Multimorbidity in Psoriasis as a Risk Factor for Psoriatic Arthritis: A Population-Based Study.

OBJECTIVES: To examine multimorbidity in psoriasis and its association with the development of PsA. METHODS: A retrospective cohort study was performed using the Rochester Epidemiology Project. Population-based incidence (2000-2009) and prevalence (Jan 1, 2010) cohorts of psoriasis were identified by manual chart review. A cohort of individuals without psoriasis (comparators) were identified (1:1 matched on age, sex, and county). Morbidities were defined using ≥2 Clinical Classification Software codes ≥30 days apart within prior five years. PsA was defined using ClASsification of Psoriatic ARthritis (CASPAR) criteria. χ2 and rank-sum tests were used to compare morbidities, and age-, sex-, and race-adjusted Cox models to examine the association of baseline morbidities in psoriasis with development of PsA. RESULTS: Among 817 incident psoriasis patients, the mean age was 45.2 years with 52.0% females, and 82.0% moderate/severe psoriasis. No multimorbidity differences were found between incident psoriasis patients and comparators. However, in the 1,088 prevalent psoriasis patients, multimorbidity was significantly more common compared with 1,086 comparators (OR : 1.35 and OR : 1.48 for ≥2 and ≥5 morbidities, respectively). Over a median 13.3-year follow-up, 23 patients (cumulative incidence: 2.9% by 15 years) developed PsA. Multimorbidity (≥2 morbidities) was associated with a 3-fold higher risk of developing PsA. CONCLUSION: Multimorbidity was more common in the prevalent but not incident cohort of psoriasis compared with the general population, suggesting patients with psoriasis may experience accelerated development of multimorbidity. Moreover, multimorbidity at psoriasis onset significantly increased the risk of developing PsA, highlighting the importance of monitoring multimorbid psoriasis patients for the development of PsA.

Time to transition from psoriasis to psoriatic arthritis: A population-based study.

OBJECTIVE: To identify demographic and clinical characteristics associated with time between psoriasis and psoriatic arthritis (PsA). METHODS: A retrospective, population-based cohort of incident PsA patients ≥18 years (2000-17) from Olmsted County, MN was identified. PsA patients were divided into two groups: patients with concurrent psoriasis and PsA (within 1 year), and patients with psoriasis before PsA (>1 year). Patients with PsA prior to psoriasis were excluded. Age- and sex-adjusted logistic regression models were used to examine factors associated with the time between psoriasis and PsA diagnosis. RESULTS: Among 164 patients with incident PsA, 158 had a current or personal history of psoriasis. The mean (SD) age at PsA diagnosis was 46.3 (12.0) years, and 46% were females. The median (interquartile range) time from psoriasis to PsA was 35.5 (0.8-153.4) months. 64 patients (41%) patients had concurrent psoriasis and PsA while 94 (59%) had onset of psoriasis before PsA. The estimated age at onset of psoriasis symptom (OR per 10-year decrease = 1.63, 95% CI: 1.26-2.11) and psoriasis severity (OR = 3.65, 95% CI: 1.18-11.32 for severe vs. mild) were associated with having a psoriasis diagnosis more than one year prior to incident PsA. CONCLUSION: In this population-based study, approximately 60% of the patients had psoriasis before PsA, and the rest had concurrent psoriasis and PsA. Patients with lower age at psoriasis onset or severe psoriasis were more likely to have a longer time to transition from psoriasis to PsA.

Tumor necrosis factor inhibitor (TNFi) persistence and reasons for discontinuation in a predominantly male cohort with axial spondyloarthritis.

Although tumor necrosis factor inhibitors (TNFi) have favorably altered the treatment landscape for patients with axial spondyloarthritis (axSpA), there is limited data regarding TNFi persistence and reasons for discontinuation. This is an observational time-to-event study utilizing data collected for a prospective multiple-disease registry of US Veterans with axSpA treated with TNFi therapies and recruited over a 10 year period. Clinical, serological, and comorbid parameters were collected. Corporate Data Warehouse Pharmacy files provided courses of the 5 TNFi agents, and response to treatment was documented. Individual TNFi persistence was established utilizing univariate and multivariate Cox proportional models, and reasons for discontinuation were obtained by physician chart review. Two-hundred and fifty-five axSpA patients received 731 TNFi courses. A majority of patients (84.3%) had TNFi persistence at 12 months; 63.5% and 47.1% at 24 and 36 months, respectively. Compared to adalimumab, infliximab demonstrated greater persistence, certolizumab the least. Age, smoking status, BMI, comorbidity burden, inflammatory markers and HLA-B27 did not predict TNFi persistence or discontinuation. Stroke and peripheral arterial disease increased the probability of TNFi discontinuation. Secondary non-response (SNR) was the most common reason for discontinuation (46% of all courses); non-adherence (6%) and clinical remission (2%) were uncommon. Pain score at enrollment, myocardial infarction, African American race and inflammatory bowel disease (IBD) predicted TNFi response. While initial persistence of TNFi treatment was high, a large proportion of the patients discontinued initial TNFi therapy by 3 years, primarily due to loss of efficacy. While further research identifying potential predictors of TNFi discontinuation in axSpA is warranted, access to alternate disease-modifying therapies is needed.

Differential Diagnosis and Workup of Monocytosis: A Systematic Approach to a Common Hematologic Finding.

PURPOSE OF REVIEW: Monocytosis is a frequently encountered clinical condition that needs appropriate investigation due to a broad range of differential diagnoses. This review is meant to summarize the latest literature in the diagnostic testing and interpretation and offer a stepwise diagnostic approach for a patient presenting with monocytosis. RECENT FINDINGS: Basic studies have highlighted the phenotypic and functional heterogeneity in the monocyte compartment. Studies, both translational and clinical, have provided insights into why monocytosis occurs and how to distinguish the different etiologies. Flow cytometry studies have illustrated that monocyte repartitioning can distinguish chronic myelomonocytic leukemia, a prototypical neoplasm with monocytosis from other reactive or neoplastic causes. In summary, we provide an algorithmic approach to the diagnosis of a patient presenting with monocytosis and expect this document to serve as a reference guide for clinicians.

The Epidemiology of Psoriatic Arthritis Over Five Decades: A Population-Based Study.

OBJECTIVE: To determine the incidence of psoriatic arthritis (PsA) in a US population and describe trends in incidence and mortality over 5 decades. METHODS: The previously identified population-based cohort that included Olmsted County, Minnesota residents ≥18 years of age who fulfilled PsA criteria during 1970-1999 was extended to include patients with incident PsA during 2000-2017. Age- and sex-specific incidence rates and point prevalence, adjusted to the 2010 US White population, were reported. RESULTS: There were 164 incident cases of PsA in 2000-2017 (mean ± SD age 46.4 ± 12.0 years; 47% female). The overall age- and sex-adjusted annual incidence of PsA per 100,000 population was 8.5 (95% confidence interval [95% CI] 7.2-9.8) and was higher in men (9.3 [95% CI 7.4-11.3]) than women (7.7 [95% CI 5.9-9.4]) in 2000-2017. Overall incidence was highest in the 40-59 years age group. The incidence rate was relatively stable during 2000-2017, with no evidence of an overall increase or an increase in men only (but a modest increase of 3% per year in women), compared to 1970-1999 when a 4%-per-year increase in incidence was observed. Point prevalence was 181.8 per 100,000 population (95% CI 156.5-207.1) in 2015. The percentage of women among those with PsA increased from 39% in 1970-1999 and 41% in 2000-2009 to 54% in 2010-2017 (P = 0.08). Overall survival in PsA did not differ from the general population (standardized mortality ratio 0.85 [95% CI 0.61-1.15]). CONCLUSION: The incidence of PsA in this predominantly White US population was stable in 2000-2017, in contrast to previous years. However, an increasing proportion of women with PsA was found in this study.

Diagnostic Delay in Psoriatic Arthritis: A Population-based Study.

OBJECTIVE: To examine demographic and clinical characteristics associated with diagnostic delay in psoriatic arthritis (PsA). METHODS: We characterized a retrospective, population-based cohort of incident adult (≥ 18 yrs) patients with PsA from Olmsted County, Minnesota, from 2000-2017. All patients met the classification criteria. Diagnostic delay was defined as the time from any patient-reported PsA-related joint symptom to a physician diagnosis of PsA. Factors associated with delay in PsA diagnosis were identified through logistic regression models. RESULTS: Of the 164 incident PsA cases from 2000 to 2017, 162 had a physician or rheumatologist diagnosis. Mean (SD) age was 41.5 (12.6) years and 46% were female. Median time from symptom onset to physician diagnosis was 2.5 years (IQR 0.5-7.3). By 6 months, 38 (23%) received a diagnosis of PsA, 56 (35%) by 1 year, and 73 (45%) by 2 years after symptom onset. No significant trend in diagnostic delay was observed over calendar time. Earlier age at onset of PsA symptoms, higher BMI, and enthesitis were associated with a diagnostic delay of > 2 years, whereas sebopsoriasis was associated with a lower likelihood of delay. CONCLUSION: In our study, more than half of PsA patients had a diagnostic delay of > 2 years, and no significant improvement in time to diagnosis was noted between 2000 and 2017. Patients with younger age at PsA symptom onset, higher BMI, or enthesitis before diagnosis were more likely to have a diagnostic delay of > 2 years, whereas patients with sebopsoriasis were less likely to have a diagnostic delay.

Giant cell arteritis associated with inflammatory bowel disease: a case-series and review of the literature.

To describe the clinical characteristics, management, and outcome of a series of patients with giant cell arteritis (GCA) and inflammatory bowel disease (IBD). Patients with both GCA and IBD evaluated between 1/1/1996 and 12/30/2018 were retrospectively identified. Clinical characteristics, laboratory parameters, radiologic features, histopathology, management and outcomes were abstracted. A systematic literature review identifying patients with IBD and GCA was performed via a Medline and EMBASE search from inception through December 31 2019. Six patients were identified with GCA and IBD (66% male). Five (83%) had ulcerative colitis (UC) and one had Crohn's disease (CD). Diagnosis of IBD preceded GCA in four patients with an average interval of 30 years (range 14-42). Average time to IBD diagnosis in those with prior GCA diagnosis was 1.5 years. During mean follow-up of 4.3 years, GCA relapse was infrequent with only one patient with relapse observed. Systematic literature review identified six additional patients with confirmed coexistence of GCA and IBD. Similar to the current series, male sex was more common and ulcerative colitis was the predominant IBD phenotype. The current study reports findings from the largest single-institution case-series of co-existent GCA and IBD. In contrast to Takayasu arteritis with co-existent IBD, which displays a predilection for female sex and Crohn's disease phenotype, both the current study and review of literature demonstrate a stronger association of GCA with male sex and ulcerative colitis. Further studies addressing a potential pathophysiologic connection between GCA and IBD are suggested.

Effects of Therapies on Cardiovascular Events in Ankylosing Spondylitis: A Systematic Review and Meta-Analysis.

INTRODUCTION: Non-steroidal anti-inflammatory drugs (NSAIDs) and tumor necrosis factor inhibitors (TNFi) are the most common therapies used in AS, however, the associated long-term cardiovascular risk is unclear. We performed a systematic review and meta-analysis on the association of therapies used for ankylosing spondylitis (AS) such as NSAIDs and TNFi on cardiovascular events (CVE) in AS. METHODS: A comprehensive search was performed from database inception to May 29, 2020 to include controlled studies of AS treated with NSAIDs, oral small molecules, or biologics reporting CVE. Study-specific risk ratios (RR) were pooled using a random effects model. RESULTS: Nine non-randomized studies from 1570 studies screened fulfilled inclusion criteria. Among NSAID users as a whole versus no NSAIDs, no increased risk of CVE (composite outcome) was observed; however, the risk of cerebrovascular accident was significantly lower (RR 0.58, 95% CI 0.37-0.93, I2 = 66%). Cox-2 inhibitor use was associated with reduced risk of all CVE (RR 0.48, 95% CI 0.33-0.70, I2 = 0%). Non-selective NSAIDs were not associated with any increased/decreased risk of any CVE. Meta-analysis of three studies of MI did not show a significant association with TNFi (RR 0.88, 95% CI 0.57-1.35, I2 = 76%). CONCLUSIONS: In this meta-analysis of non-randomized studies, NSAID users as a whole and users of non-selective NSAIDs did not seem to have a higher risk of any CVE. Limited data suggest a lower risk of composite CVE outcome with Cox-2 inhibitors, unlike the increased risk reported in the general population. No significant association between TNFi and MI was observed. The certainty in evidence was very low due to all studies being observational. More studies are needed to study the association between TNFi use and CVE in general to evaluate a possible protective role in AS.

Autoimmunity, Clonal Hematopoiesis, and Myeloid Neoplasms.

Clonal hematopoiesis has been linked with the development of hematologic malignancy and atherosclerotic cardiovascular disease; however, the association with autoimmune diseases remains to be defined. The link between autoimmune diseases and myeloid neoplasms (MNs) is complex, often multifactorial, and seems bidirectional. The limited data suggest an increased risk of MNs in rheumatoid arthritis and systemic lupus erythematosus. Paraneoplastic manifestations of MN include arthritis, vasculitis, and connective tissue disease. Treatment options for autoimmune disease such as cyclophosphamide and azathioprine have been associated with MNs, whereas the data for methotrexate and tumor necrosis factor inhibitors are equivocal.