Lipofibromatosis-like neural tumors: Report of a case and review of 73 reported cases.

Lipofibromatosis-like neural tumors (LPF-NTs) are a recently discovered group of spindle cell tumors defined by the presence of a lipofibromatosis-like pattern, CD34 and/or S100 reactivity, and frequent neurotrophic receptor tyrosine kinase 1 (NTRK1) gene rearrangements. As new cases emerge, the spectrum of features observed in LPF-NTs continues to evolve. Here we describe the case of an 11-year-old with LPF-NT with a dermatofibrosarcoma protuberans-like honeycomb pattern, CD34 and S100 co-expression, and an NTRK1 rearrangement. We also review the clinical and molecular features of the 73 cases of LPF-NT previously described in the literature.

Validity and reliability of Patient-Reported Outcomes Measurement Information System Global Health scale in adults with atopic dermatitis.

BACKGROUND: Patient-Reported Outcomes Measurement Information System Global Health (PGH) was validated to assess health-related quality of life in several diseases. Little is known about its measurement properties in adult atopic dermatitis. OBJECTIVE: Examine the measurement properties of PGH in adult atopic dermatitis. METHODS: A prospective dermatology practice-based study of 994 atopic dermatitis patients (18-97 years). RESULTS: PGH physical and mental health 4-item and abridged 2-item T scores, as well as mapped EuroQol-5D score, showed strong to very strong correlation with one another and moderate to strong Spearman correlations with Patient-Oriented Scoring Atopic Dermatitis, Patient-Health Questionnaire-9, Patient-Reported Outcomes Measurement Information System sleep disturbance and related impairment, Eczema Area and Severity Index, objective Scoring Atopic Dermatitis; and weak to moderate correlations with Patient Oriented Eczema Measure, numeric rating scale worst itch and average itch, and Scoring Atopic Dermatitis. The Dermatology Life Quality Index (DLQI) had stronger correlations with Patient Oriented Eczema Measure, Patient-Oriented Scoring Atopic Dermatitis, numeric rating scale worst itch and average itch, Eczema Area and Severity Index, and Scoring Atopic Dermatitis, but weaker correlations with Patient-Health Questionnaire-9 and Patient-Reported Outcomes Measurement Information System sleep disturbance and related impairment (convergent/divergent validity). PGH and DLQI scores had similarly poor ability to differentiate between levels of self-reported global atopic dermatitis severity (known-groups validity). No floor or ceiling effects were observed. No PGH or DLQI items had differential item functioning by demographics. PGH and DLQI scores showed fair to good responsiveness. Finally, PGH and DLQI showed similarly good test-retest reliability. LIMITATIONS: Single-center study. CONCLUSION: PGH scores had sufficient validity and reliability to assess health-related quality of life in atopic dermatitis.

Measurement Properties of Patient Health Questionnaire 9 and Patient Health Questionnaire 2 in Adult Patients With Atopic Dermatitis.

BACKGROUND: Few outcome measures were validated for assessing depressive symptoms in AD. Patient Health Questionnaire-9 (PHQ9) and the abridged PHQ2 are established patient-reported outcome measures of depressive symptoms. OBJECTIVE: We sought to examine the measurement properties of PHQ9 and PHQ2 in adult AD. A prospective dermatology-practice based study of 458 AD patients (age 18-97 years) was conducted. RESULTS: PHQ9 strongly correlated with Dermatology Life Quality Index, Patient-Reported Outcomes Measurement Information System (PROMIS) Sleep-Disturbance and Sleep-Related Impairment, and PROMIS Itch Questionnaire Mood and Sleep (PIQ-MS), and moderately correlated with Patient-Oriented Eczema Measure, Numeric Rating Scale (NRS) average-itch, NRS-sleep, Eczema Area and Severity Index, Scoring AD and Rajka-Langeland scores. PHQ2 had significantly weaker correlations than PHQ9 with PROMIS SD, SRI and PIQ-MS, but similar correlations with other outcomes. PHQ9 and PHQ2 had good discriminant validity. Changes from baseline in PHQ9 and PHQ2 were poorly or weakly correlated with changes of the other outcome measures. There was no differential item functioning of PHQ items. PHQ9 showed good reliability (intraclass correlation coefficient range: 0.80-0.87). PHQ2 had slightly lower reliability (0.76-0.82). CONCLUSIONS: PHQ9 and PHQ2 had similar measurement properties, but PHQ2 was more feasible to assess depressive symptoms in AD.

Prevalence of asthma in patients with atopic dermatitis: A systematic review and meta-analysis.

BACKGROUND: It is well established that asthma is common in patients with atopic dermatitis (AD). OBJECTIVES: We performed a systematic review and meta-analysis to determine the prevalence of asthma and respiratory symptoms in individuals with AD as well as the association between AD and asthma. METHODS: At least 2 authors independently searched the medical databases PubMed, EMBASE, LILACS, and SCOPUS for all English-language studies with data on asthma prevalence among patients with AD or the association between AD and asthma. Pooled odds ratios with 95% confidence intervals (CIs) and pooled proportions were estimated with random-effects models. The Newcastle-Ottawa scale was used to assess study quality. RESULTS: The search yielded 39,503 articles. Of these, 213 studies were included in a quantitative analysis. The overall pooled prevalence of asthma was 25.7% (95% CI, 23.7-27.7) in patients with AD and 8.1% (95% CI, 7.0-9.4) among reference individuals. There was a significant association between AD and asthma when compared with reference individuals (odds ratio, 3.03; 95% CI, 2.64-3.47). LIMITATIONS: The definitions of AD and asthma differed across the included studies and varied from self-report to physician diagnosed. CONCLUSIONS: Asthma is a common comorbidity of AD. Physicians should be cognizant of this relationship and address asthma symptoms in their patients.

Measurement Properties of 4 Patient-Reported Outcome Measures to Assess Sleep Disturbance in Adults With Atopic Dermatitis.

BACKGROUND: The ideal patient-reported outcome measure to assess sleep disturbance in atopic dermatitis (AD) has not been determined. OBJECTIVE: We sought to determine the measurement properties of the Patient-Reported Outcomes Measurement Information System (PROMIS) Itch Questionnaire Mood and Sleep (PIQ-MS), Sleep Disturbance (SD), Sleep-Related Impairment (SRI), and Epworth Sleepiness Scale (ESS) in adults with AD. METHODS: A prospective dermatology practice-based study was performed using questionnaires and evaluation by a dermatologist (n=611). RESULTS: PIQ-MS, PROMIS SD, SRI, and ESS had good convergent validity with intensity and frequency of sleep disturbance, Patient-Oriented Eczema Measure, Eczema Area and Severity Index, total and objective-Scoring AD, Numerical Rating Scale of worst-itch and average-itch, and Dermatology Life Quality Index. PIQ-MS had significantly better correlations with other severity measures than the other sleep measures (Fisher z-scores, P≤0.007). PIQ-MS, and to lesser extent PROMIS SD, PROMIS SRI and ESS had good discriminant validity. All four sleep assessments showed fair responsiveness to change of severity of sleep-disturbance, AD and itch. PIQ-MS had the best reliability. PIQ-MS, PROMIS SD, SRI and ESS showed good internal consistency and were feasible for use in clinical practice. CONCLUSIONS: PIQ-MS, followed by PROMIS SD, had the best construct validity and reliability in adult AD.

Association of itch triggers with atopic dermatitis severity and course in adults.

BACKGROUND: Atopic dermatitis (AD) is associated with heterogeneous triggers of itch, which may affect AD course and severity. OBJECTIVE: To characterize the triggers of itch in adult AD. METHODS: This was a prospective dermatology practice-based study using questionnaires and evaluation by a dermatologist (n = 587). Thirteen itch triggers were assessed using the patient-reported outcomes measurement information system Itch-Triggers. RESULTS: Overall, 381 (64.9%) patients reported greater than or equal to 1 itch trigger in the past week and 212 (36.1%) reported greater than or equal to 3 itch triggers. The most commonly reported triggers were stress (35.4%), sweat (30.5%), weather change (24.7%), dry air (24.4%), and heat (24.0%). In multivariable Poisson regression models, the number of itch triggers was associated with more severe patient-reported global AD severity, Numeric Rating Scale worst itch, Patient-Oriented Eczema Measure, Scoring Atopic Dermatitis sleep, Numeric Rating Scale skin pain, Eczema Area and Severity Index, and objective Scoring Atopic Dermatitis. The seasonality of AD was associated with distinct itch triggers. In multivariable logistic regression models, the number of itch triggers was associated with less than or equal to 3 months of AD remission during the year, greater than or equal to 2 AD flares, and AD being worse during some seasons. Four patterns of itch triggers were identified using latent class analysis, each associated with different clinical characteristics. CONCLUSION: Itch triggers are common and affect the course of AD. Itch triggers are an important end point to assess in patients with AD.

Association of atopic dermatitis severity with cognitive function in adults.

BACKGROUND: Atopic dermatitis (AD) is associated with itch, pain, and sleep disturbance, all of which may contribute toward cognitive dysfunction. OBJECTIVE: To determine the relationship of AD severity and cognitive function in adults. METHODS: We performed a prospective dermatology practice-based study using questionnaires and evaluation by a dermatologist (n = 386). Cognitive function was assessed using the Patient-Reported Outcomes Measurement Information System (PROMIS) Cognitive Function 8-item Short-Form. RESULTS: At baseline, 118 patients (58.1%) reported ≥1 symptoms of cognitive dysfunction in the past 4 weeks, with 29 (14.3%) having mild, 11 (5.4%) moderate, and 4 (2.0%) severe PROMIS Cognitive Function T-scores. In propensity score-weighted regression models, PROMIS Cognitive Function T-scores were inversely associated with patient-reported global AD severity, Patient Oriented Eczema Measure (POEM), Numeric Rating Scale worst itch and skin pain, SCORing Atopic Dermatitis (SCORAD)-sleep, POEM-sleep, Eczema Area and Severity Index, and SCORAD, with stepwise decreases of cognitive function with worsening AD severity. At all AD severity levels, cognitive dysfunction was associated with increased Dermatology Life Quality Index and ItchyQoL scores. Changes from baseline in PROMIS Cognitive Function T-scores were weakly to moderately inversely correlated with changes from baseline in multiple AD outcomes. LIMITATIONS: Single-center study without non-AD controls. CONCLUSION: Cognitive dysfunction is associated with AD severity. Cognitive function may be an important end point for monitoring treatment response in AD.

Comparison of Patient-Oriented Eczema Measure and Patient-Oriented Scoring Atopic Dermatitis vs Eczema Area and Severity Index and other measures of atopic dermatitis: A validation study.

BACKGROUND: Little is known about the measurement properties of Patient-Oriented Scoring Atopic Dermatitis (PO-SCORAD) in adults with atopic dermatitis (AD). Even less is known about how PO-SCORAD performs compared with the Patient-Oriented Eczema Measure (POEM). OBJECTIVE: To examine the measurement properties of PO-SCORAD and compare them with those of POEM. METHODS: A prospective dermatology practice-based study of 291 patients with AD (age range, 18-72 years). RESULTS: PO-SCORAD and POEM were moderately correlated with each other (Spearman ρ = 0.56) and had weak-moderate correlations with the Numeric Rating Scale (NRS) worst itch and average itch, Dermatology Life Quality Index (DLQI), ItchyQOL, Patient-Reported Outcomes Measurement Information System (PROMIS) Sleep Disturbance (SD) and Sleep-Related Impairment (SRI), Patient Health Questionnaire-9 (PHQ-9), and Eczema Area and Severity Index (EASI) (P < .001). POEM had significantly stronger correlations with DLQI, ItchyQOL, and EASI than did PO-SCORAD. PO-SCORAD and POEM had fair discriminant validity. Changes from baseline in PO-SCORAD and POEM were moderately correlated with each other; were weakly to strongly correlated with NRS worst itch and average itch, DLQI, ItchyQOL, PROMIS SD, PROMIS SRI, PHQ-9, and EASI; and had good test-retest reliability. There was no differential item functioning of items or floor or ceiling effects for PO-SCORAD or POEM. The thresholds for meaningful change for PO-SCORAD and POEM were -15.5 and -5.0, respectively. Median completion times for PO-SCORAD and POEM were 3 minutes and 1 minute, respectively. CONCLUSION: PO-SCORAD and POEM had good construct and cross-cultural validity, reliability, and responsiveness in adults with AD and were feasible for use in clinical trials and practice. However, POEM had better measurement properties than PO-SCORAD.

Association of prurigo nodularis and lichen simplex chronicus with hospitalization for mental health disorders in US adults.

Prurigo nodularis (PN) and lichen simplex chronicus (LSC) are debilitating chronic pruritic diseases that can lead to and be exacerbated by psychosocial distress. However, little is known about the mental health (MH) comorbidities of PN/LSC. We sought to evaluate the likelihood and cost-burden of MH comorbidities and emergencies associated with PN/LSC. Data were examined from the 2002-2012 Nationwide Inpatient Sample, including a representative ~ 20% sample of US hospitalizations (n = 87,053,155 admissions). Inpatients with vs. without PN/LSC had higher odds of MH disorders overall (39.4% vs. 20.0%; adjusted odds ratio [95% confidence interval, CI] 2.26 [2.13-2.41]) and in all 15 individual MH disorders examined. Inpatients with vs. without PN/LSC were more likely to be admitted with a primary diagnosis of a MH disorder (4.5% vs. 2.2%; 2.16 [1.91-2.45]), particularly developmental, psychotic, and mood disorders, history of MH disorders or substance abuse, and cognitive disorders. PN/LSC were associated with prolonged inpatient length of stay, and an excess $0.69 million in inpatient costs of care indirectly related to hospitalization for MH disorders. In conclusion, inpatients with PN/LSC had increased likelihood of comorbid MH disorders and emergencies requiring hospitalization. Optimized approaches are needed for screening and managing MH comorbidities in PN/LSC.

Risks for noncutaneous second primary malignancy in cutaneous malignant melanoma survivors: an analysis of data from the Surveillance, Epidemiology, and End Results (SEER) program.

BACKGROUND: It is known that malignant melanoma (MM) survivors are at increased risk of future primary MM. However, the risk for noncutaneous second primary malignancies (SPMs) is not as well-understood. METHODS: An observational study utilizing data from the Surveillance, Epidemiology, and End Results (SEER) database was performed, assessing data from patients diagnosed with primary cutaneous MM to measure overall, as well as specific, tumor type and risk of SPM. RESULTS: Of the 132,438 patients recruited in the study population (mean age 55.5 years; 54% male), 23,794 SPMs were observed (O) (18% of patients at a mean age of 68.8 years), while 17,923 SPMs were expected (E) to occur (O : E 1.33, 95% CI 1.31-1.34). Excluding cutaneous MM occurring as a new primary malignancy, there was a significantly increased risk for SPMs among cutaneous MM survivors for each of the following tumor types: eye and orbit melanoma, tracheal, thyroid, salivary gland, retroperitoneum, small intestine, kidney, lymphoid and hematopoietic system, lymphoma overall, non-Hodgkin lymphoma, lymphocytic leukemia overall, chronic lymphocytic leukemia, male genital system (including prostate), and breast. Certain gender-specific trends for SPMs were also detected. CONCLUSIONS: Patients with primary cutaneous MM are at increased risk for primary noncutaneous MM as well as noncutaneous SPMs that include numerous tumor types. Enhanced oncologic surveillance for a variety of tumor types in melanoma survivors is warranted.

Placebo responses in randomized controlled trials for systemic therapy in atopic dermatitis: A systematic review and meta-analysis.

BACKGROUND: Atopic dermatitis (AD) has a variable disease course and intermittent triggers, and responses to topical therapy vary, potentially affecting the magnitude of the placebo response in AD trials. OBJECTIVE: To determine the predictors of increased placebo response in randomized controlled trials of AD. METHODS: We performed a systematic review and meta-analysis of randomized controlled trials for systemic therapy in AD published during 2007-2018. We searched the Cochrane Library, Medline, Embase, Global Resource for EczemA Trials (GREAT), Literature of the Latin American and Caribbean Health Sciences (LILACS), and Scopus. Two authors performed study selection and data extraction. Multivariable mixed models were constructed for Cohen D of Eczema Area and Severity Index (EASI), SCORing Atopic Dermatitis (SCORAD), numeric rating scale (NRS)-itch and visual analog scale (VAS)-itch, and Dermatology Life Quality Index (DLQI). RESULTS: Overall, 64 trials were included. Use of concomitant topical therapy prescriptions, study duration ≥3 months, and fewer treatment arms were associated with an increased placebo response for EASI, NRS- and VAS-itch, and DLQI. For EASI, the placebo response was increased in studies with a higher proportion of male patients, mild-moderate mean baseline EASI scores, and no blinding. For NRS-itch, and VRS-itch, higher placebo responses were associated with higher proportions of male patients and moderate-severe mean itch scores at baseline. CONCLUSION: Placebo responses can be reduced in clinical trials of systemic therapy in AD by incorporating double- and triple-blinding, balancing the sex distribution of patients, disallowing concomitant use of prescription topical therapy, and having shorter study durations.

Validation of four single-item patient-reported assessments of sleep in adult atopic dermatitis patients.

BACKGROUND: The optimal approaches for monitoring sleep disturbances in adults with atopic dermatitis (AD) is not established. Multiple patient-reported outcome measures for AD and itch have sleep-related items. These items have not been validated previously. OBJECTIVE: Assess the measurement properties of sleep-related items from the Patient-Oriented Eczema Measure (POEM), SCORing AD (SCORAD), 5-dimensions of itch (5D), and ItchyQOL in adults with AD. METHODS: We performed a prospective dermatology practice-based study using questionnaires and evaluation by a dermatologist (n = 115). RESULTS: There was modest overlap and weak-moderate concordance of responses to the different assessments. Regarding concurrent validity, POEM-sleep, SCORAD-sleep, 5D-sleep, and ItchyQOL-sleep showed moderate correlations with each other. Regarding convergent validity, all items showed moderate correlation with total POEM, but weak correlations with Eczema Area and Severity Index (EASI), objective and total SCORAD, moderate to strong correlations with mean ItchyQOL and Dermatology Life Quality Index (DLQI), but poor or no significant correlation with Numeric Rating Scale (NRS) for worst or average itch. Regarding discriminant validity, all items showed significant and stepwise increases with increasing self-reported and physician-reported AD severity (Kruskal-Wallis, P < .01 for all). Floor effects were observed for POEM-sleep (n = 53, 46.1%), SCORAD-sleep (n = 28, 24.4%), 5D-sleep (n = 41, 35.7%), and ItchyQOL-sleep (n = 33, 28.7%); no ceiling effects were observed. Change in sleep-related item scores showed moderate strong correlations with change in POEM, 5Ditch, mean ItchyQOL, DLQI, objective and total SCORAD, and EASI, but inconsistent correlations with change of itch severity. CONCLUSION: Sleep-related items from POEM, SCORAD, 5D and ItchyQOL showed good validity and responsiveness to monitor sleep disturbances in adult AD patients.

Measurement properties of the Patient-Reported Outcomes Measurement Information System Itch Questionnaire item banks in adults with atopic dermatitis.

BACKGROUND: The Patient-Reported Outcomes Measurement Information System (PROMIS) Itch Questionnaire (PIQ) was recently developed. OBJECTIVE: To validate PIQ short forms in adults with AD. METHODS: Self-administered questionnaires and skin examinations were performed in 239 adults with atopic dermatitis (AD) in a dermatology practice setting. RESULTS: PIQ items had good content validity. PIQ item bank T-scores strongly correlated with each other, moderately correlated with numeric and verbal rating scales for worst or average itch and with itch frequency, moderately to strongly correlated with patient-oriented eczema measure, and weakly to moderately correlated with the Eczema Area and Severity Index and Objective-Scoring AD (Spearman correlations, P < .0001). There were significant and stepwise increases of T-scores for all item banks with increasing patient-reported global severity (Wilcoxon rank sum test, P < .0001). However, there was limited ability to discriminate between the lowest or highest 2 levels of AD or itch severity. Item banks showed good internal consistency (Cronbach α, 0.91-0.95). No differential item functioning was identified by age, sex, race/ethnicity, or educational level. There were floor effects for total scores, particularly in almost clear/mild AD or itch. LIMITATIONS: Single-center study. CONCLUSIONS: PIQ item bank short forms showed good content and construct validity and are feasible for potential use in clinical trials and practice.

Association between hidradenitis suppurativa, depression, anxiety, and suicidality: A systematic review and meta-analysis.

BACKGROUND: Previous studies found conflicting results about whether hidradenitis suppurativa (HS) is associated with depression or anxiety. OBJECTIVES: To determine the relationship of HS with depression and anxiety. METHODS: A systematic review was performed of published observational studies in MEDLINE, PubMed, Embase, Global Resource for Eczema Trials (GREAT), Latin American and Caribbean Health Sciences Literature (LILACS), Cochrane, Scopus, and PsychInfo that analyzed depression or anxiety in HS. Two reviewers performed title/abstract review and data extraction. Meta-analysis was performed with random-effects weighting. RESULTS: Thirty-eight studies met inclusion criteria; 27 had sufficient data for meta-analysis. The prevalences of depression (26.5% vs 6.6%) and anxiety (18.1% vs 7.1%) were higher in persons with versus without HS. Patients with HS had higher odds of depression in 12 of 13 studies and pooled analysis (odds ratio, 2.54; 95% confidence interval, 2.15-3.01), and anxiety in 6 of 6 studies and pooled analysis (odds ratio, 2.00; 95% confidence interval, 1.66-2.42). Similar results were found in sensitivity analyses for different methods of HS diagnosis (physician diagnosed and chart review) and control groups (healthy and dermatologic control individuals). HS was associated with higher antidepressant and anxiolytic use and with suicidality, but not mean depression and anxiety scale scores. LIMITATIONS: Individual-level data were unavailable. CONCLUSIONS: Patients with HS have higher odds of depression, anxiety, and suicidality.

Association of Psoriasis with Psychiatric Hospitalization in United States Children and Adults.

BACKGROUND: Psoriasis is associated with psychosocial distress. Little is known about the relationship between psoriasis and mental health (MH) emergencies. OBJECTIVE: To examine the associations of psoriasis and MH hospitalizations in the USA. METHODS: Data from the 2002-2012 National Inpatient Sample were analyzed, including an approximately 20% sample of all US hospitalizations (n = 87,053,155 children and adults). RESULTS: Hospitalization for MH disorders occurred more commonly in those with psoriasis compared to those without psoriasis (4.04 vs. 2.21%). In multivariable logistic regression models, psoriasis was associated with higher odds of admission for any MH disorder overall (adjusted odds ratio [95% confidence interval]: 2.32 [2.24-2.41]), as well as 9 of the 15 MH-specific disorders examined. Associated MH disorders included: anxiety, schizophrenia, personality disorder, depression, substance use disorders, history of MH disorder, alcohol-related disorders, adjustment disorders, and cognitive disorders. Children with versus those without psoriasis were also more likely to have a primary hospitalization for any MH disorder (2.82 [2.24-3.56]). Psoriasis inpatients were also more likely to have a primary hospitalization for any MH disorder compared to those with alopecia areata (1.99 [1.45-2.74]) or hidradenitis suppurativa (3.97 [3.49-4.52]). Psoriasis patients hospitalized with any MH disorder had higher mean [95% confidence interval] cost of inpatient care (USD 11,004 [10,846-11,241] vs. 9,547 [8,730-10,364]; p < 0.0001) compared to those without psoriasis, with USD 1,610,860 excess costs annually, with the majority of the costs coming from depression and mood disorders. CONCLUSIONS: Children and adults with psoriasis had increased hospitalization for multiple MH disorders, which were associated with a considerable financial burden.

Association between atopic dermatitis, depression, and suicidal ideation: A systematic review and meta-analysis.

BACKGROUND: Atopic dermatitis (AD) is associated with psychologic distress. However, previous studies found conflicting results about whether AD is associated with increased depression or suicidality. OBJECTIVES: To determine the complex relationship between AD and depression. METHODS: A systematic review of all published observational studies in the MEDLINE, PubMed, Embase, Global Resource for Eczema Trials (GREAT), Latin American and Caribbean Health Sciences (LILACS), the Cochrane Library, Scopus, and PsychInfo databases that analyzed depression in AD was performed. Two reviewers performed study title and/or abstract review and data abstraction. Pooled meta-analysis was performed by using random-effects weighting. RESULTS: Overall, 106 studies met the inclusion criteria; 36 had sufficient data for meta-analysis. The prevalence of any depression was higher in persons with versus without AD (20.1% vs 14.8%). Similar results were found in sensitivity analyses of studies assessing clinical depression, depressive symptoms, and adults; studies with healthy controls; and studies of low and high study quality. AD was associated with significantly higher depression scale scores, parental depression, antidepressant use, and suicidality. No publication bias was detected. LIMITATIONS: Individual-level data were not available. CONCLUSIONS: Patients with AD have higher odds of depression and suicidality.