Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome is the most frequent non-hereditary autoinflammatory disorder in childhood: Its onset is usually observed ...before 5 years, though reports regarding adulthood are increasing. The pathogenesis of the syndrome is not completely understood, but a multifactorial origin, probably based on a polygenic pattern of susceptibility, is the most probable rational pathogenetic hypothesis. Treatment of PFAPA syndrome relies on the administration of low-dose corticosteroids, which promptly abort flares but cannot prevent subsequent disease episodes over time. Tonsillectomy with or without adenoidectomy has proved to be successful in some pediatric patients, as proven by different studies. On the other hand, colchicine, cimetidine, nonsteroidal anti-inflammatory drugs, and interleukin-1 inhibitors have shown efficacy, which require further definite confirmations. This review is aimed at summarizing all the recent evidence about treatment options available for PFAPA syndrome both in pediatric and adult patients.
To compare the efficacy of adalimumab (ADA) and infliximab (IFX) in patients with non-infectious intermediate uveitis, posterior uveitis, and panuveitis. Demographic, clinical, instrumental, and ...therapeutic data from patients enrolled were collected at the start of treatment, at 12-month follow-up, and at the last follow-up assessment. One hundred seven patients (46 females, 187 eyes) were enrolled, 66 (61.7%) treated with ADA and 41 (38.3%) with IFX. Bilateral involvement was observed in 80 cases. The mean follow-up was 26.45 ± 21.71 months for ADA patients and 56.60 ± 56.04 months for IFX patients. The overall decrease of uveitis frequency during the first 12 months of treatment was 66.7% in the IFX group and 84.2% in the ADA group, compared to the previous 12 months (
p
= 0.09). A significantly higher corticosteroid dosage was found among patients treated with ADA at the last follow-up visit (
p
= 0.008). The percentage of patients co-administered with corticosteroids was significantly higher among ADA patients both at the 12-month visit (
p
= 0.03) and at the last visit (
p
= 0.0004). The frequency of uveitic macular edema (UME) was significantly higher among patients treated with ADA compared to those treated with IFX at the 12-month assessment (
p
= 0.015) and at the last follow-up visit (
p
= 0.011); central macular thickness was significantly higher in ADA group compared to the IFX group at the last follow-up assessment (
p
= 0.04). ADA and IFX have shown a similar efficacy in controlling uveitis relapses, but IFX showed a more pronounced corticosteroid sparing effect and a significantly higher capacity in resolving UME compared to ADA.
Background:
Despite being burdened by significant adverse events, glucocorticoids (GCs) are frequently employed in managing adult onset Still’s disease (AOSD), prompting the need for GC-sparing ...agents. In this work, we performed a systematic review and meta-analysis to synthesize the evidence about the reduction of concomitant GCs dosage and the rate of GCs discontinuation in patients with AOSD who were treated with anakinra, a recombinant IL-1 receptor antagonist.
Methods:
A systematic review of the literature was completed to identify all available data concerning the reduction of concomitant GCs dosage following anakinra in AOSD and a meta-analysis was thus performed using a random-effects model.
Results:
A significant reduction of the GCs dosage was detected by pooled analysis with mean difference of –22.4 mg/day 95% confidence interval (CI): –28.8 to –16.1, p < 0.0001 at the last follow-up; the heterogeneity was moderate (Q = 11.67 with df = 7.00, p < 0.0001, I2 = 40.01%). Furthermore, the pooled analysis under a random effects model showed an overall rate of GCs discontinuation of 0.35 (95% CI: 0.28–0.41, p < 0.0001); the heterogeneity was low (Q = 5.99 with df = 6.00, p < 0.0001, I2 = 0.00%).
Discussion:
Taking together all these findings, the reduction of concomitant GCs dosage following anakinra could be suggested, leading to a further improvement of AOSD therapeutic strategy.
Conclusion:
In conclusion, the present systematic review and meta-analysis suggests the reduction of concomitant GCs dosage following treatment with anakinra. A percentage of patients are no longer required to be treated with GCs, discontinuing these drugs without a flare of the disease.
This study aimed to investigate the trajectory of damage accrual, associated factors, and impact on health-related quality of life (HR-QoL) in a multicenter cohort of patients with Behçet's syndrome ...(BS) over 2 years of follow-up.
Patients recruited in the BS Overall Damage Index (BODI) validation study were prospectively monitored for 2 years and assessed for damage accrual, defined as an increase ≥1 in the BODI score, and HR-QoL was evaluated by the SF-36 questionnaire. Logistic and multiple linear regression models were built to determine factors associated with damage accrual and impairment in the different SF-36 domains.
During follow-up, 36 out of 189 (19.0%) patients had an increase ≥1 in the BODI score with a mean (SD) difference of 1.7 (0.8) (p <0.001). The incidence rate of damage accrual was stable over time, regardless of the disease duration. Out of 61 new BODI items, 25 (41.0%) were considered related to glucocorticoid (GC) use. In multivariate analysis, duration of GC therapy (OR per 1-year 1.15, 95% CI 1.07-1.23; p <0.001) and occurrence of ≥1 disease relapse (OR 3.15, 95% CI 1.09-9.12; p 0.038) were identified as predictors of damage accrual, whereas the use of immunosuppressants showed a protective effect (OR 0.20, 95% CI 0.08-0.54, p<0.001). Damage accrual was independently associated with the impairment of different physical domains and, to a greater extent, in emotional domains of the SF-36 questionnaire. Female sex, higher disease activity, and fibromyalgia were also significantly associated with impairment in HR-QoL.
In BS, organ damage accrues over time, also in long-standing disease, resulting in an impairment of the perceived physical and mental health. Adequate immunosuppressive treatment, preventing disease flares and minimizing exposure to GCs have a crucial role in lowering the risk of damage accrual.
The primary aim of the study was to evaluate the efficacy of tumor necrosis factor (TNF)-α blockers adalimumab (ADA) and infliximab (IFX) in refractory sight-threatening retinal vasculitis (RV) ...during a 12-month follow-up period. Secondary aims were to evaluate (i) any impact of concomitant conventional disease-modifying anti-rheumatic drugs (cDMARDs) and different lines of biologic therapy; (ii) any difference in terms of efficacy between ADA and IFX; (iii) consequences of biotherapies on the best-corrected visual acuity (BCVA); (iv) corticosteroid-sparing effect; and (vi) ocular complications during anti-TNF-α treatment. Demographic, clinical, and therapeutic data were retrospectively collected from the medical records and statistically analyzed. Forty-eight patients (82 eyes) were recruited, 22 (45.8%) of which received IFX and 26 (54.2%) ADA. The percentages of patients achieving RV remission within 3 and 12 months were 54 and 86%, respectively. A significant decrease in RV detection was identified from baseline to 3-month (
p
< 0.0001) and 12-month (
p
< 0.0001) assessments and between 3-month and 12-month visits (
p
= 0.004). No differences were identified in terms of RV resolution between (i) patients undergoing monotherapy and those co-administered with cDMARDs at 3-month (
p
= 0.560) and 12-month (
p
= 0.611) follow-up; (ii) biologic-naïve patients and those already exposed to other biologics at 3-month (
p
= 0.497) and 12-month (
p
> 0.99) visits; and (iii) patients treated with ADA and those treated with IFX (
p
= 0.357). During the study period, a statistically significant corticosteroid-sparing effect was observed (
p
= 0.0002), while BCVA values did not significantly change (
p
= 0.950). Anti-TNF-α monoclonal antibodies have proved excellent results in patients with recalcitrant sight-threatening RV.
Relapsing polychondritis is a rare multisystemic disease widely accepted as a complex autoimmune disorder affecting proteoglycan-rich structures and cartilaginous tissues, especially the auricular ...pinna, cartilage of the nose, tracheobronchial tree, eyes, and heart’s connective components. The clinical spectrum may vary from intermittent inflammatory episodes leading to unesthetic structural deformities to life-threatening cardiopulmonary manifestations, such as airway collapse and valvular regurgitation. The frequent association with other rheumatologic and hematologic disorders has been extensively reported over time, contributing to define its complexity at a diagnostic and also therapeutic level. Diagnosis of relapsing polychondritis is mainly based on clinical clues, while laboratory data have only a supportive contribution. Conversely, radiology is showing a relevant role in estimating the rate of systemic involvement as well as disease activity. The present review is aimed at providing an update on scientific data reported during the last 3 years about relapsing polychondritis in terms of pathogenesis, clinical features, diagnosis, and new treatment options.
Background. Interleukin-1 inhibition has revealed to be a successful treatment approach for patients with adult-onset Still’s disease (AOSD). However, real-life experience is focused on the use of ...anakinra, while data about canakinumab (CAN) are mainly based on case reports and small case series. Patients and Methods. Patients classified with AOSD according to Yamaguchi criteria and treated with CAN were consecutively enrolled. Their clinical and therapeutic data were retrospectively collected and statistically analysed to assess the role of CAN as a therapeutic opportunity in AOSD patients in terms of clinical and laboratory disease control along with corticosteroid-sparing effect. Results. Nine AOSD patients (8 females and 1 male) treated with CAN for 15.00±12.3 months were enrolled. Resolution of clinical manifestations was reported in 8/9 cases at the 3-month assessment; a significant decrease in the number of tender joints (p=0.009), swollen joints (p=0.027), and disease activity score on 28 joints-C-reactive protein (DAS28-CRP) (p=0.044) was observed during the study period. The systemic score of disease activity significantly decreased at the 3-month and 6-month assessments and at the last visit compared to the start of treatment (p=0.028, p=0.028, and p=0.018, respectively). The daily corticosteroid dosage was significantly reduced at the 3-month and at the last follow-up visits (p=0.017 and p=0.018, respectively). None of the patients experienced adverse events or severe adverse events during the follow-up. Conclusions. CAN has shown prompt and remarkable effectiveness in controlling AOSD activity in a real-life contest, with a significant glucocorticoid-sparing effect and an excellent safety profile.
Behçet's syndrome (BS) is a rare systemic vasculitis characterized by different clinical manifestations. As no specific laboratory tests exist, the diagnosis relies on clinical criteria, and the ...differential diagnosis with other inflammatory diseases can be challenging. Indeed, in a relatively small proportion of patients, BS symptoms include only mucocutaneous, articular, gastrointestinal, and non-typical ocular manifestations, which are frequently found also in psoriatic arthritis (PsA). We investigate the ability of serum interleukin (IL)-36α-a pro-inflammatory cytokine involved in cutaneous and articular inflammatory diseases-to differentiate BS from PsA. A cross-sectional study was performed on 90 patients with BS, 80 with PsA and 80 healthy controls. Significantly lower IL-36α concentrations were found in patients with BS as compared to PsA, although in both groups IL-36α was significantly increased compared to healthy controls. An empirical cut-off of 420.6 pg/mL displayed a specificity of 0.93, with a sensitivity of 0.70 (AUC 0.82) in discriminating PsA from BS. This cut-off displayed a good diagnostic performance also in BS patients lacking highly specific BS manifestations. Our results indicate that IL-36α might be involved in the pathogenesis of both BS and PsA, and might be a candidate biomarker to support the differential diagnosis of BS.
Introduction. Giant cell arteritis (GCA) is a large vessel (LV) vasculitis, mainly affecting elder patients. Monitoring GCA activity during tocilizumab (TCZ) treatment is an unmet need, since low ...serum levels of C-reactive protein (CRP) during treatment may underestimate disease activity. To date, few data are available on the role of different imaging techniques in monitoring GCA activity and response to treatment. We report herein a cohort of GCA patients treated with TCZ and followed up with multimodal imaging. Patients and Methods. We collected clinical, laboratory, and imaging data of 11 GCA patients treated with TCZ 162 mg subcutaneously every week. Disease activity was assessed at baseline and within 12 months from the start of treatment using different imaging techniques such as color Doppler ultrasonography (CDUS), magnetic resonance imaging/angiography (MRI/MRA), computed tomography angiography (CTA), and/or positron emission tomography (PET). Results. Four patients were affected by cranial and 7 by LV-GCA. All patients were treated with oral glucocorticoids (GCs) (mean dose 55.68 mg±8.19 of prednisone or equivalent) in combination with TCZ. Treatment was preceded in 5 cases by 3 intravenous boluses of 1000 mg methylprednisolone. A significant decrease of the mean dose of oral GCs was observed between baseline and the last follow-up visit (4.65±3.69 mg) (p=0.003). TCZ treatment significantly decreased erythrocyte sedimentation rate (p<0.01) and CRP levels (p<0.01). At follow-up (mean 8.18±3.63 months), all patients were in clinical and serological remission. Moreover, PET, CDUS, MRI/MRA, and CTA did not show any LVV finding. Conclusions. Our study highlights TCZ efficacy in inducing GCA remission and its steroid-sparing effect. We highlighted a reliability of imaging procedures in the evaluation of disease activity and treatment response. A close disease monitoring with imaging techniques should be taken into account in GCA patients during TCZ treatment.
Objectives. The primary aim of our study was to evaluate long-term efficacy of secukinumab (SCK) in patients with axial spondyloarthritis (axSpA); secondary aims were to evaluate drug retention rate ...and to identify differences in the clinical and laboratory assessment according to axSpA clinical features, dosage administered, and biologic treatment lines. Patients and Methods. We collected clinical, demographical, and treatment data from 39 patients affected by axSpA consecutively treated with SCK. Laboratory assessment was based on inflammation parameters; clinical assessment was performed with the Ankylosing Spondylitis Disease Activity Score- (ASDAS-) CRP and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Data were recorded at baseline and every 3 months for the first year and then every 6 months in the second year. Results. Twelve males and 27 females were enrolled; both BASDAI and ASDAS-CRP showed a statistically significant reduction during the observation period (p<0.0001 and p<0.0001, respectively). C-reactive protein significantly decreased (p=0.006), with significant reduction at the post hoc analysis between baseline and both 6-month evaluation (p=0.02) and 24-month visit (p=0.036). No statistical significance was observed in BASDAI and ASDAS-CRP improvement (p=0.482 and p=0.164, respectively) between different dosages administered. No significant differences emerged in the BASDAI and ASDAS-CRP variations between biologic-naïve patients and subjects previously failing to tumour necrosis factor (TNF) inhibitors (p=0.53 and p=0.148, respectively). At the end of our observation, 7 out of 39 patients discontinued SCK. The global retention rate at the end of the study period was 78.2%, without any significant differences between biologic-naïve and anti-TNF-failure patients (p=0.619) or between subjects administered with different SCK dosages (p=0.614). No adverse events were reported. Conclusions. In our cohort, SCK has proved a remarkable effectiveness regardless biologic treatment line and dosages employed. As suggested by the notable drug retention rate, SCK has been able to maintain its effectiveness over a considerable long period of treatment.
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