Evaluation of pediatric rheumatologists' approach to rituximab use: a questionnaire study.

Rituximab (RTX) is a chimeric monoclonal antibody that targets the CD20 antigen on B cells and is used in various autoimmune disorders. In this study, we aimed to measure the awareness of pediatric rheumatologists about the use of RTX through a survey. Between February and March 2023, a 42-question survey was sent via email to pediatric rheumatology specialists in Turkey. The participants were questioned for which diagnoses and system involvement they preferred to use RTX, which routine tests they performed, vaccination policy, and adverse events that occurred during or after infusion. Forty-one pediatric rheumatologists answered the survey. They prescribed RTX most frequently for systemic lupus erythematosus (87.8%) and ANCA-associated vasculitis (9.8%). Prior to the administration of RTX, 95% of clinicians checked renal and liver function tests, as well as immunoglobulin levels. The most frequently tested hepatitis markers before treatment were HBsAg and anti-HBs antibody (97.6%), while 85.4% of rheumatologists checked for anti-HCV. Clinicians (31.4%) reported that they postpone RTX infusion 2 weeks following an inactivated vaccine. Sixty-one percent of rheumatologists reported starting RTX treatment 1 month after live vaccines, while 26.8% waited 6 months. The most frequent adverse events were an allergic reaction during RTX infusion (65.9%), hypogammaglobulinemia (46.3%), and rash (36.6%). In the event of hypogammaglobulinemia after RTX treatment, physicians reported that they frequently (58.5%) continued RTX after intravenous immunoglobulin administration. CONCLUSIONS: RTX has become a common treatment option in pediatric rheumatology in recent years. Treatment management may vary between clinician such as vaccination and routine tests. WHAT IS KNOWN: • During the course of rituximab therapy, clinicians should be attentive to specific considerations in pre-treatment, during administration, and in post-treatment patient monitoring. WHAT IS NEW: • There are differences in practice among clinicians in the management of RTX therapy. These practice disparities have the potential to impact the optimal course of treatment. • This study highlights that standardized guidelines are needed for RTX treatment in pediatric rheumatology, particularly for vaccination policies and routine tests.

Altered expression of apoptosis-related, circulating cell-free miRNAs in children with familial Mediterranean fever: a cross-sectional study.

OBJECTIVES: Familial Mediterranean Fever (FMF) is the most common hereditary autoinflammatory disorder characterized by recurrent fever and serositis episodes. Identification of low penetrant or heterozygous MEFV mutations in clinically diagnosed FMF patients did raise a concern on whether epigenetic or environmental factors play an additional role in FMF pathogenesis. We aimed to investigate the expression profile of apoptosis-related miRNAs in FMF and their influence on clinical manifestations in the present study. METHOD: 191 pediatric FMF patients and 31 healthy children included in the study. Expressions of 33 apoptosis-related, circulating cell-free miRNAs were evaluated by a quantitative polymerase chain reaction, statistically calculated within ΔΔCt values and fold changes were evaluated by Welch T test, in which p < 0.05 were considered to be significant. RESULTS: Nineteen miRNAs, including let-7a-5p, let-7c, let-7 g-5p, miR-15b-5p, miR-16-5p, miR-17-5p, miR-23a-3p, miR-24-3p, miR-25-3p, miR-26a-5p, miR-26b-5p, miR-27a-3p, miR-29c-3p, miR-30a-5p, miR-30d-5p, miR-30e-5p, miR-106b-5p, miR-146a-5p, and miR-195-5p, were found down-regulated; miR-15a-5p, miR-29b-3p, miR-181a-5p, miR-181b-5p, miR-181c-5p, miR-214-3p, and miR-365a-3p were up-regulated in FMF patients. In detail, these miRNAs were similar among FMF patients in terms of genotype, colchicine response, and having an inflammatory attack during analysis. CONCLUSION: We found that 26 apoptosis-related circulating miRNAs were deregulated in children with FMF. Thus, we speculate that these miRNAs have a role in FMF pathogenesis via apoptotic mechanisms.

Twenty-Year Experience of a Single Referral Center on Pediatric Familial Mediterranean Fever: What Has Changed Over the Last Decade?

BACKGROUND/OBJECTIVE: Familial Mediterranean fever (FMF) is the most common autoinflammatory disease and is characterized by recurrent fever and serositis episodes. We aimed to share our 20-year FMF experience, clarify a phenotype-genotype correlation, and compare the characteristics and outcomes of pediatric FMF patients over the last 2 decades in this study. METHODS: This medical record review study included 714 pediatric FMF patients (340 females, 374 males), diagnosed by Tel Hashomer diagnostic criteria between January 2009 and January 2019 and followed up in our department. Demographic and disease characteristics, obtained from medical records of the patients, were compared between patients with M694V homozygosity and other genotypes and showed whether they were diagnosed before (n = 137) or after January 2010 (n = 577). χ2, Student t, and Mann-Whitney U tests were used to compare categorical and continuous variables between these groups. RESULTS: The most common symptoms were abdominal pain (92%), fever (89.5%), and arthralgia (64.5%). Mean ages at symptom onset and diagnosis were 5.16 ± 3.73 and 7.71 ± 3.87 years, respectively. M694V homozygosity was recorded in 111 patients (15.5%). Fever, arthralgia, arthritis, myalgia, erysipela-like erythema, colchicine resistance, and subclinical inflammation were more frequent, and mean disease severity score was higher in patients with M694V homozygosity. Fever, chest pain, and proteinuria were statistically more frequent in patients diagnosed before January 2010. Although M694V homozygosity rate was similar, patients diagnosed in the last decade had lower mean disease severity score. CONCLUSIONS: With this study, we speculate that although genotype and delay in diagnosis were similar, patients diagnosed in the last decade have a milder disease severity.

Unicentric Castleman Disease Mimicking an Autoinflammatory Disorder: A Diagnostic Challenge in a Pediatric Patient With Recurrent Fever.

Unicentric Castleman disease (CD) is a rare lymphoproliferative disorder that is characterized by the enlargement of lymph nodes on the neck, mediastinum, and retroperitoneum. Herein, we present a 6-year-old female patient, referred to our medical center because of recurrent fever accompanied by cervical lymphadenopathy and elevated inflammatory markers since 3 years of age. Fever episodes lasting 1 day continued irregularly without any accompanying symptom. MEditerranean FeVer (MEFV) gene analysis showed no mutations; however, as inflammatory markers including serum amyloid A remained markedly high during attack-free periods, colchicines was initiated. The patient did not respond to maximally tolerated doses of colchicine; therefore, we added canakinumab and systemic methylprednisolone, subsequently. Unresponsiveness to 3 doses of bimonthly canakinumab and new-onset hepatosplenomegaly led us to investigate large-vessel vasculitis and malignancy; therefore, we performed Position emission tomography, which further revealed a hypermetabolic retroperitoneal solid mass. After performing the excisional biopsy, the patient has been diagnosed as suffering from hyaline vascular variant CD, confirmed by histopathology. In conclusion, we report a pediatric unicentric CD, which resembled autoinflammatory diseases and responded well to surgical resection, with the normalization of inflammatory markers 1 month after the procedure. CD, even the unicentric and hyaline vascular variant, should be considered in the differential diagnosis of the patients with an autoinflammatory phenotype.

Is Henoch-Schönlein purpura a susceptibility factor for functional gastrointestinal disorders in children?

Henoch-Schönlein purpura (HSP), the most common childhood vasculitis is characterized by non-thrombocytopenic palpable purpura, arthritis/arthralgia, abdominal pain and renal involvement. Functional gastrointestinal disorders (FGIDs) are heterogeneous disease spectrum with unclear etiology and include the most common subtypes: functional dyspepsia, irritable bowel syndrome (IBS), functional abdominal pain and functional constipation. Formerly, FGIDs were known as non-organic disorders; however, recent advances revealed that low-grade inflammation may also play a role. We aimed to clarify whether HSP predisposes to FGIDs in pediatric population. Seventy-four children with HSP, diagnosed at least 6 months before the study and 78 healthy controls were enrolled to the study. Patients with red flag signs for organic GI disorders were excluded. Rome IV criteria were utilized for FGIDs diagnosis. We compared the frequencies of FGIDs between HSP patients and healthy subjects. We also examined the parameters including age, abdominal pain, arthralgia, bloody stool, renal involvement and treatment with corticosteroids and laboratory results at HSP diagnosis such as erythrocyte sedimentation rate, C-reactive protein, hemoglobin, leukocytes and platelet counts among patients with and without FGIDs. Overall FGIDs and IBS frequency were 35.1% (n = 26) and 10.8% (n = 8) in HSP patients, 19.2% (n = 15) and 2.6% (n = 2) in healthy controls, respectively. Disease characteristics and laboratory parameters at disease onset were similar between HSP patients with and without FGIDs. Overall FGIDs rate, particularly IBS were statistically higher in HSP patients. We speculate that children with preceding HSP may be predisposed to FGIDs. Since the FGIDs pathogenesis is still remains unclear, further studies are needed to confirm this hypothesis and clarify the etiology. Physicians also should pay attention to FGIDs in HSP patients with ongoing abdominal pain and thus prevent this comorbidity with dietary and psychologic measures.

Utility of renal resistive index measurement in juvenile systemic lupus erythematosus: a cross-sectional single-center study.

INTRODUCTION: Systemic lupus erythematosus (SLE) is a multisystemic autoimmune disease with a complex etiopathogenesis. Renal involvement is the most common and devastating complication of the disease. Renal resistive index (RRI) was suggested as a noninvasive biomarker for lupus nephritis in previous studies. This is the first study to investigate the role of RRI measurement in juvenile SLE patients. METHODS: This cross-sectional study included 25 juvenile SLE patients and 25 healthy controls. Demographic and clinical features were recruited from the medical files of the patients. RRI measurements were performed with color Doppler ultrasonography from intrarenal arteries when Doppler angles were 30-60 in right and left kidneys. RESULTS: Of 25 (19 female, 6 male) SLE patients, nineteen (76%) patients had urinary abnormalities during follow-up, and renal biopsy was performed in 14 patients, of which 9 (64.3%) had class 2 and 5 (35.7%) had class 4 lupus nephritis. RRI was found significantly higher in SLE group than healthy controls. RRI did not differ between SLE patients, grouped according to the presence of renal involvement and class IV lupus nephritis. RRI did not correlate with serum creatinine, GFR, spot urine protein/creatinine, and albumin/creatinine ratio. CONCLUSIONS: Although RRI was found significantly higher in juvenile SLE, it is not affected by GFR, proteinuria level, or the renal biopsy results, even the presence of proliferative nephritis. The underlying pathogenetic mechanisms of increased RRI in SLE should be clarified in further studies. Key Points • Renal resistive index (RRI) is a parameter derived from renal Doppler ultrasound imaging and shows the intrarenal arterial resistance. • This study reveals that RRI is increased in juvenile systemic lupus erythematosus. • RRI was previously related with renal involvement, particularly class 4 lupus nephritis in adults. However, RRI was not affected by the presence or degree of renal involvement in juvenile SLE patients in our study.

Utility of a targeted next-generation sequencing-based genetic screening panel in patients with periodic fever, aphthous stomatitis, pharyngitis, and adenitis syndrome.

Objectives: This study aims to investigate a genetic panel in patients with periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome and examine its performance for an accurate differential diagnosis. Patients and methods: Between January 2021 and January 2022, a total of 104 children with PFAPA syndrome (63 males, 41 females; mean age: 4.8±2.3 years; range, 1.2 to 8.9 years) were retrospectively analyzed. Next-generation sequencing test was performed using a custom QIAGEN- QIAseq™ Targeted DNA Panel which includes six genes namely ELANE, LPIN2, MEFV, MVK, NLRP3, and TNFRSF1A. Results: Of 104 patients, 38 (36.5%) had variants in the genetic panel. The most common variants were found in the MEFV gene (n=35, 33.6%), the most frequent genotype was E148Q heterozygosity (n=16). Four and two patients were eventually diagnosed with Familial Mediterranean fever (FMF) and hyperimmunoglobulin D syndrome (HIDS), since they had confirmative biallelic pathogenic in the MEFV and MVK genes, respectively. Conclusion: A genetic panel, including MEFV and MVK genes, may be useful in patients, clinically resembling PFAPA, since they may have HIDS or FMF, but lack typical features of the exact disease. Nonetheless, we believe that distinct genetic panels should be developed for different populations.

An unusual manifestation in a pediatric patient with MAFB mutation: Sacroiliitis in multicentric carpotarsal osteolysis syndrome.

Multicentric carpotarsal osteolysis (MCTO) syndrome, is typically characterized by progressive bone resorption in especially carpal and tarsal bones, in addition to abnormal facial appearance and proteinuria. This disorder is caused by monoallelic pathogenic MAFB mutations, which result in excessive osteoclastogenesis via aberrant receptor activator of nuclear factor kappa-B ligand activation. Most cases are sporadic with de-novo mutations, and it is still unclear why carpal and tarsal bones are predominantly affected. The early phases of MCTO resemble juvenile idiopathic arthritis (JIA) with ankle and wrist swelling and pain, even with inflammatory changes in magnetic resonance imaging. Herein we report a pediatric patient, previously treated with antirheumatic drugs, and eventually diagnosed with MCTO. This case was a descriptive case with exophthalmos, significant proteinuria, and total loss of carpal and tarsal bones at the time of genetic diagnosis. Similar to the literature, our case had typical radiological findings despite methotrexate and anti-tumor necrosis factor-alpha treatment. However, while arthritis affecting joints other than wrists and ankles has not been reported so far in the literature, our case had bilateral sacroiliitis which completely resolved after adalimumab treatment. We cannot be sure if sacroiliitis was incidental or occurred as a component of the disease, nonetheless, we think that sharing our experience may lead to easy and early recognition of MCTO, with more knowledge on rare manifestations of MCTO, and thus we may be able to clarify the benefits of denosumab, which is the most promising agent in early phases of the disease.

Clinical presentation of children with Deficiency of Adenosine deaminase 2: A case series.

Deficiency of Adenosine deaminase 2 (DADA2) is a monogenic inflammatory disease, caused by mutations in ADA2 gene, which encodes an extracellular enzyme acting as a monocyte differentiation factor. DADA2 is first described with the clinical picture resembling polyarteritis nodosa, including livedo racemose, recurrent fever, musculoskeletal complaints. Besides, some patients have cytopenia, lymphoproliferation and mild to moderate immunodeficiency. The most crucial complication of DADA2 is neurological involvement, especially arterial stroke, which necessitates continuous treatment with anti-tumor necrosis factor α (anti-TNFα) treatment for preventing further stroke attacks. Herein, we report 5 DADA2 patients from 5 unrelated families, all had G47R mutation in at least one allele. All patients had livedo racemose, and 4 patients suffered from recurrent fever. Besides, musculoskeletal complaints and gastrointestinal symptoms were present in 4 and 3 patients, respectively. One patient had chronic arthritis and only one patient had a history of recurrent stroke without any sequela. Hematological and immunological involvement occurred in 3 and 4 patients, respectively, whereas only one had significant panhypogammaglobulinemia, requiring replacement therapy. We started etanercept treatment to all patients, which resulted the complete resolution of systemic inflammatory attacks and skin lesions and provided neurologically symptom free during their follow-up. With this report, we emphasize the importance of early referral of the patients with suspected livedo racemose to avoid the delay of DADA2 diagnosis for favorable outcome.

Serum vitamin B12 and D levels in children with Primary Raynaud Phenomenon: a retrospective cohort study.

Primary Raynaud phenomenon (RP) is resultant from transient vasospasm of peripheral arteries and arterioles, is usually precipitated by cold exposure or emotional stress, without any clue for autoimmune connective tissue diseases. We aimed to determine the frequency of vitamin D and B12 deficiencies in pediatric patients with primary RP, and to investigate their roles on the disease course. Vitamin B12 and D were supplemented if the patients had deficiencies. The study included 40 children with primary RP, 29 (72.5%) female and 11 (27.5%) male. The mean and median age were 15.1 ± 1.8 and 15.5 (range, 11.5-17.8) years. Symptoms were improved in 31 (77.5%) patients with warming procedures. Seventeen (41.5%) and 16 (39%) patients had low serum vitamin B12 and D levels, respectively. Vasodilator treatment requirement did not change by vitamin B12 status but was significantly lower in vitamin D deficient and replaced patients. Further studies are needed to clarify our results.

A Rare Autoinflammatory Disorder in a Pediatric Patient with Favorable Response to Etanercept: Sideroblastic Anemia with B Cell Immunodeficiency, Periodic Fevers, and Developmental Delay Syndrome.

Introduction: Sideroblastic anemia with B cell immunodeficiency, periodic fevers, and developmental delay (SIFD) syndrome is caused by biallelic TRNT1 mutations. TRNT1 gene encodes a CCA-adding tRNA nucleotidyl transferase enzyme. Mutant TRNT1 results in immunodeficiency and anemia in various degrees, accompanied by several organ involvement. Case Presentation: We present here a 15-month old male, demonstrated brittle hair, growth hormone deficiency, recurrent fever, arthritis, recurrent infections, mild anemia, and hypogammaglobulinemia. The patient did not respond to colchicine treatment, and after establishing SIFD diagnosis with the presence of homozygote c.948-949delAAinsGG (p.Lys317Glu) mutation in TRNT1 gene, we commenced monthly intravenous immunoglobulin replacement and weekly subcutaneous etanercept. A rapid resolution of fever episodes and infections occurred after initiation of this treatment regimen. Afterward, both anemia and growth parameters have improved during follow-up. Conclusion: SIFD syndrome should be considered in patients with recurrent fever, arthritis, and growth retardation even in the absence of severe anemia and prominent hypogammaglobulinemia.

Evaluation of subclinical ocular involvement in patients with deficiency of adenosine deaminase 2 (DADA2).

PURPOSE: To evaluate changes in the peripapillary, macular, and choroidal microvasculature in the eyes of patients with deficiency of adenosine deaminase 2 (DADA2) and no clinical signs of ocular involvement. METHODS: The study included 12 eyes of 12 patients with DADA2 and 24 eyes of 24 healthy subjects. The foveal avascular zone (FAZ), macular vessel densities (VDs) in the superficial and deep retinal capillary plexuses, peripapillary VDs, and choroidal thickness were evaluated by optical coherence tomography angiography (OCTA). Measurements were compared between DADA2 patients and healthy controls. RESULTS: The median age was 17 (8-25) years in DADA2 patients and 17.5 (7-23) years in control group at the OCTA visit (p = 0.934). FAZ area did not differ between the groups (p = 0.224). In the superficial capillary plexus, whole-image, foveal, and parafoveal VD values were slightly lower in DADA2 patients than in controls (p = 0.054, p = 0.052, p = 0.117). In the deep capillary plexus, whole-image and parafoveal VD values were significantly lower in DADA2 patients than controls (p = 0.010, p = 0.001). VD in the radial peripapillary capillary plexus was also lower in DADA2 patients, with significantly lower peripapillary VD (p = 0.002). Subfoveal choroidal thickness was significantly higher in patients with DADA2 (p < 0.001). CONCLUSIONS: This OCTA study demonstrates that both retinal and choroidal involvement may occur in DADA2 patients before the emergence of evident clinical findings.

Monogenic lupus due to DNASE1L3 deficiency in a pediatric patient with urticarial rash, hypocomplementemia, pulmonary hemorrhage, and immune-complex glomerulonephritis.

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease and usually involves the skin, musculoskeletal system, and kidneys. More than 30 genes have been to monogenic lupus, so far. Monogenic lupus is often characterized by an early-onset, similar family history, and syndromic appearance. Herein we present a pediatric patient with DNASE1L3 deficiency, suffering from both urticarial skin lesions, recurrent hemoptysis, and renal involvement, eventually diagnosed as this rare monogenic lupus. The patient suffered from recurrent urticarial rash and hemoptysis since the age of 15 months of age. He had microscopic hematuria, mild proteinuria, hypocomplementemia, and positive antinuclear antibody, anti-dsDNA, and antineutrophil cytoplasmic antibodies. Renal biopsy yielded immunocomplex glomerulonephritis. Due to early-onset, similar sibling history and consanguineous parents, we suspected monogenic lupus and performed whole-exome sequencing, which further revealed a homozygous T97Ifs*2 mutation (NM_004944.4: c.290_291delCA/p.Thr97Ilefs*2) in DNASE1L3 gene. In conclusion, DNASE1L3 deficiency should be thought when juvenile SLE occurs with early disease-onset, pulmonary hemorrhage, glomerulonephritis, and recurrent urticarial rash along with ANCA positivity.

Differentiating children with familial Mediterranean fever from other recurrent fever syndromes: The utility of new Eurofever/PRINTO classification criteria.

Objectives: In this study, we aimed to investigate the performance of Eurofever Registry and the Paediatric Rheumatology International Trials Organisation (PRINTO) classification criteria in pediatric patients with familial Mediterranean fever (FMF). Patients and methods: This retrospective, cross-sectional study included a total of 130 pediatric FMF patients (67 males, 63 females; mean age: 12.4±3.6 years; range, 2.5 to 17.7 years) with at least one M694V mutation in MEFV gene between July 2010 and July 2019. Demographic features and disease characteristics were recorded. The control group was consisted of 41 patients (19 males, 22 females; mean age: 7.8±4.0 years; range, 2.1 to 17.8 years) with other hereditary autoinflammatory diseases (AIDs), including periodic fevers with aphthous stomatitis, pharyngitis, and adenitis syndrome (n=30), mevalonate kinase deficiency (n=9), and tumor necrosis factor receptor-associated periodic syndrome (n=2). Sensitivity and specificity of the Eurofever/PRINTO classification criteria were calculated. Results: The sensitivity and specificity were 97.7% and 56.1% for Yalcinkaya-Ozen criteria, respectively and 93.1% and 90.2% for Tel Hashomer criteria, respectively. The Eurofever/PRINTO classification criteria reached a sensitivity and specificity of 94.6% and 82.9% and 93.1% and 80.5%, respectively, when genetic plus clinical criteria and clinical-only criteria were applied. Conclusion: The Eurofever/PRINTO classification criteria have a comparable sensitivity for avoidance of FMF underdiagnosis in childhood. The Yalcinkaya-Ozen criteria have the highest sensitivity without a significant specificity. The Tel Hashomer criteria and Eurofever/PRINTO classification criteria were superior to Yalcinkaya-Ozen criteria to differentiate FMF from other AIDs, thus leading to less complications relevant to underdiagnosis of other AIDs.

Camptodactyly-Arthropathy-Coxa Vara-Pericarditis Syndrome Resembling Juvenile Idiopathic Arthritis: A Single-Center Experience from Southern Turkey.

Camptodactyly-arthropathy-coxa vara-pericarditis (CACP) syndrome, caused by biallelic pathogenic mutations in the PRG4 gene, is characterized by early-onset camptodactyly, noninflammatory arthropathy, coxa vara deformity, and rarely, pericardial effusion. Herein, we report 3 patients with CACP syndrome from 2 unrelated families. All patients are female, born to consanguineous parents, and had camptodactyly since the first years of their lives. Two patients had a prior diagnosis of juvenile idiopathic arthritis. Hip changes were present in 2 patients, and 2 of 3 patients had undergone surgery for camptodactyly. Routine echocardiographic evaluations were normal during the 2-year follow-up. This paper represents the third study including CACP patients from Turkey. Clinically, all 3 patients resembled juvenile idiopathic arthritis cases and received unnecessary medication. There is also an ongoing need for improving awareness of CACP and an effective treatment focusing on the lubrication of the joint space in CACP patients.

Phenotypic variability in two patients with tumor necrosis factor receptor associated periodic fever syndrome emphasizes a rare manifestation: Immunoglobulin A nephropathy.

Tumor necrosis factor receptor associated periodic fever syndrome (TRAPS) is caused by heterozygote mutations in TNFRSF1A, characterized by recurrent inflammatory attacks. In this report, we described two patients with different heterozygote mutations in TNFRSF1A. Patient 1, a 15-year-old male, had suffered from recurrent fever attacks accompanied by abdominal pain, eye manifestations, and myalgia with increased acute phase reactants since the age of 6-month. He had been unsuccessfully treated with colchicine for having familial Mediterranean fever without an identifiable MEFV mutation since the age of 4-year. At the age of 15 years, he was diagnosed with immunoglobulin (Ig) A nephropathy due to massive proteinuria and renal biopsy findings. Next generation sequencing revealed NM_001065.3: c.236C>T; p. (Thr79Met); T50M heterozygote mutation in TNFRFS1A. He was treated with methylprednisolone and cyclosporine for IgA nephropathy, thereafter with canakinumab for TRAPS. Patient 2, a 17-year-old female, had recurrent arthritis attacks accompanied by increased acute phase reactants for the last two months. She had neither fever attacks nor rashes or myalgia. Her physical examination was normal between attacks. Magnetic resonance imaging of both knees and ankles showed no signs of chronic arthritis. MEFV analyzes showed no mutation. Next generation sequencing revealed NM_001065.3: c.362G>A; p.(Arg121Gln); R92Q heterozygote mutation in TNFRFS1A. Arthritis attacks were treated successfully with ibuprofen thereafter. In conclusion, we wish to emphasize the diversity of the clinical manifestations between these two patients with distinct sequence variants in TNFRSF1A. Moreover, we presented a rare manifestation of TRAPS, IgA nephropathy.

Different Clinical Manifestations of Three Prime Repair Exonuclease 1 Mutation: A Case Series.

Three prime repair exonuclease 1 (TREX1) degrades single- and double-stranded DNA with 3'-5' exonuclease activity. TREX1 mutations are related to type 1 interferon-mediated autoinflammation owing to accumulated intracellular nucleic acids. Several cases of systemic lupus erythematosus, Aicardi-Goutieres syndrome (AGS), familial chilblain lupus (FCL), and retinal vasculopathy-cerebral leukodystrophy caused by TREX1 mutations have been reported, so far. In this report, we described five patients with TREX1 mutations from three families with three different disorders, which include AGS, FCL, and FCL with central nervous system vasculitis.

Retrospective Analysis of the Factors Affecting Growth Parameters in Turkish Children With Systemic Lupus Erythematosus.

OBJECTIVES: This study aims to investigate the growth parameters in Turkish children with systemic lupus erythematosus (SLE) and to compare these growth parameters according to the presence or absence of cyclophosphamide, rituximab treatment, cumulative corticosteroid dose, proliferative nephritis, and the last visit disease activity and damage index. PATIENTS AND METHODS: Medical data, growth parameters including z-scores for weight, height, and body mass index and parent-adjusted height z-scores of 45 juvenile SLE (jSLE) patients (5 males, 40 females; mean age 12.3±3.2 years; range 7.1 to 18 years) were retrospectively evaluated. Growth parameters were calculated by anthropometric references in Turkish children. The disease activity was assessed by the SLE Disease Activity Index 2000 (SLEDAI-2K). The disease outcome was measured by the Pediatric version of Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index. RESULTS: The median diagnostic delay was two months (range, 0-36 months). The median follow-up duration was 3.21 years (range, 0.63-9.48 years). Mean height z-score was significantly lower at last visit than at the time of diagnosis. The growth parameters did not differ according to age at disease onset, diagnostic delay, presence of proliferative nephritis, having cyclophosphamide and rituximab treatment and the last visit (SLEDAI-2K) scores. The median duration of corticosteroid treatment was 3.2 years (range, 0.6-9.4 years) and the median cumulative corticosteroid dosage was 13.9 g (range, 1.9-58 g) of methylprednisolone. The mean height z-score at last visit was significantly lower in those who received at least 10 g of cumulative dose of corticosteroid. The last visit mean parent-adjusted height z-scores did not differ significantly regarding the cumulative corticosteroid dose. CONCLUSION: The last visit height and parent-adjusted height z-scores of jSLE patients were significantly lower. The patients treated with at least 10 g of cumulative dose of corticosteroids had lower mean height z-score.

Recurrent macroscopic hematuria in a pediatric patient: is it early to diagnose as having type I hereditary C2 deficiency?

Hereditary C2 deficiency is the most common early complement deficiency and characterized by recurrent infections and autoimmunity despite most patients are also asymptomatic. Type I hereditary C2 deficiency is caused by a heterozygous deletion in C2 gene resulting in early stop codon and lack of C2 production. Clinical spectrum may vary and pure nephrological involvement without the presence of recurrent infections is scarce in hereditary C2 deficiency.We report here a previously healthy 14-year-old boy presenting recurrent self-limited macroscopic hematuria and persistently low serum C4 levels, diagnosed as having type I hereditary C2 deficiency with confirming a novel heterozygote deletion (c.1567 + 22_1567 + 43del) in C2 gene. He has been remained asymptomatic for the next 18 months. Since the diagnosis of C2 deficiency was made in the absence of organ-threatening involvement such as immune complex-mediated glomerulonephritis, we think that early diagnosis and optimal follow-up may improve life-span of the patients with hereditary early complement deficiencies.