Spondyloarthropathies (SpAs) represent a diverse group of seronegative immune-mediated inflammatory diseases characterized by a genetic predisposition and an association with human leukocyte antigen-B27. This narrative review aims to explore juvenile spondyloarthropathies (JSpAs), their classification, clinical manifestations, diagnostic challenges, and contemporary treatment strategies. According to the International League of Associations for Rheumatology criteria, JSpAs include several specific forms: enthesitis-related arthritis, psoriatic arthritis, and undifferentiated arthritis. Despite established classifications, the terms and definitions surrounding these conditions can often lead to confusion among healthcare professionals. This ambiguity underscores the need for a standardized approach to nosological classification. The clinical presentation of JSpAs can be multifaceted, encompassing both articular and extra-articular manifestations. Articular symptoms may include enthesitis and varying forms of arthritis, while extra-articular involvement can range from uveitis to gastrointestinal, cardiovascular, pulmonary, neurological, and renal complications. These diverse manifestations highlight the systemic nature of the disease and the importance of a holistic approach to diagnosis and treatment. While laboratory tests for SpAs are often non-specific, imaging modalities such as musculoskeletal ultrasound and magnetic resonance imaging play a crucial role in the early detection of inflammatory lesions. These imaging techniques can provide valuable insights into disease progression and aid in the formulation of appropriate treatment plans. Current treatment guidelines advocate for a "stepwise" approach to therapy, beginning with nonsteroidal anti-inflammatory drugs and progressing to glucocorticoids, disease-modifying antirheumatic drugs, and biological agents, particularly anti-tumor necrosis factor alpha agents. The primary objective of treatment is to achieve clinical remission or, at a minimum, to attain low disease activity. Regular monitoring of disease activity is imperative; however, the lack of validated assessment tools for the pediatric population remains a significant challenge. JSpAs pose unique challenges in terms of diagnosis and management due to their diverse manifestations and the complexities of their classification. Ongoing research and clinical efforts are essential to refine our understanding of these conditions, improve treatment outcomes, and enhance quality of life for affected children and their families. Effective management hinges on early detection, individualized treatment plans, and continuous monitoring, ensuring that patients receive the most appropriate care tailored to their specific needs.

The objective of this study is to develop evidence-based recommendations for the diagnosis and management of enthesitis-related arthritis (ERA) and juvenile psoriatic arthritis (JPsA) in the African context. The recommendations for ERA and JPsA were combined into a single document. The steering committee and task force identified 15 key questions and formulated 35 research questions. A comprehensive literature review, utilizing Medline and a manual search for African local data, was conducted to gather evidence. Following this synthesis, the task force developed draft recommendations and engaged in a Delphi process with an expert panel, including 17 African and three international experts, to reach a consensus and ensure alignment with global standards. The final recommendations were assigned a level of evidence and subsequently approved by the task force members, the expert panel, and the PAFLAR Board. Fifteen recommendations on the diagnosis and management of ERA and JPsA were developed, covering the role of the pediatric rheumatologist in multiple aspects of disease management, including diagnosis, monitoring of disease and extra-articular manifestations, determining treatment strategies, and guiding interventions. The level of evidence supporting these recommendations was variable, leading to the identification of a research agenda to address African particularities and answer pending questions. The final recommendations achieved a high level of agreement, with consensus ranging from 90 to 100%. These recommendations represent an important achievement for pediatric rheumatology in Africa, being the first of their kind, tailored specifically to the region. Developed through a rigorous methodology and collaboration between international and African experts, they aim to standardize care and address the unique challenges faced in African setting.

Juvenile idiopathic arthritis is a common chronic childhood disease, with a prevalence of ∼1 per 1000 children. Arthritis can also be a manifestation of other inflammatory conditions, such as inflammatory bowel disease (IBD). Studies suggest a genetic influence in IBD, including mutations in CARD8. CARD8 is a negative regulator of the NLRP3 inflammasome, and mutations in this gene are hypothesized to induce gastrointestinal inflammation. However, few studies have evaluated this association and most have included a limited number of patients. We present a case of a pediatric patient with IBD-associated arthritis and a CARD8 mutation. Our patient is a 7-year-old female who was initially evaluated by rheumatology for right leg pain and an intermittent rash. She had clinically active arthritis on exam and was started on methotrexate with only slight improvement. Additional workup revealed sacroiliitis by imaging, elevated inflammatory markers, no anemia, and a variant of unknown significance in CARD8. Adalimumab was recommended but before medication initiation, our patient's symptoms progressed to worsening joint pain, fatigue, fevers, nausea, vomiting, diarrhea, and hematochezia. Infectious testing was negative. Fecal calprotectin was >8000 µg/g. A colonoscopy revealed IBD most consistent with Crohn's disease. Adalimumab was ultimately added, and she has responded well to combination therapy. This case report highlights the association between CARD8 mutations and IBD, especially in the setting of IBD-associated arthritis.

In children with enthesitis-related arthritis (ERA), the hip and sacroiliac joint function might be impaired if not properly treated. We sought to evaluate the effectiveness of anti-tumor necrosis factor-α (TNF-α) therapy using the inflammatory indicators, Juvenile Arthritis Disease Activity Score 27 (JADAS27) and magnetic resonance imaging (MRI).

We conducted a single-center retrospective study of 134 patients with ERA. We evaluated the effect of anti-TNF therapy on the inflammatory indicators, active joint count, MRI quantitative score, and JADAS27 over 18 months. We used the Spondyloarthritis Research Consortium of Canada (SPARCC) and the Hip Inflammation MRI Scoring System (HIMRISS) scoring systems for hip and sacroiliac joints scoring.

The average age of onset of children with ERA was 11.62 ± 1.95 years, and they were treated with disease-modifying antirheumatic drugs (DMARDs) combined with biologics (n = 87, 64.93%). There were no differences in HLA-B27 positivity between the biologics and non-biologics treatment groups [66 (49.25%) vs. 68 (50.75%), P > 0.05]. Children who received anti-TNF (71 received etanercept, 13 adalimumab, 2 golimumab, and 1 infliximab) therapy improved significantly. Children with ERA used DMARDs and biologics at baseline (Group A) were followed up to 18 months, and their active joint count (4.29 ± 1.99 vs. 0.76 ± 1.33, P = 0.000), JADAS27 (13.70 ± 4.80 vs. 4.53 ± 4.52, P = 0.000) and MRI quantitative scores (P = 0.001) were significantly lower than those at baseline. Some of the patients (n = 13, 9.70%) were treated with DMARDs at the onset of the disease, but did not show significant improvement (Group B). After 6-18 months of switching to anti-TNF therapy, related indicators of the children were significantly lower than at baseline and 1 month (P < 0.013). At 18 months, a total of 33 patients (n = 74, 44.59%) in Group A and 7 (n = 13, 53.85%) in Group B reached inactive state.

Eighteen months after diagnosis, anti-TNF therapy was found to be effective in children diagnosed with ERA. MRI is important for the early diagnosis of juvenile idiopathic arthritis. TNF-α inhibitors can significantly improve the clinical manifestations of sacroiliac joint and hip involvement in patients with ERA. Overall, the real-world study provides more evidence for precision diagnosis and treatment for other hospitals, families and patients.

Epidemiological studies have demonstrated a wide, unexplained disparity in the prevalence of juvenile idiopathic arthritis (JIA) subtypes depending on geographical location, ethnicity and other factors. Enthesitis-related arthritis (ERA) is more prevalent in Southeast Asia. Axial involvement in ERA patients is increasingly recognised to occur early in the disease course. Inflammation in the sacroiliac joint (SIJ) observed on MRI seems highly predictive of subsequent structural radiographic progression. The resulting structural damage can have significant impacts on both functional status and spinal mobility. This study aimed to evaluate the clinical characteristics of ERA in a tertiary centre in Hong Kong. The primary objective of the study was to provide a comprehensive description of the clinical course and radiological findings of the SIJ among ERA patients.

Paediatric patients diagnosed with JIA attending the paediatric rheumatology clinic from January 1990 to December 2020 were recruited from our registry based at the Prince of Wales Hospital.

In our cohort, 101 children were included. The median age of diagnosis was 11 years, interquartile range (IQR) 8-15 years. The median follow-up duration was 7 years (IQR 2-11.5 years). ERA was the most prevalent subtype (40%), followed by oligoarticular JIA (17%). Axial involvement was frequently reported in our cohort of ERA patients. 78% demonstrated radiological evidence of sacroiliitis. Among those, 81% had bilateral involvement. The median duration from disease onset to confirmation of radiological sacroiliitis was 17 months (IQR 4-62 months). Among the ERA patients, 73% had structural changes of the SIJ. Alarmingly, 70% of these patients had already developed radiological structural changes when sacroiliitis was first detected on imaging (IQR 0-12 months). Erosion was the most common finding (73%), followed by sclerosis (63%), joint space narrowing (23%), ankylosis (7%) and fatty change (3%). The duration from symptom onset to diagnosis was significantly longer in ERA patients with SIJ structural changes (9 vs 2 months, p = 0.009), comparing with those without.

We found that a high proportion of ERA patients had sacroiliitis and a significant number of them had radiological structural changes during early disease. Our findings illustrate the importance of prompt diagnosis and early treatment in these children.

Psoriatic arthritis is a significant medical condition with a high prevalence, a wide variety of non-specific symptoms, and a high degree of overlap with other spondylarthritis disorders, particularly ankylosing spondylitis. Hence, knowledge of the magnetic resonance imaging (MRI) manifestations and a multidisciplinary strategy are required for the better management of these patients. We searched publications from the last 10 years and focused on the most relevant ones which discussed the classification criteria, the MRI characteristics of axial psoriatic arthritis, the importance of MRI for follow up, and the reliability of skin and synovial biopsy. Axial spondylarthritis can be diagnosed and followed up on using the well-established MRI technique and, additionally, a biopsy. The analysis and concordance between them can provide new directions for future studies.

Enthesitis-related arthritis (ERA) is a category of juvenile idiopathic arthritis which belongs to the spectrum of diseases that are included in juvenile spondyloarthropathy. In recent years, there have been significant advances in understanding pathogenesis, tools to assess disease activity, early recognition of the axial disease, and targeted therapy using IL-17 inhibitors and small molecule inhibitors. The current narrative review highlights these new advances. Among many hypotheses linking HLA B27 to ERA, one of them is the effect of HLA B27 on gut dysbiosis. However, recent data suggest that gut dysbiosis is probably not determined by HLA B27. Though children present with arthritis and enthesitis, axial disease is present in 50-60% on MRI. Using data-driven approach, discriminative MRI finding for active and chronic diseases has been defined for children. This will help in the early recognition of disease. An abridged version of juvenile spondyloarthropathy disease activity (JSpADA) score without the need for acute phase reactants and Schober test performed as well as the original score may increase its acceptance in routine practice. Secukinumab (anti-IL-17 antibody) has shown a more than 75% response rate in children with ERA and may be a good alternative to anti-TNF therapy. Initial data with tofacitinib also look promising. All these will translate into better outcomes for children with ERA.

Juvenile idiopathic arthritis (JIA) represents a chronic, autoimmune, rheumatic musculoskeletal disease with a diagnosis before 16 years of age. Chronic arthritis is a common manifestation in all JIA subtypes. The nature of JIA, in combination to its therapy often results in the development of nutrition-, gastrointestinal (GI)- or metabolic-related issues. The most-common therapy-related nutritional issues involve methotrexate (MTX) and glucocorticosteroids (GCC) adverse events. MTX is a folic acid antagonist, thus supplementation with folic acid in required for improving GI side effects and correcting low serum levels. On the other hand, long-term GCC administration is often associated with hyperglycemia, insulin resistance and growth delay. This relationship is further aggravated when more joints are affected and greater doses of GCC are being administered. Apart from stature, body mass index z-scores are also suboptimal in JIA. Other signs of malnutrition include decreased phase angle and muscle mass, especially among patients with polyarthritis JIA. Evidence also points to the existence of an inverse relationship between disease activity and overweight/obesity. Specific dietary patterns, including the anti-inflammatory diet, might confer improvements in selected JIA outcomes, but the level of available research is yet insufficient to draw safe conclusions. The majority of patients exhibit suboptimal vitamin D status; hence, supplementation is recommended. Collectively, the evidence indicates that, due to the age of onset and the complexity of the disease, along with its pharmacotherapy, children with JIA are prone to the development of several nutritional problems, warranting expert monitoring. Vitamin deficiencies, oral and GI-problems limiting dietary intake, faltering growth, overweight and obesity, physical inactivity, or impaired bone health are among the many nutritional issues in JIA requiring dietitian support.

Chronic recurrent multifocal osteomyelitis (CRMO) is an autoinflammatory disease occurring mainly in the pediatric age group (before 16 years) and generally presents as a separate entity. Synovitis, acne, pustulosis, hyperostosis and osteitis (SAPHO) syndrome combines osteoarticular and cutaneous involvement, similar to CRMO, and falls into the spectrum of spondyloarthritis (SpA). The fact that a patient can progress from one disease to another raises the question of whether CRMO, like SAPHO, could fall within the spectrum of SpA, ranging from a predominantly osteoarticular form to an enthesitic form with more or less marked skin involvement. In this review, we set out to discuss this hypothesis by highlighting the differences and similarities between CRMO and juvenile SpA in clinical, radiological and pathophysiological aspects. A common hypothesis could potentially consider intestinal dysbiosis as the origin of these different inflammatory diseases. Interindividual factors such as gender, environment, genetics and/or epigenetic background could act as combined disease modifiers. This is why we suggest that pathophysiology, rather than clinical phenotype, be used to reclassify these diseases.

Spondyloarthritis (SpA) is a group of chronic inflammatory systemic diseases mainly characterized by inflammation in the spine and/or peripheral joints. Although a link between SpA-pathogenesis, intestinal inflammation and gut dysbiosis has been proposed, studies have been focused on bacteria-host interactions and very little has been reported regarding intestinal parasites. Here, intestinal parasitic infection of 51 SpA-patients were evaluated and compared to healthy control individuals. No significant differences in the frequency of any parasite between SpA-patients and control individuals were found. Significantly higher levels of fecal calprotectin (FCP) were found in the SpA-patients compared to the control individuals. However, FCP levels were the same when comparing SpA-patients and control individuals, both colonized by Blastocystis spp. On the other hand, when comparing Blastocystis spp. colonized and Blastocystis spp. free SpA-patients, FCP levels were significantly higher in those Blastocystis spp. free. Without ignoring the small sample size as a study limitation, the results showed that in the SpA-patients colonized by Blastocystis spp., the FCP levels were significantly lower than those in the Blastocystis spp. free group and comparable to those in the control group. These findings seem to suggest a relationship between Blastocystis spp. and intestinal inflammation in SpA-patients, but studies intended to explore that interaction specifically should be designed.

Ulcerative colitis (UC) is a chronic relapsing inflammatory bowel disease with the colorectum as its major target organ. Involvement of the upper gastrointestinal tract in UC is rare and presents with nonspecific endoscopic and microscopic characteristics. Recent studies have demonstrated proteinase 3 antineutrophil cytoplasmic antibody (PR3-ANCA) to be a serological marker for differentiating UC from Crohn's disease in children and for detecting disease activity and nonresponse to steroid therapy and antitumor necrotizing factor-α agents. Herein, we report a 13-year-old female patient mainly presenting with recurrent bilious vomiting who was initially diagnosed with acute gastroenteritis. Intestinal pseudo-obstruction was confirmed through observation of a patent but segmentally dilated jejunum in the barium follow-through examination and other imaging; such obstruction can be attributed to backwash ileitis, superior mesenteric artery syndrome, ileus due to hypokalemia, or PR3-associated enteritis. Laboratory data revealed leukocytosis with neutrophil predominance and serum antinuclear antibody and PR3-ANCA positivity. Overlapping syndrome with autoimmune diseases was suspected. Pathology revealed a crypt abscess with aggregates of neutrophils consistent with UC but did not indicate vasculitis. The in situ immunohistochemical staining revealed PR3 density mainly in the colon and focally in the duodenum. To our knowledge, this is the first case report with in situ pathological evidence of PR3 in inflamed intestinal tissues in a patient with UC and with rare initial presentation of intestinal pseudo-obstruction-induced recurrent bilious vomiting. Whether the clinical features of the present case constitute overlap syndrome with other autoimmune disease or a disease variation of UC warrants further investigation. Notably, the patient's serum PR3-ANCA titers remained high in coincidence with increased disease activity and nonresponse to steroid therapy, but became lower after infliximab treatment. PR3-ANCA as a potential serum biomarker to aid in making differential diagnoses of UC in children, correlating disease activity, and predicting therapeutic responses was also reviewed.

Febrile illnesses in young children can be a major diagnostic challenge, despite the routine use of various laboratory markers. Recent advancements in the understanding of inflammatory processes have highlighted the role of calprotectin, a heterodimer consisting of S100A8 and S100A9 proteins, with many studies suggesting its clinical value as a biomarker of inflammation. This research aimed to evaluate the usefulness of serum calprotectin (sCal) as a biomarker of urinary tract infection (UTI), which was due to its high pooled prevalence and feasibility of urine culture as a diagnostic reference standard selected for a model of bacterial infection in children.

Febrile children aged 0-36 months with suspected UTI based on positive urinalysis or viral respiratory tract infection were included. Children with significant bacteriuria in urine culture were labeled as cases (n = 58), while those with confirmed viral infection (n = 51), as well as those with suspected UTI but sterile urine culture who went on to develop symptoms consistent with viral respiratory infection (n = 7), were labeled as controls. sCal levels were determined by a commercial immunoassay. Conventional inflammation markers (C-reactive protein, procalcitonin, white blood cell count, absolute neutrophil count, and neutrophil percentage) were measured on the day of the clinical examination. Differences in measured inflammatory markers between cases and controls were analyzed with Mann-Whitney U-test. ROC analysis reported cut-off values with the best sensitivity and specificity to distinguish bacterial UTI from viral respiratory infection.

All analyzed inflammatory biomarkers, including sCal, were significantly higher in cases than in controls. Median concentration of sCal was 4.97 μg/mL (IQR 3.43-6.42) and 2.45 μg/mL (IQR 1.63-3.85) for cases and controls, respectively (p < 0.001). For identifying bacterial UTI, sensitivity and specificity of sCal were 77.6 and 69.0%, respectively, at an adjusted cut-off point of >3.24 μg/mL (AUC 80.2%).

sCal could have substantial added value in the management of a child with fever and positive urinalysis and is a promising biomarker in distinction between bacterial UTI and viral respiratory causes of febrile illness in children under the age of 3 years.

Juvenile spondyloarthritis (jSpA) is a an umbrella term for heterogeneous group of related seronegative inflammatory disorders sharing common symptoms. Although it mainly affects children and adolescents, it often remains active during adulthood. Genetic and environmental factors are involved in its occurrence, although the exact underlying immunopathophysiology remains incompletely elucidated. Accumulated evidence suggests that, in affected patients, subclinical gut inflammation caused by intestinal dysbiosis, is pivotal to the future development of synovial-entheseal complex inflammation. While the predominant role of IL17/23 axis, TNF-α, and IL-7 in the pathophysiology of SpA, including jSpA, is firmly established, the role of the cytokine macrophage migration inhibitory factor (MIF) is generally overlooked. The purpose of this review is to discuss and emphasize the role of epigenetics, neuroendocrine pathways and the hypothalamic-pituitary (HPA) axis, and to propose a novel hypothesis of the role of decreased NLRP3 gene expression and possibly MIF in the early phases of jSpA development. The decreased NLRP3 gene expression in the latter, due to hypomethylation of promotor site, is (one of) the cause for inflammasome malfunction leading to gut dysbiosis observed in patients with early jSpA. In addition, we highlight the role of MIF in the complex innate, adaptive cellular and main effector cytokine network, Finally, since treatment of advanced bone pathology in SpA remains an unmet clinical need, I suggest possible new drug targets with the aim to ultimately improve treatment efficacy and long-term outcome of jSpA patients.

Spondyloarthritis represents a group of disorders characterized by enthesitis and axial skeletal involvement. Juvenile spondyloarthritis begins before age 16. Joint involvement is usually asymmetric. Bone marrow edema on noncontrast MRI of the sacroiliac joints can facilitate diagnosis. The most significant risk factor for axial disease is HLA-B27. Most patients have active disease into adulthood. Enthesitis and sacroiliitis correlate with greater pain intensity and poor quality-of-life measures. Tumor necrosis factor inhibitors are the mainstay of biologic therapy. Although other biologics such as IL-17 blockers have shown benefit in adult spondyloarthritis, none are approved by the US Food and Drug Administration.