Objectives The study aim was to prospectively evaluate the relationship between disease flare development in children with juvenile idiopathic arthritis (JIA) after discontinuation of treatment and serum calprotectin levels (MRP8/14). Material and methods Determination of blood serum level of calprotectin was performed in 54 patients with inactive JIA from various regions of Ukraine. The inclusion criterion was the existence of an inactive state of the disease in children with JIA for at least 6 months. During 1 week after blood sampling for determination of serum calprotectin (MRP8/14) level the patients were completely discontinued of all therapy. Determination of calprotectin level in blood serum was performed with reagents EK-MRP8/14 Buhlmann (MRP8/14; S100A8/9), Switzerland, using the ELISA method. Results The trial results showed that 3 months after discontinuation of treatment in patients with inactive JIA, the flares developed in 5 out of 54 patients (9.3%). The median calprotectin level before discontinuation of the treatment was 1,700 ng/ml in patients who developed a flare, and 1,500 ng/ml in other studied patients (not statistically significant). At 6 months, the flare had developed in an additional 3 out of 48 (6.3%) of patients, who continued to be followed up, while their median calprotectin serum levels were 1,300 ng/ml and 1,500 ng/ml respectively (not statistically significant). At 12 months, the flares had developed in 13 more out of 45 (28.9%) patients, who continued to be followed up, while the median calprotectin serum level in these patients before discontinuation of treatment was 1,100 ng/ml and 1,650 ng/ml respectively (not statistically significant). Conclusion After discontinuation of treatment a flare over the next year of follow-up developed in 38.9% of patients. The study results did not reveal a significant difference in calprotectin level in patients with JIA prior to complete discontinuation of treatment who developed a flare and those without a flare after 3, 6 and 12 months.

Background:Tofacitinib is an oral JAK inhibitor that is being investigated for JIA.Objectives:To assess tofacitinib efficacy and safety in JIA patients (pts).Methods:This was a Phase 3, randomised, double-blind (DB), placebo (PBO)-controlled withdrawal study in pts aged 2−<18 years with polyarticular course JIA (pcJIA), PsA or ERA (NCT02592434). In the 18-week open-label Part 1, pts received weight-based tofacitinib doses (5 mg BID or lower). Pts with ≥JIA ACR30 response at Week (W)18 were randomised 1:1 in the DB Part 2 (W18−44) to continue tofacitinib or switch to PBO. Primary endpoint: disease flare rate by W44. Key secondary endpoints: JIA ACR50/30/70 response rates; change from Part 2 baseline (Δ) in CHAQ-DI at W44. Other efficacy endpoints: time to disease flare in Part 2; JADAS27-CRP in Parts 1 and 2. PsA/ERA pts were excluded from these efficacy analyses. Safety was evaluated in all pts up to W44.Results:225 enrolled pts with pcJIA (n=184), PsA (n=20) or ERA (n=21) received tofacitinib in Part 1. At W18, 173/225 (76.9%) pts entered Part 2 (pcJIA n=142, PsA n=15, ERA n=16). In pcJIA pts, disease flare rate in Part 2 was significantly lower with tofacitinib vs PBO by W44 (p=0.0031; Fig 1a). JIA ACR50/30/70 response rates (Fig 1b) and ΔCHAQ-DI (Fig 1c) at W44, and time to disease flare in Part 2 (Fig 2a), were improved with tofacitinib vs PBO. Tofacitinib reduced JADAS27-CRP in Part 1; this effect was sustained in Part 2 (Fig 2b). Overall, safety was similar with tofacitinib or PBO (Table): 77.3% and 74.1% had adverse events (AEs); 1.1% and 2.4% had serious AEs. In Part 1, 2 pts had herpes zoster (non-serious) and 3 pts had serious infections (SIs). In Part 2, SIs occurred in 1 tofacitinib pt and 1 PBO pt. No pts died.Conclusion:In pcJIA pts, tofacitinib vs PBO resulted in significantly fewer disease flares, and improved time to flare, disease activity and physical functioning. Tofacitinib safety was consistent with that in RA pts.Table.Safety in all ptsPart 1Part 2TofacitinibaN=225TofacitinibaN=88PBO N=85Pts with events, n (%)AEs153 (68.0)68 (77.3)63 (74.1)SAEs7 (3.1)1 (1.1)2 (2.4)Permanent discontinuations due to AEs26 (11.6)16 (18.2)29 (34.1)AEs of special interest Death000 Gastrointestinal perforationb000 Hepatic eventb3 (1.3)00 Herpes zoster (non-serious and serious)2 (0.9)c00 Interstitial lung diseaseb000 Major adverse cardiovascular eventsb000 Malignancy (including non-melanoma skin cancer)b000 Macrophage activation syndromeb000 Opportunistic infectionb000 SI3 (1.3)1 (1.1)d1 (1.2) Thrombotic event (deep vein thrombosis, pulmonary embolismbor arterial thromboembolism)000 Tuberculosisb000a5 mg BID or equivalent weight-based lower dose in pts <40 kgbAdjudicated eventscBoth non-seriousdOne SAE of pilonidal cyst repair was coded to surgical procedures instead of infections, and was inadvertently not identified as an SI. Following adjudication, the SAE did not meet opportunistic infection criteria; it is also included in the table as an SIAE, adverse event; BID, twice daily; PBO, placebo; pts, patients; SAE, serious AE; SI, serious infectionAcknowledgments:Study sponsored by Pfizer Inc. Medical writing support was provided by Sarah Piggott of CMC Connect and funded by Pfizer Inc.Disclosure of Interests:Nicolino Ruperto Grant/research support from: Bristol-Myers Squibb, Eli Lily, F Hoffmann-La Roche, GlaxoSmithKline, Janssen, Novartis, Pfizer, Sobi (paid to institution), Consultant of: Ablynx, AbbVie, AstraZeneca-Medimmune, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lily, EMD Serono, GlaxoSmithKline, Hoffmann-La Roche, Janssen, Merck, Novartis, Pfizer, R-Pharma, Sanofi, Servier, Sinergie, Sobi, Takeda, Speakers bureau: Ablynx, AbbVie, AstraZeneca-Medimmune, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lily, EMD Serono, GlaxoSmithKline, Hoffmann-La Roche, Janssen, Merck, Novartis, Pfizer, R-Pharma, Sanofi, Servier, Sinergie, Sobi, Takeda, Olga Synoverska Speakers bureau: Sanofi, Tracy Ting: None declared, Carlos Abud-Mendoza Speakers bureau: Eli Lilly, Pfizer Inc, Alberto Spindler Speakers bureau: Eli Lilly, Yulia Vyzhga Grant/research support from: Pfizer Inc, Katherine Marzan Grant/research support from: Novartis, Vladimir Keltsev: None declared, Irit Tirosh: None declared, Lisa Imundo: None declared, Rita Jerath: None declared, Daniel Kingsbury: None declared, Betül Sözeri: None declared, Sheetal Vora: None declared, Sampath Prahalad Grant/research support from: Novartis, Elena Zholobova Grant/research support from: Novartis and Pfizer Inc, Speakers bureau: AbbVie, Novartis, Pfizer Inc and Roche, Yonatan Butbul Aviel: None declared, Vyacheslav Chasnyk: None declared, Melissa Lerman Grant/research support from: Amgen, Kabita Nanda Grant/research support from: Abbott, AbbVie, Amgen and Roche, Heinrike Schmeling Grant/research support from: Janssen, Pfizer Inc, Roche and USB Bioscience, Heather Tory: None declared, Yosef Uziel Speakers bureau: Pfizer Inc, Diego O Viola Grant/research support from: Bristol-Myers Squibb, GSK, Janssen and Pfizer Inc, Speakers bureau: AbbVie and Bristol-Myers Squibb, Holly Posner Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Keith Kanik Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Ann Wouters Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Cheng Chang Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Richard Zhang Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Irina Lazariciu Consultant of: Pfizer Inc, Employee of: IQVIA, Ming-Ann Hsu Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Ricardo Suehiro Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Alberto Martini Consultant of: AbbVie, Eli Lily, EMD Serono, Janssen, Novartis, Pfizer, UCB, Daniel J Lovell Consultant of: Abbott (consulting and PI), AbbVie (PI), Amgen (consultant and DSMC Chairperson), AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb (PI), Celgene, Forest Research (DSMB Chairman), GlaxoSmithKline, Hoffman-La Roche, Janssen (co-PI), Novartis (consultant and PI), Pfizer (consultant and PI), Roche (PI), Takeda, UBC (consultant and PI), Wyeth, Employee of: Cincinnati Children’s Hospital Medical Center, Speakers bureau: Wyeth, Hermine Brunner Consultant of: Hoffman-La Roche, Novartis, Pfizer, Sanofi Aventis, Merck Serono, AbbVie, Amgen, Alter, AstraZeneca, Baxalta Biosimilars, Biogen Idec, Boehringer, Bristol-Myers Squibb, Celgene, EMD Serono, Janssen, MedImmune, Novartis, Pfizer, and UCB Biosciences, Speakers bureau: GSK, Roche, and Novartis

No abstract

Gianotti-Crosti syndrome is a kind of infectious exanthem. That is characterized by the appearance of monomorphic papules, which colour may be from the skin colour to pink-red ones. The most typical location is on the face, buttocks and extensor surfaces of the limbs. Over time, the rash disappears spontaneously and the medical treatment becomes symptomatic. Currently, the pathophysiological changes are not still thoroughly studied. It is clear that the syndrome represents an immunological response to the previous viremia and bacteraemia; perhaps, it is the delayed-type hypersensitivity reaction. Purpose - to acquaint doctors with criteria of the papular acrodermatitis for a timely diagnostic and a correct treatment strategy. Clinical case. There was a described clinical case of Gianotti-Crosti syndrome in a child of 2. The parents had complained about rashes on the face, limbs, buttocks for 6 weeks. The severe restlessness and itching of the skin had been present. During the whole time, the child was examined by various specialists. Alternative diagnoses were: an atopic dermatitis, a food allergy, a worm infestation. The child was prescribed local zinc-containing agents, systemic and local glucocorticosteroids, antiviral drugs, antibacterial therapy, antihistamines, sorbents, probiotics and a three-time course of deworming in the process of the treatment. The treatment have not had a positive therapeutic effect. Conclusions. Gianotti-Crosti syndrome is most common in childhood. At present, we consider it a self-limited disease that does not require specific treatment. Recent studies proved that the syndrome is more commonly associated with a variety of viral and bacterial pathogens. However, insufficient knowledge of papular acrodermatitis may lead to groundless and continuous examinations and treatment of children. The research was carried out in accordance with the principles of the Helsinki Declaration. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors.

У статті подано результати дослідження стану вегетативної нервової системи у дітей із гострою лімфобластною лейкемією, у яких у результаті протокольної хіміотерапії із застосуванням антрациклінових антибіотиків розвинулась токсична антрациклінова кардіоміопатія. Розподіл дослідних груп проводився за віковим статусом та кумулятивною дозою доксорубіцину. Дослідження вегетативної нервової системи включало оцінку вихідного вегетативного тонусу, вегетативної реактивності та вегетативного статусу, що проводили в кінці першої фази І, ІІ протоколів та mM протоколу поліхіміотерапії. Оцінку вегетативного статусу дітей проводили шляхом аналізу варіабельності серцевого ритму. Оцінка вихідного вегетативного тонусу встановила дисбаланс між системами регуляції та переважання впливу симпатичної активності на діяльність серцево-судинної системи впродовж всього періоду поліхіміотерапії. Встановлено, що у більшості обстежених дітей має місце знижена вегетативна реактивність з переважанням парадоксального типу реагування. Визначено чітке напруження регуляторних систем організму за рахунок зростання індексу напруги протягом всього періоду хіміотерапії. Крім того, встановлено, що ряд показників варіабельності серцевого ритму у дітей тісно корелює з тривалістю поліхіміотерапії та кумулятивною дозою антрациклінових антибіотиків.