A comparison of physical function instruments in psoriatic arthritis: HAQ-DI vs MDHAQ vs PROMIS10 global physical health.

OBJECTIVES: Physical function is a core outcome in PsA. We examined the construct validity and responsiveness of three commonly used instruments to assess physical function in PsA: HAQ disability index (HAQ-DI), MultiDimensional HAQ (MDHAQ) and the Patient-Reported Outcomes Measurement Information System (PROMIS®) Global-10. METHODS: Between 2016 and 2019, patients with PsA were enrolled in the Psoriatic Arthritis Research Consortium longitudinal cohort study in the USA. Correlations were calculated at baseline and among change scores using Spearman's correlation coefficient. Standardized response means were calculated. Agreement with the 20% improvement cut-off was used to determine the potential effect of using MDHAQ or the PROMIS Global-10 physical health (GPH) subscore in place of HAQ-DI when assessing the ACR20. RESULTS: A total of 274 patients were included in the analysis. The mean age of patients was 49 years and 51% were male. At baseline, the mean HAQ-DI was 0.6 (s.d. 0.6; range 0-3), the mean MDHAQ was 1.8 (s.d. 1.6; range 0-10) and the mean GPH T-score was 43.4 (s.d. 9.3; range 0-100). All three instruments were strongly correlated at baseline (rho 0.75-0.85). Change scores were moderately correlated (rho 0.42-0.71). Among therapy initiators, the mean change between two visits in HAQ-DI, MDHAQ and GPH was -0.1 (s.d. 0.4), -0.2 (s.d. 1.2) and 2.5 (s.d. 6.1), respectively. The standardized response means were 0.18, 0.16 and 0.41, respectively. CONCLUSION: The three instruments tested are not directly interchangeable but have overall similar levels of responsiveness.

Systematic review and meta-analysis of local recurrence rates of head and neck cutaneous melanomas after wide local excision, Mohs micrographic surgery, or staged excision.

BACKGROUND: Prospective trials have not compared the local recurrence rates of different excision techniques for cutaneous melanomas on the head and neck. OBJECTIVE: To determine local recurrence rates of cutaneous head and neck melanoma after wide local excision (WLE), Mohs micrographic surgery (MMS), or staged excision. METHODS: A systematic review of PubMed, EMBASE, and Web of Science identified all English case series, cohort studies, and randomized controlled trials that reported local recurrence rates after surgery for cutaneous head and neck melanoma. A meta-analysis utilizing a random effects model calculated weighted local recurrence rates and confidence intervals (CI) for each surgical technique and for subgroups of MMS and staged excision. RESULTS: Among 100 manuscripts with 13,998 head and neck cutaneous melanomas, 51.0% (7138) of melanomas were treated by WLE, 34.5% (4826) by MMS, and 14.5% (2034) by staged excision. Local recurrence rates were lowest for MMS (0.61%; 95% CI, 0.1%-1.4%), followed by staged excision (1.8%; 95% CI, 1.0%-2.9%) and WLE (7.8%; 95% CI, 6.4%-9.3%). LIMITATIONS: Definitions of local recurrence varied. Surgical techniques included varying proportions of invasive melanomas. Studies had heterogeneity. CONCLUSION: Systematic review and meta-analysis show lower local recurrence rates for cutaneous head and neck melanoma after treatment with MMS or staged excision compared to WLE.

Stigmatizing attitudes toward persons with psoriasis among laypersons and medical students.

BACKGROUND: Perceived stigma among patients with psoriasis contributes to poor quality of life. OBJECTIVE: To determine the prevalence and predictors of stigmatizing attitudes toward persons with psoriasis among laypersons and medical trainees. METHODS: Laypersons were recruited from Amazon.com's Mechanical Turk (MTurk) (n = 198). Additionally, 187 medical students were recruited via e-mail. Participants completed an online survey in which they viewed images of persons with visible psoriasis. Participants reported their desire to socially avoid the persons in the images, their emotional responses to the persons in the images, and their endorsement of psoriasis-related stereotypes and myths. RESULTS: MTurk participants endorsed social avoidance items such as not wanting to shake hands with (39.4%) or have the persons in the images in their home (32.3%). Participants stereotyped persons with psoriasis as contagious (27.3%) and endorsed the myth that psoriasis is not a serious disease (26.8%). Linear regression analyses showed that having heard of or knowing someone with psoriasis predicted fewer stigmatizing attitudes (P < .05). The medical students reported less stigmatizing attitudes than the MTurk participants (P < .01). LIMITATIONS: Self-report, single-institution study. CONCLUSION: Stigmatizing views of persons with psoriasis are prevalent among people in the United States. Educational campaigns for the public and medical trainees may reduce stigma toward persons with psoriasis.

Lack of association of biologic therapy for psoriasis with psychiatric illness: An electronic medical records cohort study.

BACKGROUND: Psoriasis and biologic therapies have been associated with psychiatric illnesses. OBJECTIVE: To determine if persons with psoriasis or those exposed to biologics are more likely to develop a psychiatric illness. METHODS: Retrospective electronic medical records cohort study. RESULTS: Individuals with psoriasis were significantly more likely to have a history of several medical (eg, cardiovascular illnesses) and psychiatric (eg, depression, suicide) illnesses than those without psoriasis. Those with psoriasis who were prescribed a biologic therapy were significantly less likely than those with psoriasis not prescribed a biologic agent to receive a psychiatric illness diagnosis (hazard ratio for any psychiatric illness 0.52, 95% confidence interval 0.51-0.53, P < .0001). With respect to any psychiatric illness, this finding was confirmed when comparing biologic therapy versus methotrexate treatment (0.80, 95% confidence interval 0.76-0.84, P < .0001). LIMITATIONS: These findings were likely attributable to treatment selection bias. CONCLUSION: Individuals with psoriasis have an increased risk of several medical and psychiatric illnesses. Individuals with psoriasis prescribed biologic agents are less likely than those not prescribed biologic agents to develop psychiatric illnesses. Most likely because of treatment selection, individuals with psoriasis prescribed biologic therapy are not currently at increased risk of a psychiatric outcome.

Prevalence of clinically significant incidental findings by whole-body fludeoxyglucose F 18 positron emission tomography/computed tomography scanning in moderate-to-severe psoriasis patients participating in clinical trials.

BACKGROUND: There has been an increase in the number of psoriasis treatments being investigated in clinical trials. Patients may have undiagnosed issues at the start of a study which may become identified during follow-up as incident medicinal conditions. The prevalence of incidental findings in patients with moderate-to-severe psoriasis presenting for clinical trials is unknown. OBJECTIVE: Determine the prevalence of incidentalomas and rate of malignancy identified by fludeoxyglucose F 18 (FDG) positron emission tomography/computed tomography (PET/CT) imaging in clinical trial patients with moderate-to-severe psoriasis. METHODS: A cross-sectional secondary analysis of patients with moderate-to-severe psoriasis who underwent FDG PET/CT scans at the baseline visit, before randomization, for 3 phase 4 clinical trials on vascular inflammation in psoriasis. Only patients without active infection, malignancy, or uncontrolled comorbidities were eligible for the clinical trials. RESULTS: A total of 259 healthy patients with moderate-to-severe psoriasis underwent an FDG PET/CT scan as part of the study procedures. In all, 31 patients (11.97%) (95% confidence interval [CI], 8.28-16.56) had clinically significant incidentalomas on the baseline FDG PET/CT scan. Univariate logistic regression demonstrated that with every increase of 10 years of age, there was an approximate 30% increased risk of discovery of an incidentaloma (odds ratio, 1.30; 95% CI, 1.01-1.68). Of those patients with findings suggestive of malignancy (n = 28), 6 were confirmed to have cancer, resulting in a 2.31% (95% CI, 0.9-5.0) prevalence of malignancy. The positive predictive value of a true cancer was 31.58% (range, 21%-54%). LIMITATIONS: Generalizability and lost to follow-up. CONCLUSION: Incidentalomas on FDG PET/CT imaging are common in otherwise healthy, asymptomatic patients with moderate-to-severe psoriasis in clinical trials. Our results can help inform interpretation of clinical trial safety data and emphasize the importance of compliance with cancer screening recommendations.

Patient-reported outcomes of adalimumab, phototherapy, and placebo in the Vascular Inflammation in Psoriasis Trial: A randomized controlled study.

BACKGROUND: There are limited data about the impact of narrowband ultraviolet B phototherapy on patient-reported measures of health-related quality of life. OBJECTIVE: To evaluate the impact of adalimumab and phototherapy on health-related quality of life. METHODS: We examined patient-reported outcomes from a multicenter, randomized, placebo-controlled trial (ClinicalTrials.gov no. NCT01553058). The Dermatology Life Quality Index and EQ-5D-3L were evaluated every 4 weeks. RESULTS: We enrolled 97 patients: 30.9% were female, mean age was 43.5 years (standard deviation, 14.0), and median Psoriasis Area and Severity Index score was 16.7 (interquartile range, 13.9-21.6). At week 12, patients being treated with adalimumab (odds ratio [OR], 2.88; 95% confidence interval [CI], 1.02-8.17) and phototherapy (OR, 8.83; 95% CI, 2.47-31.57) were more likely to achieve the minimal clinically important difference in the Dermatology Life Quality Index compared with those receiving placebo. There were higher odds of achieving the minimal clinically important difference for the EQ-5D-3L Index score when comparing phototherapy versus placebo (OR, 9.78; 95% CI, 2.99-31.95) and phototherapy versus adalimumab (OR, 4.07; 95% CI, 1.42-11.70). LIMITATIONS: Small sample size, secondary analysis, generalizability. CONCLUSION: Phototherapy and adalimumab both improve skin-related quality of life and overall health-related quality of life compared with placebo in patients with psoriasis; however, patients treated with phototherapy achieved more improvement in overall health-related quality of life compared with patients treated with adalimumab.

Psoriasis and the risk of diabetes: A prospective population-based cohort study.

BACKGROUND: Data evaluating the impact of objectively measured psoriasis severity on type 2 diabetes mellitus (T2DM) risk are lacking. OBJECTIVE: To determine the risk for T2DM in patients with psoriasis compared with that in adults without psoriasis, stratified by categories of directly assessed body surface area (BSA) affected by psoriasis. METHODS: A prospective, population-based, cohort study from the United Kingdom in which 8124 adults with psoriasis and 76,599 adults without psoriasis were followed prospectively for approximately 4 years. RESULTS: There were 280 incident cases of diabetes in the psoriasis group (3.44%) and 1867 incident cases of diabetes in those without psoriasis (2.44%). After adjustment for age, sex and body mass index, the hazard ratios for development of incident diabetes were 1.21 (95% confidence interval [CI], 1.01-1.44), 1.01 (95% CI, 0.81-1.26), and 1.64 (95% CI, 1.23-2.18) in the groups with 2% or less of their BSA affected, 3% to 10% of their BSA affected, and 10% or more of their BSA affected compared with in the groups without psoriasis, respectively (P = .004 for trend). Worldwide, we estimate an additional 125,650 new diagnoses of T2DM per year in patients with psoriasis as compared with in those without psoriasis. LIMITATIONS: Relatively short-term follow-up and exclusion of prevalence cases, which may have masked associations in patients with less extensive psoriasis. CONCLUSION: Clinicians may measure BSA affected by psoriasis to target diabetes prevention efforts for patients with psoriasis.

Systematic Review of Surgical Treatment and Outcomes After Local Surgery of Primary Cutaneous Melanomas of the Penis and Scrotum.

BACKGROUND: Few data exist to guide surgical management and counseling about local recurrence after surgery of primary male genital melanoma. OBJECTIVE: To compile all available data on local recurrence rates after surgery of primary cutaneous melanoma of the penis and scrotum. MATERIALS AND METHODS: A systematic review of PubMed, Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS), Excerpta Medica database (EMBASE), and Web of Science identified all surgically treated penile and scrotal melanomas that reported local recurrence status and follow-up time. RESULTS: One hundred twenty-seven melanomas from 74 manuscripts were included. Eighty-six percent of melanomas were located on the penis, and 14% were located on the scrotum. Average follow-up time was 35.7 months. Scrotal melanomas were predominantly treated with organ-sparing surgeries (16/18, 88.9%), whereas penile melanomas were treated more often with amputation (61/109, 56.0%). Overall, local recurrence rate was 15.7% (20/127). Local recurrence rates for penile cases were 18.8% (9/48) after organ-sparing surgery versus 13.1% (8/61) for amputative surgery. Local recurrence rates were 66.7% (4/6) after positive surgical margins versus 10.2% (5/49) after negative surgical margins. CONCLUSION: Local recurrence rates are high after both organ-sparing and amputative surgery of primary cutaneous melanoma of the penis and scrotum. There is a need to standardize reporting for this rare tumor, as more complete data are necessary to develop consensus guidelines for surgical management of male genital melanoma.

Nestin depletion induces melanoma matrix metalloproteinases and invasion.

Matrix metalloproteinases (MMPs) are key biological mediators of processes as diverse as wound healing, embryogenesis, and cancer progression. Although MMPs may be induced through multiple signaling pathways, the precise mechanisms for their regulation in cancer are incompletely understood. Because cytoskeletal changes are known to accompany MMP expression, we sought to examine the potential role of the poorly understood cytoskeletal protein, nestin, in modulating melanoma MMPs. Nestin knockdown (KD) upregulated the expression of specific MMPs and MMP-dependent invasion both through extracellular matrix barriers in vitro and in peritumoral connective tissue of xenografts in vivo. The development of three-dimensional melanospheres that in vitro partially recapitulate noninvasive tumorigenic melanoma growth was inhibited by nestin KD, although ECM invasion by aberrant melanospheres that did form was enhanced. Mechanistically, nestin KD-dependent melanoma invasion was associated with intracellular redistribution of phosphorylated focal adhesion kinase and increased melanoma cell responsiveness to transforming growth factor-beta, both implicated in pathways of melanoma invasion. The results suggest that the heretofore poorly understood intermediate filament, nestin, may serve as a novel mediator of MMPs critical to melanoma virulence.

Interdisciplinary Management of Extramammary Paget's Disease Using Mohs Micrographic Surgery With Frozen Section Cytokeratin-7 Immunostains.

OBJECTIVE: To describe local recurrence rates and patient-reported outcomes when Mohs micrographic surgery with cytokeratin-7 immunostains (MMS-CK7) is included in the interdisciplinary management of extramammary Paget's disease (EMPD) METHODS: A retrospective study was conducted of EMPD treated with MMS-CK7 as part of an interdisciplinary team at an academic medical center between 2009 and 2016. Local recurrence rates and patient-reported outcomes were determined by record review and patient surveys. RESULTS: Twenty tumors in 19 patients were treated using MMS-CK7. After MMS-CK7 defined clear microscopic margins, 75% (15/20) of tumors underwent excision or reconstruction by a surgical colleague. Internal malignancy screening was performed by multiple specialties in 17 patients, with 1 associated malignancy of prostate cancer detected. No local recurrence was detected with a mean follow-up of 75.2 months. Most patients were satisfied with appearance (18/19, 95%) and function (16/19, 84%) after surgery. CONCLUSION: Interdisciplinary teams that include MMS-CK7 can treat EMPD with low local recurrence rates, high patient satisfaction, and thorough internal malignancy screening.

Evaluation of a Case Series of Patients With Generalized Pustular Psoriasis in the United States.

IMPORTANCE: Generalized pustular psoriasis (GPP) is a chronic, orphan disease with limited epidemiological data. OBJECTIVE: To describe the clinical characteristics, treatments, longitudinal disease course, and disease-specific health care utilization among patients with GPP across the United States. DESIGN, SETTING, AND PARTICIPANTS: A retrospective longitudinal case series involving 95 adults who met the European Rare and Severe Psoriasis Expert Network consensus definition for GPP and were treated at 20 US academic dermatology practices between January 1, 2007, and December 31, 2018. MAIN OUTCOMES AND MEASURES: The primary outcome is to describe the patient characteristics, associated medical comorbidities, treatment patterns complications, and GPP-specific health care utilization. RESULTS: Sixty-seven of 95 patients (70.5%) were women (mean age, 50.3 years [SD, 16.1 years]). In the initial encounter, 35 patients (36.8%) were hospitalized and 64 (67.4%) were treated with systemic therapies. In total, more than 20 different systemic therapies were tried. During the follow-up period, 19 patients (35.8%) reported hospitalizations at a median rate of 0.5 hospitalizations per year (IQR, 0.4-1.6). Women had a decreased risk of an emergency department or hospital encounter (odds ratio, 0.19; 95% CI, 0.04-0.83). CONCLUSIONS AND RELEVANCE: Generalized pustular psoriasis is a rare, chronic disease without standard treatment and is associated with continued health care utilization over time.

Evaluation of a Case Series of Patients With Palmoplantar Pustulosis in the United States.

IMPORTANCE: Palmoplantar pustulosis (PPP) is a is a chronic, orphan disease with limited epidemiological data. OBJECTIVE: To describe the clinical characteristics, treatments, longitudinal disease course, and health care utilization in adults with PPP across the US. DESIGN, SETTING, AND PARTICIPANTS: This retrospective, longitudinal case series from 20 academic dermatology practices in the US included a consecutive sample of 197 adults who met the European Rare and Severe Psoriasis Expert Network consensus definition for PPP between January 1, 2007, and December 31, 2018. Data analysis was performed June 2020 to December 2020. MAIN OUTCOMES AND MEASURES: The primary outcome was to describe the patient characteristics, associated medical comorbidities, treatment patterns, complications, and PPP-specific health care utilization. RESULTS: Of 197 patients, 145 (73.6%) were female, and the mean (SD) age at presentation was 53.0 (12.6) years, with a mean (SD) follow-up time of 22.1 (28.0) months. On initial presentation, 95 (48.2%) patients reported skin pain, and 39 (19.8%) reported difficulty using hands and/or feet. Seventy patients (35.5%) were treated with systemic treatments, and use of more than 20 different systemic therapies was reported. In patients with at least 6 months of follow-up (n = 128), a median (IQR) of 3.7 (4-10) dermatology visits per year were reported; 24 (18.8%) patients had 5 or more visits during the study period. CONCLUSIONS AND RELEVANCE: In this case series, PPP was associated with persistent symptoms, continued health care utilization, and a lack of consensus regarding effective treatments, emphasizing the unmet medical need in this population. Additional research is necessary to understand treatment response in these patients.

Measuring Outcomes in Psoriatic Arthritis: Comparing Routine Assessment of Patient Index Data and Psoriatic Arthritis Impact of Disease.

OBJECTIVE: To examine the construct validity of Routine Assessment of Patient Index Data 3 (RAPID3) and Psoriatic Arthritis Impact of Disease (PsAID) in patients with psoriatic arthritis (PsA). In examining construct validity, we also addressed scores among subgroups with severe psoriasis, poly articular disease, enthesitis, and dactylitis, and evaluated influences of sociodemographic factors and comorbidities (contextual factors) on these patient-reported outcomes (PRO). METHODS: Patients with PsA were enrolled in the Psoriatic Arthritis Research Consortium (PARC) between 2014 and 2016. PARC is a longitudinal observational cohort study conducted at 4 US institutions. In this cross-sectional study, construct validity was assessed by examining Spearman correlation coefficients for RAPID3 and PsAID with physician-reported disease activity measures and other PRO [e.g., Medical Outcomes Study Short Form-12 physical component summary/mental component summary (SF-12 PCS/MCS), Functional Assessment of Chronic Illness Therapy-Fatigue scale (FACIT-F)]. Contextual factors and disease subgroups were assessed in multivariable linear regression models with RAPID3 or PsAID12 as outcomes of interest and the hypothesized contextual factors as covariates. RESULTS: Among 401 patients enrolled in PARC, 347 completed RAPID3 or PsAID12. Of these, most were white females with a mean age of 51.7 years (SD 14.02). RAPID3 and PsAID were highly correlated (r = 0.90). These measures were also correlated with the SF-12 PCS (r = -0.67) and FACIT-F (r = -0.77). Important contextual factors and disease subgroups included enthesitis, joint counts, education, insurance type, and depression. CONCLUSION: RAPID3 and PsAID12 have excellent construct validity in PsA and are strongly correlated despite differing items. Contextual factors (i.e., the presence of depression and obesity) should be considered when interpreting raw scores of the RAPID3 and PsAID12.

Anticipated and Perceived Stigma Among Patients With Psoriasis.

BACKGROUND: Perceived stigma among patients with psoriasis (PWP) is associated with poorer quality of life. OBJECTIVE: To determine the prevalence and predictors of stigmatizing attitudes that PWP expect and experience from others. METHODS: We conducted a survey using validated outcome measures to assess the extent to which PWP anticipate and perceive stigma from others. Demographic and clinical characteristics were obtained from electronic medical records. RESULTS: Patients (n = 106) were 48.11% female, 70.75% white, and had a mean age ± SD of 47.90 ± 16.19 years old. Of all, 25.47% self-reported their psoriasis as severe. Mean physician global assessment score ± SD was 2.98 ± 1.81. Two-thirds (66.98%) of patients reported that, in response to seeing their psoriasis-affected skin, they anticipated others to stereotype them as "contagious." Linear regression analyses demonstrated that patient-reported severe psoriasis, compared to mild psoriasis, was associated with greater anticipation of negative stereotypes, social avoidance, and perceived stigma from others (P values < .05). Physician-measured body surface area and global assessment scores were not significantly associated with any outcome. CONCLUSION: Prevalence of anticipated and perceived stigma among PWP is high. Our results suggest that objective measures of severity may not identify patients at risk of stigma-related distress. Additional methods, such as directly inquiring about stigmatizing experiences, may be needed.