An Update on the Pathogenesis and Treatment of Chronic Recurrent Multifocal Osteomyelitis in Children

Chronic recurrent multifocal osteomyelitis (CRMO), also known as chronic non-bacterial osteomyelitis (CNO), is a rare inflammatory disorder that primarily affects children. It is characterized by pain, local bone expansion, and radiological findings suggestive of osteomyelitis, usually at multiple sites. CRMO predominantly affects the metaphyses of long bones, but involvement of the clavicle or mandible are suggestive of the diagnosis. CRMO is a diagnosis of exclusion, and its pathogenesis remains unknown. Differential diagnosis includes infection, malignancies, benign bone tumors, metabolic disorders, and other autoinflammatory disorders. Biopsy of the bone lesion is not often required but could be necessary in unclear cases, especially for differentiation from bone neoplasia. Non-steroidal anti-inflammatory drugs (NSAIDs) are the first-line treatment. Alternative therapies have been used, including corticosteroids, methotrexate, bisphosphonates, and tumor necrosis factor (TNF)-\u3b1 inhibitors. No guidelines have been established regarding diagnosis and treatment options. This manuscript gives an overview of the most recent findings on the pathogenesis of CRMO and clinical approaches for patients with the condition

Recent advances in the use of Anti-TNF\u3b1 therapy for the treatment of juvenile idiopathic arthritis

Juvenile Idiopathic Arthritis (JIA) encompasses a group of diseases of unknown etiology having in common arthritis in at least 1 joint that persists for 6 weeks and begins before 16 years of age, with other conditions excluded. With a prevalence of 1 per 1,000 children in the USA, JIA is the most common pediatric rheumatic illness and a major cause of acquired childhood disability. During the last 20 years, the advent of host immune response modifiers known as biologic agents, in particular the anti-TNF\u3b1 agents (etanercept, infliximab, adalimumab), which directly inhibit the action of pro-inflammatory mediators, has revolutionized the treatment and the expected outcome of JIA. This article highlights treatment indications of anti-TNF\u3b1 drugs and their more frequent side effects in JIA patients

A bullous rash

A 3-year-old boy presented with a 5-day history of bullous skin lesions localised mainly in the upper and lower limbs and in the genital region (figure 1). Lesions were not pruritic nor painful and showed a central crust. There was no family history of skin disorders or autoimmune diseases. The child never had fever and his physical examination was otherwise unremarkable. edpract;archdischild-2020-319179v1/BLKF1F1BLK_F1Figure 1Bullous skin lesions forming around a central crust, localised in the upper and lower limbs. QUESTIONS: What is the most likely diagnosis based on this clinical presentation?Bullous impetigo.Bullous pemphigoid.Linear IgA bullous dermatosis.Dermatitis herpetiformis.What would be the next step in the investigation to confirm your diagnosis?Skin biopsy.Swab test for bacterial culture with an antibiogram.Anti-transglutaminase antibody detection.What is the mainstay of management?Dapsone.Systemic steroids.Topical steroids.All of the above answers are correct, according to the severity of the disease

Elevated creatine kinase is mainly harmless in children but persistent and severe hyperCKaemia should raise suspicions of serious muscle damage

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Ultrasonographic Assessment for Tenosynovitis in Juvenile Idiopathic Arthritis with Ankle Involvement: Diagnostic and Therapeutic Significance

Background: The role of musculoskeletal ultrasound in JIA is still controversial, although there is growing evidence on its utility, especially in the diagnosis of tenosynovitis. Methods: We presented a retrospective cross-sectional study of a group of patients with JIA with ankle swelling followed in a Pediatric Rheumatology Service of a tertiary-level pediatric hospital in Northern Italy during the follow-up period between January 1st 2003 and December 31st 2019. Preliminary results have been presented at the EULAR Congress 2021. We enrolled only patients who underwent msk-US, and we identified those with a clinical and sonographic diagnosis of tenosynovitis. For each patient, we collected data on demographics, clinical characteristics, and therapeutic strategies during the follow-up. Results: On December 31st 2019, 56 swollen ankles of 48 patients were assessed with msk-US. Twenty-two ankles showed sonographic signs of joint synovitis, sixteen ankles presented signs of both joint synovitis and tenosynovitis, and fourteen ankles presented sonographic signs of tenosynovitis only. Overall, tenosynovitis was detected on 27 (56%) out of 48 children with at least a swollen ankle. In 13 patients out of 27 with tenosynovitis (48%), there was no joint synovitis of ankle or foot. Twenty-five patients with tenosynovitis (92%) achieved clinical and radiological remission: seven patients achieved remission of tenosynovitis with methotrexate only, and fifteen patients with biological drugs alone or in combination therapy. Conclusions: We observed that more than half of the patients with ankle swelling presented a tenosynovitis, and about 50% of them did not show sonographic signs of an active joint synovitis. Among patients with tenosynovitis, biological therapy alone or in association with DMARDs showed effectiveness in inducing disease remission

Fever tree revisited: From malaria to autoinflammatory diseases

Over the centuries the idea of recurrent fevers has mainly been associated with malaria, but many other fevers, such as typhoid and diphtheria were cause for concern. It is only in recent times, with the more severe forms of fever from infectious origin becoming less frequent or a cause for worry that we started noticing recurrent fevers without any clear infectious cause, being described as having a pathogenesis of autoinflammatory nature. The use of molecular examinations in many cases can allow a diagnosis where the cause is monogenic. In other cases, however the pathogenesis is likely to be multifactorial and the diagnostic-therapeutic approach is strictly clinical. The old fever tree paradigm developed to describe fevers caused by malaria has been revisited here to describe today's periodic fevers from the periodic fever adenitis pharyngitis aphthae syndrome to the more rare autoinflammatory diseases. This model may allow us to place cases that are yet to be identified which are likely to be of multifactorial origin

Infant with a big head and 'crossed' polysyndactyly

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An Easy and Reliable Strategy for Making Type I Interferon Signature Analysis Comparable among Research Centers

Interferon-stimulated genes (ISGs) are a set of genes whose transcription is induced by interferon (IFN). The measure of the expression of ISGs enables calculating an IFN score, which gives an indirect estimate of the exposition of cells to IFN-mediated inflammation. The measure of the IFN score is proposed for the screening of monogenic interferonopathies, like the Aicardi-Gouti\ue8res syndrome, or to stratify subjects with systemic lupus erythematosus to receive IFN-targeted treatments. Apart from these scenarios, there is no agreement on the diagnostic value of the score in distinguishing IFN-related disorders from diseases dominated by other types of cytokines. Since the IFN score is currently measured in several research hospitals, merging experiences could help define the potential of scoring IFN inflammation in clinical practice. However, the IFN score calculated at different laboratories may be hardly comparable due to the distinct sets of IFN-stimulated genes assessed and to different controls used for data normalization. We developed a reliable approach to minimize the inter-laboratory variability, thereby providing shared strategies for the IFN signature analysis and allowing different centers to compare data and merge their experiences

Acute Acalculous Cholecystitis: Think of Hepatitis A Infection and Do Not Underestimate Pain

A 14-year-old adolescent girl presented with severe abdominal pain, tenderness, and guarding in the right upper quadrant associated with nonbilious vomiting, scleral icterus, and fever. Laboratory tests were consistent with acute hepatitis A virus-related cholestatic hepatitis. A point-of-care ultrasound showed mild gallbladder wall thickening with increased color Doppler flow and pericholecystic fluid collection, in the absence of gallstones or biliary ducts dilatation, thus suggesting acute acalculous cholecystitis. Both the clinical symptoms and the point-of-care ultrasound findings completely resolved within 1 week after admission with conservative treatment