Drug-induced lupus erythematosus in childhood: Case-based review.

BACKGROUND: Drug-induced lupus erythematosus (DILE) is the development of lupus-like syndrome following a drug exposure. DILE has been reported less frequently among children than adults. METHODS: In this study, we present four children with DILE and similar published cases through a systematic literature review. RESULTS: We report four children (three girls and one boy) who developed DILE associated with the use of topiramate, doxycycline, etanercept, and ethosuximide. Three of them were positive for anti-histone antibodies. In all patients, the drug was discontinued and symptoms resolved completely. The literature review revealed 48 articles describing 61 children with DILE. In the evaluation of 65 patients (our 4 patients and 61 patients from the literature), the most frequently reported drugs associated with DILE were ethosuximide (n = 13) and minocycline (n = 12). Fever (n = 33), arthralgia (n = 31), rash (n = 30), and arthritis (n = 29) were the most common clinical manifestations. Antinuclear antibody (ANA) was positive in 93.5% of patients and anti-histone antibodies were detected in 72.2% of the patients. As for treatment, the responsible drug was discontinued in all patients, and corticosteroids were initiated in 53.3%. Improvement was achieved in 92.0% of patients. CONCLUSION: For children presenting with SLE features, proper drug history is crucial since DILE may be more frequent than anticipated. An association of the relevant drug with the symptoms, and resolution of symptoms on drug withdrawal provides evidence for the diagnosis of DILE.

Thrombotic manifestations in pediatric Behcet syndrome: A multicenter comparative study from the EUROFEVER registry.

INTRODUCTION: Vascular events account for a considerable burden of morbidity and mortality in Behçet syndrome (BS). Thrombosis occurs in 1.8-21 % pediatric BS patients, even if the real prevalence is still largely unknown. OBJECTIVES: To report clinical features and outcomes of pediatric BS patients with thrombosis and to compare the demographic and clinical characteristics of BS patients with and without thrombosis. METHODS: Retrospective data collection of BS patients with thrombosis (T+) included in the EUROFEVER registry. BS patients without thrombosis (T-), belonging to the same rheumatology units, were matched in a 2:1 ratio. RESULTS: 37 T+ were compared to 74 T- patients. At onset, ICBD criteria fulfillment was higher in the T- group (p = 0.015). Caucasian patients were more often T-, Turkish patients were more frequent in T+ group (p = 0.002). At onset, pustulosis was most frequently observed in the T- (p < 0.001) as well as gastrointestinal symptoms (p < 0.001) and ocular involvement (p = 0.022). Neurological symptoms were more often described in T+ (p = 0.034). As for T+, thrombosis was reported at BS presentation in 8/37 (21.6 %). For the T + e patients who developed thrombosis later, oral aphthosis (p = 0.003), genital aphthosis (p = 0.014) were more frequently observed at BS onset, while pustulosis (p = 0.005) and fever (p = 0.043) coexisted with thrombosis. Thrombosis was mainly venous (26/37,70.3 %), involving the cerebral sinuses (21/37, 56.8 %). After thrombosis, 35/37 (94.6 %) T+ patients received an immunomodulatory treatment compared with 16/29 (55.2 %) pre-thrombosis. A recurrence was reported in 6/31(19.4 %). CONCLUSION: Thrombosis was reported at BS presentation in one fifth of cases. Pustolosis and fever were more frequently concomitant to thrombosis. Sinus veins were the most frequent site.

Differentiating Multisystem Inflammatory Syndrome in Children from Kawasaki Disease During the Pandemic.

OBJECTIVE: We aimed to delineate the distinctive characteristics that aid in distinguishing between Kawasaki disease (KD) and multisystem inflammatory syndrome in children (MIS-C) with KD-like manifestations during the pandemic. MATERIALS AND METHODS: We evaluated KD patients and MIS-C patients with KD-like symptoms admitted during the pandemic (between January 2021 and December 2022). RESULTS: Thirty-three MIS-C patients and 15 KD patients were included. Kawasaki disease patients were younger than MIS-C patients (3.4 vs. 7.6 years). Rash (P = .044, 100% vs. 75.7%), oral mucosal changes (P = .044, 100% vs. 75.7%), and cervical lymphadenopathy (P = .001, 93.3% vs. 42.4%) were more common in KD. Multisystem inflammatory syndrome in children: patients had more hypotension (P = .002, 45.4% vs. 0), gastrointestinal (P .001, 72.7% vs. 13.3%), and respiratory symptoms (P = .044, 24.2% vs. 0). Multisystem inflammatory syndrome in children patients also had low lymphocyte and thrombocyte counts and elevated levels of d-dimer, ferritin, and cardiac parameters, unlike KD patients. Multisystem inflammatory syndrome in children patients exhibited a notable reduction in left ventricular systolic function in echocardiography. Another significant difference with regard to management was the anakinra treatment, which was prescribed for MIS-C patients. CONCLUSION: Although MIS-C patients might display a clinical resemblance to KD, several features could help differentiate between MIS-C and classical KD. Specific clinical (hypotension, gastrointestinal, and respiratory symptoms) and laboratory (low lymphocyte and thrombocyte counts with higher C-reactive protein, ferritin, d-dimer, and cardiac parameters) features are characteristic of MIS-C. In addition, divergence in management strategies is evident between the 2 diseases, as biologic drugs were more prevalently employed in MIS-C patients than in classical KD patients.

Rhupus syndrome in children: A multi-center retrospective cohort study and literature review.

OBJECTIVE: In this study, we aimed to evaluate the characteristics of pediatric rhupus patients including all the related series in the literature. METHODS: Thirty pediatric patients with rhupus syndrome from 12 different centers in Turkey were included in this study. The literature was also reviewed for pediatric patients with rhupus syndrome. RESULTS: The most prominent phenotype of these 30 patients was juvenile idiopathic arthritis (JIA) (60%) at the disease onset and SLE (73.3%) at the last visit. Major SLE-related organ involvements were skin (80%), hematological system (53.3%), and kidney (23.3%). Arthritis was polyarticular (73.3%), asymmetric (66.7%), and erosive (53.3%) in most patients. Hydroxychloroquine (100%), glucocorticoids (86.7%), and mycophenolate mofetil (46.7%) were mostly used for SLE, while glucocorticoids (76.6%), methotrexate (73.3%), and nonsteroidal anti-inflammatory drugs (NSAIDs) (57.6%) were mainly preferred for JIA. Our literature search revealed 20 pediatric patients with rhupus syndrome (75% were RF positive). The most prominent phenotype was JIA (91.7%) at the disease onset and SLE (63.6%) at the last visit. Major SLE-related organ involvements were skin (66.7%), hematological system (58.3%), and kidney (58.3%). Arthritis was polyarticular (77.8%), asymmetric (63.6%), and erosive (83.3%) in most patients. Glucocorticoid (100%), hydroxychloroquine (76.9%), and azathioprine (46.2%) were mostly used for SLE, while methotrexate (76.9%) and NSAIDs (46.2%) were mainly preferred for the JIA phenotype. CONCLUSION: Our study is the largest cohort in the literature evaluating pediatric rhupus cases. Most of the pediatric patients had polyarticular, asymmetric, and erosive arthritis, as well as organ involvements associated with SLE, including the skin, hematological system, and kidney.

Evaluation of clinical outcomes in systemic juvenile idiopathic arthritis patients treated with biological agents in Turkey: the TURSIS study.

OBJECTIVES: Biological drugs are one of the most effective treatment methods for systemic juvenile idiopathic arthritis (SJIA) and can significantly prevent morbidity and mortality. This study aimed to evaluate the efficacy and safety of biologics in patients with SJIA and provide real-life data that might help improve the outcomes. METHODS: TURSIS was a retrospective multicentre study carried out in patients with SJIA for whom a biological treatment had been initiated between 1st March 2013 and 30th December 2018. Data include patients' characteristics, laboratory-clinical results, outcomes, and safety-related variables. The 24-month follow-up data of the patients and the efficacy and safety of biological drugs were evaluated. RESULTS: 147 patients were enrolled. The clinical course of the disease was as follows; it was monocyclic in 38.1%, polycyclic in 49%, and persistent in 12.9% of patients. First-choice biologics were interleukin (IL)-1 blockers in the majority of patients (56.5%), followed by the anti-IL-6 (25.2%) and anti-TNF-alpha drugs (18.4%). Anakinra was the most preferred biologic agent in patients with macrophage activation syndrome (MAS), and tocilizumab was used more frequently in patients with persistent type (p=0.000 and p=0.003). The most frequent switch rate was seen in patients receiving anakinra (n=40/68, 58.8%), and it was most frequently switched to canakinumab (n=32/40, 80%). Better physician's global assessment scores were achieved in patients treated with anakinra in Month 3, compared to other treatments (p=0.04). CONCLUSIONS: The results of our study support the efficacy of biological drugs in particular anti-IL-1 and anti-IL-6 drugs, in the treatment of SJIA. These treatments resulted in improvement in activity of disease and provide a considerable decrease in the frequency of MAS.

Chronic non-bacterial osteomyelitis and immune checkpoint molecules.

OBJECTIVE: We aimed to investigate the plasma levels and cell surface expression of two checkpoint molecules, TIM-3 (T cell immunoglobulin and mucin domain-containing protein 3) and PD-1 (programmed cell death protein 1), in pediatric patients with chronic non-bacterial osteomyelitis (CNO). METHODS: Plasma samples of CNO patients were collected at diagnosis or during biologic agent treatment. Plasma levels of TIM-3 and PD-1 were measured using the sandwich enzyme-linked immunosorbent assay method, and the expression of the two immune checkpoint molecules on the cell surface was analyzed by isolating peripheral blood mononuclear cells by density gradient centrifugation technique. RESULTS: Twenty-seven patients with CNO (14 boys, 51.9%) and six healthy controls (3 boys, 50%) were enrolled in the study. There were no age differences between CNO patients and healthy controls (median age 14.5 vs. 13.5 years, respectively, p=0.762). Of the CNO patients, 18 were included at the time of diagnosis while 9 were receiving biologic treatment at enrollment. The median plasma PD-1 levels were significantly lower in the CNO group than in the healthy controls (p=0.011). However, no significant difference was found in the cellular expression of PD-1 and TIM-3 on CD3+CD4+ T cells in patients and healthy controls (p=0.083 and p=0.245, respectively). There was also no statistically significant difference in plasma TIM-3 levels of the patient and control groups (p=0.981). CONCLUSION: CNO is an autoinflammatory disease, and overall, our results suggest that T cell exhaustion may not be significant in CNO. Further research is needed to find out whether the immune checkpoints are mainly associated with autoimmunity but not autoinflammation. Key Points • The median plasma PD-1 levels were significantly lower in the CNO group than in the healthy controls. • No significant difference was found in the cellular expression of PD-1 and TIM-3 on CD3+CD4+ T cells in patients and healthy controls. • Our results suggest that T cell exhaustion may not be significant in CNO pathogenesis.

Comparison of EULAR/PRINTO/PReS Ankara 2008 and 2022 ACR/EULAR Classification Criteria for Granulomatosis with Polyangiitis in Children.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSION: In children, both the ACR/EULAR and EULAR/PRINTO/PReS Ankara 2008 classification criteria for GPA perform well and similarly.

The Effect of Biologics in the Treatment of Multisystem Inflammatory Syndrome in Children (Mis-C): A Single-Center Propensity-Score-Matched Study.

Multisystem inflammatory syndrome in children (MIS-C) is a serious condition characterized by excessive inflammation that can arise as a complication of SARS-CoV-2 infection in children. While our understanding of COVID-19 and MIS-C has been advancing, there is still uncertainty regarding the optimal treatment for MIS-C. In this study, we aimed to compare the clinical and laboratory outcomes of MIS-C patients treated with IVIG plus corticosteroids (CS) to those treated with IVIG plus CS and an additional biologic drug. We used the propensity score (PS)-matching method to assess the relationships between initial treatment and outcomes. The primary outcome was a left ventricular ejection fraction of less than 55% on day 2 or beyond and/or the requirement of inotrope support on day 2 or beyond. We included 79 MIS-C patients (median age 8.51 years, 33 boys) followed in our center. Among them, 50 children (25 in each group) were allocated to the PS-matched cohort sample. The primary outcome was observed in none of the patients in the IVIG and CS group, while it occurred in eight patients in the IVIG plus CS and biologic group (p = 0.04). MIS-C is a disorder that may progress rapidly and calls for extensive care. For definitive recommendations, further studies, including randomized control trials, are required.

Patients Without a Rheumatic Disease Diagnosis in a Pediatric Rheumatology Unit: Retrospective Analysis and Comparison Between Pre-pandemic and Pandemic Periods.

OBJECTIVE: Children with suspicious complaints of rheumatic diseases are generally referred to a pediatric rheumatologist. We aimed to evaluate the profile of patients referred to the pediatric rheumatology unit and were not diagnosed with a rheumatic disease and to assess the impact of the coronavirus disease-2019 pandemic on referral complaints. MATERIALS AND METHODS: All new outpatients who applied to the pediatric rheumatology department between March 2019 and February 2021 and were not diagnosed with rheumatic disease were included. We also compared the frequency of admission symptoms during the pre-pandemic (March 2019-February 2020) and pandemic periods (March 2020-February 2021). RESULTS: A total of 1089 patients without a rheumatic disease diagnosis (568 female, 52.2%; median age 10.0 years) were included in this study. The most common complaint for referral was prolonged or recurrent fevers (13.4%) followed by anti-nuclear antibody positivity (13.1%), arthralgia (13.0%), skin findings (7.5%), and the presence of heterozygous mutations in the Mediterranean fever gene (6.9%). During the pandemic year, the number of patients referred for back pain increased significantly (P = .028). A total of 682 of 1089 patients were consulted from other departments in our center (62.6%). Of these, the most frequent consultation request was from general pediatrics (43.6%). The rheumatic disease was excluded in 11.3% of the patients. CONCLUSION: Prolonged or recurrent fever and anti-nuclear antibody positivity were the most frequent complaints of referrals to a pediatric rheumatology unit in patients who did not have a rheumatic disease. The rate of back pain was more common in children during the pandemic period.

Report of 2 pediatric cases with atypical Cogan's syndrome and a systematic review.

Cogan's syndrome (CS) is a rare inflammatory disease characterized by interstitial keratitis or uveitis, vestibular impairment, and progressive hearing loss, commonly bilateral. Although glucocorticoids are fundamental treatment options, in most cases, hearing loss gradually worsens. Herein we report 2 pediatric cases of CS who were treated with corticosteroids and methotrexate. One patient had a cochlear implant, and the hearing of the other patient improved with treatment. Also, a systematic literature review was conducted for articles including pediatric CS patients. In the literature, 34 articles describing 44 pediatric patients with CS were identified. Sudden hearing loss (95.3%) and ocular symptoms (92.5%) were the most common manifestations in these patients. Also, aortic involvement was present in 19.5% of patients in the literature. Otorhinolaryngologists, ophthalmologists, and pediatricians should collaborate to diagnose and manage CS to prevent progressive hearing loss and eye involvement.

The Characteristics of Patients With COVID-19-Associated Pediatric Vasculitis: An International, Multicenter Study.

OBJECTIVE: COVID-19-associated pediatric vasculitis, other than Kawasaki disease (KD)-like vasculitis in multisystem inflammatory syndrome in children (MIS-C), is very rare. This study sought to analyze the characteristics, treatment, and outcomes in patients with COVID-19-associated pediatric vasculitis (excluding KD-like vasculitis in MIS-C). METHODS: The inclusion criteria were as follows: 1) age <18 years at vasculitis onset; 2) evidence of vasculitis; 3) evidence of SARS-CoV-2 exposure; and 4) ≤3 months between SARS-CoV-2 exposure and vasculitis onset. Patients with MIS-C were excluded. The features of the subset of patients in our cohort who had COVID-19-associated pediatric IgA vasculitis/Henoch Schönlein purpura (IgAV/HSP) were compared against a pre-pandemic cohort of pediatric IgAV/HSP patients. RESULTS: Forty-one patients (median age 8.3 years; male to female ratio 1.3) were included from 14 centers and 6 countries. The most frequent vasculitis subtype was IgAV/HSP (n = 30). The median duration between SARS-CoV-2 exposure and vasculitis onset was 13 days. Involvement of the skin (92.7%) and of the gastrointestinal system (61%) were the most common manifestations of vasculitis. Most patients (68.3%) received glucocorticoids, and 14.6% also received additional immunosuppressive drugs. Remission was achieved in all patients. All of the patients with IgAV/HSP in our cohort had skin manifestations, while 18 (60%) had gastrointestinal involvement and 13 (43.3%) had renal involvement. When we compared the features of this subset of 30 patients to those of a pre-pandemic pediatric IgAV/HSP cohort (n = 159), the clinical characteristics of fever and renal involvement were more common in our COVID-19-associated pediatric IgAV/HSP cohort (fever, 30% versus 5%, respectively [P < 0.001]; renal involvement, 43.3% versus 17.6%, respectively [P = 0.002]). Recovery without treatment and complete recovery were each less frequent among our COVID-19-associated pediatric IgAV/HSP patients compared to the pre-pandemic pediatric IgAV/HSP cohort (recovery without treatment, 10% versus 39%, respectively [P = 0.002]; complete recovery, 86.7% versus 99.4%, respectively [P = 0.002]). CONCLUSION: This is the largest cohort of children with COVID-19-associated vasculitis (excluding MIS-C) studied to date. Our findings suggest that children with COVID-19-associated IgAV/HSP experience a more severe disease course compared to pediatric IgAV/HSP patients before the pandemic.

A new tool supporting the diagnosis of childhood-onset Behçet's disease: venous wall thickness.

OBJECTIVES: The lower extremity venous wall thickness (VWT) of Behçet's disease (BD) patients was reported to be significantly increased in adults, suggesting its use for the support of BD diagnosis. This prospective study aimed to investigate the lower extremity VWT in childhood-onset definite and incomplete BD patients and compare it to healthy age-matched controls. METHODS: Paediatric patients classified with BD according to the 2015 international paediatric BD criteria in our centre were included in the study. Intima-media thickness of the lower extremity veins to evaluate VWT was measured by ultrasonography, including common femoral vein (CFV), femoral vein (FV), vena saphena magna, vena saphena parva and popliteal vein (PV). RESULTS: In this cross-sectional study, VWT was measured in 35 patients (63% male) and 27 healthy controls (55% male). Thirteen (37%) of 35 patients met the criteria for the diagnosis of BD. The remaining 22 (63%) had incomplete BD and met two criteria. The median VWT values of both definite and incomplete BD patients were significantly higher than the control group in all veins on both sides. Regarding the best cut-off values of VWT for all lower extremity veins, the sensitivity rates were between 63% and 86%, while specificity rates were between 71% and 100%. CONCLUSION: Increased VWT was present not only in BD patients with vascular involvement but also in those without. We suggest that VWT may be a new criterion in supporting the diagnosis of childhood BD both in definite and incomplete BD patients.

The Asthma Risk Is Increased in Children with Severe Allergic Rhinitis.

OBJECTIVE: The aim of the study was to evaluate the allergic rhinitis severity, to identify risk fac- tors associated with asthma, and to determine the frequency of comorbid conditions in allergic rhinitis patients with positive skin prick test. MATERIALS AND METHODS: Clinical characteristics of pediatric patients with allergic rhinitis were investigated. The frequency of comorbidities and risk factors for asthma development were investigated. RESULTS: A total of 120 patients with a mean age of 13.05 ± 3.20 years were included in the study. Dermatophagoides pteronyssinus was the most common source of allergic sensitization (n = 78, 61.0%), whereas mild-persistent disease was the most common type of allergic rhini- tis severity (n = 44, 36.6%). Sensitization to Dermatophagoides farinea, Dermatophagoides pteronyssinus, and Alternaria was more common in patients with a moderate-severe course of allergic rhinitis than in the mild group (P = .006, P = .008, and P = .005, respectively). The most frequent comorbidity in children with allergic rhinitis was allergic conjunctivitis (71.7%). The inci- dence of asthma in those with moderate-severe allergic rhinitis was found to be significantly higher compared to those with mild disease severity (P = .009). Also, the multivariate analysis disclosed moderate-severe allergic rhinitis severity and persistent allergic rhinitis symptoms (OR: 3.822; 95% CI: 1.587-9.200; P =0.003 and OR: 0.333; 95% CI: 0.150-0.737; P =.007, respec- tively) as risk factors for asthma development. CONCLUSION: Sensitization to Dermatophagoides farinea, Dermatophagoides pteronyssinus, and Alternaria was more frequent in patients with moderate-severe allergic rhinitis course. Also, having moderate-severe allergic rhinitis severity and persistent allergic rhinitis symptoms are associated with the development of asthma. Awareness of the risk factors could prevent the progression and complications of allergic rhinitis in children.

The challenges in diagnosing pediatric primary antiphospholipid syndrome.

Pediatric primary antiphospholipid syndrome (APS) is a very rare disease with significant distinctions from the APS in adults. Herein, we present our experience in the diagnosis and treatment of six pediatric primary APS patients, who met the updated Sapporo criteria for the APS diagnosis. One of them was also diagnosed as having probable catastrophic APS (CAPS) due to the involvement of three different organ systems simultaneously. Besides vascular involvement, four patients had thrombocytopenia, one had psychiatric disorder, and one had chorea and valvular heart disease. All patients received immunosuppressive treatment along with long-term anticoagulation therapy. Specific neurologic and hematologic manifestations that are not part of the classification criteria can be seen in children with primary APS. Therefore, using the adult criteria for diagnosing pediatric APS may result in missed or delayed diagnoses in children.

Treatment of childhood-onset Takayasu arteritis: switching between anti-TNF and anti-IL-6 agents.

OBJECTIVES: Biologics are new treatment alternatives in Takayasu arteritis (TA), although data in childhood are limited. The aim of this study was to share our experience in seven childhood-onset TA patients who received a TNF-α inhibitor (adalimumab) or an IL-6 receptor inhibitor (tocilizumab) and the effect of switching therapy. METHODS: We retrospectively evaluated the medical treatment records of seven patients with TA, followed between August 2005 and January 2021 at the Pediatric Rheumatology Department of Hacettepe University Faculty of Medicine. RESULTS: The median age of patients was 14 (IQR 4) years, and six were female. All of the patients had severe disease and high acute-phase reactants. The patients initially received only steroids or steroids+CYC. Prednisone was decreased, and biologic agents were started once the acute phase reactants decreased, and the Indian Takayasu Activity Score (ITAS) returned to normal. Initially, four patients received tocilizumab (TCZ) [median 25.5 (IQR 41) months] and three patients received adalimumab (ADA) [median 13 (IQR 31) months]. However, due to the progression of MR angiography findings or persistent elevation in acute-phase reactants, the biologic agents were switched from TCZ to ADA in four patients and from ADA to TCZ in three patients. The patients' median follow-up time after changing was 50 (IQR 77) months, and median ITAS was evaluated as '0' after 2 (IQR 4) months. CONCLUSIONS: In conclusion, both TNF-α and IL-6 inhibitors are effective alternatives in treating patients with childhood-onset TA. However, prospective randomized controlled trials are needed for the comparison of their effectiveness.

Probiotic use in the prophylaxis of periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome: a retrospective cohort study.

Periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome is an autoinflammatory recurrent fever syndrome that mainly affects children. Probiotics are currently used to prevent upper respiratory tract infections and flares of diseases associated with immune dysregulation. We aimed to evaluate the response to probiotic treatment in PFAPA patients. Patients with PFAPA syndrome who received probiotics and were followed between July 2019 and July 2021 were included in this retrospective study. Demographic and clinical features and response to probiotics were assessed. Twenty out of 111 children with PFAPA syndrome (F/M:1) were included. The median (min-max) ages at symptoms onset and diagnosis were 24 (3-72) and 51.5 (11-120) months, respectively. All 20 patients received probiotics during the disease course. The probiotic preparation they received included a combination of two lactobacilli as Lactobacillus plantarum HEAL9 (Lp HEAL9) and Lactobacillus paracasei 8700:2 (Lpa 8700:2). The median age at probiotic onset was 60 (33-192) months, while the duration of probiotic use was 4.5 (3-19) months. All patients except one experienced a decrease in attack frequency with probiotic use. After probiotic treatment, the median number of episodes during 3 months decreased from 3 to 1 (p < 0.001). Eight (40%) patients had no attacks during the 3 months after probiotic initiation. And, 5 (45%) of 11 patients who had ≥ 1 attacks on probiotics mentioned that the attack severity decreased significantly after probiotic initiation. Our results suggest that probiotic strains Lactobacillus plantarum HEAL9 and Lactobacillus paracasei 8700:2 could be beneficial in PFAPA patients by decreasing the attack frequency.

The performances of the ILAR, ASAS, and PRINTO classification criteria in ERA patients: a comparison study.

BACKGROUND: Enthesitis-related arthritis (ERA) could be considered the pediatric equivalent of ankylosing spondylitis in adults albeit with certain significant differences. We aim to evaluate the sensitivity and specificity of the International League of Associations for Rheumatology (ILAR), the Assessment of Spondyloarthritis International Society (ASAS), and the preliminary Pediatric Rheumatology International Trials Organization (PRINTO) classification criteria in ERA patients. METHOD: The medical records of ERA patients who were followed up between January 2005 and September 2020 have been analyzed. The control group consisted of patients with oligoarticular JIA (n = 146), polyarticular JIA (n = 55), and psoriatic arthritis (n = 20). RESULTS: This retrospective study included 108 ERA (73.1% male) and 221 control patients (25.8% male). The median age at diagnosis for ERA and control patients were 12.5 and 4.0 years, respectively (p < 0.001). Arthritis was observed more frequently in the control group at diagnosis and in the follow-up (p < 0.001 for both), while enthesitis, sacroiliac joint tenderness, and inflammatory back pain were more common in the ERA group both at diagnosis and in the follow-up (p < 0.001 for all). In sacroiliac imaging, 70.1% of ERA patients had positive findings suggestive of sacroiliitis at diagnosis and 78% in the follow-up. The sensitivities of ILAR, PRINTO, ASAS criteria for axial SpA, and peripheral SpA at diagnosis were 74.0%, 57.4%, 21.3%, and 85.1%, respectively which increased to 82.4%, 78.7%, 35.1%, and 92.5%, respectively at follow-up. The specificities were 100%, 100%, 99.1%, and 90.9%, respectively at both diagnosis and follow-up. CONCLUSION: The ASAS criteria for peripheral SpA were the most sensitive while ILAR and the preliminary PRINTO criteria were the most specific criteria for classifying ERA patients. KEY POINTS: The ASAS criteria for peripheral SpA were the most sensitive criteria for classifying ERA patients. The use of ASAS axial SpA criteria may provide early detection of axial involvement.

Impact of the COVID-19 pandemic on the frequency of the pediatric rheumatic diseases.

The impact of the COVID-19 pandemic, and implemented restrictions on the frequency of pediatric rheumatic diseases remain unknown, while they have probably prevented common infections in children. We present the effects of the COVID-19 on our pediatric rheumatology practice in a main referral center. We retrospectively reviewed the medical records of patients presenting to pediatric rheumatology department in 4 years before March 2020 and compared it to the pandemic year (March 2020-March 2021). Since there was an overall decrease in patient numbers, we calculated the percentage according to the total number of that year. A total of 32,333 patients were evaluated. The mean annual number of patients decreased by 42% during the COVID-19 pandemic. When follow-up visits (25,156) were excluded, there were 2818 new diagnoses of rheumatic diseases. In the pre-pandemic period, familial Mediterranean fever (FMF) (n = 695, 28.1%) was the most frequent, whereas in the pandemic period multisystem inflammatory syndrome in children (MIS-C) (n = 68, 19.2%) was the most common diagnosis. There were no significant differences in the percentages of juvenile idiopathic arthritis, autoimmune diseases, rare autoinflammatory diseases, and other vasculitides. However, there was a significant decrease in patients diagnosed with FMF, IgA vasculitis (IgAV), acute rheumatic fever (ARF), classic Kawasaki disease (KD), and macrophage activation syndrome (MAS) (all p < 0.05). During the pandemic year, the percentage of most common diseases did not differ. On the other hand, we suggest that the decreases in IgAV, KD (classic), and MAS, which parallels the decrease in ARF, confirm the role of infections in the pathogenesis for these diseases.