Delays to Care in Pediatric Lupus Patients: Data From the Childhood Arthritis and Rheumatology Research Alliance Legacy Registry

Objective

Prompt treatment for lupus is important to prevent morbidity. A potential barrier to early treatment of pediatric lupus is delayed presentation to a pediatric rheumatologist. To better understand factors contributing to delayed presentation among pediatric lupus patients, we examined differences in demographic and clinical characteristics of lupus patients within the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Legacy Registry with regard to time between symptom onset and presentation to a pediatric rheumatologist.

Methods

We analyzed data from 598 CARRA Legacy Registry participants for differences between those who presented early (within <1 month of symptom onset), between 1–3 months (typical presentation), with moderate delays (3–12 months), and with severe delays (≥1 year). Factors associated with early presentation, moderate delay, and severe delay were determined by multinomial logistic regression.

Results

Forty‐four percent of patients presented early, while 23% had moderate delays and 9% had severe delays. Family history of lupus, absence of discoid rash, and location in a state with a higher density of pediatric rheumatologists were associated with earlier presentation. Younger age, low household income (<$25,000 per year), and a family history of lupus were associated with severe delay.

Conclusion

Delays to care ≥1 year exist in a notable minority of pediatric lupus patients from the CARRA Legacy Registry. In this large and diverse sample of patients, access to care and family resources played an important role in predicting time to presentation to a pediatric rheumatologist.

     

Foot Barriers in Patients With Early Rheumatoid Arthritis: An Interview Study Among Swedish Women and Men

Objective

Foot impairments are related to reduced mobility and participation restrictions in daily activities in patients with established rheumatoid arthritis (RA). The new biologic medications are effective and reduce disease activity, but not disability to the same extent. Foot impairments are assumed to be related to participation restrictions also in patients with early RA, diagnosed after the introduction of biologic medications. Knowledge of foot impairments needs to be explored further after the introduction of biologic disease‐modifying antirheumatic drugs (bDMARDs). The aim of this study was to explore the patients’ perspective of foot impairments related to early RA.

Methods

The sample included 59 patients (ages 20–63 years) who were interviewed about participation dilemmas in daily life using the critical incident technique. The interviews were audio‐recorded and transcribed. Data related to foot impairments were extracted and analyzed thematically. A research partner validated the analysis.

Results

Patients with early RA described a variety of participation restrictions related to foot impairments: foot hindrances in domestic life, foot impairments influencing work, leisure activities restricted by one's feet, struggling to be mobile, and foot impairments as an early sign of rheumatic disease.

Conclusion

There is a need to focus on foot impairments related to early RA, and for health care professionals to understand these signs. A suggestion for future research is to conduct a longitudinal followup of foot impairment related to medication, disease activity, and disability in patients diagnosed after the introduction of bDMARDs.

     

Subjective and Objective Measures of Dryness Symptoms in Primary Sjögren's Syndrome: Capturing the Discrepancy

Objective

To develop a novel method for capturing the discrepancy between objective tests and subjective dryness symptoms (a sensitivity scale) and to explore predictors of dryness sensitivity.

Methods

Archive data from the UK Primary Sjögren's Syndrome Registry (n = 688) were used. Patients were classified on a scale from ?5 (stoical) to +5 (sensitive) depending on the degree of discrepancy between their objective and subjective symptoms classes. Sensitivity scores were correlated with demographic variables, disease‐related factors, and symptoms of pain, fatigue, anxiety, and depression.

Results

Patients were on average relatively stoical for both types of dryness symptoms (mean ± SD ocular dryness ?0.42 ± 2.2 and ?1.24 ± 1.6 oral dryness). Twenty‐seven percent of patients were classified as sensitive to ocular dryness and 9% to oral dryness. Hierarchical regression analyses identified the strongest predictor of ocular dryness sensitivity to be self‐reported pain and that of oral dryness sensitivity to be self‐reported fatigue.

Conclusion

Ocular and oral dryness sensitivity can be classified on a continuous scale. The 2 symptom types are predicted by different variables. A large number of factors remain to be explored that may impact symptom sensitivity in primary Sjögren?s syndrome, and the proposed method could be used to identify relatively sensitive and stoical patients for future studies.

     

From Childhood to Adulthood: Disease Activity Trajectories in Childhood‐Onset Systemic Lupus Erythematosus

Objective

No previous study has studied the longitudinal disease course of childhood‐onset systemic lupus erythematosus (cSLE). Our objectives are to assess distinguishable differences in disease activity trajectories in cSLE patients, determine baseline factors predictive of disease trajectory membership, and assess if the different disease activity trajectories are associated with different damage trajectories.

Methods

This is a retrospective, longitudinal inception cohort of cSLE patients. Patients were followed from diagnosis as children, until they were adults. SLE disease activity was modeled as a latent characteristic, jointly using the Systemic Lupus Erythematosus Disease Activity Index 2000 and prednisone in a Bayesian growth mixture model. Baseline factors were tested for membership prediction of the latent classes of disease trajectories. Differences in damage trajectories by disease activity classes were tested using a mixed model.

Results

A total of 473 patients (82% females), with median age at diagnosis of 14.1 years, were studied. We studied 11,992 visits (2,666 patient‐years). We identified 5 classes of disease activity trajectories. Baseline major organ involvement, number of American College of Rheumatology criteria, and age at diagnosis predicted memberships into different classes. A higher proportion of Asians was in class 2 compared to class 5. Class 1 was associated with the most accrual of damage, while class 5 was associated with no significant damage accrual, even after 10 years.

Conclusion

There are 5 distinct latent classes of disease trajectory in patients with cSLE. Membership within disease trajectories is predicted by baseline clinical and demographic factors. Membership in different disease activity trajectory classes is associated with different damage trajectories.

     

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 .

     

Training Physical Therapists in Person‐Centered Practice for People With Osteoarthritis: A Qualitative Case Study

Objective

To explore physical therapists’ experiences with, and the impacts of, a training program in person‐centered practice to support exercise adherence in people with knee osteoarthritis.

Methods

This was a qualitative case study using semi‐structured interviews, nested within a clinical trial. Eight Australian physical therapists were interviewed before, and after, training in person‐centered practice for people with knee osteoarthritis. Training involved a 2‐day workshop, skills practice, and audit of 8 consultations with 4 patients (per therapist), and a final single‐day workshop for audit feedback and consolidation. Semi‐structured interviews were audio‐recorded and transcribed verbatim. Data were thematically analyzed.

Results

Three pretraining themes arose regarding usual communication style, definitions of person‐centered care, and sharing exercise adherence responsibility. Three themes related to the training experience emerged: learning a new language, challenging conceptions of practice, and putting it into practice. Post‐training, 3 themes arose regarding new knowledge deepening understanding of person‐centered care, changing beliefs about sharing responsibilities, and changed conceptions of role.

Conclusion

Although physical therapists found training overwhelming initially as they realized the limitations of their current knowledge and clinical practice, they felt more confident and able to provide person‐centered care to people with knee osteoarthritis by the end of training. Training in structured person‐centered methodology that provides opportunity for skills practice with patients using a restructured consultation framework can change physical therapists’ beliefs about their roles when managing patients with osteoarthritis and positively impact their clinical practice.

     

Evaluation of a Methodologic Approach to Define an Inception Cohort of Rheumatoid Arthritis Patients Using Administrative Data

Objective

Identifying incident rheumatoid arthritis (RA) is desirable in order to create inception cohorts. We evaluated an approach to identify incident RA in health plan claims data.

Methods

Both Medicare and commercial claims data were linked to Corrona, a US RA registry. We evaluated the accuracy of year of RA onset in the registry (gold standard) versus different claims algorithms, varying International Classification of Diseases, Ninth Revision codes for RA/arthritis, duration of health plan enrollment preceding diagnosis (minimum of 1 versus 2 years), and use of RA medications. Results were reported as positive predictive values (PPVs) of the claims‐based algorithm for incident RA.

Results

Depending on the algorithm tested and whether patients were enrolled in Medicare or the commercial health plan, the PPVs for incident RA ranged from 68–81%. A 2‐year clean period free of all RA‐related diagnoses and medications was somewhat more optimal although, by comparison, a 1‐year clean period yielded similar PPVs and retained approximately 90% more RA patients for analysis.

Conclusion

Claims‐based algorithms can accurately identify incident RA.

     

Trends in Hospitalizations for Serious Infections in Patients With Rheumatoid Arthritis in the US Between 1993 and 2013

Objective

The epidemiology of hospitalizations with infections among patients with rheumatoid arthritis (RA) is unknown, despite an increase in RA treatments that confer a risk of infection.

Methods

We examined National Inpatient Sample data from 1993–2013. We identified hospitalizations among adults with RA, defined by International Classification of Diseases, Ninth Revision, Clinical Modification codes (714.xx) in any secondary diagnosis field. We evaluated 5 infections as the primary diagnosis: pneumonia, sepsis, urinary tract infection (UTI), skin and soft tissue infections (SSTIs), and opportunistic infections (OIs). The primary outcome was the proportion of hospitalizations for each infection among all hospitalizations with a secondary diagnosis of RA.

Results

There were 792,921 hospitalizations for infection with a secondary diagnosis of RA, with the rates increasing from 90 to 206 per 100,000 persons from 1993–2013. The proportion of hospitalizations decreased for pneumonia (from 5.4% to 4.6%), UTI (from 0.4% to 0.38%), and OIs (from 0.44% to 0.26%). The proportion of hospitalizations for SSTIs increased slightly (from 2.3% to 2.5%), while hospitalizations for sepsis more than tripled (from 1.9% to 6.4%).

Conclusion

Between 1993 and 2013, the proportion of hospitalizations for infections among RA patients appeared to decline for pneumonia and OIs, with a slight decrease in UTI, a slight increase in SSTIs, and a substantial increase in hospitalizations with sepsis. Our results are consistent with previous reports that the sensitivity of sepsis coding has increased over time.

     

Treating Early Undifferentiated Arthritis: A Systematic Review and Meta‐Analysis of Direct and Indirect Trial Evidence

Objective

We undertook a systematic review and meta‐analysis of direct and indirect trial evidence to evaluate the efficacy of treatments for patients with undifferentiated arthritis (UA).

Methods

We searched 4 electronic databases from inception to January 2016, clinicaltrials.gov, and bibliographies of relevant articles. Two reviewers independently screened and evaluated the studies. The primary outcome was development of rheumatoid arthritis (RA).

Results

Nine studies were included. Interventions included methotrexate, abatacept, infliximab, intraarticular or intramuscular glucocorticoids, and radiation synovectomy. Treating patients resulted in lower rates of RA at 12 months compared to placebo or no treatment (odds ratio [OR] 0.49 [95% confidence interval (95% CI) 0.26, 0.90]). From direct meta‐analysis, patients treated with methotrexate were less likely to develop RA at 12 months compared to patients treated without methotrexate (OR 0.13 [95% CI 0.03, 0.48]). This difference was no longer significant at 30 or 60 months. From indirect comparisons, most interventions showed decreased risk of developing RA compared to placebo at 12 months, reaching statistical significance for methotrexate (OR 0.16 [95% CI 0.08, 0.33]) and intramuscular methylprednisolone (OR 0.72 [95% CI 0.53, 0.99]). Most individual interventions included a limited number of studies.

Conclusion

Treating patients with UA resulted in a statistically significant delay in the development of RA, with the largest effect observed for methotrexate. These findings suggest that there is a window of opportunity to treat patients with UA early, to delay subsequent progression to RA.

     

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.

     

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.

     

Trends and Determinants of Osteoporosis Treatment and Screening in Patients With Rheumatoid Arthritis Compared to Osteoarthritis

Objective

To profile osteoporosis (OP) care in patients with rheumatoid arthritis (RA) over the past decade.

Methods

Patients with RA or osteoarthritis (OA) were followed from 2003 through 2014. OP care was defined as receipt of OP treatment (with the exception of calcium/vitamin D) or screening (OPTS). Adjusted trends over followup, and the factors associated with OP care, were examined using multivariable Cox proportional hazards.

Results

OPTS was reported in 67.4% of 11,669 RA patients and in 64.6% of 2,829 OA patients during a median (interquartile range) 5.5 (2–9) years of followup. In patients for whom treatment was recommended by the 2010 American College of Rheumatology (ACR) glucocorticoid‐induced OP (GIOP) guidelines (48.4% of RA patients and 17.6% of OA patients), approximately 55% overall reported OP medication use. RA patients were not more likely to undergo OPTS compared to OA patients (hazard ratio 1.04 [95% confidence interval 0.94–1.15]). Adjusted models showed a stable trend for OPTS between 2004 and 2008 compared to 2003, with a significant downward trend after 2008 in both RA and OA patients. Factors associated with receipt of OP care in RA patients were older age, postmenopausal state, prior fragility fracture or diagnosis of OP, any duration of glucocorticoid treatment, and use of biologic agents.

Conclusion

Approximately half of RA patients for whom treatment was indicated never received an OP medication. OP care in RA patients was not better than in OA patients, and the relative risk of the application of this care has been decreasing in RA and OA patients since 2008 without improvement after the release of the 2010 ACR GIOP guideline.

     

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.

     

“Sounds a Bit Crazy,But It Was Almost More Personal:” A Qualitative Study of Patient and Clinician Experiences of Physical Therapist–Prescribed Exercise For Knee Osteoarthritis Via Skype

Objective

To explore the experience of patients and physical therapists with Skype for exercise management of knee osteoarthritis (OA ).

Methods

This was a qualitative study. The Donabedian model for quality assessment in health care (structure, process, and outcomes) informed semistructured individual interview questions. The study involved 12 purposively sampled patients with knee OA who received physical therapist–prescribed exercise over Skype, and all therapists (n = 8) who delivered the intervention in a clinical trial were interviewed about their experiences. Interviews were audio recorded and transcribed. Two investigators undertook coding and analysis using a thematic approach.

Results

Six themes arose from both patients and therapists. The themes were Structure: technology (easy to use, variable quality, set‐up assistance helpful) and patient convenience (time efficient, flexible, increased access); Process: empowerment to self‐manage (facilitated by home environment and therapists focusing on effective treatment) and positive therapeutic relationships (personal undivided attention from therapists, supportive friendly interactions); and Outcomes: satisfaction with care (satisfying, enjoyable, patients would recommend, therapists felt Skype more useful as adjunct to usual practice) and patient benefits (reduced pain, improved function, improved confidence and self‐efficacy). A seventh theme arose from therapists regarding process: adjusting routine treatment (need to modify habits, discomfort without hands‐on, supported by research environment).

Conclusion

Patients and physical therapists described mostly positive experiences using Skype as a service delivery model for physical therapist–supervised exercise management of moderate knee OA . Such a model is feasible and acceptable and has the potential to increase access to supervised exercise management for people with knee OA , either individually or in combination with traditional in‐clinic visits.

     

Perioperative Timing of Infliximab and the Risk of Serious Infection After Elective Hip and Knee Arthroplasty

Objective

The optimal timing of tumor necrosis factor antagonists before elective surgery is unknown. This study evaluated the association between infliximab timing and serious infection after elective hip or knee arthroplasty.

Methods

A retrospective cohort study evaluated US Medicare patients with rheumatoid arthritis, inflammatory bowel disease, psoriasis, psoriatic arthritis, or ankylosing spondylitis who received infliximab within 6 months of elective knee or hip arthroplasty from 2007 to 2013. Propensity‐adjusted analyses examined whether infliximab stop timing (time between the most recent infusion and surgery) was associated with hospitalized infection within 30 days or prosthetic joint infection (PJI ) within 1 year.

Results

Hospitalized infection within 30 days occurred after 270 of 4,288 surgeries (6.3%). Infliximab stop timing <4 weeks versus 8–12 weeks was not associated with an increase in infection within 30 days (propensity‐adjusted odds ratio [OR ] 0.90 [95% confidence interval (95% CI ) 0.60–1.34]). The rate of PJI was 2.9 per 100 person‐years and was not increased in patients with stop timing <4 weeks versus 8–12 weeks (hazard ratio [HR ] 0.98 [95% CI 0.52–1.87]). Glucocorticoid dosage >10 mg/day was associated with increased risk of 30‐day infection (OR 2.11 [95% CI 1.30–3.40]) and PJI (HR 2.70 [95% CI 1.30–5.60]). Other risk factors for infection included elderly age, comorbidities, revision surgery, and previous hospitalized infection.

Conclusion

Administering infliximab within 4 weeks of elective knee or hip arthroplasty was not associated with a higher risk of short‐ or long‐term serious infection compared to withholding infliximab for longer time periods. Glucocorticoid use, especially >10 mg/day, was associated with an increased infection risk.

     

Mortality in Patients With Giant Cell Arteritis: A Cohort Study in UK Primary Care

Objective

To examine whether giant cell arteritis (GCA) is associated with increased all‐cause mortality and whether mortality differs according to age, sex, and calendar year of cohort entry.

Methods

Using the UK‐based Clinical Practice Research Datalink, we identified 9,778 newly diagnosed GCA patients from 1990–2014, and up to 10 nonvasculitis patients randomly matched to each case on age, sex, practice, and years of history before cohort entry. We used Cox regression to estimate adjusted hazard ratios (HRs) for mortality of GCA patients in comparison to nonvasculitis patients, then stratified by age, sex, and calendar year of cohort entry.

Results

Compared with nonvasculitis patients, GCA patients had increased mortality during the first year following diagnosis (adjusted HR 1.51, 95% confidence interval [95% CI] 1.40–1.64), and marginally increased mortality between 1 and 5 years after the diagnosis (adjusted HR 1.16, 95% CI 1.09–1.23), but not >5 years after the diagnosis (adjusted HR 1.06, 95% CI 1.00–1.12). GCA patients diagnosed before age 65 years had the highest mortality risk during the first year following diagnosis (adjusted HR 2.32, 95% CI 1.60–3.35). The mortality risk did not differ substantially by sex or calendar year of cohort entry.

Conclusion

GCA patients had an increased risk of mortality during the period shortly after the GCA diagnosis, in particular during the first year, but no increased risk after 5 years postdiagnosis. The mortality risk differed by age with an even greater increased 1‐year mortality in those age <65 years at diagnosis, but not by sex or calendar year of cohort entry.

     

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.

     

Endothelial Dysfunction in Early Systemic Lupus Erythematosus Patients and Controls Without Previous Cardiovascular Events

Objective

To assess the prevalence and risk factors for endothelial dysfunction detected by peripheral artery tonometry in systemic lupus erythematosus patients with early disease without cardiovascular disease and risk factors.

Methods

All the consecutive adult lupus patients, with a disease duration <5 years, seen in our hospital from December 2014 to March 2016 were considered. We excluded patients with any history of cardiovascular disease or risk factors possibly affecting peripheral artery tonometry. Enrolled patients were matched for sex, age, body mass index, and blood pressure with healthy controls with the same exclusion criteria. Patients and controls received a transthoracic Doppler echocardiogram and an evaluation of endothelial function by peripheral artery tonometry.

Results

Twenty patients (100% female) with a median disease duration of 14 months (range 1–58 months), a mean ± SD age of 42 ± 15 years, and a mean ± SD age at diagnosis of 40 ± 16 years were enrolled and matched with 20 controls. Peripheral artery tonometry showed a significantly higher prevalence of endothelial dysfunction (P = 0.003) and vascular stiffness (P = 0.02), while echocardiography detected a significantly higher prevalence of left ventricular concentric remodeling (P = 0.003), grade I diastolic dysfunction (P = 0.047), and subclinical increase of filling pressures (P = 0.039) in lupus patients compared to controls. Among lupus patients, no features were associated with endothelial dysfunction.

Conclusion

A high rate of endothelial dysfunction and vascular stiffness occurs in early lupus patients without cardiovascular risk factors and disease. Larger studies are needed to confirm our results and to look for patients’ characteristics possibly associated with these abnormalities.