BackgroundThe sensitivity and specificity of the ACR-1997 and SLICC-2012 classification criteria in juvenile-onset systemic lupus erythematosus (SLE) are already studied. In previous reports, the ...main limitations of the ACR-1997 and SLICC-2012 were low sensitivity and low specificity, respectively. To avoid misclassifications, a new set of classification criteria have been developed by the collaboration of the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR) and the draft was presented at the 2017 ACR/ARHP Annual Meeting in San Diego, California. After application on 500 SLE patients and 500 controls, the sensitivity and specificity were found as 98% and 97%, respectively.ObjectivesTo compare the sensitivity of the new EULAR/ACR criteria with those of the 1997 American College of Rheumatology (ACR) criteria and 2012 Systemic Lupus International Collaborating Clinics criteria in juvenile-onset SLE patients.MethodsPatients initially were evaluated by ACR-1997, SLICC-2012 and EULAR/ACR classification criteria at baseline, when the diagnosis for the first time had been established by an expert paediatric rheumatologist (OK). All data were obtained from patient records. The diagnostic sensitivity of the three sets of classification criteria were further tested within 1 year of diagnosis and at last patient visit, longitudinally.ResultsA total of 104 juvenile-onset SLE patients were enrolled for the sensitivity performance of classification criteria at diagnosis. Since the follow-up period was less than 1 year, 12 subjects excluded after baseline evaluation. Finally, 92 subjects were eligible for sensitivity evaluation within 1 year of diagnosis and at last visit. The median age at diagnosis of clinician was 13.0 years (range 3.1–17.9 years, interquartile range (IQR) 11.1–16.5 years) with a median disease duration of 5.0 years (IQR 3.0–8.0 years). The female-to-male ratio was 4.7:1. The newly developed EULAR/ACR classification criteria were more sensitive than SLICC-2012 and ACR-1997 at diagnosis (93.3% versus 91.3% and 85.6%, respectively), and at first year (95.7% versus 94.6% and 90.2%, respectively (p>0.05). At last visit the sensitivity of the new set of criteria and SLICC-2012 were same (97.8%), but higher compared to ACR-1997 criteria (95.7%).ConclusionsJuvenile-onset systemic lupus erythematosus was classified by the newly proposed EULAR/ACR criteria with higher sensitivity compared with SLICC-2012 and ACR-1997 at disease onset and within one year of diagnosis. However, last visit assessment demonstrated equal sensitivity between new EULAR/ACR criteria and SLICC-2012. Although the difference was not significant, the new set of criteria seem to be capable of recruiting more children with juvenile SLE to clinical trials.Reference1 Johnson S. European League Against Rheumatism and American College of Rheumatology present new SLE classification criteria at the 2017 ACR/ARHP annual meeting. Presentation at: ACR/ARHP 2017 Annual Meeting; San Diego, CA 2017November 3–8.Disclosure of InterestNone declared
BackgroundFamilial Mediterranean fever (FMF) is the most common monogenic autoinflammatory disease characterised with fever, recurrent episodes of self-limiting polyserositis and arthritis. FMF ...arthritis is generally acute monoarthritis especially in the larger joints of the lower extremities, healing without a sequelae. However some of the patients develop different type of chronic arthritis, predominantly oligoarticular juvenile idiopathic arthritis (JIA) and juvenile pondyloarthropathies (JSpA). Studies on JSpA among childhood FMF patients are spare.ObjectivesTo evaluate frequency of JSpA in a large childhood FMF cohort. Furthermore, we aimed to define main characteristics of JSpA among childhood FMF patients.MethodsA total of 320 juvenile FMF patients were blindly questioned according to recently proposed criteria for JSpA by 3 researchers (EO, DS, ET) that were previously educated for FMF and JSpA. A standardised case report form was prepared and completed for each patient. This form was including demographic data, clinical features, MEFV mutation and treatment. Patients fulfilled the JSpA criteria and were classified as probable JSpA. Afterwards, an expert in paediatric rheumatology (OK) reevaluated the classified patients and some of them were confirmed to be a definite while some of them were accepted as potential JSpA patients.ResultsAs a result, 37 patients (11.5%) were initially classified as potential JSpA. Furthermore, 32 (10%) of them were accepted as definite and 5 (1.5%) patients as probable JSpA in childhood FMF. Demographic, clinical and treatment data of definitive JSPA patients are shown in Table I. The most frequent MEFV mutation among JSPA patients was M694V (63.33%).Table I. Demographic, clinical and genetic features of childhood FMF patients.FMF +Definite JSPAFMF +Probable JSPAFMF patients without JIA and JSpAFMF+JIA (except ERA or JSpA) Patients, n32526815Female, n (%)10 (31.25%)1 (20%)148 (55.22%)10 (66.66%)Age of disease onset, mean±SD years7.19±3.685.60±4.934.91±3.404.93±3.32Age at study, mean±SD years14.84±3.7013.40±1.6712.51±4.4310.73±3.57Family History of FMF, n (%)15 (46.87%)1 (20%)132 (49.25%)6 (40%)Colchicine resistance in FMF patients, n(%)2 (6.25%)014 (5.22%)1 (6.66%)M694V mutation n(%)Homozygote, n(%)Heterozygote, n(%)Compound heterozygote, n(%)NA, n(%)19/30 (63.33%)7 (36.84%)5 (26.31%)7 (36.84%)2 (6.25%)3 (60%)2 (66.66%)1 (33.33%)00148/245 (60.40%)51 (34.45%)54 (36.48%)43 (29.05%)23 (8.58%)11 (73.33%)8 (72.72%)2 (18.18%)1 (9.09%)0Disease onset over 6 years,n (%) years26 (81.25%)5 (100%)6 (40%)Oligorthritis, n(%)21 (65.62%)1 (20%)14 (93.33%)Inflammatory back pain, n(%)17/32 (53.12%)3/5 (60%)0Enthesopathy22/32 (68.75%)3/5 (60%)0Sacroiliitis14/21 (66.66%)0/1 (0)0/5 (0)ConclusionsArticular involvement compatible with JSpA could be seen in childhood FMF patients. Spondyloarthropathy was detected in 10% of childhood FMF cases. The M694V mutation is the most common MEFV mutation among JSpA patients with FMF. JSpA should be considered in childhood FMF patients, especially in those chronic arthritis, axial involvement and enthesopathy.Reference1 Adrovic A, Sezen M, Barut K, et al. The performance of classification criteria for juvenile spondyloarthropathies. Rheumatol Int2017;37:2013–2018.Disclosure of InterestNone declared
Background:
Familial Mediterranean Fever (FMF) is the most common periodic fever syndrome in childhood with an autosomal recessive inheritance pattern and is characterized by unprovoked fever ...attacks, serositis episodes. The causative gene of the disease is MEFV that encodes pyrin protein. The pyrin protein takes a role in pathways related to inflammation, and mutations of it lead to increased inflammation. It is already shown that frequencies of some certain diseases like PAN, HSP increase in patients with FMF. Nevertheless, frequencies of inflammatory diseases in families of patient with FMF haven’t been investigated.
Objectives:
In this study, we have aimed to evaluate the comorbid disorders in a large cohort of families of patients with FMF.
Methods:
Four hundred and ninety-eight children with FMF, one hundred and forty patients with JIA and ninety-two healthy children were interviewed between December 2019 and January 2020. In JIA group and healthy control group, patients who have family history for FMF were excluded from the study. Patients were asked about characteristics of their disease attacks and if there is a relative with any inflammatory diseases who does not have FMF in patient’s 1
st
and 2th degree relatives.
Results:
Demographic features of study group have shown in Table 1. The most common MEFV mutations in patients with FMF were: M694V homozygotes (13.2 %), M694V heterozygotes (12 %), M694V homozygotes and R202Q homozygotes (6,8 %). Type II diabetes, asthma and hypothyroidism were the most commonly detected diseases in all cohorts. Frequency of Behçet’s disease, allergic rhinitis and type II diabetes were significantly higher in families of patients with FMF than other groups (p<0.05) (Table 2).
Table 1.
Demographic features of study population.
FMF
†
JIA
††
Healthy Control
n: 498 (%
)
mean +/- SD
n: 140 (%
)
mean +/- SD
n: 92 (%
)
mean +/- SD
Female
284 (57)
91 (65)
55 (59.8)
Age (years)
12.9 ± 8.2
11.7 ± 5.1
7.4 ± 4.6
Age at Onset (years)
4.3 ± 3.3
5.4 ± 4.1
-
Age at Diagnosis (years)
6.3 ± 3.6
6.3 ± 4.5
-
Delay in Diagnosis (months)
23.8 ± 29.2
11.3 ± 28.2
-
Follow-up Duration (years)
6.9 ± 8.3
5.3 ± 4.0
-
Consanguinity
100 (20)
25 (17.8)
8 (8.6)
Family History of FMF
282 (56.6)
0 (0)
0 (0)
JIA subgroup
-
-
Oligoarticular
72 (51.4)
Polyarticular (RF negative
)
16 (11.4)
Polyarticular (RF positive
)
3 (2.1)
Enthesitis Related Arthritis
14 (10)
Psoriatic Arthritis
7 (5)
Systemic
23 (16.4)
Other
5 (3.5)
Clinical Findings
-
-
Fever
392 (78.1)
Abdominal Pain
429 (86.1)
Chest Pain
102 (20.5)
Arthralgia
334 (67.1)
Arthritis
157 (31.5)
Extremity Pain
64 (12.8)
Heel Pain
44 (8.8)
Myalgia
43 (8.6)
*ELE
13(2.6)
Serositis
10 (2)
†
Familial Mediterranean Fever
††
Juvenile Idiopathic Arthritis
*Erysipelas like erythema
Table 2.
Comparison of frequencies of diseases detected among families of patient groups (shortened).
Diseases
FMF
JIA
Healthy Control
p
1
Type II Diabetes
284 (57)
64(45.7)
44 (47.8)
0.02
Asthma
139 (27.9)
30 (21.4)
20 (21.7)
0.19
Hypothyroidism
122 (24.4)
27 (19.2)
14 (15.2)
0.09
Eczema
68 (13.6)
14 (10)
5 (5.4)
0.06
Psoriasis
49 (9.8)
6 (4.2)
7 (7.6)
0.10
Allergic Rhinitis
49 (9.8)
3 (2.1)
1 (1)
0.001
Hyperthyroidism
40 (8)
9 (6.4)
3 (3.2)
0.24
Behçet’s Disease
31 (6.2)
1 (1)
2 (2.1)
0.01
Rheumatic Fever
30 (6)
10 (7.1)
2 (2.1)
0.25
Conclusion:
In this study, we have reported increased frequencies of Behçet’s disease, allergic rhinitis and type II diabetes in families of patients with FMF. Our results suggest that possible increased mutation load among families of patients with FMF may cause increased inflammatory diseases.
References:
1Yildiz M, Adrovic A, Tasdemir E, et al. Evaluation of co-existing diseases in children with familial Mediterranean fever.
Rheumatol Int
. 2020;40(1):57–64. doi:10.1007/s00296-019-04391-9
Disclosure of Interests:
None declared
Background:
Anti-nuclear antibodies (ANA) are a group of the antibodies that develop against intracellular components of the cells. It is usually useful for diagnosing some of the connective tissue ...diseases like systemic lupus erythematosus, mixed connective tissue disease. But it is reported that its positivity rate is about %20 in healthy individuals. Therefore, it can be confusing to check ANA test, if there is not really high suspicion for connective tissue diseases or juvenile idiopathic arthritis.
Objectives:
We aimed to evaluate results of long-term follow-up of the patients with ANA positivity who had initially no identifiable rheumatic diseases.
Methods:
Six hundred and ninety-four patients with ANA positivity who did not diagnosed as any of the rheumatic diseases at the first examination were found in database. Two hundred and eighty- two patients of them were called so far and questioned about their demographic features and symptoms that are related with rheumatic diseases.
Results:
Mean age of the patients at the time of study and at the time of testing were 13.4± 4.5 and 9.1±4.0 years. The female: male ratio was 1.05. Mean follow-up duration was 4.3±2.8 years. Most common reasons for the request for ANA test were arthralgia and skin eruptions. ANA testing was most commonly requested by a general pediatrists. Demographic features of the patients were summarized in Table 1.
Table 1.
Demographic features of the patients.
n (%)
Age (years)
13.4± 4.5
Female
145 (51.4)
Age at the time of testing (years)
9.1±4.0
Follow-up Duration (years)
4.3±2.8
Reason for testing
Arthralgia
99 (44.1)
Skin Eruption
54 (24.1)
Check-Up
20 (8.9)
Arthritis
13 (5.8)
Gait abnormalities
7 (3.1)
Hair Loss
6 (2.6)
Fever
5 (2.2)
Uveitis
2 (0.8)
Recurrent abdominal pain
2 (0.8)
Who suggested testing?
Pediatrician
196 (87.5)
Parents
13 (5.8)
Dermatologist
7 (3.1)
Ophthalmologist
3 (1.3)
Rheumatologist
2 (0.8)
Other
3 (1.3)
Positivity of acute phase reactants
15 (5.3)
History of infection before testing
56 (24.3)
History of drug-using before testing
39 (17)
Most of the diseases were diagnosed in patients with ANA positivity were not related with autoimmune mechanisms that associated with ANA positivity therefore, these diseases are thought to be coincidence. Only in 1 patients, systemic lupus erythematosus that has certain association with ANA positivity were diagnosed. All diseases that are diagnosed were shown in Table 2.
Table 2.
All diseases that are diagnosed in patients during the follow-up period.
n (%)
Hypermobility Syndrome
29 (10.2)
Urticaria
7 (2.4)
Hypothyroidism
6 (2.1)
Transient synovitis
4 (1.4)
Chronic ITP*
4 (1.4)
Scoliosis
4 (1.4)
Familial Mediterranean Fever
3 (1)
Cryopyrin associated periodic Syndrome
2 (0.7)
PFAPA syndrome**
2 (0.7)
Celiac Disease
2 (0.7)
Acute Rheumatic Fever
2 (0.7)
Fibromyalgia
1 (0.3)
Bone Tumor
1 (0.3)
Juvenile Idiopathic Arthritis
1 (0.3)
Henoch-Shöenlein Purpura
1 (0.3)
Myastenia Graves
1 (0.3)
Sever Disease
1 (0.3)
Vitiligo
1 (0.3)
Systemic Lupus Erythematosus
1 (0.3)
*Idiopathic Thrombocytopenic Purpura, **Periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis syndrome.
Conclusion:
We are reporting that in only 0.3% of patients with ANA positivity who don’t have any diseases diagnosed initially, were diagnosed as rheumatologic diseases during to the follow-up period. Since positivity of ANA is also common in the healthy population, requesting this test in only patients with high suspicion for connective tissue disease will reduce confusion in terms of diagnosis.
References:
1Kasapcopur O, Ozbakir F, Arisoy N, Ingol H, Yazici H, Ozdogan H. Frequency of antinuclear antibodies and rheumatoid factor in healthy Turkish children. Turk J Pediatr 1999;41:67-71.
Disclosure of Interests:
None declared
Granulomatosis with polyangiitis (GPA) is an antineutrophil cytoplasmic antibody-associated vasculitis. The 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology ...(ACR/EULAR)-endorsed classification criteria for GPA was derived using data only from adult patients. We aimed to assess the performance of the ACR/EULAR classification criteria for GPA in pediatric patients and compare it with the EULAR/Pediatric Rheumatology International Trials Organization (PRINTO)/Pediatric Rheumatology European Society (PReS)-endorsed Ankara 2008 criteria for GPA.
Retrospective data of pediatric patients with GPA in 20 centers from 9 countries were evaluated. The diagnosis of GPA was made according to the expert opinion. The sensitivity, specificity, positive predictive value, and negative predictive value of the criteria sets were evaluated.
The study included 77 patients with GPA and 108 controls (immunoglobulin A vasculitis (n = 44), Takayasu's arteritis (n = 20), microscopic polyangiitis (n = 16), polyarteritis nodosa (n = 14), Behçet's disease (n = 12), eosinophilic granulomatosis with polyangiitis (n = 1), and Cogan's syndrome (n = 1)) with a median age of 17.8 and 15.2 years, respectively. Of patients with GPA, constitutional symptoms (85.7%) and ear-nose-throat involvement (79.2%) were the most common presentations. In the GPA group, 73 patients fulfilled the Ankara 2008 criteria and 69 the ACR/EULAR classification criteria. Sensitivities of the Ankara 2008 criteria and the ACR/EULAR classification criteria were 94.8% and 89.6%, while specificities were 95.3% and 96.3%, respectively. No significant difference was found between sensitivities and specificities of both classification criteria (p= 0.229 and p= 0.733, respectively).
In children, both the ACR/EULAR and EULAR/PRINTO/PReS Ankara 2008 classification criteria for GPA perform well and similarly.
Congenital afibrinogenemia is characterized by the absence of fibrinogen. Congenital fibrinogen disorders result from several mutations in FGA, FGB, or FGG. Their epidemiology is not well known.
The ...present study reports on 2 children with congenital afibrinogenemia. The first child, a male who is now 9 years old, was diagnosed with afibrinogenemia after spontaneous intracranial bleeding at the age of 3 years. The second child is a 2-year-old female cousin of the first patient, who was diagnosed with afibrinogenemia after coagulation tests were carried out due to frequent epistaxis and mucocutaneous bleeding. At follow-up, blood samples of the patients and their parents were sent to the Department of Genetic Medicine and Development, University Medical Center, Switzerland, for polymerase chain reaction analysis. In both patients, the novel homozygous frameshift mutation in the FGA exon 3: c.196 delT was detected. The parents of the patients were both heterozygous for the same mutation.
Congenital afibrinogenemia is a rare coagulation disease. The molecular epidemiology of congenital fibrinogen disorders is complex, and the identification of new mutations will help shed light on this complex molecular structure. Therefore, a genetic analysis that includes more centers is needed.
To date, the mRNA delivery field has been heavily dominated by lipid-based systems. Reports on the use of nonlipid carriers for mRNA delivery in contrast are rare in the context of mRNA vaccination. ...This paper describes the potential of a cell-penetrating peptide containing the amphipathic RALA motif to deliver antigen-encoding mRNA to the immune system. RALA condenses mRNA into nanocomplexes that display acidic pH-dependent membrane disruptive properties. RALA mRNA nanocomplexes enable mRNA escape from endosomes and thereby allow expression of mRNA inside the dendritic cell cytosol. Strikingly, RALA mRNA nanocomplexes containing pseudouridine and 5-methylcytidine modified mRNA elicit potent cytolytic T cell responses against the antigenic mRNA cargo and show superior efficacy in doing so when compared to RALA mRNA nanocomplexes containing unmodified mRNA. RALA's unique sequence and structural organization are vital to act as mRNA vaccine vehicle, as arginine-rich peptide variants that lack the RALA motif show reduced mRNA complexation, impaired cellular uptake and lose the ability to transfect dendritic cells in vitro and to evoke T cell immunity in vivo.
The strength and toughness of material extrusion 3D printed parts is increased through the extrusion of core-sheath dual material thermoplastic filament feedstocks in which the filament core has a ...significantly higher glass transition temperature (Tg) than the filament sheath. Parts printed with these dual material filaments can thus be annealed after printing to increase bonding between printed layers while maintaining dimensional stability. In the present study, scaled production of a dual-material filament with a star-shaped polycarbonate core and an acrylonitrile butadiene styrene sheath is demonstrated via polymer co-extrusion. Laser powder bed fusion is used to rapidly prototype dies to achieve the desired polymer arrangement in the filament. Compared to conventional as-printed mono-material filaments, parts printed and annealed using this dual material filament show a 5-fold increase in z-direction impact toughness, and a 4-fold increase in z-direction tensile strength. Part dimensional accuracy and surface quality are excellent, even when using elevated printer nozzle temperatures, due the stabilizing effect of the polycarbonate core.
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