Search

Objectives: Fibrodysplasia ossificans progressiva (FOP) is one of the most catastrophic forms of genetic heterotopic ossification (HO). FOP is characterized by severe, progressive inflammatory flare-ups, that often lead to HO. The flare-ups are associated with increased inflammatory cytokine production, suggesting auto-inflammatory features driven by IL-1β. This study describes the short- and long-term responses of FOP patients to anti-IL-1 therapy., Methods: Previously, we reported that a patient with FOP treated with anti-IL-1 agents showed dramatically lower rates of flare-ups, improved flare-up symptoms, decreased use of glucocorticoids and apparently decreased size of residual lesions. Plasma analyses also showed marked elevation in IL-1β levels during a FOP flare, further supporting a role of IL-1β in the pathogenesis of FOP flares. Here, we report results from long-term therapy with IL-1 inhibitors in that patient and describe 3 additional patients, from two medical centres., Results: All 4 patients showed persistent improvement in flare activity during treatment with IL-1 inhibitors, with minimal formation of new HO sites. Two patients who stopped therapy experienced a resurgence of flare activity that was re-suppressed upon re-initiation. These patients had IL-1β levels comparable to those in IL-1β-driven diseases. Child Health Assessment Questionnaires confirmed extensive subjective improvements in the pain and general health visual analogue scales., Conclusion: This case series demonstrates significant benefits from IL-1 inhibitors for reducing flare activity and improving the general health of patients with FOP. These data provide strong support for additional studies to better understand the function of IL-1 inhibition, primarily in reducing the formation of new HO., Funding: RH received support from the International FOP Association ACT grant; ECH received support from NIH/NIAMS R01AR073015 and the UCSF Robert Kroc Chair in Connective Tissue and Rheumatic Diseases III., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Background/purpose: Adequate transition from pediatric to adult care is associated with better adherence to treatment and better outcomes in pediatric patients with chronic diseases. There are little data on transition programs, outcomes, use of transition guidelines, and available tools in pediatric rheumatology centers from Latin America (LATAM). In this study, we described the characteristics of transition programs from 3 pediatric rheumatology centers. We also introduced results of the first survey examining the transition experience in countries from LATAM., Methods: The experience and implementation process of transition programs from 3 pediatric rheumatology centers were described. A survey based on a questionnaire created by Chira et al (J Rheumatol. 2014;41:768-779) from the Childhood Arthritis and Rheumatology Research Alliance was also administrated to pediatric rheumatology centers from LATAM., Results: A total of 49 (68%) pediatric rheumatologists answered the survey. Most centers do not have an official and written transition program and reported a need for more tools and resources in their services to facilitate the transition experience., Conclusions: Transition guidelines culturally tailored to developing countries are needed in LATAM., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Fibrodysplasia ossificans progressiva (FOP) is an ultrarare genetic disorder with episodic and progressive heterotopic ossification. Tissue trauma is a major risk factor for flareups, heterotopic ossification (HO), and loss of mobility in patients with FOP. The International Clinical Council on FOP generally recommends avoiding surgery in patients with FOP unless the situation is life-threatening, because soft tissue injury can trigger an FOP flareup. Surprisingly little is known about flareups, HO formation, and loss of mobility after fractures of the normotopic (occurring in the normal place, distinct from heterotopic) skeleton when treated nonoperatively in patients with FOP., Questions/purposes: (1) What proportion of fractures had radiographic evidence of union (defined as radiographic evidence of healing at 6 weeks) or nonunion (defined as the radiographic absence of a bridging callus at 3 years after the fracture)? (2) What proportion of patients had clinical symptoms of an FOP flareup because of the fracture (defined by increased pain or swelling at the fracture site within several days after closed immobilization)? (3) What proportion of patients with fractures had radiographic evidence of HO? (4) What proportion of patients lost movement after a fracture?, Methods: We retrospectively identified 36 patients with FOP from five continents who sustained 48 fractures of the normotopic skeleton from January 2001 to February 2021, who were treated nonoperatively, and who were followed for a minimum of 18 months after the fracture and for as long as 20 years, depending on when they sustained their fracture during the study period. Five patients (seven fractures) were excluded from the analysis to minimize cotreatment bias because these patients were enrolled in palovarotene clinical trials (NCT02190747 and NCT03312634) at the time of their fractures. Thus, we analyzed 31 patients (13 male, 18 female, median age 22 years, range 5 to 57 years) who sustained 41 fractures of the normotopic skeleton that were treated nonoperatively. Patients were analyzed at a median follow-up of 6 years (range 18 months to 20 years), and none was lost to follow-up. Clinical records for each patient were reviewed by the referring physician-author and the following data for each fracture were recorded: biological sex, ACVR1 gene pathogenic variant, age at the time of fracture, fracture mechanism, fracture location, initial treatment modality, prednisone use at the time of the fracture as indicated in the FOP Treatment Guidelines for flare prevention (2 mg/kg once daily for 4 days), patient-reported flareups (episodic inflammatory lesions of muscle and deep soft connective tissue characterized variably by swelling, escalating pain, stiffness, and immobility) after the fracture, follow-up radiographs of the fracture if available, HO formation (yes or no) as a result of the fracture determined at a minimum of 6 weeks after the fracture, and patient-reported loss of motion at least 6 months after and as long as 20 years after the fracture. Postfracture radiographs were available in 76% (31 of 41) of fractures in 25 patients and were independently reviewed by the referring physician-author and senior author for radiographic criteria of fracture healing and HO., Results: Radiographic healing was noted in 97% (30 of 31) of fractures at 6 weeks after the incident fracture. Painless nonunion was noted in one patient who sustained a displaced patellar fracture and HO. In seven percent (three of 41) of fractures, patients reported increased pain or swelling at or near the fracture site within several days after fracture immobilization that likely indicated a site-specific FOP flareup. The same three patients reported a residual loss of motion 1 year after the fracture compared with their prefracture status. HO developed in 10% (three of 31) of the fractures for which follow-up radiographs were available. Patient-reported loss of motion occurred in 10% (four of 41) of fractures. Two of the four patients reported noticeable loss of motion and the other two patients reported that the joint was completely immobile (ankylosis)., Conclusion: Most fractures treated nonoperatively in individuals with FOP healed with few flareups, little or no HO, and preservation of mobility, suggesting an uncoupling of fracture repair and HO, which are two inflammation-induced processes of endochondral ossification. These findings underscore the importance of considering nonoperative treatment for fractures in individuals with FOP. Physicians who treat fractures in patients with FOP should consult with a member of the International Clinical Council listed in the FOP Treatment Guidelines ( https://www.iccfop.org )., Level of Evidence: Level IV, therapeutic study., Competing Interests: All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research ® editors and board members are on file with the publication and can be viewed on request., (Copyright © 2023 by the Association of Bone and Joint Surgeons.)

Introduction: The continuity of care from pediatrics to adult medicine is key to optimal health care., Objective: To describe the experience of the transition process of adolescent patients with chronic diseases from pediatric to adult care in a general hospital., Population and Methods: Cross-sectional study of patients aged 16-24 years with a history of liver transplantation, kidney transplantation, endocrine, metabolic, rheumatic diseases, and myelomeningocele seen at a tertiary care teaching general hospital between 2015 and 2019 during the transition process. The process of health care and transition success were assessed. The Transition Readiness Assessment Questionnaire (TRAQ) was used., Results: A total of 372 patients were included. The myelomeningocele clinic, the kidney transplant and the liver transplant teams were the most common specialties. Thirty-seven percent of participants were involved in the transition process. The mean duration of follow-up by pediatrics until transition initiation was 9 years. The mean age at the beginning of transition was 19 years, and the mean age at the end, 21 years. The joint clinic transition strategy was the most frequent, used in 96% of cases. The median value of the ordinal TRAQ was 4; of these, 32% had already seen adult care physicians. A successful transition was achieved by 32.7%., Conclusions: The continuity of care during transition is a process that took almost 2 years; more than one third of the patients had a successful transition., Competing Interests: None., (Sociedad Argentina de Pediatría.)

Fibrodysplasia ossificans progressiva (FOP) is a rare and devastating genetic disease, in which soft connective tissue is converted into heterotopic bone through an endochondral ossification process. Patients succumb early as they gradually become trapped in a second skeleton of heterotopic bone. Although the underlying genetic defect is long known, the inherent complexity of the disease has hindered the discovery of effective preventions and treatments. New developments in the gene therapy field have motivated its consideration as an attractive therapeutic option for FOP. However, the immune system's role in FOP activation and the as-yet unknown primary causative cell, are crucial issues which must be taken into account in the therapy design. While gene therapy offers a potential therapeutic solution, more knowledge about FOP is needed to enable its optimal and safe application.

Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare progressive genetic disease effecting one in a million individuals. During their life, patients with FOP progressively develop bone in the soft tissues resulting in increasing immobility and early death. A mutation in the ACVR1 gene was identified as the causative mutation of FOP in 2006. After this, the pathophysiology of FOP has been further elucidated through the efforts of research groups worldwide. In 2015, a workshop was held to gather these groups and discuss the new challenges in FOP research. Here we present an overview and update on these topics., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 de Ruiter, Smilde, Pals, Bravenboer, Knaus, Schoenmaker, Botman, Sánchez-Duffhues, Pacifici, Pignolo, Shore, van Egmond, Van Oosterwyck, Kaplan, Hsiao, Yu, Bocciardi, De Cunto, Longo Ribeiro Delai, de Vries, Hilderbrandt, Jaspers, Keen, Koolwijk, Morhart, Netelenbos, Rustemeyer, Scott, Stockklausner, ten Dijke, Triffit, Ventura, Ravazzolo, Micha and Eekhoff.)

Progressive heterotopic ossification (HO) is a hallmark of fibrodysplasia ossificans progressiva (FOP); however, this tissue transformation is not random. Rather, we noticed that HO in FOP progresses in well-defined but inexplicable spatial and temporal patterns that correlate precisely with infrared thermographs of the human body. FOP is caused by gain-of-function mutations in Activin A receptor type I (ACVR1/ALK2), a bone morphogenetic protein (BMP) type I receptor kinase. As with all enzymes, the activity of ACVR1 is temperature-dependent. We hypothesized that connective tissue progenitor cells that express the common heterozygous ACVR1 R206H mutation (FOP CTPCs) exhibit a dysregulated temperature response compared to control CTPCs and that the temperature of FOP CTPCs that initiate and sustain HO at various anatomic sites determines, in part, the anatomic distribution of HO in FOP. We compared BMP pathway signaling at a range of physiologic temperatures in primary CTPCs isolated from FOP patients (n = 3) and unaffected controls (n = 3) and found that BMP pathway signaling and resultant chondrogenesis were amplified in FOP CTPCs compared to control CTPCs (p < 0.05). We conclude that the anatomic distribution of HO in FOP may be due, in part, to a dyregulated temperature response in FOP CTPCs that reflect anatomic location. While the association of temperature gradients with spatial patterns of HO in FOP does not demonstrate causality, our findings provide a paradigm for the physiologic basis of the anatomic distribution of HO in FOP and unveil a novel therapeutic target that might be exploited for this disabling condition., (Copyright © 2021. Published by Elsevier Inc.)

Introduction: Health-related quality of life (HRQoL) is a measure of health outcomes. It assesses the subjective and overall impact of diseases on daily life. It also provides multidimensional data about physical wellbeing, family and peers relations. HRQoL studies on siblings are limited., Objective: To compare HRQoL among siblings of pediatric patients with chronic rheumatic diseases, kidney or liver transplant and healthy children whose siblings had no chronic conditions., Results: The siblings of children with kidney transplant (n: 65), liver transplant (n: 35), and chronic rheumatic diseases (n: 36) were compared to the healthy children group (n: 51). The total siblings group had a lower, statistically significant score in the physical well-being, social support and peers, and financial resources dimensions. The siblings of kidney transplant patients had a low score in the physical wellbeing (p < 0.02; effect size [ES]: 0.66) andfinancial resources (p < 0.01; ES: 0.66) dimensions. The siblings of liver transplant patients perceived a lower physical well-being (p = 0.04), less social support and peers (p < 0.01), and difficulties in relation to school environment (p < 0.02) and financial resources (p <0.01). The siblings of those with chronic rheumatic diseases had a lower score in the physical well-being (p < 0.05; ES: 0.44) and social support and peers (p <0.01; ES: 0.58) dimensions., Conclusion: HRQoL among healthy children whose siblings have a chronic disease was lower in the physical well-being, social support and peers, and financial resources dimensions compared to the healthy children group., Competing Interests: None, (Sociedad Argentina de Pediatría.)

Introduction: Hidden curricula are those contents learned that do not belong to the formal curriculum. Narrative medicine allows knowledge of health professionals' experiences. Approaching to the hidden curriculum can allow modifying or reinforcing instances of the nonformal learning., Objective: Analyze narrative medical students' productions to identify hidden curriculum contents., Population and Methods: A cross-sectional study was conducted with Pediatric students during 2017., Results: All the students of the course (14) participated and performed 50 narrative productions: 53 % corresponded to the hospitalization context, 17 % to ambulatory care, 17 % to the emergency center and 13 % to neonatology. The main topics described were doctor-patient communication, importance of family inclusion in the pediatric consultation, empathy, impact of chronic disease in children and communication of bad news., Conclusions: Narrative productions allowed an approximation to the hidden curriculum through reflections on professional actions., Competing Interests: None, (Sociedad Argentina de Pediatría.)

Fibrodysplasia ossificans progressiva (FOP), a disabling disorder of progressive heterotopic ossification (HEO), is caused by heterozygous gain-of- function mutations in Activin receptor A, type I (ACVR1, also known as ALK2), a bone morphogenetic protein (BMP) type I receptor. Presently, symptomatic management is possible, but no definitive treatments are available. Although extensive guidelines for symptomatic management are widely used, regional preferences exist. In order to understand if there was worldwide consensus among clinicians treating FOP patients, an expert panel of physicians directly involved in FOP patient care was convened. Using a modified Delphi method, broad international consensus was reached on four main topics: diagnosis, prevention of flare-ups, patient and family-centered care and general clinical management issues. This study of physician preferences provides a basis for standardization of clinical management for FOP.

In Argentina, there was not an adapted and validated instrument to evaluate readiness for the transition to adult health care. The purpose of this study was to describe the process of cross-cultural adaptation of the Transition Readiness Assessment Questionnaire 5.0 to Argentinian Spanish. The authors of the instrument were contacted to this effect. Stage 1: two translators performed the translation to Spanish. Stage 2: based on these two versions, version 1 was agreed upon. Stage 3: two back-translations were performed. Stages 4 and 5: both back-translated versions were compared, and the Spanish version was adapted to ensure correspondence with the original. Subheads were added in each domain, and version 2 was obtained. Stage 6: the questionnaire was field tested to ensure the cultural adequacy of the vocabulary, thus obtaining version 3. In the last stage (stage 7), the instrument was tested in two hospitals. Finally, the cross-cultural adaptation of the Transition Readiness Assessment Questionnaire 5.0 for the Argentinian population was obtained., (Sociedad Argentina de Pediatría.)

The number of adolescent patients with chronic diseases and special heath needs are increasing, and they are reaching adulthood. Sometimes the passage to the adult health care is abrupt, depending upon the chronological age reached or because of an acute health problem that requires hospitalization. In order to facilitate the transition process, preparation of the child, the family and the health professionals involved is needed, as well as the coordination between the pediatric group and the adult team that will be incharge of the patient. This review shows the obstacles to this process and the recommended implementation steps required to a successful transition. It also describes the main aspects of a program that we implemented at the Hospital Italiano de Buenos Aires in conjunction with some departments of adult health care high lighting the main steps to follow before and during program´s implementation.

Introduction: Musculoskeletal pain is a common symptom in childhood. It is estimated that 5 to 19% of healthy children experience musculoskeletal pain., Aims: To estimate the prevalence of musculoskeletal pain and to describe epidemiological characteristics in children 3 to 12 years of age, who attend a community hospital., Population, Material and Methods: This is an observational transversal study. A self-administered questionnaire was completed in the waiting room of the Pediatric ambulatory area. Children with chronic diseases were excluded. Statistical tests used included chi(2) test, Mc Nemar and a logistic regression model analysis., Results: A total of 240 questionnaires were distributed and 229 were returned. Median age of children was 6 years and 36 (25-50) years in their mothers. Fifty four percent were girls. Pain was present in 21.4% in the last year, and 19.2% in the past 3 months, both groups were concordant (Mc Nemar test not significant). Associated factors with pain in the last year were: age and family history of current pain and during childhood (logistic regression model). No relation was found with sex of the child, mother age, mono-parental family, siblings or stress family factors in the last year. The musculoskeletal pain was localized in: lower limbs (66%), muscles (52%), joints (38%) and was bilateral in 33%. In 40% of children the pain duration was transient (minutes), 55% developed pain, at least, once a month and in 51% was related to exercise. Limitation of daily living activities due to pain was seen in 16%. The pain resolved spontaneously in 50%. Pediatricians were consulted in 63% of the cases and 8% consulted in Orthopedics. When comparing the pain pattern in 2 groups of children (< and > 6 years), we found that older children tended to present pain more than once a month and related to exercise., Conclusions: The prevalence of musculoskeletal pain was 21.4%. Pain was associated to child age and family history of musculoskeletal pain. Pain was referred to lower limbs (mainly muscles), periodic (more than once a month) and related to exercise.

We describe four unrelated children with neonatal maculopapular rash, fever, arthritis, hepatosplenomegaly, lymphadenopathy, eye involvement, and neurologic symptoms. Radiographs of the joints were surprisingly similar, showing an abnormal epiphyseal and metaphyseal appearance. These clinical and radiologic findings allowed us to include these children in a very peculiar syndrome described as infantile-onset multisystemic inflammatory disease. A chondrosarcoma developed in one of our patients.

Patients with Group A beta-hemolytic streptococcal infection and articular disease who do not fulfill the modified Jones criteria for a diagnosis of acute rheumatic fever (ARF) have been classified as poststreptococcal reactive arthritis/arthralgia. We reviewed the initial clinical characteristics and outcome of 12 poststreptococcal reactive arthritis/arthralgia patients. During the initial episode all had arthritis or arthralgia and a documented streptococcal infection. None had carditis and none received prophylactic antibiotic therapy during an average follow-up of 17 months (range, 6 to 42 months). One patient developed classic ARF with valvulitis 18 months after the initial episode. Two children had later episodes of arthritis and two had at least one additional episode of arthralgia. Poststreptococcal reactive arthritis/arthralgias seems to be part of the disease spectrum of ARF and therefore the use of prophylactic antibiotic therapy to prevent subsequent development of ARF and carditis in these patients should, perhaps, be reconsidered.