utilization behavior (i.e. the total number of physician contacts due to reasons other than AD), AD was associated with decreased risk of stroke, type 2 diabetes, hypertension, and higher risk of angina pectoris in the sub-group of AD patients with systemic medication. These findings were limited to patients more than 40 years old and, except for stroke, stronger in patients with more severe AD. When analysing the GINIplus and LISAplus cross-sectionally, a direct association between HDL and AD was observed at age 15 years. Our findings do not confirm the hypothesis that AD is a risk factor for cardiometabolic diseases and risk factors. To the contrary, sensitivity analyses indicate an inverse association, if any.
Psychiatric and neurological disorders are associated with bullous pemphigoid e nationwide Finnish Care Register study A Fo¨rsti1, J Jokelainen2, H Ansakorpi3, A Seppa¨nen4, K Majamaa3, M Timonen5 and K Tasanen1 1 Department of Dermatology, Oulu University Hospital, Oulu, Finland, 2 Unit of General Practice, Oulu University Hospital, Oulu, Finland, 3 Department of Neurology, Oulu University Hospital, Oulu, Finland, 4 Psychoses and forensic psychiatry, Helsinki University Hospital, Helsinki, Finland and 5 Center for Life Course Epidemiology and Systems Medicine, University of Oulu, Oulu, Finland Bullous pemphigoid (BP) is an autoimmune blistering skin disease of the elderly with increasing incidence. BP has been shown to be associated with neurological disorders. So far, it has not been exactly established, for example, what subtypes of dementia and stroke are associated with BP, and what is the temporal relation between these diseases. Also, the association between BP and psychiatric disorders has remained controversial in previous studies. To answer these questions, we conducted a retrospective nationwide study using the statutory Finnish Care Register diagnoses between 1987 and 2013. The study population of 4524 BP patients were compared with 66138 patients with basocellular carcinoma (BCC), neurological as well as psychiatric comorbid disorders were evaluated for both groups, and association was estimated by Cox regression analysis and logistic regression analysis. The strongest risk of developing BP was found after diagnosis of multiple sclerosis (MS) (OR¼5.8, 95% CI 3.9-8.5) and dementias including other or unspecified dementia (3.8, 95% CI 3.44.4), vascular dementia (3.6, 95% CI 2.8-4.5), as well as Alzheimer’s disease (OR¼ 2.6, 95% CI 2.3-3.0). Among psychiatric diseases, the corresponding risk was strongest in schizophrenia (OR¼2.6, 95% CI 2.0-3.5), schizotypal and delusional disorders (OR¼2.1, 95% CI 1.6-2.6), and as a novel finding, also personality disorders (OR¼2.2, 95% CI 1.3-3.3) preceded BP. In conclusion, many psychiatric disorders, especially schizophrenia, other psychoses, and personality disorders preceded BP. Furthermore, several neurological diseases which cause central nervous system degeneration or inflammation were related to BP, and the association was strongest between MS and BP.
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Development and clinical evaluation of a “Traffic-light” design dermatology outpatient discharge checklist NA Harun1, S Salek2, V Piguet1 and A Finlay1 1 Department of Dermatology and Wound Healing, Division of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, United Kingdom and 2 Department of Pharmacy, Pharmacology & Postgraduate Medicine, School of Life and Medical Sciences, University of Hertfordshire, Hatfield, United Kingdom Our aims were to develop and evaluate a high quality discharge checklist, to assist clinicians make appropriate discharge decisions. Seventeen (100% response) consultant dermatologists anonymously completed a Delphi 3-Round questionnaire survey, using a 5-point Likert scale (1¼unimportant, 2¼of least importance, 3¼moderately important, 4¼important and 5¼very important). Consensus was reached when at least 75% of the dermatologists rated an item as very important or important. Twenty-six items that met this criterion were divided into three categories: disease related, patient empowerment and patient concerns. Items with related meanings were combined into one statement. There were 13 statements in the checklist, including certainty of diagnosis, disease severity, appropriateness of treatment, patient manageable in primary care, patient’s benefit from follow-up, patient’s understanding of diagnosis, disease outcome and treatment side effects, the availability of a clear and effective plan, patient’s ability to self-manage, patient’s easy re-access to secondary care, patient’s concerns and whether the patient and clinician are happy with the decision to discharge. Eighteen dermatology clinicians of different grades evaluated the checklist. 67% accepted the use of the checklist, 56% felt it was applicable to the outpatient setting, 17% felt it guided their thought processes and 8% wanted slight modification of the checklist. Consultants suggested that the checklist could be used to guide hospital managers on understanding how clinicians take discharge decisions. The findings of this study indicate that the Delphi exercise had identified appropriate criteria for the discharge checklist, as demonstrated by its high level of acceptability and applicability.
A novel mechanism of skin reaction related to Helicobacter pylori treatment T Ito1, H Ujiie1, Y Fujita1, H Shimizu1 and R Abe2 1 Hokkaido University Graduate School of Medicine, Sapporo, Japan and 2 Niigata University Graduate School of Medicine, Niigata, Japan Helicobacter pylori (HP) is a gram-negative bacterium that colonizes the human stomach. At least half of the world’s population has been estimated to be carriers of HP, and infection with HP has been implicated in the pathogenesis of gastric disorders. HP infection also has been recognized as elevating the risk of extragastric diseases such as idiopathic thrombocytopenic purpura. Recently we encountered patients who exhibited skin eruptions after treatment for HP infection and whose drug lymphocyte transformation test for HP treatment drugs was negative. In most of the cases, the onset of the cutaneous reaction was at three days after the cessation of treatment. Therefore, we investigated whether HP induces an adaptive immune reaction in patients with skin eruptions after HP eradication therapy. The concentrations of IL-2, IL-4 and IFN-g in the supernatants of patients’ PBMCs cultured with HP were found to be higher than those in controls. In addition, the results of lymphocyte transformation test, ELISpot analysis for IFN-g, and flow cytometry analysis for CD154 proved the existence of antigen-specific reactions to HP in these patients. These findings indicate that there is a specific immune reaction to HP in patients who have a skin reaction after completing HP eradication therapy and that this reaction could be the cause of the skin eruptions.
www.jidonline.org S165
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Neurofibromatosis type 1 related breast cancer: Increased risk, exceptional histopathological characteristics and poor survival S Peltonen1, E Uusitalo2, R Kallionpa¨a¨2, S Kurki3, R Matti4 and J Peltonen2 1 Dept. of Dermatol., Univ. of Turku and Turku Univ. Hosp., Turku, Finland, 2 Dept. of Cell Biol. and Anatomy, Univ. of Turku, Turku, Finland, 3 Auria Biobank, Univ. of Turku and Turku Univ. Hosp., Turku, Finland and 4 Finnish Cancer Registry, Helsinki, Finland Neurofibromatosis type 1 (NF1) is an autosomal dominant tumor predisposition syndrome with an incidence as high as 1/2000. We have recently shown that the incidence of breast cancer in NF1 women <40 years is 11 times higher than that of normal population. The aim of the current study was to further analyze the NF1-associated breast cancer in terms of histopathology, clinical characteristics and survival. A population based cohort of 1404 NF1 patients (20,248 person-years of follow-up) was cross-referenced with the Finnish Cancer Registry. A total of 31 NF1 breast cancers were diagnosed during 1987-2013. The estimated lifetime risk for breast cancer in NF1 women was 18.0%. Archival tissue specimens were obtained from 26 invasive breast cancers of female NF1 patients. Age and sex matched breast cancer control data was used to further study the breast cancer survival and the tumor characteristics. In this analysis, NF1 breast cancer patients had significantly worse survival (p¼0.001) and the NF1 breast cancers were more commonly associated with unfavorable prognostic factors such as estrogen receptor and progesterone receptor negativity and HER2amplification. However, these characteristics did not solely explain the poor survival of the NF1 breast cancer since a further analysis with a control group matched by age, sex and estrogen receptor status still revealed a worse survival in the NF1 group (p¼0.022). Analysis of the TCGA dataset showed that NF1 mutations and deletions were associated with similar characteristics in the breast cancers of the general population as those observed in breast cancers of NF1 patients. The results are in accordance to previous findings showing that NF1 gene is one of the driver genes of breast cancer. The results also emphasize a need for follow-up of NF1 patients.
Hidradenitis suppurativa prevalence and disease associations using the Clinical Practice Research Datalink JR Ingram1, S Jenkins-Jones2, D Knipe3, C Morgan2 and V Piguet1 1 Cardiff University, Cardiff, United Kingdom, 2 Pharmatelligence, Cardiff, United Kingdom and 3 Bristol University, Bristol, United Kingdom The European prevalence of hidradenitis suppurativa (HS) remains highly uncertain, with estimates ranging from 0.05% to 4%; our study was designed to determine HS prevalence more accurately and to investigate disease associations. The Clinical Practice Research Datalink (CPRD), a primary care database of 12 million UK residents, was analysed to determine the prevalence of documented HS cases. To identify undiagnosed ‘proxy’ cases, algorithms were created to detect multiple skin boils in flexural sites. Proxy cases were validated in a subgroup of patients by sending questionnaires to their general practitioners (GPs), requesting confirmation of at least five skin boils on separate occasions in flexural sites. A case-control study compared disease associations between documented HS cases, proxy patients and age and gender-matched controls, one control matched to each case. In 2013, there were 23,353 documented HS cases from a total of 4,364,308 research-standard patient records. Read code algorithms identified a further 68,890 proxy HS patients. Diagnostic accuracy of each algorithm was established from 80 GP questionnaires, reducing the number of validated proxy patients to 13,016. Therefore overall HS point prevalence for 30 June 2013 was 0.84% (95% CI 0.83, 0.85%). Average incidence rate from 2003 to 2013 was 37.9 per 100,000 person-years (95% CI 37.4, 38.5). In documented HS cases, the female: male ratio was 3:1 and odds ratios (ORs) for current smoker, ex-smoker and obesity (BMI>30) were 3.61 (95% CI 3.44, 3.79), 1.93 (1.81, 2.05) and 3.29 (3.14, 3.45). ORs for disease associations were as follows: Crohn’s disease 2.65 (95% CI 1.89, 3.72), ulcerative colitis 1.24 (0.79, 1.94), acne 1.77 (1.66, 1.88), depression 1.69 (1.62, 1.77), polycystic ovary syndrome (PCOS) 1.19 (0.96, 1.49), hyperlipidaemia 1.79 (1.59, 2.02). In summary, using CPRD, the UK prevalence of HS is 0.84% and HS is associated with smoking, obesity, Crohn’s disease, acne, depression and hyperlipidaemia, but not ulcerative colitis or PCOS.
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Association of atopic dermatitis with cardiometabolic diseases and risk factor M Standl1, E Rodrı´guez2, H Baurecht2, A Peters1, J Schmitt3 and S Weidinger2 1 Institute of Epidemiology, Helmholtz Zentrum Mu¨ncheneGerman Research Center for Environmental Health, Neuherberg, Germany, 2 Department of Dermatology, Allergology and Venereology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany and 3 Center for Evidence-Based Healthcare, University Hospital Carl Gustav Carus, Technical University Dresden, Dresden, Germany Atopic dermatitis (AD) has been recently reported to increase the risk for cardiovascular diseases in adults, as well as related risk factors in children. These findings were mainly reported for US populations. Therefore, in the present analysis, we aim to investigate the association of AD with cardiometabolic diseases and related risk factors using data of three German cohorts of children and adults: a prospective analysis using data of 1925696 subjects of the cohort of German National Health Insurance beneficiaries, a cross-sectional analysis of 2990 individuals of the KORA F4 cohort and a longitudinal analysis of 3665 participants of the 10 and 15 year follow-ups of the GINIplus and LISAplus birth cohort studies. None of the adjusted regression models yielded significant associations of AD with any of the tested cardiometabolic diseases or related risk factors. In a sensitivity analysis of the German National Health Insurance beneficiaries, after further adjustment for health care utilization behavior (i.e. the total number of physician contacts due to reasons other than AD), AD was associated with decreased risk of stroke, type 2 diabetes, hypertension, and higher risk of angina pectoris in the sub-group of AD patients with systemic medication. These findings were limited to patients more than 40 years old and, except for stroke, stronger in patients with more severe AD. When analysing the GINIplus and LISAplus cross-sectionally, a direct association between HDL and AD was observed at age 15 years. Our findings do not confirm the hypothesis that AD is a risk factor for cardiometabolic diseases and risk factors. To the contrary, sensitivity analyses indicate an inverse association, if any.
Psychiatric and neurological disorders are associated with bullous pemphigoid e nationwide Finnish Care Register study A Fo¨rsti1, J Jokelainen2, H Ansakorpi3, A Seppa¨nen4, K Majamaa3, M Timonen5 and K Tasanen1 1 Department of Dermatology, Oulu University Hospital, Oulu, Finland, 2 Unit of General Practice, Oulu University Hospital, Oulu, Finland, 3 Department of Neurology, Oulu University Hospital, Oulu, Finland, 4 Psychoses and forensic psychiatry, Helsinki University Hospital, Helsinki, Finland and 5 Center for Life Course Epidemiology and Systems Medicine, University of Oulu, Oulu, Finland Bullous pemphigoid (BP) is an autoimmune blistering skin disease of the elderly with increasing incidence. BP has been shown to be associated with neurological disorders. So far, it has not been exactly established, for example, what subtypes of dementia and stroke are associated with BP, and what is the temporal relation between these diseases. Also, the association between BP and psychiatric disorders has remained controversial in previous studies. To answer these questions, we conducted a retrospective nationwide study using the statutory Finnish Care Register diagnoses between 1987 and 2013. The study population of 4524 BP patients were compared with 66138 patients with basocellular carcinoma (BCC), neurological as well as psychiatric comorbid disorders were evaluated for both groups, and association was estimated by Cox regression analysis and logistic regression analysis. The strongest risk of developing BP was found after diagnosis of multiple sclerosis (MS) (OR¼5.8, 95% CI 3.9-8.5) and dementias including other or unspecified dementia (3.8, 95% CI 3.44.4), vascular dementia (3.6, 95% CI 2.8-4.5), as well as Alzheimer’s disease (OR¼ 2.6, 95% CI 2.3-3.0). Among psychiatric diseases, the corresponding risk was strongest in schizophrenia (OR¼2.6, 95% CI 2.0-3.5), schizotypal and delusional disorders (OR¼2.1, 95% CI 1.6-2.6), and as a novel finding, also personality disorders (OR¼2.2, 95% CI 1.3-3.3) preceded BP. In conclusion, many psychiatric disorders, especially schizophrenia, other psychoses, and personality disorders preceded BP. Furthermore, several neurological diseases which cause central nervous system degeneration or inflammation were related to BP, and the association was strongest between MS and BP.
029
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Development and clinical evaluation of a “Traffic-light” design dermatology outpatient discharge checklist NA Harun1, S Salek2, V Piguet1 and A Finlay1 1 Department of Dermatology and Wound Healing, Division of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, United Kingdom and 2 Department of Pharmacy, Pharmacology & Postgraduate Medicine, School of Life and Medical Sciences, University of Hertfordshire, Hatfield, United Kingdom Our aims were to develop and evaluate a high quality discharge checklist, to assist clinicians make appropriate discharge decisions. Seventeen (100% response) consultant dermatologists anonymously completed a Delphi 3-Round questionnaire survey, using a 5-point Likert scale (1¼unimportant, 2¼of least importance, 3¼moderately important, 4¼important and 5¼very important). Consensus was reached when at least 75% of the dermatologists rated an item as very important or important. Twenty-six items that met this criterion were divided into three categories: disease related, patient empowerment and patient concerns. Items with related meanings were combined into one statement. There were 13 statements in the checklist, including certainty of diagnosis, disease severity, appropriateness of treatment, patient manageable in primary care, patient’s benefit from follow-up, patient’s understanding of diagnosis, disease outcome and treatment side effects, the availability of a clear and effective plan, patient’s ability to self-manage, patient’s easy re-access to secondary care, patient’s concerns and whether the patient and clinician are happy with the decision to discharge. Eighteen dermatology clinicians of different grades evaluated the checklist. 67% accepted the use of the checklist, 56% felt it was applicable to the outpatient setting, 17% felt it guided their thought processes and 8% wanted slight modification of the checklist. Consultants suggested that the checklist could be used to guide hospital managers on understanding how clinicians take discharge decisions. The findings of this study indicate that the Delphi exercise had identified appropriate criteria for the discharge checklist, as demonstrated by its high level of acceptability and applicability.
A novel mechanism of skin reaction related to Helicobacter pylori treatment T Ito1, H Ujiie1, Y Fujita1, H Shimizu1 and R Abe2 1 Hokkaido University Graduate School of Medicine, Sapporo, Japan and 2 Niigata University Graduate School of Medicine, Niigata, Japan Helicobacter pylori (HP) is a gram-negative bacterium that colonizes the human stomach. At least half of the world’s population has been estimated to be carriers of HP, and infection with HP has been implicated in the pathogenesis of gastric disorders. HP infection also has been recognized as elevating the risk of extragastric diseases such as idiopathic thrombocytopenic purpura. Recently we encountered patients who exhibited skin eruptions after treatment for HP infection and whose drug lymphocyte transformation test for HP treatment drugs was negative. In most of the cases, the onset of the cutaneous reaction was at three days after the cessation of treatment. Therefore, we investigated whether HP induces an adaptive immune reaction in patients with skin eruptions after HP eradication therapy. The concentrations of IL-2, IL-4 and IFN-g in the supernatants of patients’ PBMCs cultured with HP were found to be higher than those in controls. In addition, the results of lymphocyte transformation test, ELISpot analysis for IFN-g, and flow cytometry analysis for CD154 proved the existence of antigen-specific reactions to HP in these patients. These findings indicate that there is a specific immune reaction to HP in patients who have a skin reaction after completing HP eradication therapy and that this reaction could be the cause of the skin eruptions.
www.jidonline.org S165