Antibiotic prescriptions to children with periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis.

AIM: To investigate the rate of dispensed antibiotic prescriptions to children and adolescents with PFAPA and compare this with the rate for children in the general population. Furthermore, to compare dispensed antibiotic prescription rates before and after a diagnosis of PFAPA was established. METHODS: Patients aged 0-17 years and diagnosed with PFAPA between 1 January 2006 to 31 October 2017 were included retrospectively. Data on dispensed drug prescriptions were obtained from the Swedish National Prescribed Drug Register. RESULTS: The PFAPA cohort received more antibiotic prescriptions than the general population in all but one of the age groups and time periods that were analysed. The largest difference was seen in 2014-2017 in the youngest age group (0-4 years) when children with PFAPA received 1218 antibiotic prescriptions per 1000 person years compared to 345 in the general population (IRR 3.5; 95% CI 2.8-4.4). The yearly number of antibiotic prescriptions to PFAPA patients was reduced from 2.1 before diagnosis to 0.8 after diagnosis, a reduction of 62%. CONCLUSION: This study shows higher rates of dispensed antibiotic prescriptions for children with PFAPA than in the general population. The reduction of prescriptions after an established PFAPA diagnosis indicates that antibiotics were previously incorrectly prescribed for PFAPA episodes.

Severe chronic non-bacterial osteomyelitis in combination with total MPO deficiency and responsiveness to TNFα inhibition.

We describe a female patient suffering from severe chronic non-bacterial osteomyelitis (CNO) with systemic inflammation and advanced malnutrition and complete deficiency of myeloperoxidase (MPO). CNO is a rare autoinflammatory bone disorder associated with dysregulation of the innate immune system. MPO deficiency is a genetic disorder with partial or complete absence of the phagocyte peroxidase MPO. MPO deficiency has no established clinical phenotype but reports indicate increased susceptibility to infection and chronic inflammation. The patient's symptoms began at 10 years of age with pain in the thighs, systemic inflammation and malnutrition. She was diagnosed with CNO at 14 years of age. Treatment with nonsteroidal anti-inflammatory drugs, corticosteroids, bisphosphonates or IL1-receptor antagonists (anakinra) did not relieve the symptoms. However, the patient responded instantly and recovered from her clinical symptoms when treated with TNFα blockade (adalimumab). Three years after treatment initiation adalimumab was withdrawn, resulting in rapid symptom recurrence. When reintroducing adalimumab, the patient promptly responded and went into remission. In addition to clinical and laboratory profiles, neutrophil functions (reactive oxygen species, ROS; neutrophil extracellular traps, NETs; degranulation; apoptosis; elastase activity) were investigated both in a highly inflammatory state (without treatment) and in remission (on treatment). At diagnosis, neither IL1ß, IL6, nor TNFα was significantly elevated in serum, but since TNFα blockade terminated the inflammatory symptoms, the disease was likely TNFα-driven. All neutrophil parameters were normal both during treatment and treatment withdrawal, except for MPO-dependent intracellular ROS- and NET formation. The role of total MPO deficiency for disease etiology and severity is discussed.

Tonsillectomy reduces the family impact of periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA) syndrome and improves health-related quality of life in affected children.

BACKGROUND: Periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA) syndrome is an autoinflammatory disorder that primarily affects young children, and typically gives rise to fever episodes that recur monthly for several years. This study investigated the impact of PFAPA syndrome on the families of affected children, the health-related quality of life (HRQOL) of children with the syndrome, and how these factors were influenced by tonsillectomy. METHODS: This prospective cohort study included 24 children with typical PFAPA syndrome that were referred for tonsillectomy, of whom 20 underwent the procedure. The control group consisted of randomly selected children from the general population. Family impact and HRQOL were measured using the standardized, validated questionnaires Pediatric Quality of Life Inventory™ (PedsQL™) Family Impact Module (FIM) and PedsQL™ 4.0 Generic Core Scales (GCS). Parents to children with PFAPA completed the questionnaires before and 6 months after their child underwent tonsillectomy, and HRQOL was measured both between and during PFAPA episodes. The Wilcoxon signed-rank test was used to compare data before and after tonsillectomy in the patient group, while the Mann-Whitney test was used for comparison of the patient and control groups. RESULTS: Before tonsillectomy, children with PFAPA had significantly lower scores than the control group on the PedsQL™ FIM and the PedsQL™ 4.0 GCS during fever episodes. After tonsillectomy, all patients improved with diminished febrile episodes, which resulted in significantly higher scores regarding both family impact and HRQOL at the time of follow-up. HRQOL of in children with PFAPA improved after tonsillectomy even when compared to afebrile intervals before the procedure. The differences between PFAPA patients and controls were eliminated after tonsillectomy. CONCLUSION: PFAPA syndrome has a profound negative impact on the families of affected children. Tonsillectomy that leads to cessation or reduction of fever episodes eases the impact of the disease on the family. HRQOL in children with PFAPA is low during febrile episodes and similar to healthy controls in between episodes. The improvement of HRQOL in patients with PFAPA after tonsillectomy compared to the afebrile intervals before tonsillectomy highlights that the constantly recurring fevers may affect the children's well-being even between fever episodes.

Paediatric on-call consultants' learning within and beyond the objectives of a coherent CPD program.

BACKGROUND: Evaluations, using questionnaires, of a two-year long CPD program for on-call consultant paediatricians, showed that the overall objective of the program was largely met. We stipulate that the coherency of the CPD program contributed to the learning. To gains a deeper understanding of the participants learning within and beyond the overall objectives of the program, we decided to conduct an interview study enrolling participants from the first two CPD courses. METHODS: Nine experienced paediatric consultants were interviewed 1-4 years after completing a coherent two-year long CPD program, focusing on what and how they learned. The interviews were audio-recorded and transcribed as text, analysed, and categorised using qualitative content analysis. RESULTS: What the participants learned: improved medical competences, greater confidence in the role of an on-call consultant, better understanding of the role of an on-call consultant and importance of professional networks. Several categories were outside the overall objective, at personal level: an understanding of one's own and other's competences, taking responsibility for one's own CPD and managing things one does not know. At professional level: more secure as an individual and with colleagues. How it was learned: relevant objectives, preparatory material and case discussions were important. Participants learned by preparing, repeating, reflecting, and participating actively, and by applying what they learned in clinical practice. The participants learned from one other over a period of two years, when they also got to know one another and created networks. A safe learning environment imposed demands and enabled participants to define their competence and learn accordingly. CONCLUSIONS: This study describes what and how on-call consultant paediatricians learned during a coherent two-year long CPD program. The learning took place within and beyond the framework of the overall objectives. The study suggests that evaluation methods based on objectives may be blind to important areas of learning and need to be combined with qualitative methods that examine a broad impact of learning. Taken together, the analysis of what and how the participants learned shows that they were better equipped to work as consultant on call and deal with the things they did not know.

Epidemiology and clinical features of PFAPA: a retrospective cohort study of 336 patients in western Sweden.

BACKGROUND: Periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA) syndrome is generally regarded as the most common autoinflammatory disease, but the epidemiology of the disease is largely unknown. The objectives of this study were to estimate the annual incidence and describe the clinical features of PFAPA in a large cohort from western Sweden. METHODS: The study retrospectively included children < 18 years of age diagnosed with PFAPA between 2006 and 2017 at three hospitals: NU Hospital Group, Skaraborg Hospital and Queen Silvia Children's Hospital. Patients were identified by searching for relevant diagnostic ICD-10 codes in the comprehensive electronic medical records and data were retrieved by reviewing case records. To estimate incidence, patients with symptom onset from January 1, 2006, to December 31, 2016, were included. Population data for the study area during this period were retrieved from Statistics Sweden. RESULTS: In this study, 336 patients with PFAPA were identified. Of these, 156 (46%) were girls and 180 (54%) were boys. Almost 90% of the children with PFAPA (291 patients) experienced their first symptoms before the age of 5 years and fewer than 3% presented at ages above 10 years. Pharyngitis was the most common symptom during febrile episodes, followed by cervical adenitis and aphthous stomatitis. Fourteen percent of the patients displayed atypical features, of which skin rash was the most common. To calculate incidence, 251 patients with symptom onset during the study period were identified. The mean annual incidence was estimated at 0.86/10,000 for children < 18 years of age and 2.6/10,000 for children < 5 years of age. CONCLUSIONS: This study adds to the understanding of the epidemiology of PFAPA syndrome by presenting incidence rates based on a large cohort and in different age groups in a population-based setting. It also shows the distribution of age of onset of PFAPA, with a peak in 1-year-olds and waning at older ages. Signs and symptoms of PFAPA syndrome were similar in children with symptom onset before vs. after 5 years of age.

Familial Mediterranean fever may mimic acute appendicitis in children.

Acute appendicitis is the most common surgical emergency in children. Diagnosis and management are often straightforward. However, familial Mediterranean fever is an important condition to consider in the assessment of children with acute abdominal pain, particularly in children with an origin in eastern Mediterranean basin where the disease is common. The key feature of familial Mediterranean fever is relapsing episodes of fever and serositis including peritonitis, pleurisy, or arthritis. The disease is treated with colchicine that prevents acute attacks, control subclinical inflammation between the attacks and the long-term complication of amyloidosis. The acute attacks may be a challenge to identify and distinguish from other causes of acute abdomen, including acute appendicitis, but also small bowel obstruction. Ultrasound and CT scan findings are nonspecific during acute attacks of familial Mediterranean fever, but imaging is useful to identify acute appendicitis and small bowel obstruction. The purpose of this article was to increase the awareness and knowledge of familial Mediterranean fever and provide support for the paediatric surgeon in the clinical care of these children in parts of the world where familial Mediterranean fever is rare.

Decreased Memory Bias via a Mobile Application: A Symptom Tracker to Monitor Children's Periodic Fever.

Memory bias, the tendency to rely on certain events over others, can become an issue in chronic illnesses, especially when symptoms are reported retrospectively. This paper examines a case where continuous symptom registration can be facilitated, memory supported, and memory bias reduced by introducing a mobile application. The aim of the paper is to report on the design of an app for collecting subjective data over an extended period to continuously follow children with periodic fever. The research approach is qualitative, building on interview data. The design method is co-design, a collaborative and participatory approach involving researchers, physicians and other key stakeholders, with focus on the views of the parents. We argue that collecting data continuously through an app moves the discussion from memory to the specific data points, which is illustrated through trends shown in the visualizations of the data. Moreover, we highlight the importance of systematically collecting data over an extended period through a data-driven approach to both forward clinical practice and research on complex, often chronic topics such as periodic fever, which is genuinely under-researched to date.

Strengthening paediatric competencies and educational skills among general paediatricians.

AIM: To develop a coherent programme that addresses the need for continuing professional development in general paediatrics and educational skills for senior paediatricians at outpatient clinics in Sweden today. METHODS: Educational needs in the target group were investigated using a questionnaire. Themes and sub-themes extracted from responses informed the curriculum formulation of the continuing professional development (CPD) programme, which was completed using a variety of learning, assessment and evaluation methods. RESULTS: Forty-six paediatricians identified 355 clinical situations. Competencies in general paediatrics and educational skills were incorporated in a CPD programme, implemented in western Sweden between 13 October 2016 and 23 May 2019, with 23 learning modules and 18 participants (male/female 3/15, median age 55 years). The participants' evaluation emphasised the importance of adult learning principles. Their responses to open reflective questions on 23 May 2109 suggested that the programme offered a learning environment in which they could develop their paediatric and educational practices and improve their mentorship, networks and work-based learning environment. They also described an enhanced feeling of joy at work. CONCLUSION: The involvement of experienced paediatricians in the programme formulation may be inspirational to clinicians and contribute to the definition, revitalisation and prioritisation of general paediatrics in Sweden in the future.

Integrating a pedagogic course in a CPD programme for paediatricians at out-patient clinics.

Equipping paediatricians for the challenges of the explosive development of knowledge and specialised health care calls for a well-planned continuing professional development (CPD) strategy which updates paediatric competencies and the pedagogic skills among paediatricians. The purpose of the study was to evaluate the effects of a pedagogic course, integrated into a CPD programme for paediatricians at out-patient clinics. The pedagogic course comprised three learning components, participation in a CPD programme, during two and a half years, a pedagogic learning module and a pedagogic assignment. The objectives of all the learning activities, including the pedagogic course, were developed according to adult learning theories. Evaluations were made using questionnaires. Seventeen paediatricians participated in the CPD programme; 13 of them completed the pedagogic learning module and six the full pedagogic course, including the pedagogic assignment - teaching at one's own clinic. Evaluation of the pedagogic assignment at the participants' own clinics by 64 co-workers revealed that the co-workers appreciated the training activities and would recommend them to a colleague. We conclude that it is possible to combine medical and pedagogic education in a CPD programme for paediatricians and that the participants were able to digest and apply the pedagogic principles used in the course.

[PFAPA syndrome - An important differential diagnosis in children with recurrent fever]. / PFAPA-syndrom ­ en viktig differential­diagnos hos barn med återkommande feberepisoder.

Periodic Fever, Aphthous Stomatitis, Pharyngitis and Cervical Adenitis (PFAPA) syndrome is the most common autoinflammatory disorder among children in many parts of the world and an important differential diagnosis in children presenting with recurrent fever episodes. Commonly, PFAPA has an onset under the age of 5 years. Fever episodes in PFAPA usually last 3-6 days and are associated with one or more of the cardinal symptoms aphthous stomatitis, pharyngitis and cervical adenitis. The fever episodes typically recur with an interval of 3-6 weeks, often with a striking regularity. During the episodes, the patient has elevated inflammatory variables such as CRP and serum amyloid A (SAA) and may sometimes have additional symptoms such as abdominal pain, nausea and leg pain. Between the fever episodes, the patient is typically free of symptoms with normalized inflammatory variables and grows normally. Awareness and recognition of PFAPA is key to providing the patient with adequate treatment and avoiding misdiagnosis.

An overview of how on-call consultant paediatricians can recognise and manage severe primary immunodeficiencies.

Severe primary paediatric immunodeficiency syndromes are rare and potentially fatal unless suspected, diagnosed and treated early. We provide clinical guidance and support for on-call consultant paediatricians working in secondary level hospitals on how to recognise and manage children with these conditions. Our paper addresses four conditions that risk the most severe outcomes if they are not adequately cared for during on-call periods, such as weekends: severe combined immunodeficiency, haemophagocytic lymphohistiocytosis, severe congenital neutropaenia and chronic granulomatous disease. CONCLUSION: On-call paediatricians are provided with advice on handling the most severe primary immunodeficiencies.

Fifteen-minute consultation: Recognising primary immune deficiencies in children.

Children with primary immunodeficiency syndromes present with broad variation of clinical features and the consequences are often severe if not promptly recognised. Here, support is provided for the general paediatrician to recognise primary immunodeficiencies among the many children they meet in their clinical practice.

Combining learning for educators and participants in a paediatric CPD programme.

BACKGROUND: Most continuing professional development (CPD) programmes do not include an educational training module. In our country, educational practice in the areas of CPD and continuing medical education relies traditionally on conventional lectures. This is in sharp contrast to the educational research that clearly demonstrates that educational programmes emphasising adult learning methods have greater potential to change physicians' clinical practice. To investigate whether lecture-oriented educators were prepared to change their educational practice towards principles of adult learning, we decided to combine learning for educators and participants in a paediatric CPD programme. The aim of the study was to investigate educators' reflections on their learning and educational practice after they have undergone an educational skills component integrated in the implementation of a CPD learning module for paediatricians and evaluate the results from the participants' perspective. METHODS: The objectives of the educational skills component of the learning module were developed according to adult learning theories. The learning objectives for the CPD learning module were based on a pre-course needs assessment. Evaluations were made using questionnaires. RESULTS: Seven of 10 participants in the educational skills component of the learning module and all the participants, 13 paediatricians and 14 nurses, who participated in the learning module, answered the questionnaires. The results of this pilot study show that educators whose main experience of teaching was based on lectures were strengthened in their practice; they defined their competence and were prepared to move towards adult learning principles. The participants in the learning module expressed a high degree of satisfaction. CONCLUSIONS: We conclude that it is feasible to combine learning for educators and participants in a paediatric CPD programme and that lecture-oriented educators are prepared to change their educational practice towards principles of adult learning.

Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis syndrome - PFAPA syndrome.

Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome is a complex autoinflammatory disease with a clinical phenotype characterised by recurrent episodes of fever, systemic inflammation and symptoms and signs depicted in disease acronym. Although PFAPA is the most common autoinflammatory disease among children in many parts of the world, the condition is still an enigma, which include the regular episodes, the prompt responses to corticosteroids, the genetic bases for the familial clustering and therapeutic effects of tonsillectomy. This review explores PFAPA syndrome with the aim of describing the current clinical and scientific understanding of the condition.

Using scenario-based training to promote information literacy among on-call consultant pediatricians.

BACKGROUND: Traditionally, teaching hospital staff to search for medical information relies heavily on educator-defined search methods. In contrast, the authors describe our experiences using real-time scenarios to teach on-call consultant pediatricians information literacy skills as part of a two-year continuing professional development program. CASE PRESENTATION: Two information-searching workshops were held at Sahlgrenska University Hospital in Gothenburg, Sweden. During the workshops, pediatricians were presented with medical scenarios that were closely related to their clinical practice. Participants were initially encouraged to solve the problems using their own preferred search methods, followed by group discussions led by clinical educators and a medical librarian in which search problems were identified and overcome. The workshops were evaluated using questionnaires to assess participant satisfaction and the extent to which participants intended to implement changes in their clinical practice and reported actual change. CONCLUSIONS: A scenario-based approach to teaching clinicians how to search for medical information is an attractive alternative to traditional lectures. The relevance of such an approach was supported by a high level of participant engagement during the workshops and high scores for participant satisfaction, intended changes to clinical practice, and reported benefits in actual clinical practice.

Toward an Inclusive, Congruent, and Precise Definition of Autoinflammatory Diseases.

Autoinflammatory disease was introduced as a concept in 1999, demarcating an entirely new group of diseases in clinical, immunological, and conceptual terms. During recent years, the preconditions for the definition of autoinflammatory conditions have changed. This includes the recent discovery of a number of monogenic autoinflammatory conditions with complex phenotypes that combine autoinflammation with defects of the adaptive and/or innate immune system, resulting in the occurrence of infection, autoimmunity, and/or uncontrolled hyperinflammation in addition to autoinflammation. Further, there are strong indications that classical IL-1-driven autoinflammatory diseases are associated with activation of adaptive immunity. As suggested by this development, we are of the opinion that an all-encompassing definition of autoinflammatory diseases should regard autoinflammatory conditions and innate dysregulation as inseparable and integral parts of the immune system as a whole. Hence, in this article, we try to advance the conceptual understanding of autoinflammatory disease by, proposing a modification of the definition by Daniel Kastner et al., which allows for a congruent and precise description of conditions that expand the immunological spectrum of autoinflammatory disease.

[Familial Mediterranean fever ­ an important disease in a globalised world]. / Familjär medelhavsfeber - viktig sjukdom i en globaliserad värld - Särskilt vanlig hos personer från östra Medelhavsområdet.

Familial Mediterranean fever - an important disease in a globalised world Familial Mediterranean fever (FMF) is characterized by recurrent febrile attacks during 1/2-3 days associated with peritonitis, pleuritis and arthritis. FMF is the most common monogenic autoinflammatory disease in the world, with over 100 000 affected individuals. It is particularly common in individuals with an origin in the eastern Mediterranean Basin, where the disease has a prevalence of 100-200 per 100 000. The gene for FMF (MEFV) was identified in 1997 with an autosomal recessive inheritance; however, a significant proportion (≈25%) of clinical patients lack two mutations. MEFV codes for the protein pyrin, whose exact function still needs to be defined. The most serious complication of FMF is amyloid A amyloidosis, in particular renal amyloidosis. FMF is efficiently treated with daily doses of colchicine resulting in an almost normal life expectancy and amyloidosis confined to non-compliant patients. In today's globalized world we need to adapt to a new context that includes inherited conditions, which have historically been uncommon in our part of the world. One of these conditions is FMF, that should primarily be suspected in individuals with an origin in the eastern Mediterranean Basin and recurrent attacks of fever.

Review of autoinflammatory diseases, with a special focus on periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis syndrome.

UNLABELLED: There have been remarkable developments in the field of autoinflammatory diseases over the last 20 years. Research has led to definitions of new conditions, increased understanding of disease mechanisms and specific treatment. The polygenic autoinflammatory condition of periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA) is the most common autoinflammatory disorder among children in many parts of the world. The clinical features often include clockwork regularity of episodes, prompt responses to corticosteroids and therapeutic effects of tonsillectomy, but the disease mechanisms are largely unknown. CONCLUSION: This review discusses the emerging understanding of autoinflammatory diseases, with special emphasis on PFAPA.

Neutrophils from patients with SAPHO syndrome show no signs of aberrant NADPH oxidase-dependent production of intracellular reactive oxygen species.

OBJECTIVE: We aimed to investigate if aberrant intracellular production of NADPH oxidase-derived reactive oxygen species (ROS) in neutrophils is a disease mechanism in the autoinflammatory disease SAPHO syndrome, characterized by synovitis, acne, pustulosis, hyperostosis and osteitis, as has previously been suggested based on a family with SAPHO syndrome-like disease. METHODS: Neutrophil function was explored in a cohort of four patients with SAPHO syndrome, two of whom were sampled during both inflammatory and non-inflammatory phase. Intracellular neutrophil ROS production was determined by luminol-amplified chemiluminescence in response to phorbol myristate acetate. RESULTS: Cells from all patients produced normal amounts of ROS, both intra- and extracellularly, when compared with internal controls as well as with a large collection of healthy controls assayed in the laboratory over time (showing an extensive inter-personal variability in a normal population). Further, intracellular production of ROS increased during the inflammatory phase. Neutrophil activation markers were comparable between patients and controls. CONCLUSION: Dysfunctional generation of intracellular ROS in neutrophils is not a generalizable feature in SAPHO syndrome. Secondly, serum amyloid A appears to be a more sensitive inflammatory marker than CRP during improvement and relapses in SAPHO syndrome.

[On call education for paediatricians may improve patient safety. Continuing professional development project in western Sweden evaluated]. / Bakjoursutbildning för barnläkare kan stärka patientsäkerheten - Fortbildningsprojekt utvärderas i Västra Götalandsregionen.

As part of a mandate to provide continuing professional development (CPD) for paediatricians in western Sweden and to support patient safety, we have addressed the professional demands which are imposed on today's consultant paediatricians on call, by designing and implementing a CPD programme for this group. Learning objectives for specific learning modules were developed from a pre-course needs assessment among consultants. The implemented programme included a variety of learning, assessment and evaluation methods. Each specific learning module began with a reading assignment exploring the key concept. This prepared the participants for the case discussion, in which they would analyse, reflect and achieve a deeper level of understanding. We believe that the educational methods used and the approach of the programme are applicable to specialist training as well as to CPD programmes in general, as part of a lifelong learning process.