When flexibility is not necessarily a virtue: a review of hypermobility syndromes and chronic or recurrent musculoskeletal pain in children

Chronic or recurrent musculoskeletal pain is a common complaint in children. Among the most common causes for this problem are different conditions associated with hypermobility. Pediatricians and allied professionals should be well aware of the characteristics of the different syndromes associated with hypermobility and facilitate early recognition and appropriate management. In this review we provide information on Benign Joint Hypermobility Syndrome, Ehlers-Danlos Syndrome, Marfan Syndrome, Loeys-Dietz syndrome and Stickler syndrome, and discuss their characteristics and clinical management

Anti-IL1 in patients with low penetrance mutations for autoinflammatory diseases: tuscany and sicilian case series from paediatric to adult age

Patients with low penetrance mutations for Autoinflammatory syndromes (AID) can have severe clinical manifestations, which require to be treated with biological drugs anti-IL-1. Objectives: To evaluate the response of AID to treatment with the recombinant human IL-1 receptor antagonist anakinra or with the anti-IL-1b

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

In vivo utjecaj imunosupresije u majki za vrijeme trudnoće na imunosni sustav novorođenčadi

When used in pregnancy, immunosuppressants can cross the placental barrier and enter foetal circulation, possibly affecting the immune system of the foetus. This study evaluated the immune function in eight children born by mothers with connective tissue diseases who received immunosuppressants (cyclosporine A or dexamethasone) during pregnancy and in six babies from mothers with similar diseases, but who did not receive any treatment. Judging by the cytokine production of interleukin-2 and interferon-γ in peripheral blood mononuclear cells stimulated by phorbol-myristate-acetate (PMA) and ionomycin, immunosuppressive drugs given for rheumatic disorders during pregnancy do not induce significant immunosuppression in babies.Imunosupresivni lijekovi davani za vrijeme trudnoće mogu proći placentalnu barijeru i ući u cirkulaciju fetusa, s mogućim utjecajem na njegov imunosni sustav. U radu je praćena imunosna funkcija kod osmero djece rođene od majki s bolestima vezivnog tkiva, koje su tretirane za vrijeme trudnoće imunosupresivnim lijekovima (ciklosporin A ili deksametazon) i kod osmero novorođenč adi rođene od majki sa sličnim bolestima, ali koje nisu bile tretirane. Imunosupresivni lijekovi primijenjeni za vrijeme trudnoće kod majki koje boluju od reumatskih bolesti ne izazivaju značajniju imunosupresiju u novorođenčadi praćenu nastajanjem citokina, interleukina 2 i interferona γ_ u perifernim mononuklearnim krvnim stanicama pod djelovanjem forbol-miristat-acetata (PMA) i ionomicina

20 Paediatric SLE

Case 1: 9-year-old female with rash and oral ulcer Alexandre Belot Alisson is 9 years old and came to the outpatient unit with a rash and oral ulcer. Her past medical history highlighted two invasive infections (meningitidis and pneumonia). She had no muscular weakness, no lymphoproliferative disease and no fever. Her laboratory exams revealed: WBC: 2.5 G/L, with PNM=1.2G/L, Hb = 10 g/dl, Platelet = 135G/L, CRP = 10 mg/L. CPK and aldolase were within normal values. Serology for Epstein-Barr Virus, parvovirus B19 and measles were negative. Autoimmune check-up showed: ANA+ 1/1280, C3 and C4 normal, anti-dsDNA negative, anti SSA+ >8. The dosage of immunoglobulins was normal (including subclasses). She further developed severe systemic disease with lupus nephritis, white matter lesions at the cerebral MRI. Complement CH50 was dramatically decreased and her C1q level was undetectable. Discussion Points Explore complement deficiency in juvenile systemic lupus erythematosus (SLE) Discuss monogenic SLE Case 2: 13-year-old female with skin rash and chilblain Alexandre Belot Jade is 13 years old and has been recently diagnosed with juvenile SLE. Her past medical history revealed a pervasive developmental disorder with features of autism and mental delay. Her parents are first cousins. Her first symptoms were skin rash, chilblain. Following first-line therapy with hydroxychloroquine and topical steroids, she developed a polyarthritis with hepatitis and leukopenia. Abdominal sonography was normal. Autoantibodies for autoimmune liver disease (dot hepatitis) were negative. Treatment with steroids and methotrexate was introduced and effective on the joints. Further genetic exploration revealed a biallelic mutation of TREX1. Later on, she was treated with a JAK inhibitor in addition to methotrexate resulting in a positive outcome. Discussion Points Type I interferon in juvenile SLE Interferonopathies Case 3: 14-year-old male with haematuria and renal colic Alexandre Belot Michael presented a macroscopic hematuria with renal colic at the age of 14 years old. Sonography revealed a left nephromegaly without evidence of urinary tract obstruction. A CT scan showed a left renal venous thrombosis. Initial work-up identified a triple positivity for lupus anticoagulant, anti-B2 Gp-I and anti-cardiolipin antibodies. Anticoagulant therapy was initiated. dsDNA and ANA were negative and complement was normal. Six months later, the hematuria had completely disappeared, according to a urine dipstick test, but proteinuria was still present with a protein:creatinine ratio of 120 mg/mmol in the urine. A new doppler sonography and CT scan showed the absence of perfusion in the left kidney. Considering the proteinuria, a percutaneous biopsy was performed on the contralateral kidney and histology revealed Class V lupus nephritis. Notably, autoantibodies and complement were still normal. Rituximab and ACE inhibitors were introduced, and proteinuria rapidly disappeared. Discussion Points How to explore APS in children Management of thrombosis in pediatric autoimmune diseases Case 4: Anti-histone antibodies: does it always mean drug-induced lupus erythematosus? Rolando Cimaz A South-American 14-year-old girl presented with arthralgia, weakness and alopecia. As she was under antiepileptic treatment since she was 5 years old, on suspicion of drug-induced lupus erythematosus (DILE) anti-histone antibodies were dosed and showed positive results. She presented with mild anemia, leukopenia, hypocomplementemia, ANA, anti-dsDNA and LAC positivity. The antiepileptic therapy was initially modified and then, as no more crises were present, interrupted. However, anemia, leukopenia, hypocomplementemia, ANA and anti-dsDNA persisted, and the diagnosis of idiopathic systemic lupus erythematosus (SLE) was made. After treatment with hydroxychloroquine and low dose prednisone the girl clinically improved and her laboratory results normalized. This case report is suggestive of the complexity in differentiating SLE and DILE and underlines the importance of a long and careful follow-up. Discussion Points Medications that can trigger lupus symptomatology Triggers of lupus or of lupus-like disease (autoimmunity in general) with TNF inhibitors used for arthritis Risks of prescribing such medications (i.e. anti-TNF) in patients with inflammatory arthritis and pre-existing autoantibodies or a family history of autoimmune disease Case 5: Bleeding and thrombosis in juvenile systemic lupus erythematosus Rolando Cimaz A young girl with immune thrombocytopenic purpura was also found to have antiphospholipid antibody syndrome. This case describes the complexity of therapeutic management linked to the risk of bleeding and thrombosis. Irene is 15-year-old. In recent hours she has experienced intermittent claudication and lower right limb pain. Her physical exam reveals swelling and tenderness of right calf, pain to compression and mobilization of right foot. Laboratory tests reveal WBC 21.610 (N 77%); Hb 13.1 g/dl; PLT 91000/mmc; aPTT 48.4 sec, PT 99%; fibrinogen 236 mg/dl; D-Dimer 0.59 mg/L. Ultrasound revealed thrombosis. Past medical history showed that 8 months before she had suffered from severe metrorrhagia. Laboratory tests had shown: PLT 7000, Hb 10.2 g/dl, Coombs direct test +, PT 1.18, aPTT 76 sec; IgM e IgG anticardiolipin +. Therapy consisted in intravenous immunoglobulin (two infusions) and then oral steroids. Five relapses occurred, and laboratory showed: ANA+ (1:160), ENA -, anticardiolipin -, C3 85, C4 7.5, LAC +. Repeat laboratory test showed ANA+, ENA-, anticardiolipin +, anti-b2 glycoprotein -, LAC +. Discussion Points For thrombosis Heparin 6000U/x2/day. For how long? And for thrombocytopenia? Oral steroids (2 mg/kg/day); Mycophenolate mofetil (750 mg/m2 x 2/day). But despite this therapy, she relapsed. So > rituximab 750 mg/m2/2 weeks. For SLE hydroxychloroquine was given. Learning Objectives Distinguish between idiopathic and drug-induced SLE Describe the treatment of APS in children Discuss treatment options for hematologic SL