Flares After Withdrawal of Biologic Therapies in Juvenile Idiopathic Arthritis: Clinical and Laboratory Correlates of Remission Duration

Objective

To assess the time in remission after discontinuing biologic therapy in patients with juvenile idiopathic arthritis (JIA).

Methods

We enrolled 135 patients followed in 3 tertiary‐care centers. The primary outcome was to assess, once remission was achieved, the time in remission up to the first flare after discontinuing treatment. Mann‐Whitney U test, Wilcoxon's signed rank test for paired samples, chi‐square tests, and Fisher's exact test were used to compare data. Pearson's and Spearman's correlation tests were used to determine correlation coefficients for different variables. To identify predictors of outcome, Cox regression model and Kaplan‐Meier curves were constructed, each one at the mean of entered covariates.

Results

The majority of enrolled patients flared after stopping treatment with biologics (102 of 135, 75.6%) after a median followup time in remission off therapy of 6 months (range 3–109 months). A higher probability of maintaining remission after discontinuing treatment was present in systemic‐onset disease compared to the rest of the JIA patients (Mantel‐Cox χ² = 8.31, P < 0.004). In analysis limited to children with JIA with polyarticular and oligoarticular disease, patients who received biologics >2 years after achieving remission had a higher probability of maintaining such remission off therapy (mean ± SD 18.64 ± 3.3 months versus 11.51 ± 2.7 months [P < 0.009]; Mantel‐Cox χ² = 9.06, P < 0.002). No other clinical variable was significantly associated with a long‐lasting remission.

Conclusion

Children with oligoarticular and polyarticular JIA who stop treatment before 2 years from remission have a higher chance of relapsing after biologic withdrawal.

     

Physical Functioning,Pain, and Health‐Related Quality of Life in Adults With Juvenile Idiopathic Arthritis: A Longitudinal 30‐Year Followup Study

Objective

To describe physical functioning, pain, and health‐related quality of life (HRQoL) in adults with juvenile idiopathic arthritis (JIA), investigate changes over time, and identify predictors of poorer HRQoL after 30 years of disease.

Methods

Patients (n = 176) clinically examined after 15 years were reassessed using the Health Assessment Questionnaire disability index (HAQ DI), the visual analog scale pain subscale (VAS pain), and the Medical Outcomes Study Short Form 36 (SF‐36) after 23 years and 30 years. Patients with signs of active disease after a minimum of 15 years were clinically examined again at 30 years. Patients were compared to matched controls.

Results

At the 30‐year followup, 82 patients (47%) had HAQ DI scores >0, and the median VAS pain score in patients was 0.6 (range 0–10). Patients had lower SF‐36 physical component summary (PCS) scores compared with controls (P < 0.001), and this was evident for patients both with and without clinical remission (P ≤ 0.01). No group differences were found in SF‐36 mental component summary scores. Patients also scored worse than controls on all SF‐36 subscales (P ≤ 0.01) except mental health. PCS scores worsened significantly between the 15‐ and 30‐year followup time points (P = 0.001). Worse HAQ DI, VAS pain, and patient's global assessment of well‐being scores, and receiving disability/social living allowance at 30 years, were correlated with lower PCS scores. Worse HAQ DI, patient's global assessment of well‐being, and VAS fatigue scores at 15‐year followup predicted lower PCS scores at 30‐year followup.

Conclusion

JIA had a detrimental effect on physical HRQoL as measured by the PCS of the SF‐36. The strongest correlates were physical disability, pain, fatigue, well‐being, and receiving disability/social living allowance.

     

Validation of Classification Criteria of Macrophage Activation Syndrome in Japanese Patients With Systemic Juvenile Idiopathic Arthritis

Objective

To validate whether the 2016 American College of Rheumatology/European League Against Rheumatism classification criteria of macrophage activation syndrome (MAS) complicating systemic juvenile idiopathic arthritis (JIA) is practical in the real world.

Methods

A combination of expert consensus and analysis of real patient data was conducted by a panel of 15 pediatric rheumatologists. A total of 65 profiles comprised 18 patients with systemic JIA–associated MAS and 47 patients with active systemic JIA without evidence of MAS. From these profiles, 10 patient data points for full‐blown MAS, 11 patient data points for MAS onset, and 47 patient data points for acute systemic JIA without MAS were evaluated.

Results

Evaluation of the classification criteria to discriminate full‐blown MAS from acute systemic JIA without MAS showed a sensitivity of 1.000 and specificity of 1.000 at the time of full‐blown MAS. Sensitivity was 0.636 and specificity was 1.000 at the time of MAS onset. The number of measurement items that fulfilled the criteria increased in full‐blown MAS compared to that at MAS onset. At MAS onset, the positive rates of patients who met the criteria for platelet counts and triglycerides were low, whereas those for aspartate aminotransferase were relatively high. At full‐blown MAS, the number of patients who met the criteria for each measurement item increased.

Conclusion

The classification criteria for MAS complicating systemic JIA had a very high diagnostic performance. However, the diagnostic sensitivity for MAS onset was relatively low. For the early diagnosis of MAS in systemic JIA, the dynamics of laboratory values during the course of MAS should be further investigated.

     

Antinuclear Matrix Protein 2 Autoantibodies and Edema,Muscle Disease,and Malignancy Risk in Dermatomyositis Patients

Objective

Dermatomyositis (DM ) patients typically present with proximal weakness and autoantibodies that are associated with distinct clinical phenotypes. We observed that DM patients with autoantibodies recognizing the nuclear matrix protein NXP ‐2 often presented with especially severe weakness. The aim of this study was to characterize the clinical features associated with anti–NXP ‐2 autoantibodies.

Methods

There were 235 DM patients who underwent testing for anti–NXP ‐2 autoantibodies. Patient characteristics, including muscle strength, were compared between those with and without these autoantibodies. The number of cancer cases observed in anti–NXP ‐2‐positive subjects was compared with the number expected in the general population.

Results

Of the DM patients, 56 (23.8%) were anti–NXP ‐2‐positive. There was no significant difference in the prevalence of proximal extremity weakness in patients with and without anti–NXP ‐2. In contrast, anti–NXP ‐2‐positive patients had more prevalent weakness in the distal arms (35% versus 20%; P = 0.02), distal legs (25% versus 8%; P < 0.001), and neck (48% versus 23%; P < 0.001). Anti–NXP ‐2‐positive subjects were also more likely to have dysphagia (62% versus 35%; P < 0.001), myalgia (46% versus 25%; P = 0.002), calcinosis (30% versus 17%; P = 0.02), and subcutaneous edema (36% versus 19%; P = 0.01) than anti–NXP ‐2‐negative patients. Five anti–NXP ‐2‐positive subjects (9%) had cancer‐associated myositis, representing a 3.68‐fold increased risk (95% confidence interval 1.2–8.6) compared to the expected prevalence in the general population.

Conclusion

In DM , anti–NXP ‐2 autoantibodies are associated with subcutaneous edema, calcinosis, and a muscle phenotype characterized by myalgia, proximal and distal weakness, and dysphagia. As anti–NXP ‐2‐positive patients have an increased risk of cancer, we suggest that they undergo comprehensive cancer screening.

     

Effect of Biologic Therapy on Clinical and Laboratory Features of Macrophage Activation Syndrome Associated With Systemic Juvenile Idiopathic Arthritis

Objective

To assess performance of the 2016 macrophage activation syndrome (MAS) classification criteria for patients with systemic juvenile idiopathic arthritis (JIA) who develop MAS while treated with biologic medications.

Methods

A systematic literature review was performed to identify patients with MAS while being treated with interleukin (IL)‐1 and IL‐6 blocking agents. Clinical and laboratory information was compared to a large previously compiled historical cohort.

Results

Eighteen publications were identified, and after removing duplicates, 35 patients treated with canakinumab and 49 patients with tocilizumab were available for analysis; 5 anakinra‐treated patients were excluded due to limited numbers. MAS classification criteria were less likely to classify tocilizumab‐treated patients as having MAS compared to the historical cohort or canakinumab‐treated patients (56.7%, 78.5%, and 84%, respectively; P < 0.01). Patients who developed MAS while treated with canakinumab trended towards lower ferritin at MAS onset than the historical cohort (4,050 versus 5,353 ng/ml; P = 0.18) but had no differences in other cardinal clinical or laboratory features. In comparison, patients who developed MAS while treated with tocilizumab were less likely febrile and had notably lower ferritin levels (1,152 versus 5,353 ng/ml; P < 0.001). Other features of MAS were more pronounced in patients treated with tocilizumab, including lower platelet counts, lower fibrinogen, and higher aspartate aminotransferase levels. Mortality rates for patients with MAS treated with tocilizumab or canakinumab were not significantly different from the historical cohort.

Conclusion

These findings show substantial alterations in MAS features that may limit utility of defined criteria for diagnosis of systemic JIA patients treated with biologic agents.

     

Impact of Disease Severity,Illness Beliefs,and Coping Strategies on Outcomes in Psoriatic Arthritis

Objective

Little is known about how people with psoriatic arthritis (PsA) cope with and manage their condition, but data show that psychological problems are underrecognized and undertreated. The Common Sense Self‐Regulatory Model (CS‐SRM) suggests illness beliefs, mediated by coping, may influence health outcomes. The study aimed to investigate the roles of disease severity, illness beliefs, and coping strategies in predicting depression, anxiety, and quality of life (QoL) in people with PsA. Additionally, we aimed to assess the role of depression and anxiety in predicting QoL.

Methods

We conducted a cross‐sectional observational study, where adults with PsA (n = 179) completed validated measures of predictor (illness beliefs, coping strategies, disease severity) and outcome variables (depression, anxiety, QoL) using an online survey distributed via social media.

Results

The participants were a community sample of 179 adults with PsA, ages 20 to 72 years (77.1% female). After controlling for disease severity, hierarchical multiple regression models indicated that more negative beliefs about consequences and behavioral disengagement as a coping method predicted levels of depression, and self‐blame predicted anxiety. Beliefs about consequences and the presence of depression predicted quality of life scores after controlling for disease severity.

Conclusion

This study offers support for the use of the CS‐SRM in explaining variation on psychological outcomes in individuals with PsA. The illness beliefs and coping strategies identified as predictors in this article are potential targets for interventions addressing PsA‐related distress and QoL.

     

Does Education Level Mitigate the Effect of Poverty on Total Knee Arthroplasty Outcomes?

Objective

Total knee arthroplasty (TKA) outcomes are worse for patients from poor neighborhoods, but whether education mitigates the effect of poverty is not known. We assessed the interaction between education and poverty on 2‐year Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and function.

Methods

Patient‐level variables from an institutional registry were linked to US Census Bureau data (census tract [CT] level). Statistical models including patient and CT‐level variables were constructed within multilevel frameworks. Linear mixed‐effects models with separate random intercepts for each CT were used to assess the interaction between education and poverty at the individual and community level on WOMAC scores.

Results

Of 3,970 TKA patients, 2,438 (61%) had some college or more. Having no college was associated with worse pain and function at baseline and 2 years (P = 0.0001). Living in a poor neighborhood (>20% below poverty line) was associated with worse 2‐year pain (P = 0.02) and function (P = 0.006). There was a strong interaction between individual education and community poverty with WOMAC scores at 2 years. Patients without college living in poor communities had pain scores that were ~10 points worse than those with some college (83.4% versus 75.7%; P < 0.0001); in wealthy communities, college was associated with a 1‐point difference in pain. Function was similar.

Conclusion

In poor communities, those without college attain 2‐year WOMAC scores that are 10 points worse than those with some college; education has no impact on TKA outcomes in wealthy communities. How education protects those in impoverished communities warrants further study.

     

Fear of Movement and Associated Factors Among Adults With Symptomatic Knee Osteoarthritis

Objective

To examine the frequency of and factors associated with fear of movement (FOM ) among patients with symptomatic knee osteoarthritis (KOA ), using the new Brief Fear of Movement (BFOM ) measure.

Methods

Participants (n = 350) enrolled in a clinical trial completed the BFOM scale prior to randomization. The relationships of BFOM with the following characteristics were examined: age, sex, race, education, pain and activities of daily living (ADL ) subscales of the Knee Injury and Osteoarthritis Outcome Score (KOOS ), knee symptom duration, depressive symptoms (8‐item Patient Health Questionnaire [PHQ ‐8]), history of falls and knee injury, family history of knee problems, self‐efficacy for exercise (SEE ), and unilateral balance test. A proportional odds logistic regression model examined multivariable associations of participant characteristics with a 3‐level BFOM variable (agreement with 0, 1–2, or ≥3 items).

Results

The majority of participants (77%) agreed with at least 1 item on the BFOM scale, and 36% endorsed 3+ items, suggesting a high degree of FOM . In the multivariable model, the following remained significant after backward selection: age (odds ratio [OR ] 0.79 per 10‐point increase, 95% confidence interval [95% CI ] 0.66–0.95), KOOS ADL (OR 0.86 per 10‐point increase, 95% CI 0.76–0.97), PHQ ‐8 (OR 1.15, 95% CI 1.08–1.22), and SEE (OR 0.87 per 10‐point increase, 95% CI 0.78–0.96).

Conclusion

FOM was common among patients with symptomatic KOA , and this could negatively impact physical activity. Psychological variables were significantly associated with FOM , suggesting behavioral and psychological interventions may decrease FOM and improve outcomes among individuals with symptomatic KOA .

     

Preoperative Lund‐Mackay computed tomography score is associated with preoperative symptom severity and predicts quality‐of‐life outcome trajectories after sinus surgery

Background

Disagreement exists about the relationship between Lund‐Mackay CT scores (LMCTS) and quality‐of‐life outcome (QoL) measures. We investigated whether preoperative LMCTS are associated with preoperative QoL, and whether LMCTS is predictive of postoperative QoL outcomes in chronic rhinosinusitis (CRS) patients.

Methods

Adult patients with medically recalcitrant CRS (n = 665) were enrolled in a prospective, observational cohort study. Preoperative LMCTS and pre‐ and postoperative self‐reported QoL outcomes (22‐item Sino‐Nasal Outcomes Test [SNOT‐22]) were collected and evaluated over 12 months. Five hundred sixty‐eight patients met the inclusion criteria. Longitudinal linear mixed‐effects modeling was used to investigate the effect of LMCTS on QoL after functional endoscopic sinus surgery (FESS).

Results

Preoperative LMCTS were significantly associated with preoperative SNOT‐22 scores (p < 0.01) and postoperative SNOT‐22 scores (p < 0.001), driven by Extranasal and Rhinologic subdomains of the QoL questionaire. Patients in the lowest preoperative LMCTS quartile had the lowest mean change in SNOT‐22 scores at 12 months (16.8 points; 95% confidence interval [CI], 12.2‐21.3). Patients in the second and third lowest preoperative LMCTS quartiles had mean changes at 12 months of 21.1 points (95% CI, 16.7‐25.4) and 23.1 points (95% CI, 18.3‐27.9). Patients in the highest preoperative LMCTS quartile had the greatest improvement in SNOT‐22 scores after FESS (29.9 points; 95% CI, 24.9‐34.8). The difference in QoL change at 12 months between the highest and lowest preoperative LMCTS quartiles was 13.1 points (95% CI, 6.0‐20.2; p < 0.001).

Conclusion

Our study demonstrates that preoperative LMCTS correlate with preoperative extranasal and rhinologic symptom severity and that the LMCTS is an indicator of postsurgical QoL outcomes for medically recalcitrant chronic rhinosinusitis patients in a large tertiary otolaryngology setting.

     

Pain Catastrophizing,Subjective Outcomes,and Inflammatory Assessments Including Ultrasound: Results From a Longitudinal Study of Rheumatoid Arthritis Patients

Objective

Pain catastrophizing is conceptualized as a negative cognitive–affective response to anticipated or actual pain and has been associated with important pain‐related outcomes. The objective of this prospective study of established rheumatoid arthritis (RA) patients was to explore how pain catastrophizing was related to patient‐reported outcomes (PROs), composite scores, and assessments of inflammatory activity.

Methods

RA patients starting biologic disease‐modifying antirheumatic drugs were examined at baseline and after 1, 2, 3, 6, and 12 months with PROs (joint pain/patient's global visual analog scale [VAS], modified Health Assessment Questionnaire, Rheumatoid Arthritis Impact of Disease score), clinical and laboratory assessments (tender/swollen joint count, assessor's global VAS, erythrocyte sedimentation rate/C‐reactive protein [CRP] level), ultrasound (US) (gray scale [GS]/power Doppler [PD] of 36 joints and 4 tendons), and pain catastrophizing. The composite scores for Disease Activity Score in 28 joints, Clinical Disease Activity Index, and Simplified Disease Activity Index were calculated. Statistical calculations included independent samples t‐test, paired samples t‐test, one‐way analysis of variance, Pearson's correlations, and linear and logistic regression.

Results

Of 209 patients included, 152 (72.7%) completed 12‐month followup. Pain catastrophizing, PROs, and clinical and inflammatory assessments decreased significantly (P < 0.001). Pain catastrophizing was strongly correlated with the PROs and composite scores (P < 0.001) but not with the inflammatory parameters (swollen joint count, CRP level, and GS/PD US). Patients with higher levels of pain catastrophizing had higher PROs and composite scores during the study (P < 0.001) but not inflammatory assessments. Baseline pain catastrophizing was negatively associated with achievement of remission at 6 and 12 months (P < 0.05).

Conclusion

Pain catastrophizing was strongly associated with PROs and composite measures, but not with markers of inflammation. High levels of pain catastrophizing reduced the likelihood of achieving composite score remission and should be a factor to consider in a treat‐to‐target strategy.

     

Accuracy of Magnetic Resonance Imaging for Grading of Subglottic Stenosis in Patients With Granulomatosis With Polyangiitis: Correlation With Pulmonary Function Tests and Laryngoscopy

Objective

To compare magnetic resonance imaging (MRI)–based and laryngoscopy‐based subglottic stenosis (SGS) grading with pulmonary function testing (PFT) in patients with granulomatosis with polyangiitis (GPA).

Methods

In this retrospective study, we included 118 examinations of 44 patients with GPA and suspected SGS. All patients underwent MRI, laryngoscopy, and PFT. Stenosis was graded on a 4‐point scale by endoscopy and MRI using the Meyer‐Cotton (MC) score (score 1: ≤50%, 2: 51–70%, 3: 71–99%, and 4: 100%) and as percentage by MRI. Results were compared with peak expiratory flow (PEF) and maximum inspiratory flow (MIF) from PFT, serving as objective functional reference.

Results

In MRI, 112 of 118 examinations (95%) were rated positive for SGS (grade 1 [n = 82], grade 2 [n = 26], and grade 3 [n = 4]), whereas in laryngoscopy 105 of 118 examinations (89%) were rated positive for SGS (grade 1 [n = 73], grade 2 [n = 24], and grade 3 [n = 8]). MRI and laryngoscopy agreed in 75 of 118 examinations (64%). MRI determined higher scores in 20 examinations (17%) and lower scores in 23 examinations (19%) compared to laryngoscopy. MC scores as determined by both MRI and laryngoscopy showed comparable correlations with PEF (r = ?0.363, P = 0.016, and r = ?0.376, P = 0.012, respectively) and MIF (r = ?0.340, P = 0.024, and r = ?0.320, P = 0.034, respectively). The highest correlation was found between MRI‐based stenosis grading in percentage with PEF (r = ?0.441, P = 0.003) and MIF (r = ?0.413, P = 0.005).

Conclusion

MRI and laryngoscopy provide comparable results for grading of SGS in GPA and correlate well with PFT. MRI is an attractive noninvasive and radiation‐free alternative for monitoring the severity of SGS in patients with GPA.

     

Radiographic Progression in Psoriatic Arthritis Achieving a Good Response to Treatment: Data Using Newer Composite Indices of Disease Activity

Objective

To compare radiographic outcomes according to the magnitude of the response utilizing 3 new psoriatic composite disease activity measures (the Psoriatic Arthritis Disease Activity Score [PASDAS], the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis Composite Exercise [GRACE], and the Disease Activity in PsA [DAPSA]).

Methods

The data were taken from the GO‐REVEAL data set, a large randomized, double‐blind study that evaluated the safety and efficacy of 2 doses of the tumor necrosis factor inhibitor golimumab in subjects with active psoriatic arthritis (PsA). Response criteria at 24 weeks were applied across the whole data set, irrespective of treatment group. Radiographic scores at baseline and 24 weeks were assessed using the modified Sharp/van der Heijde method for PsA.

Results

Overall, for each measure, radiographic progression was significantly greater in subjects with a moderate or poor outcome, and absent in those with a good outcome. The proportion of subjects without radiographic progression in the good outcome group was 83% using the PASDAS (χ² = 7.9; P = 0.02), 80% using the GRACE (χ² = 5.8; P = 0.05), and 76% using the DAPSA (χ² = 3.4; P = 0.19).

Conclusion

Response criteria for disease‐specific composite measures enable separation between groups in terms of radiographic progression and may therefore be used as suitable targets for interventional studies, as well as in the clinic.

     

Prevalence and Disease‐Specific Risk Factors for Lower Urinary Tract Symptoms in Systemic Sclerosis: An International Multicenter Study

Objective

To determine the prevalence of lower urinary tract symptoms (LUTS) in systemic sclerosis (SSc), to find specific risk factors, and to assess their impact on quality of life (QoL).

Methods

In a multicenter study, 334 patients completed a self‐administered questionnaire on LUTS and QoL. LUTS were classified into 3 main categories: storage, voiding, and post‐micturition symptoms. Digestive symptoms burden was captured by a visual analog scale, divided into 5 equal categories. Multivariable logistic regressions were performed to test association between risk factors and LUTS categories. Linear regression adjusted the association between LUTS and QoL.

Results

LUTS were recorded in 311 SSc patients (96.0%) and classified as severe in 120 (38.0%). The storage category of LUTS was the most prevalent (91.9%), followed by voiding (72.2%) and then by post‐micturition symptoms (49.8%). Risk factors identified in the multivariable models were higher than the median Health Assessment Questionnaire disability index (HAQ DI; odds ratio [OR] 4.2 [95% confidence interval (95% CI) 1.4–12.9]) in the storage category; higher than the median HAQ DI (OR 2.4 [95% CI 1.2–4.9]) for digestive symptoms burden (OR 1.9 [95% CI 1.3–2.7]) and synovitis (OR 4.8 [95% CI 1.0–22.6) in the voiding category; and higher for digestive symptoms burden (OR 1.2 [95% CI 1.0–1.5]) in the post‐micturition category of symptoms. These factors also increased the odds of having further severe symptoms. QoL was affected by the 3 categories of LUTS and decreased progressively with increasing frequency of symptoms.

Conclusion

Self‐reported LUTS are among the most frequent symptoms in SSc and are associated with digestive symptoms. SSc patients with LUTS have lower QoL.

     

Personality Changes During the Transition from Cognitive Health to Mild Cognitive Impairment

Background/Objectives

Behavioral problems in individuals with Alzheimer's disease (AD ) impose major management challenges. Current prevention strategies are anchored to cognitive outcomes, but behavioral outcomes may provide another, clinically relevant opportunity for preemptive therapy. We sought to determine whether personality changes that predispose to behavioral disorders arise during the transition from preclinical AD to mild cognitive impairment (MCI ).

Design

Longitudinal observational cohort study.

Setting

Academic medical center.

Participants

Members of an apolipoprotein E (APOE ) ?4 genetically enriched cohort of Maricopa County residents who were neuropsychiatrically healthy at entry (N = 277). Over a mean interval of 7 years, 25 who developed MCI and had the Neuroticism, Extraversion, and Openness Personality Inventory—Revised (NEO ‐PI ‐R) before and during the MCI transition epoch were compared with 252 nontransitioners also with serial NEO ‐PI ‐R administrations.

Intervention

Longitudinal administration of the NEO ‐PI ‐R and neuropsychological test battery.

Measurements

Change in NEO ‐PI ‐R factor scores (neuroticism, extraversion, openness, agreeableness, conscientiousness) from entry to the epoch of MCI diagnosis or an equivalent follow‐up duration in nontransitioners.

Results

NEO ‐PI ‐R neuroticism T‐scores increased significantly more in MCI transitioners than in nontransitioners (mean 2.9, 95% confidence interval (CI ) = 0.9–4.9 vs 0, 95% CI = ?0.7–0.7, P = .02), and openness decreased more in MCI transitioners than in nontransitioners (?4.8, 95% CI = ?7.3 to ?2.4 vs ?1.0, 95% CI = ?1.6 to ?0.4, P < .001). Concurrent subclinical but statistically significant changes in behavioral scores worsened more in MCI transitioners than nontransitioners for measures of depression, somatization, irritability, anxiety, and aggressive attitude.

Conclusion

Personality and subclinical behavioral changes begin during the transition from preclinical AD to incident MCI and qualitatively resemble the clinically manifest behavioral disorders that subsequently arise in individuals with frank dementia.

     

Nationwide Experience With Off‐Label Use of Interleukin‐1 Targeting Treatment in Familial Mediterranean Fever Patients

Objective

Approximately 30–45% of patients with familial Mediterranean fever (FMF) have been reported to have attacks despite colchicine treatment. Currently, data on the treatment of colchicine‐unresponsive or colchicine‐intolerant FMF patients are limited; the most promising alternatives seem to be anti–interleukin‐1 (anti–IL‐1) agents. Here we report our experience with the off‐label use of anti–IL‐1 agents in a large group of FMF patients.

Methods

In all, 21 centers from different geographical regions of Turkey were included in the current study. The medical records of all FMF patients who had used anti–IL‐1 treatment for at least 6 months were reviewed.

Results

In total, 172 FMF patients (83 [48%] female, mean age 36.2 years [range 18–68]) were included in the analysis; mean age at symptom onset was 12.6 years (range 1–48), and the mean colchicine dose was 1.7 mg/day (range 0.5–4.0). Of these patients, 151 were treated with anakinra and 21 with canakinumab. Anti–IL‐1 treatment was used because of colchicine‐resistant disease in 84% and amyloidosis in 12% of subjects. During the mean 19.6 months of treatment (range 6–98), the yearly attack frequency was significantly reduced (from 16.8 to 2.4; P < 0.001), and 42.1% of colchicine‐resistant FMF patients were attack free. Serum levels of C‐reactive protein, erythrocyte sedimentation rate, and 24‐hour urinary protein excretion (5,458.7 mg/24 hours before and 3,557.3 mg/24 hours after) were significantly reduced.

Conclusion

Anti–IL‐1 treatment is an effective alternative for controlling attacks and decreasing proteinuria in colchicine‐resistant FMF patients.

     

Determining the Risk Factors and Clinical Features Associated With Severe Gastrointestinal Dysmotility in Systemic Sclerosis

Objective

A subset of patients with systemic sclerosis (SSc) develop severe gastrointestinal (GI) dysmotility. We sought to determine predictors of severe SSc GI dysmotility and to identify distinct features associated with this phenotype.

Methods

Patients with SSc who required supplemental nutrition (enteral or parenteral tube feeding) were compared to SSc patients with mild GI symptoms in a cross‐sectional analysis. The association between severe GI dysmotility and clinical and serologic features was examined using logistic regression. Baseline data were examined to determine predictors of developing severe GI dysfunction using Cox regression.

Results

SSc patients with severe GI dysmotility (n = 66) were more likely than those patients with mild GI symptoms (n = 1,736) to be male (odds ratio [OR] 2.47 [95% confidence interval (95% CI) 1.34–4.56]; P = 0.004), and to have myopathy (OR 5.53 [95% CI 2.82–10.82]; P < 0.001), and sicca symptoms (OR 2.40 [95% CI 1.30–4.42]; P = 0.005), even after adjustment for potential confounders. Baseline features that were associated with the future development of severe GI dysfunction included male sex (hazard ratio [HR] 2.99 [95% CI 1.53–5.84]; P = 0.001) and myopathy (HR 5.08 [95% CI 2.21–11.67]; P < 0.001).

Conclusion

Distinct clinical features are present in SSc patients who are at risk of developing severe GI dysmotility. This finding is not only important clinically but also suggests that a unique pathologic process is at work in these patients.

     

Validation of the Social Appearance Anxiety Scale in Patients With Systemic Sclerosis: A Scleroderma Patient‐Centered Intervention Network Cohort Study

Objective

Systemic sclerosis (SSc) is an autoimmune disease that can cause disfiguring changes in appearance. This study examined the structural validity, internal consistency reliability, convergent validity, and measurement equivalence of the Social Appearance Anxiety Scale (SAAS) across SSc disease subtypes.

Methods

Patients enrolled in the Scleroderma Patient‐centered Intervention Network Cohort completed the SAAS and measures of appearance‐related concerns and psychological distress. Confirmatory factor analysis (CFA) was used to examine the structural validity of the SAAS. Multiple‐group CFA was used to determine whether SAAS scores can be compared across patients with limited and diffuse disease subtypes. Cronbach's alpha was used to examine internal consistency reliability. Correlations of SAAS scores with measures of body image dissatisfaction, fear of negative evaluation, social anxiety, and depression were used to examine convergent validity. SAAS scores were hypothesized to be positively associated with all convergent validity measures, with correlations significant and moderate to large in size.

Results

A total of 938 patients with SSc were included. CFA supported a 1‐factor structure (Comparative Fit Index 0.92, Standardized Root Mean Residual 0.04, and Root Mean Square Error of Approximation 0.08), and multiple‐group CFA indicated that the scalar invariance model best fit the data. Internal consistency reliability was good in the total sample (α = 0.96) and in disease subgroups. Overall, evidence of convergent validity was found with measures of body image dissatisfaction, fear of negative evaluation, social anxiety, and depression.

Conclusion

The SAAS can be reliably and validly used to assess fear of appearance evaluation in patients with SSc, and SAAS scores can be meaningfully compared across disease subtypes.

     

Risk factors for development of uveitis differ between girls and boys with juvenile idiopathic arthritis

Objective

Uveitis is the most common extraarticular manifestation of juvenile idiopathic arthritis (JIA) and is associated with considerable morbidity. The aim of this study was to examine the risk factors associated with uveitis in JIA.

Methods

We conducted a chart review of 1,047 patients with JIA from a single tertiary care pediatric rheumatology center for factors associated with the development of uveitis. Special emphasis was put on the following known risk factors: oligoarthritis, antinuclear antibody (ANA) status, sex, and age at the time of onset of JIA.

Results

The risk of uveitis developing was age dependent in girls but not in boys. Among girls, the risk was maximal (47%) in those who were ANA positive and were ages 1–2 years at the time of the onset of JIA; this risk decreased to <10% in those in whom the age at onset was >7 years. Only girls had an age‐dependent and ANA‐associated increased risk of uveitis. The time interval from the diagnosis of JIA to the diagnosis of uveitis was statistically significantly longer in patients in whom the onset of JIA occurred at a younger age (P = 0.04). This effect was even more pronounced in ANA‐positive patients (P = 0.004). The JIA subtype did not influence a patient's risk of the development of uveitis.

Conclusion

An age‐associated risk of uveitis was observed only in girls who were younger than 7 years of age at the time of the onset of JIA. The duration of time between the diagnosis of JIA and the onset of uveitis was longer in patients in whom JIA was diagnosed at a younger age, especially in those who were ANA positive. We suggest that our findings have implications for uveitis screening in patients with JIA.

     

Geriatric Assessment of Physical and Cognitive Functioning in a Diverse Cohort of Systemic Lupus Erythematosus Patients: A Pilot Study

Objective

To use multidomain functional assessment, which is commonly performed in geriatric patients but is novel in patients with systemic lupus erythematosus (SLE), to better understand functional impairment in patients with SLE.

Methods

We recruited 60 adult participants (aged 20–39 years [26.7%], 40–59 years [50.0%], and ≥60 years [23.3%]; 80.0% African American and 90.0% female) from an existing cohort of SLE patients. During in‐person visits (from October 2016 to April 2017), we evaluated physical performance (range 0–4, with higher scores indicating better performance), cognitive performance (5 fluid cognition domains; adjusted T scores), and self‐reported measures including physical functioning (T scores), activities of daily living (ADLs), falls, and life‐space mobility.

Results

In the SLE patients, the mean balance score (3.7) and gait speed score (3.4) were high, while the mean lower body strength score was low (1.8). Cognitive performance was average (score of 5.0) for episodic (47.7) and working (48.6) memory and low average for cognitive flexibility (43.7), processing speed (42.6), and attention/inhibitory control (38.8 [>1 SD below average]) when compared with healthy individuals of the same age, sex, race, ethnicity, and education level. Most participants reported the ability to independently perform basic ADLs, but many reported the inability to independently perform instrumental ADLs. Nearly half (45.0%) of participants reported falling in the prior year. Only 40.0% reported unlimited ability to travel without the help of another person. Scores generally did not differ substantially according to age.

Conclusion

Our results suggest a high prevalence of impairment across multiple domains of function in SLE patients of all ages, similar to or exceeding the prevalence observed in much older geriatric populations. Further research into the added value of geriatric assessment in routine care for SLE is warranted.

     

Association of High Mobility Group Box Chromosomal Protein 1 and Receptor for Advanced Glycation End Products Serum Concentrations With Extraglandular Involvement and Disease Activity in Sjögren's Syndrome

Objective

To assess serum levels of high mobility group box chromosomal protein 1 (HMGB‐1) and the soluble receptor for advanced glycation end products (sRAGE) in patients with Sjögren's syndrome (SS) and explore correlations with disease activity.

Methods

Thirty‐nine patients with SS and 21 healthy controls were included in this cross‐sectional study. Clinical and laboratory values were obtained from all patients. Disease activity was assessed using the European League Against Rheumatism SS Disease Activity Index (ESSDAI). Serum samples were collected and HMGB‐1 and sRAGE levels were measured using enzyme‐linked immunosorbent assay (ELISA), and HMGB‐1 concentrations were semiquantified by Western blotting.

Results

In ELISA, HMGB‐1 serum levels did not differ between healthy controls and patients with SS (P = 0.783). When measured by semiquantitative Western blotting, HMGB‐1 levels were increased in patients with SS compared to healthy controls (P = 0.012). HMGB‐1 serum levels detected by Western blotting were higher in patients with extraglandular manifestations (P = 0.003) and were correlated with ESSDAI disease activity (r = 0.544, P < 0.0001). Furthermore, sRAGE was elevated in the sera of patients with SS (P = 0.003) compared to healthy controls and was also correlated with the ESSDAI (r = 0.545, P = 0.002).

Conclusion

Serum levels of total HMGB‐1 and sRAGE were elevated in patients with SS compared to healthy controls and correlated with disease activity as measured by the ESSDAI. Patients with extraglandular involvement had high serum levels of HMGB‐1.