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.
Chronic anterior uveitis is the most frequent among extra-articular manifestations of juvenile idiopathic arthritis (JIA) and a relevant cause of ocular morbidity in children. Asymmetric arthritis, ...early onset disease, female sex, and anti-nuclear antibody (ANA) positivity are counted among risk factors for developing this complication. It usually has insidious onset and asymptomatic chronic-relapsing course, but the persistence of low-grade chronic inflammation can lead to irreversible structural ocular damage and to vision-threatening complications. For such reasons, achieving a complete absence of inflammation through early targeted and aggressive treatments is a primary therapeutic goal in these patients. This review is aimed at summarizing scientific evidence about biologic rescue therapy of JIA-related uveitis in patients who fail to achieve clinical remission, in spite of being treated with conventional disease-modifying anti-rheumatic drugs (cDMARDs) and at least one biologic tumor necrosis factor (TNF)-α inhibitor. Interleukin (IL)-6 inhibition appears a promising and safe option for refractory JIA-related uveitis. Abatacept and rituximab proved to be beneficial as well, but their efficacy together with some safety concerns needs to be more extensively evaluated.
Introduction
Familial Mediterranean fever (FMF) is the most prevalent monogenic autoinflammatory disease, caused by recessively inherited MEFV gene mutations. The most frequent MEFV mutations differ ...in penetrance and disease severity. We investigated the genotype–phenotype associations of the three most frequent MEFV gene mutations (M680I, M694V, and V726A) in Egyptian FMF children, regarding clinical features, severity, and colchicine response.
Methods
We conducted a retrospective analysis of the medical registries of 500 FMF pediatric patients from Metropolitan Cairo between 2010 and 2015. The diagnosis was based on the Tel-Hashomer clinical diagnostic criteria. Clinical data and baseline investigations were collected. Mutation analysis was performed by the amplification-refractory mutation system (ARMS)-PCR method.
Results
Males represented 54% and ages ranged from 2 to 18 years. The most frequent symptoms were abdominal pain, fever, and arthralgia. Clinical features mostly associated with M694V mutation either homozygous or heterozygous whether simple, double, or triple. Of the patients, 94.6% completely responded to colchicine. Among patients benefiting from colchicine, 42.5% had M694V/V726A, 21.6% had M694V/V726A/M680I, and 21.1% had M694V genotype. Simple heterozygous M694V or V726A mutations conveyed a moderate phenotype in 57.1% and 50% of cases, respectively. Homozygous M694V mutation showed moderate and severe phenotypes in 21.7% and 65.2% of cases, respectively. Compound M694V/V726A mutation associated with moderate or severe disease in 48.3% and 33.8% of cases, respectively.
Conclusion
This study encompasses the largest group of Egyptian pediatric FMF up to date to explore their genotype–phenotype associations. Our results support the notion that the genotype influences the phenotype as regards clinical manifestations, disease severity, and colchicine response.
Key Points:
• This study encompasses the largest group of Egyptian pediatric patients affected by FMF up to date to explore their genotype–phenotype associations.
• Our results support the notion that the genotype influences the phenotype as regards the clinical manifestations, the disease severity, and the response to colchicine treatment.
Behçet’s syndrome (BS) represents an understudied topic in pediatrics: the main aims of our study were to characterize demographic and clinical features of a cohort of BS patients with juvenile-onset ...managed in three tertiary referral centers in Italy, evaluate their evolution in the long-term, and detect any potential differences with BS patients having an adult-onset. Medical records of 64 juvenile-onset and 332 adult-onset BS followed-up over a 2-year period were retrospectively analyzed and compared. Mean age ± SD of first symptom-appearance was 10.92 ± 4.34 years with a female-to-male ratio of 1.06:1. Mucocutaneous signs were the most frequent initial manifestations, followed by uveitis. Throughout the disease course, genital aphthae (76.56%) and pseudofolliculitis (40.63%) prevailed among the mucocutaneous signs, while major organ involvement was represented by gastrointestinal and ocular involvement (43.75 and 34.38%, respectively). No significant differences emerged for both mucocutaneous signs and specific major organ involvement between juvenile-onset and adult BS patients. After excluding nonspecific abdominal pain, juvenile-onset BS patients were less frequently characterized by the development of major organ involvement (
p
= 0.027). Logistic regression detected the juvenile-onset as a variable associated with reduced risk of long-term major organ involvement (OR 0.495 0.263–0.932,
p
= 0.029). In our cohort, juvenile-onset BS resembled the clinical spectrum of adult-onset patients. Pediatric patients with a full-blown disease at onset showed a more frequent mucocutaneous involvement. In addition, patients with juvenile-onset seemed to develop less frequently major organ involvement and had an overall less severe disease course.
Monogenic autoinflammatory diseases (mAIDs) are inherited errors of innate immunity characterized by systemic inflammation recurring with variable frequency and involving the skin, serosal membranes, ...synovial membranes, joints, the gastrointestinal tube, and/or the central nervous system, with reactive amyloidosis as a potential severe long-term consequence. Although individually uncommon, all mAIDs set up an emerging chapter of internal medicine: recent findings have modified our knowledge regarding mAID pathophysiology and clarified that protean inflammatory symptoms can be variably associated with periodic fevers, depicting multiple specific conditions which usually start in childhood, such as familial Mediterranean fever, tumor necrosis factor receptor-associated periodic syndrome, cryopyrin-associated periodic syndrome, and mevalonate kinase deficiency. There are no evidence-based studies to establish which potential genotype analysis is the most appropriate in adult patients with clinical phenotypes suggestive of mAIDs. This review discusses genetic and clinical hints for an ideal diagnostic approach to mAIDs in adult patients, as their early identification is essential to prompt effective treatment and improve quality of life, and also highlights the most recent developments in the diagnostic work-up for the most frequent hereditary periodic febrile syndromes worldwide.
Massive lamotrigine poisoning. A case report Grosso, Salvatore; Ferranti, Silvia; Gaggiano, Carla ...
Brain & development (Tokyo. 1979),
04/2017, Volume:
39, Issue:
4
Journal Article
Peer reviewed
Abstract Lamotrigine (LTG) represents the most commonly prescribed of the so-called new generation antiepileptic drugs. We describe a child who was admitted to the emergency room because of ...generalized tonic–clonic status epilepticus followed by a complex neurological picture with hyperkinesia and acute ataxia as a result of a LTG intoxication. The experience on acute LTG intoxication is very limited in pediatrics. The present case provides information on the clinical picture related to LTG overdose and confirms that drug intoxications should be considered in the differential diagnosis strategy when severe and polymorphic neurological symptoms occur acutely.
Only a few studies have reported long-term efficacy of interleukin (IL)-1 inhibition in systemic juvenile idiopathic arthritis (sJIA) and adult-onset Still disease (AOSD). Herein we report on the ...effectiveness of anakinra (ANA), expressed in terms of drug retention rate (DRR), and evaluate the predictive factors of drug survival in a cohort of patients with sJIA and AOSD.
This is a multicenter study reviewing retrospectively the medical records from 61 patients with sJIA and 76 with AOSD, all treated with ANA in 25 Italian tertiary referral centers.
The cumulative retention rate of ANA at 12-, 24-, 48-, and 60-month of follow-up was 74.3%, 62.9%, 49.4%, and 49.4%, respectively, without any significant differences between sJIA and AOSD patients (
= 0.164), and between patients treated in monotherapy compared with the subgroup coadministered with conventional disease-modifying antirheumatic drugs (cDMARDs) (
= 0.473). On the other hand, a significant difference in DRR was found between biologic-naïve patients and those previously treated with biotechnologic drugs (
= 0.009), which persisted even after adjustment for pathology (
= 0.013). In the regression analysis, patients experiencing adverse events (AEs) {hazards ratio (HR) = 3.029 confidence interval (CI) 1.750-5.242,
< 0.0001} and those previously treated with other biologic agents HR = 1.818 (CI 1.007-3.282),
= 0.047 were associated with a higher HR of ANA discontinuation. The median treatment delay was significantly higher among patients discontinuing ANA (
< 0.0001). Significant corticosteroid-sparing (
= 0.033) and cDMARD-sparing effects (
< 0.0001) were also recorded. Less than one-third of our cohort developed AEs, and 85% were deemed mild in nature, with 70% of them involving the skin.
Our findings display an overall excellent DRR of ANA on the long run for both sJIA and AOSD, that may be further optimized by closely monitoring patient's safety issues and employing this IL-1 inhibitor as a first-line biologic as early as possible. Moreover, ANA allowed a significant drug-sparing effect and showed an overall good safety profile.
Non-infectious inflammatory ocular diseases pose significant challenges in diagnosis and management, often requiring systemic immunosuppressive therapy. Since Janus kinase (JAK) inhibitors may ...represent a novel therapeutic option for these disorders, the present study aimed to expand current knowledge about their efficacy and safety in patients with these conditions.IntroductionNon-infectious inflammatory ocular diseases pose significant challenges in diagnosis and management, often requiring systemic immunosuppressive therapy. Since Janus kinase (JAK) inhibitors may represent a novel therapeutic option for these disorders, the present study aimed to expand current knowledge about their efficacy and safety in patients with these conditions.This prospective cohort study included 12 adult patients from the international AutoInflammatory Disease Alliance (AIDA) Network registries dedicated to non-infectious ocular inflammatory conditions. We assessed ocular flares, visual acuity, disease course, and complications before and after initiating JAK inhibitor therapy.MethodsThis prospective cohort study included 12 adult patients from the international AutoInflammatory Disease Alliance (AIDA) Network registries dedicated to non-infectious ocular inflammatory conditions. We assessed ocular flares, visual acuity, disease course, and complications before and after initiating JAK inhibitor therapy.Ocular inflammation was related to a systemic disease in 8 (66.7%) patients as follows: spondyloarthritis (n = 3), peripheral psoriatic arthritis (n = 1), rheumatoid arthritis (n = 1), antinuclear antibodies (ANA) positive juvenile idiopathic arthritis (n = 1), Behçet's syndrome (n = 1), Vogt-Koyanagi-Harada syndrome (n = 1). In total, 4 patients received baricitinib, 1 patient received tofacitinib, and 7 patients underwent upadacitinib treatment. The overall average duration of JAK inhibitors treatment was 8.6 ± 5.5 months (ranging from 3 to 20 months). At the last assessment, ocular disease control was complete in 12/12 patients. One patient discontinued baricitinib due to poor compliance after a 12-month relapse-free period. The incidence of ocular flares was 125 episodes/1.000 person-months prior to the initiation of JAK inhibitors and 28.6 episodes/1.000 person-months thereafter. The incidence rate ratio for experiencing a relapse before starting a JAK inhibitor compared to the following period was 4.37 (95% CI 1.3-14.7, p-value: 0.02).ResultsOcular inflammation was related to a systemic disease in 8 (66.7%) patients as follows: spondyloarthritis (n = 3), peripheral psoriatic arthritis (n = 1), rheumatoid arthritis (n = 1), antinuclear antibodies (ANA) positive juvenile idiopathic arthritis (n = 1), Behçet's syndrome (n = 1), Vogt-Koyanagi-Harada syndrome (n = 1). In total, 4 patients received baricitinib, 1 patient received tofacitinib, and 7 patients underwent upadacitinib treatment. The overall average duration of JAK inhibitors treatment was 8.6 ± 5.5 months (ranging from 3 to 20 months). At the last assessment, ocular disease control was complete in 12/12 patients. One patient discontinued baricitinib due to poor compliance after a 12-month relapse-free period. The incidence of ocular flares was 125 episodes/1.000 person-months prior to the initiation of JAK inhibitors and 28.6 episodes/1.000 person-months thereafter. The incidence rate ratio for experiencing a relapse before starting a JAK inhibitor compared to the following period was 4.37 (95% CI 1.3-14.7, p-value: 0.02).JAK inhibitors demonstrate efficacy and safety in controlling ocular inflammatory relapses, confirming that they represent a valuable treatment option for patients with non-infectious inflammatory ocular diseases resistant to conventional treatments.ConclusionJAK inhibitors demonstrate efficacy and safety in controlling ocular inflammatory relapses, confirming that they represent a valuable treatment option for patients with non-infectious inflammatory ocular diseases resistant to conventional treatments.
Introduction
Scientific evidence of the effectiveness of the tumor necrosis factor inhibitor adalimumab (ADA) in pediatric patients with non-infectious non-anterior uveitis is still limited. The aim ...of this study is to investigate the therapeutic role of ADA in a cohort of pediatric patients with non-anterior uveitis.
Methods
This is an international multicenter study analyzing real-life data referred to pediatric patients treated with ADA for intermediate uveitis/pars planitis, posterior uveitis and panuveitis. Data were drawn from the AutoInflammatory Disease Alliance (AIDA) registry for patients with uveitis.
Results
Twenty-one patients (36 affected eyes) were enrolled, and all patients benefited from ADA administration. In detail, 11 patients (19 affected eyes) did not experience further ocular inflammation after ADA introduction; 10 cases (17 affected eyes) showed a significant clinical improvement consisting of a decrease in severity and/or frequency of ocular relapses. The number of ocular flares dropped from 3.91 to 1.1 events/patient/year after ADA introduction (
p
= 0.0009); macular edema and retinal vasculitis were respectively observed in 18 eyes and 20 eyes at the start of ADA and in 4 eyes and 2 eyes at the last assessment. The mean daily glucocorticoid dosage significantly decreased from 26.8 ± 16.8 mg/day at the start of ADA to 6.25 ± 6.35 mg/day at the last assessment (
p
= 0.002). Intermediate uveitis/pars planitis (
p
= 0.01) and posterior uveitis (
p
= 0.03) were more frequently observed in patients with full response to ADA; panuveitis (
p
= 0.001) was significantly more frequent among patients continuing to experience uveitic flares. This could be related to a higher use of systemic glucocorticoids (
p
= 0.002) and conventional immunosuppressants (
p
= 0.007) at the start of ADA when treating intermediate uveitis/pars planitis. Regarding the safety profile, only one adverse event was reported during ADA treatment, consisting of the development of generalized adenopathy.
Conclusions
ADA proved to have an effective therapeutic role in all pediatric patients with non-anterior uveitis enrolled in the study. An overall glucocorticoid-sparing effect was observed despite the severity of cases enrolled. A more aggressive treatment of panuveitis and posterior uveitis at start of ADA could increase the likelihood of full response to therapy.
Introduction
This study aims to characterize ocular manifestations of juvenile Behçet’s disease (jBD).
Methods
This was a registry-based observational prospective study. All subjects with jBD from ...the Autoinflammatory Diseases Alliance (AIDA) Network BD Registry showing ocular manifestations before 18 years were enrolled.
Results
We included 27 of 1000 subjects enrolled in the registry (66.7% male patients, 45 affected eyes). The median (interquartile range IQR) age at ocular involvement was 14.2 (4.7) years. Uveitis affected 91.1% of eyes (anterior 11.1%, posterior 40.0%, panuveitis 40.0%), retinal vasculitis 37.8% and other manifestations 19.8%. Later onset (
p
= 0.01) and male predominance (
p
= 0.04) characterized posterior involvement. Ocular complications occurred in 51.1% of eyes. Patients with complications had earlier onset (
p
< 0.01), more relapses (
p
= 0.02) and more prolonged steroidal treatment (
p
= 0.02). The mean (standard deviation SD) central macular thickness (CMT) at the enrolment and last visit was 302.2 (58.4) and 293.3 (78.2) μm, respectively. Fluorescein angiography was pathological in 63.2% of procedures, with a mean (SD) Angiography Scoring for Uveitis Working Group (ASUWOG) of 17.9 (15.5). At the last visit, ocular damage according to the BD Overall Damage Index (BODI) was documented in 73.3% of eyes. The final mean (SD) best corrected visual acuity (BCVA) logMAR was 0.17 (0.47) and blindness (BCVA logMAR < 1.00 or central visual field ≤ 10°) occurred in 15.6% of eyes. At multivariate regression analysis, human leukocyte antigen (HLA)-B51 + independently predicted a + 0.35 change in the final BCVA logMAR (
p
= 0.01), while a higher BCVA logMAR at the first assessment (odds ratio OR 5.80;
p
= 0.02) independently predicted blindness.
Conclusions
The results of this study may be leveraged to guide clinical practice and future research on this rare sight-threatening condition.
PDF
