A treatment algorithm for familial Mediterranean fever patients with menstruation-associated attacks.

OBJECTIVES: Familial Mediterranean fever (FMF) is characterized by febrile polyserositis attacks. Menstruation could be a trigger for attacks. We aimed to analyze the features of adolescent FMF patients with menstruation-associated attacks and propose a management algorithm. METHODS: All female FMF patients who had menarche and visited the Pediatric Rheumatology Unit between January-December 2022, were included into this study. Demographics, general characteristics, and the features of menstrual cycle and FMF attacks were noted. RESULTS: A total of 151 female FMF patients were included. Thirty-five (23.2%) had menstruation-associated attacks. Fever and arthritis were less frequent during the menstruation-associated attacks than the attacks not associated with menstruation in these patients (65.7% vs 88.6%, p= 0.01 and 2.9% vs 20%, p= 0.04; respectively). Patients with menstruation-associated FMF attacks were younger at symptom onset and diagnosis (2.5 vs 5 years, p= 0.004 and 4 vs 7 years, p= 0.01; respectively), had a higher rate of dysmenorrhea (74.3% vs 38.8%, p< 0.001, respectively) and higher pre- and post-menarche attack frequency (4 vs 2 and 10 vs 0, respectively; p< 0.001 for both) than patients whose attacks were not associated with menstruation. The interventions for menstruation-associated attacks included initiating colchicine, increasing the dose of colchicine, switching from coated to compressed colchicine tablets or anti-interleukin 1 drugs, and on-demand non-steroidal anti-inflammatory drugs, on-demand glucocorticoids, and on-demand anakinra. On-demand therapies were beneficial in controlling menstruation-associated attacks. CONCLUSIONS: This is the largest cohort of adolescent FMF patients with menstruation-associated attacks. Severe FMF may cause tendency to this association. On-demand therapies could be preferred in the management.

Transitioning from pediatric to adult-oriented healthcare in rheumatology: the pediatric side of the coin.

OBJECTIVES: The transition of adolescents and young adults (AYAs) from pediatric to adult-oriented healthcare may be affected by many factors, including the personal and cultural settings. We aimed to analyze the transition readiness and the factors affecting the transition success in rheumatology. METHODS: Patients older than 12 years were included in this prospective study. All filled out the Transition Readiness Assessment Questionnaire (TRAQ) 5.0. AYAs were phone-interviewed after their transfer to adult-oriented healthcare. Drug adherence was evaluated with 4-item Morisky Medication Adherence Scale (MMAS-4). AYAs rated their transitional care experience with visual analogue scale (VAS 0-10; 0, the worst; 10, the best). RESULTS: A total of 504 TRAQs were filled out by 406 patients (F/M = 1.5). The total TRAQ score was positively correlated with age and higher in the forms filled out by girls than boys (4.2 vs 4.0, respectively; p= 0.005). The transition was successful for 78 (83.9%) out of 93 patients transferred to adult-oriented healthcare. The VAS for the transition process was lower and the post-transfer MMAS-4 score was worse (8 vs 9, p= 0.030 and 3 vs 4, p= 0.020; respectively) in patients whose transition was not successful when compared with the successfully-transitioned ones. The best-performing TRAQ cut-off value was >4.0 for predicting transfer readiness in rheumatology. CONCLUSION: A TRAQ score of > 4 could be used while deciding about the transfer readiness of AYAs in rheumatology. Improving the AYAs' experience of the transition process and closely monitoring medication adherence during transition are essential for a successful transition.

A score for predicting colchicine resistance at the time of diagnosis in familial Mediterranean fever: data from the TURPAID registry.

OBJECTIVES: Colchicine forms the mainstay of treatment in FMF. Approximately 5-10% of FMF patients are colchicine resistant and require anti-IL-1 drugs. We aimed to compare the characteristics of colchicine-resistant and colchicine-responsive patients and to develop a score for predicting colchicine resistance at the time of FMF diagnosis. METHODS: FMF patients (0-18 years) enrolled in the Turkish Paediatric Autoinflammatory Diseases (TURPAID) registry were included. The predictive score for colchicine resistance was developed by using univariate/multivariate regression and receiver operating characteristics analyses. RESULTS: A total of 3445 FMF patients [256 (7.4%) colchicine-resistant and 3189 colchicine-responsive) were included (female:male ratio 1.02; median age at diagnosis 67.4 months). Colchicine-resistant patients had longer, more frequent attacks and were younger at symptom onset and diagnosis (P < 0.05). Fever, erysipelas-like erythema, arthralgia, arthritis, myalgia, abdominal pain, diarrhoea, chest pain, comorbidities, parental consanguinity and homozygosity/compound heterozygosity for exon 10 MEFV mutations were significantly more prevalent among colchicine-resistant than colchicine-responsive patients (P < 0.05). Multivariate logistic regression analysis in the training cohort (n = 2684) showed that age at symptom onset, attack frequency, arthritis, chest pain and having two exon 10 mutations were the strongest predictors of colchicine resistance. The score including these items had a sensitivity of 81.3% and a specificity of 49.1%. In the validation cohort (n = 671), its sensitivity was 93.5% and specificity was 53.8%. CONCLUSION: We developed a clinician-friendly and practical predictive score that could help us identify FMF patients with a greater risk of colchicine resistance and tailor disease management individually at the time of diagnosis.

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 ANCA-associated vasculitis. The 2022 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 paediatric 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 paediatric patients with GPA in 20 centres 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 [IgA 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. Among patients with GPA, constitutional symptoms (85.7%) and ENT 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.

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.

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.

Exploring gastrointestinal manifestations in childhood onset systemic lupus erythematosus - Insights from a multicenter study.

OBJECTIVE: Systemic lupus erythematosus (SLE) constitutes an autoimmune disorder with potential involvement of the gastrointestinal system (GIS). Our objective was to assess the gastrointestinal (GI) manifestations in patients diagnosed with childhood onset SLE. METHODS: The study cohort consisted of 123 patients with childhood onset-SLE and GIS involvement from 16 referral departments of pediatric rheumatology. All participants met the Systemic Lupus International Collaborating Clinics criteria. RESULTS: Out of 123 patients, 78 (63.4%) exhibited GIS involvement at the initial SLE diagnosis, whereas the remaining 45 (36.6%) developed GI symptoms after a median duration of 12 (3-140) months. Eighty-two (66.7%) individuals experienced symptoms related to the GI tract, whereas the remaining patients received a diagnosis of GI involvement through laboratory assessments. The predominant initial GIS involvement symptom was abdominal pain, observed in 77 (62.6%) patients, followed by elevated hepatic transaminases in 70 (56.9%), hepatomegaly in 40 (32.5%), diarrhea in 26 (21.1%), and jaundice in 11 (8.9%) patients. The GIS involvement was associated with SLE in 82 (78.6%), while it resulted from drug-related adverse events in 35 (28.5%) patients or comorbidities in 6 (0.5%) patients. CONCLUSION: GIS involvement should be considered in all childhood onset-SLE patients, especially in the presence of suggestive symptoms or elevated hepatic transaminases. It is also crucial to consider SLE in the differential diagnosis of GIS manifestations in children. Apart from GIS involvement directly associated with SLE, adverse events of drugs should be kept in mind.

Preferential involvement of the pelvis and hips along with active sacroiliitis in chronic nonbacterial osteomyelitis: MRI of 97 patients from a single tertiary referral center.

OBJECTIVE: To present MRI distribution of active osteitis in a single tertiary referral center cohort of patients with chronic nonbacterial osteomyelitis (CNO). METHODS: Two musculoskeletal radiologists retrospectively reviewed MRI examinations of all patients with a final clinical diagnosis of CNO over 15 years. Sites of active osteitis at any time during the course of disease were divided into seven groups: (A) mandible, sternum, clavicles, or scapulas; (B) upper extremities; (C) subchondral sacrum and ilium immediately subjacent to sacroiliac joints (active osteitis denoting "active sacroiliitis" here); (D) pelvis and proximal 1/3 of femurs (excluding group C); (E) bones surrounding knees including distal 2/3 of femurs and 1/2 of proximal tibias and fibulas; (F) distal legs (including distal 1/2 of tibias and fibulas), ankles, or feet; (G) spine (excluding group C). Temporal changes of lesions in response to treatment (or other treatment-related changes such as pamidronate lines) were not within the scope of the study. RESULTS: Among 97 CNO patients (53 males [55%], 44 females; age at onset, mean ± SD, 8.5 ± 3.2 years; age at diagnosis, 10.3 ± 3.3 years), whole-body (WB) MRI was performed in 92%, mostly following an initial targeted MRI (94%). A total of 557 (346 targeted and 211 WB) MRIs were analyzed. Biopsy was obtained in 39 patients (40%), all consistent with CNO or featuring supporting findings. The most common locations for active osteitis were groups D (78%; 95% CI 69‒85%) and C (72%; 95% CI 62‒80%). CONCLUSION: Pelvis and hips were preferentially involved in this cohort of CNO patients along with a marked presence of active sacroiliitis. CLINICAL RELEVANCE STATEMENT: When suggestive findings of CNO are identified elsewhere in the body, the next targeted site of MRI should be the pelvis (entirely including sacroiliac joints) and hips, if whole-body MRI is not available or feasible. KEY POINTS: • Heavy reliance on MRI for diagnosis of CNO underscores the importance of suggestive distribution patterns. • Pelvis and hips are the most common (78%) sites of CNO involvement along with active sacroiliitis (72%). • Pelvis including sacroiliac joints and hips should be targeted on MRI when CNO is suspected.

Other Immunomodulatory Treatment for Cytokine Storm Syndromes.

Cytokine storm syndromes (CSS) include different entities such as macrophage activation syndrome, primary and secondary hemophagocytic lymphohistiocytosis (HLH), and multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19. An effective management strategy is critical in CSS. While biologics have become an essential part of CSS treatment, hematopoietic stem cell transplantation (HSCT) has changed the fate of primary HLH patients. This chapter will focus on the available alternative immunomodulatory therapies in CSS, which include corticosteroids, cyclosporine A, intravenous immunoglobulin, interleukin 18 binding protein, therapeutic plasmapheresis, HSCT, and mesenchymal stromal cell-based therapies.

Subclinical enthesitis in enthesitis-related arthritis and sacroiliitis associated with familial Mediterranean fever.

OBJECTIVES: In our study, we investigated the presence of subclinical enthesitis by ultrasonography (US) in asymptomatic patients with enthesitis-related arthritis (ERA) and sacroiliitis associated with familial Mediterranean fever (FMF). METHODS: A total of 50 patients, including 35 patients with ERA and 15 with sacroiliitis associated with FMF, were included in the study. All patients were evaluated with US by a paediatric radiologist. Enthesis of seven tendons (common extensor and flexor tendons, quadriceps tendon, proximal and distal patellar tendon, Achilles tendon, and plantar fascia) was examined on both sides. RESULTS: Subclinical enthesitis was detected in 10 ERA (28.5%) and three FMF (20%) patients. Enthesitis was radiologically diagnosed in 16 (2.3%) out of 700 evaluated entheseal sites. The most frequent sites of enthesitis were Achilles (37.5%) and quadriceps (31.3%) tendons. All patients were in clinical remission and had no active complaints, and acute phase reactants were within normal limits. Therefore, the patients were followed up without treatment change. However, disease flare-up was observed in three of these patients (23.1%) during the follow-up, and their treatments were intensified. CONCLUSIONS: Our results showed that the US can be particularly helpful in detecting subclinical enthesitis and predicting disease flare-ups.

Feasibility of canakinumab withdrawal in colchicine-resistant familial Mediterranean fever.

OBJECTIVES: There is no consensus on canakinumab treatment tapering and discontinuation strategies in colchicine-resistant FMF patients. In this study, we aimed to establish a treatment management and discontinuation protocol in paediatric FMF patients treated with canakinumab. METHODS: Fifty-eight FMF patients treated with canakinumab were included. Since 2020, we have applied a protocol based on our experience whereby canakinumab is administered monthly in the first 6 months, followed by bimonthly for 6 months, and a final period of every 3 months (for 6 months). The patients were divided into two groups: 2012-2019 (group A) and 2020-2022 (group B). RESULTS: In group A (n = 33), the median duration of canakinumab treatment was 2.5 years [interquartile range (IQR) 1.9-3.7]. A total of 25 of 33 patients discontinued canakinumab after a median of 2.1 years (IQR 1.8-3.4). In two patients, canakinumab was restarted because of relapse. In group B (n = 25), canakinumab was discontinued in 18 patients at the end of 18 months. After a median follow-up of 0.8 years (IQR 0.6-1.1), two patients had a relapse and canakinumab treatment was reinitiated. The remaining 16 patients still have clinically inactive disease and are receiving only colchicine. When we compared the characteristics between groups A and B, there were no significant differences regarding demographics, clinical features, and outcomes. CONCLUSION: This is the largest study in the literature suggesting a protocol for discontinuing canakinumab in paediatric FMF patients. It was possible to discontinue canakinumab successfully in more than half of the patients in 18 months. Thus we suggest that this protocol can be used in paediatric FMF patients.

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.

Pediatric mixed connective tissue disease versus other overlap syndromes: a retrospective multicenter cohort study.

Pediatric mixed connective tissue disease (MCTD) is a subgroup of overlap syndromes. We aimed to compare the characteristics and outcomes in children with MCTD and other overlap syndromes. All MCTD patients met either Kasukawa or Alarcon-Segovia and Villareal criteria. The patients with other overlap syndromes had the features of ≥ 2 autoimmune rheumatic diseases but did not meet MCTD diagnostic criteria. Thirty MCTD (F/M = 28/2) and thirty (F/M = 29/1) overlap patients were included (disease onset < 18 years). The most prominent phenotype at disease onset and the last visit was systemic lupus erythematosus (SLE) in the MCTD group; juvenile idiopathic arthritis and dermatomyositis/polymyositis, respectively, in the overlap group. At the last visit, systemic sclerosis (SSc) phenotype was more frequent among MCTD than overlap patients (60% vs. 33.3%; p = 0.038). The frequency of the predominant SLE phenotype had decreased (60% to 36.7%), while predominant SSc phenotype had increased (13.3% to 33.3%) during follow-up in MCTD patients. Weight loss (36.7% vs. 13.3%), digital ulcers (20% vs. 0), swollen hands (60% vs. 20%), Raynaud phenomenon (86.7% vs. 46.7%), hematologic involvement (70% vs. 26.7%), and anti-Sm positivity (29% vs. 3.3%) were more common, while Gottron papules (16.7% vs. 40%) were less frequent among MCTD than overlap patients (p < 0.05). A higher percentage of overlap patients achieved complete remission than MCTD patients (51.7% vs. 24.1%; p = 0.047). The disease phenotype and outcome differ between pediatric MCTD and other overlap syndromes where MCTD may be regarded as a more severe disease. Analyzing these patients could pave the way for early and effective treatment.

Evaluation of periodontal status and cytokine response in children with familial Mediterranean fever or systemic juvenile idiopathic arthritis.

OBJECTIVES: Familial Mediterranean fever (FMF) and systemic juvenile idiopathic arthritis (sJIA) are chronic inflammatory diseases and anti-inflammatory agents are used in their treatment. This study evaluates the periodontal status and cytokine response in pediatric patients with FMF or sJIA. MATERIALS AND METHODS: Forty-eight FMF/sJIA patients were under treatment/control and in attack-free period; 20 systemically healthy children participated in the study. FMF/sJIA patients were divided into two subgroups based on the treatment they received: receiving anti-IL-1 therapy (anti-IL-1 ( +)) and not receiving anti-IL-1 therapy (anti-IL-1 ( -)). The clinical periodontal indices were recorded. Gingival crevicular fluid (GCF) and serum samples were collected. Cytokine levels (IL-1ß, IL-1α, TNF-α, IL-6, IL-8, IL-10, IL-17, IL-33) in GCF and serum were measured using ELISA kits. RESULTS: There was no significant difference between the groups in terms of GCF IL-1ß and IL-1α levels although, BoP and GI were significantly lower in the anti-IL-1 ( +) group compared to the control group. GCF IL-10 level was higher in the anti-IL-1 ( -) group than in the control group; GCF IL-8 levels were lower in both FMF/sJIA subgroups versus controls. There was no significant difference between serum cytokine levels of FMF/sJIA subgroups. CONCLUSIONS: Considering the significant decrease in GI, BoP, and GCF IL-8 levels in the anti-IL-1 ( +) group, it can be concluded that anti-IL-1 medications may suppress periodontal inflammation clinically and immunologically. CLINICAL RELEVANCE: Anti-IL agents are not currently used in periodontal therapy. However, this study demonstrated the positive effect of anti-IL-1 medications on periodontal inflammation in pediatric patients with FMF or sJIA.

Rice bodies in children with rheumatic disorders: A case series and systematic literature review.

OBJECTIVES: Rice body (RB) formation is an uncommon inflammatory process seen in systemic disorders. In this study, we aimed to assess characteristic features of RBs in pediatric patients. METHOD: We retrospectively evaluated pediatric patients who underwent joint/extremity magnetic resonance imaging. A systematic literature review was conducted for articles including children with RBs. RESULTS: We found 24 patients (median age 6.1 years; F/M = 2.4) with RBs [23 with juvenile idiopathic arthritis (JIA) and one with arthralgia]. The most prevalent location for RBs was the knee joint (75%). RBs were most frequently seen as diffuse multiple millimetric structures. In three out of five patients with follow-up magnetic resonance imaging, resolution or regression of RBs was observed without surgical intervention. Our literature search identified 13 pediatric patients with RBs. Most (84.6%) had JIA, and the knee joint (71.4%) was the most commonly affected joint. Surgery was preferred in our 3 patients (12.5%) and 10 literature patients (83.3%) in the treatment. CONCLUSION: Our results showed that RBs were most commonly detected in the knee joint, and most cases were secondary to JIA. Although surgery is used as a treatment option, we observed that RBs can occasionally disappear during follow-up without surgical intervention.

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.

Comparison of IVIG resistance predictive models in Kawasaki disease.

BACKGROUND: We aimed to compare the ten different scores (by Kobayashi, Egami, Harada, Formosa, Sano, Piram et al., Wu et al., Yang et al., Tan et al., and Kanai et al.) to assess their performance in predicting IVIG resistance in Turkish children. METHODS: Complete and incomplete KD patients diagnosed with KD at Hacettepe University between June 2007 and September 2019 were evaluated retrospectively. RESULTS: A total of 129 patients, 79 boys (61.2%), with a median age 36 (IQR 19.5-57.0) months were evaluated. Sixteen patients (12.4%) had IVIG resistance. Sensitivity was low for all the ten scores. Tan, Sano, and Egami predictive models had the highest specificity (97.3, 89.4, 86.7%, respectively). Almost all scoring systems distinguished the group of patients with low risk for IVIG resistance but could not differentiate IVIG-resistant patients. Multivariate analysis for the laboratory features showed that platelet count <300 × 109/L and GGT serum levels were independent risk factors for IVIG resistance (OR: 3.896; 95% CI: 1.054-14.404; p = 0.042 and OR: 1.008; 95% CI: 1.001-1.015; p = 0.050). CONCLUSIONS: The current scoring systems had a low sensitivity for predicting the risk for IVIG resistance in Turkish children. On the other hand, increased serum GGT levels and low platelet count were risk factors for predicting IVIG resistance. IMPACT: Intravenous immunoglobulin (IVIG) resistance may be observed in 10-20% of patients diagnosed with Kawasaki disease. Coronary artery involvement is more frequent in IVIG-resistant patients. It is important to predict the patients who might develop IVIG resistance to improve prognosis. The performance of the IVIG resistance predictive models in Kawasaki disease in our population is limited due to the low sensitivity.

Long-term renal survival of paediatric patients with lupus nephritis.

BACKGROUND: Childhood-onset systemic lupus erythematosus (SLE) is more severe than adult-onset disease, including more frequent kidney involvement. This study aimed to investigate baseline clinical features, treatment modalities and short- and long-term renal outcomes of paediatric patients with lupus nephritis (LN). MATERIALS AND METHODS: This study enrolled 53 LN patients out of 102 childhood-onset SLE patients followed at Hacettepe University between 2000 and 2020. The demographic and clinical data were reviewed retrospectively from the medical charts and electronic records. All SLE patients with renal involvement underwent renal biopsy either at the time of diagnosis or during follow-up. RESULTS: The median age at onset of SLE was 13.3 years [interquartile range (IQR) 10.4-15.8]. The median follow-up duration was 43.1 months (IQR 24.3-69.3). Of the 102 SLE patients, 53 (52%) had LN. The most frequent histopathological class was Class IV LN (54.7%), followed by Class III (22.6%). The proportion of patients who achieved either complete or partial remission was 77.3% and 73% at 6 and 12 months, respectively. In the overall LN cohort, 5- and 10-year renal survival rates were 92% and 85.7%, respectively. The remission rate at Month 6 was significantly higher in mycophenolate mofetil (MMF)- and cyclophosphamide (CYC)-treated groups than other combination therapies (P = 0.02). Although no difference was found between the CYC and MMF response rates (P = 0.57) in proliferative LN (Classes III and IV), the majority of Class IV patients (79%) received CYC as induction therapy. There was no difference between the response rates in any treatment regimens at Month 12 (P = 0.56). In the multivariate analysis, male gender, requiring dialysis at the time of LN diagnosis and failure to achieve remission at 6 and 12 months were found to be associated with poor renal outcome. CONCLUSIONS: Our study demonstrated that male gender, failure to achieve remission at 6 and 12 months and requiring dialysis at the time of diagnosis were the best predictors of poor renal outcome. Therefore appropriate and aggressive management of paediatric LN is essential to achieve and maintain remission.

Familial Mediterranean Fever: How to Interpret Genetic Results? How to Treat? A Quarter of a Century After the Association with the Mefv Gene.

PURPOSE OF REVIEW: To provide an up-to-date approach to diagnosis and management of FMF patients. RECENT FINDINGS: Familial Mediterranean fever (FMF) is the most common monogenic autoinflammatory disease and prototype monogenic autoinflammatory recurrent fever syndrome. Although it is one of the well-known autoinflammatory disorders, evaluations in the etiopathogenesis and genetics of the disease have shown that FMF is more complex than previously known. Since the number of reported MEFV variants increased, evaluating the genetic test results has become more challenging. Here, we suggest a roadmap for clinicians to facilitate their decisions regarding diagnosis, treatment, and follow-up in FMF patients with different genotype-phenotype combinations. The correct interpretation of genetic test results is crucial for timely diagnosis, appropriate treatment, and follow-up of FMF patients.

IgG4-related disease in pediatric patients: a single-center experience.

OBJECTIVE: Immunoglobulin G4-related disease (IgG4-RD) is a systemic, immune-mediated, and fibroinflammatory disease that can affect almost any organ system. We aimed to present our single-center experience of pediatric patients with IgG4-RD, a rare disease in children. METHODS: Pediatric patients diagnosed with IgG4-RD at the Hacettepe University between June 2014 and September 2020 were evaluated retrospectively. Patients with definite, probable, or possible diagnosis of IgG4-RD were included. RESULTS: A total of eight patients with a median age of 13.4 (IQR 9.5-15.0) years were included in the study. Clinical presentations were IgG4-related ophthalmic disease in six patients, IgG4-related lymphadenopathy in one patient, and IgG4-related sialadenitis and lymphadenopathy of several lymph nodes accompanied by pancreatitis, ulcerative colitis, and pulmonary manifestations in one patient. Elevated serum IgG4 was detected in three of eight patients (37.5%). The main histopathological feature was fibrosis and lymphoplasmacytic infiltrates. Corticosteroids were used as first-line treatment in almost all patients with or without steroid-sparing agents. Azathioprine, methotrexate and rituximab were used as steroid-sparing agents. Relapse occurred in two of seven patients. Radiotherapy was used as the last resort in one patient with severe orbital disease. CONCLUSION: IgG4 RD mainly presents with orbital manifestations in pediatric population but has wide phenotypic clinical variability. Although rare, early recognition and treatment are essential for a better outcome in these patients.