Risk of Inflammatory Bowel Disease in Patients With Atopic Dermatitis.

Importance: Data on the association between atopic dermatitis (AD) and inflammatory bowel disease (IBD) are inconsistent. Few studies have examined the association of AD or AD severity with risk of ulcerative colitis (UC) and Crohn disease (CD) separately. Objectives: To examine the risk of new-onset IBD, UC, and CD in children and adults with AD. Design, Setting, and Participants: This population-based cohort study assessed patients with AD matched with up to 5 controls on age, practice, and index date. Treatment exposure was used as a proxy for AD severity. Data were retrieved from The Health Improvement Network, a UK electronic medical record database, for January 1, 1994, to February 28, 2015. Data analysis was performed from January 8, 2020, to June 30, 2023. Main Outcomes and Measures: Outcomes of interest were incident IBD, UC, and CD. Logistic regression was used to examine the risk for each outcome in children and adults with AD compared with controls. Results: A total of 1 809 029 pediatric controls were matched to 409 431 children with AD (93.2% mild, 5.5% moderate, and 1.3% severe). The pediatric cohort ranged in median age from 4 to 5 years (overall range, 1-10 years), was predominantly male (936 750 [51.8%] controls, 196 996 [51.6%] with mild AD, 11 379 [50.7%] with moderate AD, and 2985 [56.1%] with severe AD), and with similar socioeconomic status. A total of 2 678 888 adult controls were matched to 625 083 adults with AD (65.7% mild, 31.4% moderate, and 2.9% severe). The adult cohort ranged in median age from 45 to 50 years (overall range, 30-68 years) and was predominantly female (1 445 589 [54.0%] controls, 256 071 [62.3%] with mild AD, 109 404 [55.8%] with moderate AD, and 10 736 [59.3%] with severe AD). In fully adjusted models, children with AD had a 44% increased risk of IBD (hazard ratio [HR], 1.44; 95% CI, 1.31-1.58) and a 74% increased risk of CD (HR, 1.74; 95% CI, 1.54-1.97), which increased with worsening AD; however, they did not have increased risk of UC (HR, 1.09; 95% CI, 0.94-1.27) except for those with severe AD (HR, 1.65; 95% CI, 1.02-2.67). Adults with AD had a 34% (HR, 1.34; 95% CI, 1.27-1.40) increased risk of IBD, a 36% (HR, 1.36; 95% CI, 1.26-1.47) increased risk of CB, and a 32% (HR, 1.32; 95% CI, 1.24-1.41) increased risk of UC, with risk increasing with worsening AD. Conclusion and Relevance: In this cohort study, children and adults with AD had an increased risk of IBD, with risk varying by age, AD severity, and IBD subtype. These findings provide new insights into the association between AD and IBD. Clinicians should be aware of these risks, particularly when selecting systemic treatments for AD in patients who may have coincident gastrointestinal symptoms.

Misconceptions of photoprotection in skin of color.

Terrestrial sunlight is the portion of electromagnetic radiation that is emitted by the sun and reaches Earth's surface. It encompasses 3 major components: UV radiation (290-400 nm), visible light (400-700 nm), and infrared radiation. The deleterious effects of UV radiation have been appreciated for decades, particularly among those with light skin tones (Fitzpatrick skin types I-II) who primarily manifest with burns of varying degrees of severity with sun exposure. In recent years, studies have increasingly shown the negative impact of visible light on skin health, particularly in individuals with skin of color (Fitzpatrick skin types IV-VI), including the exacerbation of hyperpigmentation disorders such as melasma and post-inflammatory hyperpigmentation, as well as induction of the former. Recommendations from medical societies and the US Food and Drug Administration for photoprotection have been evolving along with the knowledge base. Yet, misconceptions about skin damage related to sunlight and the benefits of photoprotection (particularly among those with Fitzpatrick skin types V-VI) are still prevalent among both clinicians and patients. Among patients with skin of color, disorders of hyperpigmentation and other consequences from sun exposure have been associated with impaired skin health and negative burden on quality of life. This review summarizes currently available evidence of the impact of both UV and visible wavelengths and the low utilization of photoprotection measures among people with skin of color, with the goal of providing recommendations to help educate patients.

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.

Timing of Onset of Adverse Cutaneous Reactions Associated With Programmed Cell Death Protein 1 Inhibitor Therapy.

Importance: An increasing number of cutaneous adverse reactions resulting from use of programmed cell death protein 1 (PD-1) inhibitors have been described, but with relatively little focus to date on the timing of these reactions. Objective: To determine the timing of cutaneous drug reactions after initiation of PD-1 inhibitor therapy. Design, Setting, and Participants: This retrospective observational study included patients referred to an academic dermatology clinic by an oncologist from January 1, 2014, through February 28, 2018, with at least 1 skin biopsy specimen of a skin reaction associated with PD-1 inhibitor use. Participants were included if they had a biopsy-proven cutaneous reaction in response to a PD-1 inhibitor used alone or in combination with ipilimumab. Exposures: All patients included in this study received pembrolizumab, nivolumab, or nivolumab with ipilimumab as immunotherapy for cancer. Main Outcomes and Measures: The main outcome measure was time to onset of biopsy-proven cutaneous reactions that occurred during or after use of pembrolizumab or nivolumab. Results: A total of 17 patients (12 men, 5 women; mean [SD] age, 68.6 [11.1] years) were identified who presented with cutaneous adverse reactions associated with PD-1 inhibitor therapy; these reactions included lichenoid dermatitis, bullous pemphigoid, erythema multiforme, eczema, lupus, and sarcoidosis. Twelve patients presented with reactions at least 3 months after beginning pembrolizumab or nivolumab therapy. The skin reactions presented a median (range) of 4.2 months (0.5-38.0 months) after drug initiation. In 5 cases, the cutaneous adverse reactions attributed to the PD-1 inhibitor therapy developed after the drug therapy was terminated. Conclusions and Relevance: Diverse cutaneous adverse reactions secondary to PD-1 inhibitor use may present with delayed onsets and even after discontinuation of therapy. Dermatologists should be aware of the potential for delayed presentations of cutaneous adverse reactions.

Risk of venous thromboembolism in patients with psoriatic arthritis, psoriasis and rheumatoid arthritis: a general population-based cohort study.

Aims: To determine the risk of venous thromboembolism (VTE) defined as the combined endpoint of deep venous thrombosis (DVT) and pulmonary embolism (PE) among patients with psoriatic arthritis (PsA), psoriasis and rheumatoid arthritis (RA) compared with population controls. Methods and results: A cohort study was conducted in a primary care medical record database in the UK with data from 1994-2014 among patients with PsA, RA, or psoriasis. Cox proportional hazards models were used to calculate the relative hazards for DVT, PE, and VTE. An interaction with disease modifying anti-rheumatic drugs (DMARD) was hypothesized a priori and was significant. Patients with PsA (n = 12 084), RA (n = 51 762), psoriasis (n = 194 288) and controls (n = 1 225 571) matched on general practice and start date were identified. Patients with RA (with and without a DMARD prescription) and patients with mild psoriasis had significantly elevated risks of VTE (HR 1.35, 1.29, and 1.07, respectively) after adjusting for traditional risk factors. Severe psoriasis and PsA prescribed a DMARD had an elevated but not statistically significant risk for VTE. Findings were similar for DVT. The age-and-sex-adjusted risk of PE was elevated in RA, severe psoriasis and PsA patients prescribed a DMARD. Conclusion: While systemic inflammation is a risk factor for VTE, the risk of VTE compared with controls is different among patients with three different inflammatory disorders: RA, PsA, and psoriasis.

Risk of Incident Liver Disease in Patients with Psoriasis, Psoriatic Arthritis, and Rheumatoid Arthritis: A Population-Based Study.

Relatively little is known about the risk for incident liver disease in psoriasis (PsO), psoriatic arthritis (PsA), and rheumatoid arthritis (RA). We performed a cohort study among patients with PsO, PsA, or RA and matched controls in The Health Improvement Network from 1994 to 2014. Outcomes of interest were any liver disease, nonalcoholic fatty liver disease, and cirrhosis (any etiology). Among patients with PsO (N = 197,130), PsA (N = 12,308), RA (N = 54,251), and matched controls (N = 1,279,754), the adjusted hazard ratios for any liver disease were elevated among patients with PsO (without systemic therapy [ST] 1.37; with ST 1.97), PsA (without ST 1.38; with ST 1.67), and RA without an ST (1.49) but not elevated in patients with RA prescribed an ST (0.96). Incident nonalcoholic fatty liver disease was highest in patients with PsO prescribed an ST (2.23) and PsA with an ST (2.11). The risk of cirrhosis was highest among patients with PsO with an ST (2.62) and PsA without an ST (3.15). Additionally, the prevalence of liver disease and cirrhosis increased in a stepwise fashion with increasing body surface area affected by PsO (P for trend <0.001). More so than RA, PsO and PsA are associated with liver disease, particularly nonalcoholic fatty liver disease and cirrhosis, and this was true even among patients without ST exposure.

Preoperative telephone consultation does not decrease patient anxiety before Mohs micrographic surgery.

BACKGROUND: Many factors influence anxiety and satisfaction of patients undergoing Mohs micrographic surgery (MMS). OBJECTIVE: We sought to determine the effect of a preoperative educational telephone call on anxiety and satisfaction for patients undergoing same-day office consultation and MMS. METHODS: Patients with skin cancer (N = 104) scheduled for same-day office consultation and MMS were randomly assigned to receive or not to receive an educational telephone call during the week before surgery. All patients rated their anxiety levels immediately before and after the same-day office consultation and MMS by completing the State-Trait Anxiety Inventory and an anxiety visual analog scale. Patients also rated satisfaction immediately after MMS by completing the Visit-Specific Patient Satisfaction Questionnaire. RESULTS: Patients undergoing same-day office consultation and MMS reported similar levels of increased anxiety and high satisfaction, regardless of whether they received a preoperative educational telephone call. LIMITATIONS: Lack of control for patients' prior surgery or self-education is a limitation. CONCLUSION: Preoperative educational telephone calls did not relieve anxiety or improve satisfaction for patients undergoing same-day office consultation and MMS. Preoperative education and counseling has uncertain benefits to anxiety and satisfaction of patients undergoing MMS.

Risk of Nonmelanoma Skin Cancer Associated With the Use of Immunosuppressant and Biologic Agents in Patients With a History of Autoimmune Disease and Nonmelanoma Skin Cancer.

IMPORTANCE: Immune dysfunction underlies the pathogenesis of rheumatoid arthritis (RA) and inflammatory bowel disease (IBD). Immunosuppressive therapy is the standard of care for these diseases. Both immune dysfunction and therapy-related immunosuppression can inhibit cancer-related immune surveillance in this population. Drug-induced immunosuppression is a risk factor for nonmelanoma skin cancer (NMSC), particularly squamous cell tumors. For patients with a history of NMSC, data are limited on the effect of these drugs on the risk of additional NMSCs. OBJECTIVE: To determine the relative hazard of a second NMSC in patients with RA or IBD who use methotrexate, anti-tumor necrosis factor (anti-TNF) therapy, or thiopurines after an initial NMSC. DESIGN, SETTING, AND PARTICIPANTS: In this retrospective cohort study, we studied 9460 individuals with RA or IBD enrolled in Medicare from January 1, 2006, through December 31, 2012. EXPOSURES: Exposure to methotrexate, thiopurines, anti-TNFs, sulfasalazine, hydroxychloroquine, abatacept, or rituximab after the incident NMSC surgery. MAIN OUTCOMES AND MEASURES: A second NMSC occurring 1 year or more after the incident NMSC using Cox proportional hazards regression models. RESULTS: Among 9460 individuals (6841 with RA and 2788 with IBD), the incidence rate of a second NMSC per 1000 person-years was 58.2 (95% CI, 54.5-62.1) and 58.9 (95% CI, 53.2-65.2) in patients with RA and IBD, respectively. Among patients with RA, methotrexate used in conjunction with other medications was associated with an increased risk of a second NMSC (hazard ratio [HR], 1.60; 95% CI, 1.08-2.37). Adjusted for other medications, the risk of NMSC increased with 1 year or more of methotrexate use (HR, 1.24; 95% CI, 1.04-1.48). Compared with methotrexate alone, the addition of anti-TNF drugs was significantly associated with risk of NMSC (HR, 1.49; 95% CI, 1.03-2.16). Abatacept and rituximab were not associated with increased NMSC risk. The nonsignificant HRs for 1 year or more of thiopurine and anti-TNF use for IBD were 1.49 (95% CI, 0.98-2.27) and 1.36 (95% CI, 0.76-2.44), respectively. CONCLUSIONS AND RELEVANCE: Methotrexate use is associated with an increased risk of a second NMSC. Anti-TNF use may increase the risk of a second NMSC when used with methotrexate for RA. Further long-term studies are required before one can conclude that thiopurine and/or anti-TNF do not increase the risk of a second NMSC in patients with IBD.

The Risk of Cancer in Patients With Psoriasis: A Population-Based Cohort Study in the Health Improvement Network.

IMPORTANCE: The risk of cancer in patients with psoriasis remains a cause of special concern due to the chronic inflammatory nature of the disease, the use of immune-suppressive treatments and UV therapies, and the increased prevalence of comorbid, well-established risk factors for cancer, such as smoking and obesity, all of which may increase the risk of carcinogenesis. OBJECTIVE: To compare the overall risk of cancer, and specific cancers of interest, in patients with psoriasis compared with patients without psoriasis. DESIGN, SETTING, AND PARTICIPANTS: Population-based cohort study of patients ages 18 to 89 years with no medical history of human immunodeficiency virus, cancer, organ transplants, or hereditary disease (albinism and xeroderma pigmentosum), prior to the start date, conducted using The Health Improvement Network, a primary care medical records database in the United Kingdom. The data analyzed had been collected prospectively from 2002 through January 2014. The analysis was completed in August 2015. EXPOSURES OF INTEREST: Patients with at least 1 diagnostic code for psoriasis were classified as having moderate-to-severe disease if they had been prescribed psoralen, methotrexate, cyclosporine, acitretin, adalimumab, etanercept, infliximab, or ustekinumab or phototherapy for psoriasis. Patients were classified as having mild disease if they never received treatment with any of these agents. MAIN OUTCOMES AND MEASURES: Incident cancer diagnosis. RESULTS: A total of 937,716 control group patients without psoriasis, matched on date and practice visit, and 198,366 patients with psoriasis (186,076 with mild psoriasis and 12,290 with moderate-to-severe disease) were included in the analysis. The adjusted hazard ratios (aHRs) with 95% CIs for any incident cancer excluding nonmelanoma skin cancer (NMSC) were 1.06 (95% CI, 1.02-1.09), 1.06 (95% CI, 1.02-1.09), and 1.08 (95% CI, 0.96-1.22) in the overall, mild, and severe psoriasis group. The aHRs for incident lymphoma were 1.34 (95% CI, 1.18-1.51), 1.31 (95% CI, 1.15-1.49), and 1.89 (95% CI, 1.25-2.86); for NMSC, 1.12 (95% CI, 1.07-1.16), 1.09 (95% CI, 1.05-1.13), and 1.61 (95% CI, 1.42-1.84); and for lung cancer, 1.15 (95% CI, 1.03-1.27), 1.12 (95% CI, 1.01-1.25), and 1.62 (95% CI, 1.16-2.28) in the overall, mild, and severe psoriasis groups, respectively. No significant association was seen with cancer of the breast, colon, prostate, or leukemia. CONCLUSIONS AND RELEVANCE: The association between psoriasis and cancer, albeit small, was present in our cohort of patients with psoriasis. This association was primarily driven by NMSC, lymphoma, and lung cancer.

Extracorporeal photopheresis: a review on the immunological aspects and clinical applications.

Extracorporeal photopheresis (ECP) was hailed as a new therapeutic concept for the treatment of diseases caused by aberrant T lymphocytes since it was first described more than twenty years ago. Advances in molecular biology and immunology have allowed a greater understanding of the mechanisms involved in ECP. As a result, ECP is being increasingly considered as a safe and promising immunomodulatory therapy with diverse clinical applications. At present ECP is approved by the FDA for the treatment of cutaneous T-cell lymphoma (CTCL). ECP is considered a relatively safe and promising immunomodulatory therapy with diverse clinical applications reported in the literature. ECP has been used in the treatment of patients following acute allograft rejection in cardiac, lung, renal or liver transplantation, graft-versus-host disease, systemic lupus erythematosus, systemic scleroderma, rheumatoid arthritis and pemphigus vulgaris. The use of ECP as a novel form of therapy is in constant evolution with newer studies focusing on the treatment of patients with Crohn's disease and the immunological effects of ECP in children with type 1 diabetes mellitus. However, because the exact mechanism by which ECP exerts its effects remains to be described in detail and because important questions regarding the use of ECP in the clinical setting, such as length of therapy or design of specific protocols, concomitant use of immunosupressive therapy, patient characteristics, long term side effects, assessment of therapy efficacy and cost effectiveness continue to remain unanswered, the exact role of ECP cannot be fully established except in the case of patients with CTCL and GvHD. Nevertheless, future clinical studies with ECP can be done with the objective of designing more appropriate treatment protocols based on expected patient response and with a side effect profile that is fairly tolerable.