Correction: Exome sequencing of Pakistani consanguineous families identifies 30 novel candidate genes for recessive intellectual disability.

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Association between Rare Variants in AP4E1, a Component of Intracellular Trafficking, and Persistent Stuttering.

Stuttering is a common, highly heritable neurodevelopmental disorder characterized by deficits in the volitional control of speech. Whole-exome sequencing identified two heterozygous AP4E1 coding variants, c.1549G>A (p.Val517Ile) and c.2401G>A (p.Glu801Lys), that co-segregate with persistent developmental stuttering in a large Cameroonian family, and we observed the same two variants in unrelated Cameroonians with persistent stuttering. We found 23 other rare variants, including predicted loss-of-function variants, in AP4E1 in unrelated stuttering individuals in Cameroon, Pakistan, and North America. The rate of rare variants in AP4E1 was significantly higher in unrelated Pakistani and Cameroonian stuttering individuals than in population-matched control individuals, and coding variants in this gene are exceptionally rare in the general sub-Saharan West African, South Asian, and North American populations. Clinical examination of the Cameroonian family members failed to identify any symptoms previously reported in rare individuals carrying homozygous loss-of-function mutations in this gene. AP4E1 encodes the ε subunit of the heterotetrameric (ε-ß4-µ4-σ4) AP-4 complex, involved in protein sorting at the trans-Golgi network. We found that the µ4 subunit of AP-4 interacts with NAGPA, an enzyme involved in the synthesis of the mannose 6-phosphate signal that targets acid hydrolases to the lysosome and the product of a gene previously associated with stuttering. These findings implicate deficits in intracellular trafficking in persistent stuttering.

Exome sequencing of Pakistani consanguineous families identifies 30 novel candidate genes for recessive intellectual disability.

Intellectual disability (ID) is a clinically and genetically heterogeneous disorder, affecting 1-3% of the general population. Although research into the genetic causes of ID has recently gained momentum, identification of pathogenic mutations that cause autosomal recessive ID (ARID) has lagged behind, predominantly due to non-availability of sizeable families. Here we present the results of exome sequencing in 121 large consanguineous Pakistani ID families. In 60 families, we identified homozygous or compound heterozygous DNA variants in a single gene, 30 affecting reported ID genes and 30 affecting novel candidate ID genes. Potential pathogenicity of these alleles was supported by co-segregation with the phenotype, low frequency in control populations and the application of stringent bioinformatics analyses. In another eight families segregation of multiple pathogenic variants was observed, affecting 19 genes that were either known or are novel candidates for ID. Transcriptome profiles of normal human brain tissues showed that the novel candidate ID genes formed a network significantly enriched for transcriptional co-expression (P<0.0001) in the frontal cortex during fetal development and in the temporal-parietal and sub-cortex during infancy through adulthood. In addition, proteins encoded by 12 novel ID genes directly interact with previously reported ID proteins in six known pathways essential for cognitive function (P<0.0001). These results suggest that disruptions of temporal parietal and sub-cortical neurogenesis during infancy are critical to the pathophysiology of ID. These findings further expand the existing repertoire of genes involved in ARID, and provide new insights into the molecular mechanisms and the transcriptome map of ID.

Conceptualization, development and validation of T-QoL© (Teenagers' Quality of Life): a patient-focused measure to assess quality of life of adolescents with skin diseases.

BACKGROUND: Skin disease can affect the quality of life (QoL) of teenagers in a variety of different ways, some being unique to this age group. OBJECTIVES: To develop and validate a dermatology-specific QoL instrument for adolescents with skin diseases. METHODS: Qualitative semistructured interviews were conducted with adolescents with skin disease to gain in-depth understanding of how skin diseases affect their QoL. A prototype instrument based on the themes identified from content analysis of interviews was tested in several stages, using classical test theory and item response theory models to develop this new tool and conduct its psychometric evaluation. RESULTS: Thirty-three QoL issues were identified from semistructured interviews with 50 adolescents. A questionnaire based on items derived from content analysis of interviews was subjected to Rasch analysis: factor analysis identified three domains, therefore not supporting the validity of T-QoL as a unidimensional measure. Psychometric evaluation of the final 18-item questionnaire was carried out in a cohort of 203 adolescents. Convergent validity was demonstrated by significant correlation with Skindex-Teen and Dermatology Life Quality Index (DLQI) or Children's DLQI. The T-QoL showed excellent internal consistency reliability: Cronbach's α = 0·89 for total scale score and 0·85, 0·60 and 0·74, respectively, for domains 1, 2 and 3. Test-retest reliability was high in stable volunteers. T-QoL showed sensitivity to change in two subgroups of patients who indicated change in their self-assessed disease severity. CONCLUSIONS: Built on rich qualitative data from patients, the T-QoL is a simple and valid tool to quantify the impact of skin disease on adolescents' QoL; it could be used as an outcome measure in both clinical practice and clinical research.

Determining the minimal clinically important difference and responsiveness of the Dermatology Life Quality Index (DLQI): further data.

AIMS: To determine the minimal clinically important difference (MCID) of the Dermatology Life Quality Index (DLQI) and its responsiveness to change in inflammatory skin diseases. METHODS: A longitudinal study: at stage 1, patients completed the DLQI and a disease severity global question; at stage 2, a global rating of change in quality of life (QoL; Global Rating of Change Questionnaire, GRCQ) was added and used as an anchor to measure the MCID of the DLQI. RESULTS: 192 patients completed stage 1 and 107 completed stage 2. The mean DLQI score at stage 1 was 9.8 and 7.4 at stage 2 with a mean change of 2.4 (p < 0.0001). 31 patients experienced a 'small change' in their QoL (±3 and ±2) on the GRCQ. The mean corresponding change in DLQI scores was 3.3, which is regarded as the approximate MCID. CONCLUSIONS: Previous estimates of the MCID of the DLQI have varied from 3 to 5. Although this study demonstrated a MCID of 3.3, we recommend that the MCID in inflammatory skin diseases should be 4.

Comparison of the impairment of family quality of life assessed by disease-specific and dermatology-specific instruments in children with atopic dermatitis.

BACKGROUND: Quality of life (QoL) of family members of patients with chronic skin diseases is often impaired. Disease-specific family QoL instruments for most of the skin conditions are not available. Family Dermatology Life Quality Index (FDLQI) is a dermatology-specific family QoL instrument that has been used in few studies to assess the impact of skin diseases on family members of mixed adult and children patient population. However, its use in families of exclusively paediatric patients with skin conditions needs further investigation. OBJECTIVES: The aim of this study was to compare the results of two family QoL instruments; the disease-specific Dermatitis Family Impact (DFI) questionnaire and the dermatology-specific FDLQI. METHOD: The original UK English version of the FDLQI was translated into Ukrainian using the standard translation guidelines. Parents of 30 children with AD were asked to complete the Ukrainian versions of the FDLQI and the DFI questionnaires. Disease severity was estimated using the Scoring Atopic Dermatitis (SCORAD). RESULTS: Mean FDLQI score was 11.8 (±5.8; range = 0-30) and the mean DFI score was 10.7 (±5.6; range = 0-30). Mean SCORAD was 40.6 (±11.3; range = 0-103). Both questionnaires showed good internal consistency with a Cronbach's alpha value of 0.83 for both. The FDLQI showed high correlation with the DFI (r = 0.68, P < 0.0001). Items of each questionnaire having similar themes also demonstrated high correlation. CONCLUSION: Family Dermatology Life Quality Index may be effectively used by parents of children as it can be used by family members of adult dermatology patients. Although, in some clinical and research situations, disease-specific measures could be replaced by the dermatology-specific measures, in most situations combining the disease-specific and dermatology-specific measures would be the most suitable approach to gain comprehensive insight into the impact of a dermatological condition on family members.

Preliminary reliability and validity of Persian version of the Family Dermatology Life Quality Index (FDLQI).

PURPOSE: Family Dermatology Life Quality Index (FDLQI) is an instrument for assessing the quality of life of family members of dermatologic patients. The aim of this study was to describe the cultural adaptation of this questionnaire and to assess psychometric properties of the Persian version. METHODS: At first, the questionnaire was translated into Persian, and then back-translation was performed. The whole cycle was repeated until a consensus was reached about the optimal translation. In the next step, cognitive debriefing was performed, and after approval of the Persian version by FDLQI developers, it was distributed among 100 family members of dermatological patients in order to evaluate its validity and reliability. RESULTS: Mean age of participants was 37.1 years (±12.3). Mean score of FDLQI was 15.4 (±5.5) with maximum and minimum scores of 30 and 6, respectively. The quality of life of studied participants showed no significant difference based on age-group, sex, educational level and the family relationship. Cronbach's alpha was calculated as 0.87. Exploratory factor analysis revealed a one-factor solution that accounted for 40.7 % of the variance. The unidimensional model was supported by confirmatory factor analysis. CONCLUSIONS: The results of the present study showed that the Persian version of FDLQI has acceptable factorial validity and internal consistency reliability.

Infants' Dermatitis Quality of Life Index: a decade of experience of validation and clinical application.

The Infants' Dermatitis Quality of Life Index (IDQoL) is a questionnaire completed by parents to assess the impact of atopic dermatitis on the quality of life of infants aged 0-3 years. The aim was to review all clinical and psychometric data on the use of the IDQoL from its inception in 2001 until November 2012, to serve as a single reference source. A literature search was carried out using Medline, PubMed, EBSCOhost, Science Direct and Google Scholar. Articles and abstracts that described the clinical use of the IDQoL and those that investigated its psychometric properties were included. Articles not in English were excluded. Fifty-one publications were identified, of which 46 fulfilled the inclusion criteria. IDQoL data relating to psychometric, descriptive and clinical practice research, drug trials and therapeutic interventions were extracted. The IDQoL has been translated into 21 languages and used in 18 countries, including two multinational studies. Thirty-one studies demonstrated its psychometric properties, such as test-retest reliability, internal consistency, validity, responsiveness to change and interpretability. No studies investigated dimensionality, carried out factor analysis or described the minimal clinically important difference of the tool. Eight studies used the IDQoL to assess the effectiveness of therapeutic interventions such as education programmes, consultations and wet-wrap therapy, while seven studies described the use of IDQoL in topical interventions. When deciding whether to use the IDQoL, researchers and clinicians should consider the validation data, the relevant comparative clinical data available and the potential burden on the respondents.

The Dermatitis Family Impact questionnaire: a review of its measurement properties and clinical application.

The Dermatitis Family Impact (DFI) questionnaire is a disease-specific measure to assess the impact of atopic eczema on the quality of life (QoL) of the parents and family members of affected children. We set out to review the published literature and to collate data on the clinical and psychometric aspects of the DFI questionnaire from its development in 1998-2012, in order to create a single source of reference for users of the DFI. A literature search was performed of publications, including abstracts, describing the use of the DFI between 1998 and 2012. In total, we identified 53 publications (37 full articles and 16 abstracts) describing the use of the DFI in 50 studies. Only one study demonstrated test-retest reliability (r = 0 . 95). Three studies demonstrated internal consistency, with Cronbach α ranging from 0.85 to 0.90. Fifteen studies showed sensitivity to change of DFI scores, with significant differences between baseline and the end of the study. Twenty-six studies correlated the DFI to other objective and subjective instruments to demonstrate its construct (convergent) validity. Seventeen validated translations of the DFI have been used in 16 different countries (including two multinational studies). Nine clinical studies have assessed the effectiveness of five different topical drugs and one probiotic supplement. Two studies have assessed the effectiveness of care by dermatology nurses and dermatologists. The use of the DFI has revealed the major impact of atopic eczema on the QoL of families of affected children. The strengths of the DFI include wide international experience of its use, defined test-retest reliability, good internal consistency, sensitivity to change, and good construct (convergent) validity. Areas requiring further research include creation of validated score descriptors, assessment of minimum important clinical difference and testing of dimensionality, factor structure and differential item functioning.

Clinical experience and psychometric properties of the Children's Dermatology Life Quality Index (CDLQI), 1995-2012.

The Children's Dermatology Life Quality Index (CDLQI) is a widely used questionnaire to measure the quality of life of children aged from 4 to 16 years. The purpose of this review is to summarize all published data regarding the clinical experience of the CDLQI and its psychometric properties as a single reference source for potential users. A literature search was carried out to identify all articles describing the use of the CDLQI from 1995 to November 2012. One hundred and six articles were identified, with four excluded. The CDLQI has been used in 28 countries in 102 clinical studies and is available in 44 languages, including six cultural adaptations; a cartoon version is available in 10 languages. It has been used in 14 skin conditions and used in the assessment of 11 topical drugs, nine systemic drugs, 13 therapeutic interventions and two epidemiological and other studies. There is evidence of high internal consistency, test-retest reliability, responsiveness to change, and significant correlation with other subjective and objective measures. Rasch analysis has not been carried out and more information is needed concerning minimal clinically important difference; these are areas requiring further study.

Psychometric properties of the Chinese version of Dermatology Life Quality Index (DLQI) in 851 Chinese patients with psoriasis.

BACKGROUND: The Dermatology Life Quality Index (DLQI) is one of the most frequently used scales to evaluate the impact of skin disease on patients' quality of life (QoL). There has not been psychometric evaluation of the Chinese version of DLQI in Chinese patients with psoriasis. OBJECTIVE: The objective of this study was to evaluate the psychometric properties of the Chinese version of DLQI. METHODS: Patients with psoriasis (≥ 18 years old) visiting nine hospitals in various regions of China were enrolled in the study. The DLQI, Psoriasis Disability Index (PDI) and Health Survey Short Form (SF-36) were completed. Severity of psoriasis was assessed by the Psoriasis Area Severity Index (PASI). Reliability was estimated by internal consistency. Validity was assessed using known-groups comparison, convergent validity and construct validity. RESULTS: In all, 851 patients were included in the study. The internal consistency reliability of the DLQI was high (Cronbach's alpha = 0.91). Known-groups comparison showed that the DLQI discriminated well among patients who differed in age, geographical region, duration of psoriasis and the PASI score. Evidence of convergent validity of the DLQI was proved by high correlations with the PDI and four subscales of SF-36 (role-physical, bodily pain, social functioning and role-emotional): r = 0.52-0.78. Construct validity was proved by the presence of one-factor structure that accounted for 55.9% of the variance and fitted well into the unidimensional model. CONCLUSION: The Chinese version of DLQI is a reliable and valid measure to assess patient-reported impact of skin disease and could be used in QoL and health outcome studies on Chinese psoriasis patients.

Measurement of health-related quality of life in dermatological research and practice: outcome of the EADV Taskforce on Quality of Life.

In the last decade, the importance of the measurement of health-related quality of life (HRQoL) has grown significantly. Today, HRQoL measurement is generally considered to be important in clinical trials, in the assessment of disease severity, in patient management and in the field of health economics. Therefore, a good understanding of the concept of HRQoL and its measurement instruments is a prerequisite for both researchers and clinicians. The European Academy for Dermatology and Venereology (EADV) Taskforce on Quality of Life encourages the application of HRQoL instruments in research and clinical practice, and with this manuscript, the Taskforce aims to contribute to the quality of this application. In dermatology, a large number of HRQoL instruments exist and herewith, we summarize the most commonly used generic and dermatology-specific HRQoL instruments. Information is given on the most important psychometric characteristics of these instruments, including: scale structure, reliability, validity and responsiveness. Furthermore, a flow chart is provided to support researchers and clinicians in selecting an existing instrument or, in case an appropriate instrument does not exist, in finding alternative solutions. The present manuscript is the first of a series of manuscripts to be written on behalf of the EADV Taskforce on Quality of Life, aiming to contribute to the scientific knowledge and measurement of patient reported outcomes in dermatological research and practice.

The role of the EQ-5D in the economic evaluation of dermatological conditions and therapies.

Economic evaluation is an increasingly important aspect of assessment of the burden of skin diseases. Although dermatology data were not used in its development, the use of the EQ-5D questionnaire has been encouraged by the requirement of health technology assessment agencies for utility comparisons informing reimbursement decisions. The aim of this review was to examine the use of the EQ-5D in dermatology and to consider its future role in the economic evaluation of skin diseases. Published studies reporting the use of the EQ-5D in the economic analysis of skin diseases were carefully examined. Nineteen articles and 1 abstract published between 2003 and 2011 were identified, in which cost-of-illness, cost-effectiveness and cost-utility analyses were described. The EQ-5D is not a dermatology-specific measure, and it is not yet clear whether it is the most appropriate measure to support economic evaluation in the context of dermatology.

Can we reduce excision margins for head and neck melanoma? A 12-year retrospective study.

Although wide local excision is the standard treatment for primary melanoma, the surgical margin remains controversial. Melanomas of the head and neck exhibit higher recurrence rates and worse prognosis than lesions in other body locations, and their close proximity to critical anatomical and functional structures means that wide excision margins are often not feasible. Surgeons must therefore achieve a balance of oncological safety and functional and aesthetic needs. The aim of this study was to retrospectively analyse melanoma data over a 12-year period at a large skin surgery unit to identify potential differences in outcomes in patients who had reduced wide local excision margins for primary head and neck melanoma. The study would provide further evidence for the need for large randomised prospective trials to reduce excision margins for head and neck melanoma. Local cancer network data were retrospectively analysed over a period of 12 years (2008-2019). Data included site, initial stage, multidisciplinary team (MDT) meeting recommendations for excision margins and the actual wide local excision margin taken, recurrence rate, and disease-specific and absolute survival. A total of 222/305 patients (73%) had the recommended excision margin, while in 27% margins were reduced due to anatomical or functional considerations. Recurrence rates were similar (recommended 11.7% vs narrow 13.3% excision margins) (p = 0.64). The mean follow-up time for all patients was 48.5 months. In aesthetically and functionally sensitive areas of the head and neck, wide local excision margins need to be carefully considered after MDT discussion and discussion with the patient. This study suggests the need for further multicentre trials to address the uniqueness of head and neck melanoma.

Study of rare genetic variants in TM4SF20, NFXL1, CNTNAP2, and ATP2C2 in Pakistani probands and families with language impairment.

Language impairment (LI) is highly heritable and aggregates in families. Genetic investigation of LI has revealed many chromosomal regions and genes of interest, though very few studies have focused on rare variant analysis in non-English speaking or non-European samples. We selected four candidate genes (TM4SF20, NFXL1, CNTNAP2 and ATP2C2) strongly suggested for specific language impairment (SLI), a subtype of LI, and investigated rare protein coding variants through Sanger sequencing of probands with LI ascertained from Pakistan. The probands and their family members completed a speech and language family history questionnaire and a vocabulary measure, the Peabody Picture Vocabulary Test-fourth edition (PPVT-4), translated to Urdu, the national language of Pakistan. Our study aimed to determine the significance of rare variants in these SLI candidate genes through segregation analysis in a novel population with a high rate of consanguinity. In total, we identified 16 rare variants (according to the rare MAF in the global population in gnomAD v2.1.1 database exomes), including eight variants with a MAF <0.5 % in the South Asian population. Most of the identified rare variants aggregated in proband's families, one rare variant (c.*9T>C in CNTNAP2) co-segregated in a small family (PKSLI-64) and another (c.2465C>T in ATP2C2) co-segregated in the proband branch (PKSLI-27). The lack of complete co-segregation of most of the identified rare variants indicates that while these genes could be involved in overall risk for LI, other genes are likely involved in LI in this population. Future investigation of these consanguineous families has the potential to expand our understanding of gene function related to language acquisition and impairment.

Nonclinical influences, beyond diagnosis and severity, on clinical decision making in dermatology: understanding the gap between guidelines and practice.

BACKGROUND: Clinical decision making in dermatology is a complex process and might be influenced by a wide range of nonclinical factors. OBJECTIVES: The aim of this study was to explore the role of nonclinical influences, beyond diagnosis and severity, on clinical decision making in dermatology. METHODS: Semi-structured qualitative interviews were conducted with 46 clinicians working in departments of dermatology of nine different hospitals in Wales. Interviews were audio-recorded and later transcribed and their contents analysed. RESULTS: Nonclinical factors influencing patient management decisions in dermatology that were identified related to patients, clinicians and practice characteristics. Patient-related factors included place of residence, socioeconomic circumstances, education and intelligence, ethnicity, age, treatment adherence, expectations from treatment, quality of life, concerns and worries, difficult patients, and family members or friends. Clinician-related factors included time constraints in clinic, clinicians' personal circumstances, relationship with colleagues, and relationship with pharmaceutical companies. Practice-related factors included working in private practice, cost of treatment to the National Health Service (NHS), prescribing bureaucracy, and availability of treatment service in the work place. There was a difference between the consultants' views and those of the other clinicians over the impact of pharmaceutical companies on clinicians' prescribing and the awareness of treatment costs to the NHS. Most of the factors identified could potentially influence the clinicians' decision-making process subconsciously. Some clinicians highlighted that these factors are untaught in the medical curriculum, and are usually ignored in clinical guidelines, and therefore represent a challenge to the practice of evidence-based medicine. CONCLUSIONS: This study has described one aspect of the reality of medical decision making beyond the conventional evidence-based guidelines approach. Proper understanding of nonclinical influences on decision making is of paramount importance for the best patient-centred treatment outcomes.

Clinical decision making in dermatology: observation of consultations and the patients' perspectives.

BACKGROUND: Clinical decision making is a complex process and might be influenced by a wide range of clinical and non-clinical factors. Little is known about this process in dermatology. AIMS: The aim of this study was to explore the different types of management decisions made in dermatology and to identify factors influencing those decisions from observation of consultations and interviews with the patients. METHODS: 61 patient consultations were observed by a physician with experience in dermatology. The patients were interviewed immediately after each consultation. Consultations and interviews were audio recorded, transcribed and their content analysed using thematic content analysis. RESULTS: The most common management decisions made during the consultations included: follow-up, carrying out laboratory investigation, starting new topical treatment, renewal of systemic treatment, renewal of topical treatment, discharging patients and starting new systemic treatment. Common influences on those decisions included: clinical factors such as ineffectiveness of previous therapy, adherence to prescribing guidelines, side-effects of medications, previous experience with the treatment, deterioration or improvement in the skin condition, and chronicity of skin condition. Non-clinical factors included: patient's quality of life, patient's friends or relatives, patient's time commitment, travel or transportation difficulties, treatment-related costs, availability of consultant, and availability of treatment. CONCLUSION: The study has shown that patients are aware that management decisions in dermatology are influenced by a wide range of clinical and non-clinical factors. Education programmes should be developed to improve the quality of decision making.

The psoriasis family index: preliminary results of validation of a quality of life instrument for family members of patients with psoriasis.

BACKGROUND: Psoriasis can have a major impact on the lives of patients, the members of their families and their partners. OBJECTIVES: To develop and validate a disease-specific instrument to measure the secondary impact of psoriasis on the health-related quality of life (HRQoL) of family members of psoriasis patients. METHODS: The development of the new questionnaire involved a number of different stages: qualitative interviews with family members/partners, formulation of the first draft, refinement, initial validation, further refinement and finally revalidation of the questionnaire. RESULTS: Items for the measure were generated from the content analysis of interview transcripts. The psychometric evaluation of the final draft of the Psoriasis Family Index (PFI-15) was carried out in a new cohort of participants. The PFI-15 demonstrated high internal consistency (Cronbach's alpha = 0.86) and high test-retest reliability (intraclass correlation coefficient = 0.93). The construct validity was assessed by testing a number of a priori hypotheses about its construct; a moderate to strong correlation was seen between families' PFI scores and patients' Dermatology Life Quality Index scores (r = 0.54, p < 0.01) and Psoriasis Disability Index scores (r = 0.59, p < 0.01), and between families' PFI scores and patients' Psoriasis Area and Severity Index scores (r = 0.43, p < 0.01). CONCLUSIONS: The PFI is a simple and practical measure to assess the HRQoL of family members/partners of patients with psoriasis.

Adolescents with skin disease have specific quality of life issues.

BACKGROUND: Adolescence is a period of life with its own unique characteristics. OBJECTIVES: To provide an in-depth understanding of the impact of skin disease on different aspects of adolescents' health-related quality of life (HRQoL). METHODS: Semi-structured qualitative interviews were conducted with a sample of dermatology patients between 12 and 19 years of age, attending the dermatology outpatient clinic of a secondary referral centre. Participants were invited to talk in detail about all the ways their lives had been affected by their skin disease. Interviews were transcribed verbatim. RESULTS: Thirty-two adolescents (males = 10, females = 22) with a mean age of 15.7 years (range = 12-18 years) participated in the interviews. Twenty-eight HRQoL themes adversely affected by skin diseases were identified from the interviews which were grouped under 6 main HRQoL domains - psychological impact (91% of patients), physical impact (81%), social impact (81%), impact on lifestyle (63%), need for support (41%) and education and employment (34%). The number of HRQoL themes affected in each individual varied between 1 and 23 (mean = 8.1). CONCLUSIONS: The results of this study revealed the extent and nature of the impact of skin diseases on adolescents' HRQoL. A number of issues identified were specific to adolescents, highlighting the need for specific HRQoL assessment.

The Dermatology Life Quality Index 1994-2007: a comprehensive review of validation data and clinical results.

BACKGROUND: The Dermatology Life Quality Index (DLQI) is one of the most widely used dermatology-specific quality of life instruments. Over the last 5 years there has been great interest in its use. OBJECTIVES: To collect and present all information regarding the technical properties and the clinical use of the DLQI from the date it was published to the end of 2007 for use as a single source of reference. METHODS: A detailed literature search was conducted using electronic reference databases and the DLQI library in the Department of Dermatology, Cardiff University. All publications mentioning any aspect of the DLQI, from the time of its development to the end of 2007, were identified and the data concerning the DLQI in terms of its psychometric analysis, and use in clinical trials, epidemiological studies and health services research, were extracted and tabulated with all the relevant references. RESULTS: In total, 272 full articles which have included the DLQI were reviewed. Studies described in these articles were divided into five main categories: psychometric studies, descriptive/epidemiological studies, drug (topical and systemic) trials, clinical practice research, and therapeutic interventions. The DLQI has been used in 33 different skin conditions in 32 countries and is available in 55 languages. Psychometric aspects of the DLQI such as validity, reliability, responsiveness to change, factor structure, and minimal important difference were described in 115 studies. The DLQI has been used in 33 studies assessing the effectiveness of 14 different types of therapeutic interventions and in 37 studies evaluating nine types of clinical practice research. Sixty studies have used it alone or in parallel with other instruments as an outcome measure in clinical trials of 18 systemic drugs while 22 studies have used it in 14 different topical drug trials. The DLQI has also been used in 27 multinational studies. CONCLUSIONS: During the last 14 years there has been a gradual increase in the international use of the DLQI. The brevity and simplicity of use of the DLQI has resulted in its popularity both in clinical practice and in research. However, there are various issues in particular regarding its unidimensionality, differential item functioning, and minimal clinically important difference, which require further research. This article should facilitate the work of potential users of the DLQI by providing a readily available source of references for different aspects of the DLQI.