Exploring pediatric onset Still’s disease patient journey and parental perceptions in Türkiye through a survey

Abstract

AbstractSection Objective

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This survey-based study aimed to explore the journey to the diagnosis and management of children with pediatric onset Still’s disease (PoSD) in Türkiye. This sought to understand parents’ perceptions, feelings, and expectations, enabling the identification of unmet needs and fostering improvements in PoSD care.

AbstractSection Methods

A 42-question survey was administered to patients (< 21 years) with PoSD or their parents (the primary caregiver of each child younger than middle school age) by pediatric rheumatologists, during their clinic visits between January and May 2024. Data were descriptively analyzed.

AbstractSection Results

The study included 39 children (mean age: 9.92 ± 4.93 years; 66.7% female). Ten children and 29 parents completed the survey. Persistent fever (84.6%), swollen joints and rash (64.1% each) were the most common initial manifestations. No patient received the diagnosis of PoSD at their initial visit: two-thirds were referred to other physicians and one-third were misdiagnosed, primarily with other inflammatory conditions (15.4%) and infections (12.8%). The median diagnostic delay was 1 (1–4) months. At the time of the survey, 21 patients (53.8%) had been receiving biologics (monthly (n = 10), bimonthly or weekly (n = 5, each) injections); 19 patients were compliant with this treatment. Seven patients (17.9%) had used biologics in past. PoSD substantially affected psychological well-being (33.3%) and daily tasks (13%). Fifteen of 26 school-age children missed school for a mean of 17.7 ± 15.9 days/year due to PoSD. Most parents (90%) had not heard of PoSD at the time of diagnosis. Overall, 28% of parents hardly accepted the diagnosis. PoSD worsening in the future was their main concern (68.9%). The parents’/patients’ primary expectation was to achieve a cure (82.1%). The main sources of information for parents were the physicians treating their children (96.6%), internet (72.4%) and other patient relatives (20.7%).

AbstractSection Conclusion

This survey of the PoSD patient journey in Türkiye identified several areas of improvement for better disease management. It underscores the need for enhanced continuous medical education for physicians and parental awareness of PoSD, higher access to credible information resources, and greater parental engagement in activities organized by pediatric rheumatology associations. Collecting quantitative and qualitative data on various aspects of PoSD could further refine approaches to optimize patient care.

Introduction

Pediatric onset Still's disease (PoSD) is a rare rheumatological disease characterized by the presence of systemic manifestations that may precede or accompany articular involvement. Daily spiking fever and a transient, erythematous rash are the most common systemic findings of PoSD. Less common manifestations of the disease include hepatosplenomegaly, lymphadenopathy, and serositis [1]. The heterogeneous clinical manifestations of PoSD usually make an accurate diagnosis challenging, especially in the absence of arthritis at initial presentation. A number of infectious, malignant and autoimmune diseases should be ruled out to establish a definitive diagnosis of PoSD), often leading to a delay in diagnosis and initiation of treatment [2, 3].

A comprehensive understanding of patients’ and their families’ experiences throughout their healthcare journey is crucial for identifying and resolving the challenges they may face during diagnosis, treatment and follow-up. This is of particular importance in the context of rare diseases, given the lack of knowledge and experience among healthcare providers in such conditions [4]. Given the rarity of PoSD, healthcare providers may have limited exposure to this condition, which can complicate the diagnostic process [4, 5]. Few studies have provided data on patient pathways in PoSD, focusing primarily on the diagnosis stage [5,6,7,8].

The objective of this survey-based study is to gain insight into the journey to the diagnosis and management of children with PoSD in Türkiye and to understand their parents’ perceptions, feelings and expectations. This will enable the identification of unmet needs, which will inform future improvements in PoSD care with the goal of achieving better outcomes.

Methods

Study population and definitions

A quantitative 42-question online survey that was made available to physicians via the website of the Pediatric Rheumatologist’s Association was administered by pediatric rheumatologists to patients with PoSD or their parent during their visits to clinics. The physicians read the questions and marked the answers from the patients or their parent (primary caregiver only; if child ≤ middle school age [10 years]) in the online survey database.

The study was conducted between January and May 2024. Individuals aged >6 months to < 21 years and diagnosed with PoSD on the basis of the International League of Associations for Rheumatology (ILAR) classification criteria were included in the study [1]. All study participants were native Turkish speakers. The patients and/or their parent (the primary caregiver) were required to provide informed consent prior to data collection. The exclusion criteria were as follows: (1) patients not meeting the ILAR classification criteria for PoSD; (2) nonnative Turkish speakers or those unable to adequately comprehend the questionnaire; and (3) patients or caregivers who declined to provide informed consent. Figure 1 shows the study flowchart.

Fig. 1

Study flowchart

The survey collected information on key patient demographics (age, sex, educational/working status), the diagnostic process (initial manifestations, laboratory PoSD treatment. The survey also investigated primary caregiver’s perceptions and emotions at the time of diagnosis, the information sources they consulted, and their future expectations. Furthermore, the respondents were asked to rate the impact of PoSD on patients’ lives on an 11-point numerical scale where 0 represented no impact and 10 represented severe impact. The scores were categorized as mild impact (0 − 3), moderate impact (4 − 7) or significant impact (8 − 10).

Statistical analysis

The IBM SPSS 21.0 program was used for the statistical analyses (SPSS Inc., Chicago, IL, USA). The Kolmogorov‒Smirnov test and/or Shapiro‒Wilk test were used to determine the distribution of the variables. Categorical variables are presented as numbers (percentages). Continuous variables with a normal distribution are presented as the mean ± standard deviation (SD), and nonnormally distributed data are reported as the median (minimum‒maximum).

Results

Ten patients and 29 parents completed the survey, providing data on a total of 39 patients with PoSD residing in 13 cities in Türkiye. The mean age was 9.92 ± 4.93 years, and 66.7% of the patients were female. Table 1 presents the characteristics of the study population.

Table 1 Characteristics of the pediatric onset Still’s disease patients in the study (N = 39)

Diagnostic journey

The primary reason for seeking medical attention was persistent fever (n = 33; 84.6%), followed by swollen joints and rash (n = 25; 64.1% each) (Table 1). The joints that were most commonly affected at initial presentation were the knees (n = 17; 68%) and ankles (n = 13; 52%).

Most of the patients (n = 22; 56.4%) initially sought care from pediatricians for their symptoms. The remainder were first seen by emergency physicians (n = 11; 28.2%), family physicians (n = 4; 10.3%), dermatology and gastroenterology specialists (n = 1; 2.6% each). The most common initial investigations used in the diagnostic process were blood tests (n = 35; 90%) and X-rays (n = 16; 41%). None of the patients were diagnosed with PoSD by the physicians who initially assessed them. While two-thirds of patients (n = 26; 66.7%) were referred to other physicians for further assessment, the remaining 13 children (33.3%) were misdiagnosed, most frequently with other inflammatory conditions (n = 7; 15.4%) and infections (n = 5; 12.8%) (Fig. 2).

Fig. 2

Diagnosis at initial clinical evaluation (n = 39)

The median diagnostic delay was 1 (1–4) month. Information about the diagnosing physician was available for 13 patients. While pediatric rheumatologists diagnosed PoSD in 77% of the patients (n = 10), two patients were diagnosed by pediatricians (15%), and one patient was prediagnosed by an emergency physician (8%). Following the diagnosis of PoSD, nine patients (23.1%) contacted an average of three physicians to confirm the diagnosis.

Treatment experience

Most of the study subjects (n = 33; 84.6%) were followed by the physician, who had diagnosed PoSD. The median number of visits was 5 (1 − 12) per year.

At the time of the survey, 21 patients (53.8%) were using biologics, which they started on a median of 1 (1–22) months after the diagnosis of PoSD. The second most frequently used group of medications was conventional disease-modifying antirheumatic drugs (DMARDs) (n = 8; 20.5%). Corticosteroids were mainly used (6/7; 85.7%) as an adjunct to biologics or conventional DMARDs. Seven (17.9%) patients had a history of prior biologic use, which was discontinued at the discretion of their treating physicians because the disease was under control. A total of 25.6% of patients (n = 10) were not receiving any treatment at the time of the survey.

Among the 21 current biologic agent users, 10 (47.6%) were on monthly formulations. Bimonthly and weekly formulations were each used by 24% (n = 5) of the study population. Approximately half of the patients (10/21; 47.6%) were receiving biologics at the clinics where they were followed up for PoSD, and 6 patients (6/21; 28.6%) were treated at home. Other healthcare facilities utilized for the administration of biologic agents included primary care centers (4/21; 19%) and private hospitals (1/21; 4.8%).

While 90.5% (19/21) of patients who were receiving biologics were compliant with the treatment, two patients reported nonadherence due to concerns about potential drug side effects and low symptom severity. Treatment interruption was reported by 19% (4/21) of patients on biologics; physician discretion (n = 2), patient decision (n = 1), and difficulty accessing the product (n = 1) were the reasons for interruption.

Impact of pediatric onset Still’s disease on patients’ lives

Pediatric onset Still’s disease had the greatest negative impact on patients’ psychological well-being, followed by their educational and social lives, with mean scores of 5.64, 4.51 and 4.00 out of 10.00, respectively. While one-third of patients (33%; n = 13) reported a substantial negative impact on psychological functioning, 13% (n = 5) noted significant difficulty in performing daily tasks (Fig. 3).

Fig. 3

Impact of pediatric onset Still’s disease on various aspects of life. Note: Evaluated based on a 11-point Likert scale, ranging from 0 (no impact) to 10 (the highest impact)

Overall, 26 participants were of school age and were attending school at the time of the survey. Fifteen of these subjects (57.7%) lost a total of 266 school days due to PoSD in the past year, with an average of 17.7 ± 15.9 missed school days per year.

Fatigue and pain were the symptoms with the greatest impact on patients’ daily activities, experienced by 66.6% (n = 26) and 56.4% (n = 22) of the study subjects, respectively.

Parents’ perceptions and feelings at the time of diagnosis

The primary caregivers of the participating patients (n = 29) provided insight into their perceptions and feelings following the diagnosis of PoSD in their children. The most prevalent negative emotions experienced by parents at the time of PoSD diagnosis in their children were concerns about their disease becoming worse in the future (n = 20; 68.9%) and fear (n = 17; 58.6%). Nevertheless, almost two-thirds were optimistic that the disease could be overcome with adequate treatment (n = 20; 68.9%). A total of 28% of parents found it hard to accept the diagnosis, and 14% sought a second opinion (Fig. 4).

Fig. 4

Parents’ beliefs and feelings at the time of diagnosis (n = 29). Note: Responses from the primary caregivers of participants ≤ 10 years old (n = 29). Percentages are calculated based on this number. **Personal comment

The primary expectation of the study participants (parents and patients) was to achieve a cure for PoSD (n = 32; 82.1%), followed by the availability of treatment options with minimal or no side effects (n = 3; 7.7%) (Fig. 5).

Fig. 5

Parents’ and patients’ expectations (n = 39). Note: Responses from 10 children and 29 primary caregivers who completed the questionnaire. Percentages are calculated based on the total number of patients. Abbreviations: PoSD Pediatric onset Still’s disease; SE side effect

Most parents (90%) had not heard of PoSD until their children were diagnosed with the disease. The primary sources of information for parents were the physicians treating their children (96.6%), followed by the internet (72.4%) and other patient relatives (20.7%) (Fig. 6). Nevertheless, 67% of parents were unable to recall any specific social media accounts or websites that were pertinent to PoSD. There was only one parent who followed the Turkish Society for Rheumatology and the rheumatology patient groups.

Fig. 6

Parents’ sources of information about pediatric onset Still’s disease (n = 29). Note: Responses from the primary caregivers of participants ≤ 10 years old (n = 29). Percentages are calculated based on this number

Discussion

This survey-based study revealed a considerable delay in the diagnosis of PoSD and highlighted the disease’s negative impact on various aspects of life, including psychosocial wellbeing and educational and social activities. To the best of our knowledge, this is the first study to examine the experiences of patients with PoSD from diagnosis to follow-up, as well as their parents’ perceptions, emotions, and expectations regarding the management and outcomes of the disease in Türkiye.

Although PoSD is recognized as a disease affecting both sexes equally, real-world data from various countries suggest variability across studies and populations. The percentage of female patients varies between 30.8% and 71.7% in real-life studies from abroad [5,6,7,8,9,10,11,12,13]. While females constituted 44% to 60% of patients with PoSD in most of the recent studies from Türkiye [14,15,16,17,18,19,20,21], we found a greater female predominance (68%) in the present study. A small-size study of 18 patients with PoSD from Türkiye reported a male predominance unlike other real-world studies [22].

The age at diagnosis of PoSD patients varies across studies, with a median value ranging from 4.5 to 7.3 years [7, 11,12,13, 20,21,22]. The mean age at diagnosis in the current study, which was approximately six years, was higher than the median values reported in several earlier real-world studies [7, 11, 12, 19, 20, 22]. This is most likely caused by differences in age distributions across the studies and the presence of outliers but did not indicate a significant delay in diagnosis, as the median time from the onset of symptoms to the diagnosis of PoSD was one month, which is consistent with previously published data from abroad and Türkiye [5, 6, 8, 9, 19, 22]. Nevertheless, our findings concerning misdiagnosis rates and referral patterns indicate that there is still scope for improvement in achieving an earlier diagnosis of PoSD.

The initial healthcare provider consulted by patients presenting with symptoms associated with PoSD may vary depending on the clinical manifestations at disease onset and the existing healthcare system in the country. Unlike a real-world study from France, where most patients (56%) with PoSD were initially seen by general practitioners (GPs) [5], our patients mostly visited pediatricians for their symptoms. The dissimilarity can be attributed to the fact that in Türkiye, there is no obligation for patients to visit a GP or a family physician prior to being referred to a specialist. Notably, physicians from different specialties, including emergency and family medicine, dermatology and gastroenterology, evaluated our patients at the onset of their symptoms. The heterogeneity of early manifestations of the disease, which results in patients consulting physicians specialized in areas other than rheumatology seems to be a major obstacle leading to a misdiagnosis and delay in initiating appropriate treatment for PoSD. In our study, one-third of patients were treated for other inflammatory, infective or allergic conditions prior to receiving a diagnosis of PoSD and the remaining two-third were referred to other physicians. This shows that ensuring physicians are well-informed about the early signs and symptoms of PoSD is essential during undergraduate medical education and in continuing postgraduate training, so that this rare disease is considered a potential diagnosis, particularly in patients with fever of unknown origin. Lower awareness of rheumatology as a medical speciality among the Turkish population is also a major contributor to a delay in diagnosis.

In the present study, none of the patients were initially seen by pediatric rheumatologists. There are approximately 90 pediatric rheumatologists across Türkiye, indicating a higher number of pediatric rheumatologists per pediatric population (0.41 per 100,000 children in 2024) than in countries like Canada [23] and the United States where the median clinical full-time equivalent (cFTE) of pediatric rheumatologists were 0.2 (IQR 0.3) per 75,000 children in 2019 and 0.27 per 100,000 in 2020 [24], respectively. However, patients can experience difficulties in reaching pediatric rheumatologists who work primarily in major urban cities in Türkiye.

Owing to the rarity of PoSD, many physicians may not encounter patients with this condition during their practice and therefore may not consider it in the differential diagnosis process in patients with nonspecific systemic signs and symptoms, especially fever of unknown origin. In line with previously published real-world data [5, 18, 20], a notable proportion of patients in the present study did not present with articular involvement at the onset of PoSD. Among the 13 patients who were initially misdiagnosed, five did not report painful or swollen joints as a presenting symptom. A recent survey from China reported that complex clinical manifestations, a lack of specific diagnostic tests, and challenges in differential diagnosis were among the primary issues that physicians experienced during the PoSD diagnostic process [3]. It is crucial to enhance the knowledge and awareness of PoSD, particularly among pediatricians, emergency physicians, GPs and family physicians, to achieve timely and accurate diagnosis and treatment initiation. In recent years, there has been a proposal to revert to the original designation of Still’s disease instead of systemic juvenile idiopathic arthritis (SJIA). This is the rationale that the term ‘arthritis’, as currently employed in the nomenclature of the disease, may result in erroneous exclusion of the diagnosis of PoSD in patients who do not initially manifest arthritis [25]. Furthermore, in November 2024, the European Alliance of Associations for Rheumatology/ Paediatric Rheumatology European Society (EULAR/PReS) published a series of recommendations aimed at improving the diagnosis and management of PoSD, highlighting that overt arthritis is only supportive and not a necessary criterion for diagnosing PoSD [26].

Although major disparities in access to effective treatment options may be reduced in Türkiye due to the broad coverage of DMARDs and biologics by the national health insurance system without co-payment, variations in prescribing preferences among physicians, clinical experience, and patient-specific factors may still influence treatment selection and outcomes. In Türkiye, biologics are approved as second-line treatment options for PoSD in patients with inadequate response to corticosteroids and nonsteroidal anti-inflammatory drugs. Despite that the introduction of biologic treatments to the Turkish market is relatively recent compared to Western markets, several recent local studies have demonstrated that biologics have been increasingly utilized in clinical practice for the treatment of PoSD, with the objective of rapidly improving the disease activity and reducing the adverse effects associated with corticosteroid exposure [16,17,18,19]. In a 24-month retrospective study of 147 children with PoSD from Türkiye, which assessed the outcomes with biologic therapy between March 2013 and December 2018, the mean age at the initiation of biologic therapy was 8 years, which was almost 4 years after the onset of disease [16]. In the present study, the time from diagnosis to initiation of biologic therapy was only four months. Accumulating scientific evidence on the long-term safety and effectiveness of anti-interleukin (IL)-1 and anti-IL-6 therapies in PoSD might have led to earlier use of biologics in PoSD over time. The First-line Options for SJIA Treatment (FROST) study [10], which compared the effectiveness of the PoSD consensus treatment plans employed in research using the Childhood Arthritis and Rheumatology Research Alliance (CARRA) registry [27], confirmed the beneficial effects of early initiation of biologic therapy on the basis of the low rates of glucocorticosteroid use within the first month of biologic therapy and the high rates of achieving clinically inactive disease in more than half of the patients within nine months despite not receiving corticosteroids [10]. Few studies evaluated the impact of PoSD and treatment approaches on long-term disease outcomes in Türkiye. In a retrospective study of 168 patients treated for PoSD between 2003 and 2017, macrophage activation syndrome (MAS) was present in 11.9% of patients, three of whom (1.8%) died due to secondary multiorgan insufficiency and infection [19]. Growth retardation and low bone mineral density were also reported in 11.3% and 8% (4 out of 50) of patients, respectively, in that study [19]. Other studies have also pointed out the reduced risk of osteoporosis and growth retardation with biologic therapy due to limited corticosteroid exposure [17, 18]. A retrospective review of medical records of patients treated for PoSD in a tertiary referral rheumatology clinic in Türkiye between 2010 and 2017, showed that 36% of 75 patients experienced at least one MAS attack during their follow-up [14]. In a more recent 24-month retrospective study that evaluated the effectiveness of biologics in PoSD, a rapid improvement in inflammatory markers and a prompt decline in the number of active joints and of patients who experienced macrophage activating syndrome (MAS) was observed after initiation of biologics [16]. Overall, these findings support the beneficial effects of an earlier initiation of biologics in PoSD. There is no data concerning the impact of delays in PoSD diagnosis on long-term outcomes, which deserves to be investigated in future studies.

In contrast to the findings of Shenoi et al. [28], who reported that PoSD had a greater impact on physical activities than on the psychosocial life of affected children, our study revealed that PoSD had a moderate negative impact on the psychological, educational and social lives of children. This discrepancy may be attributed to variations in the severity of the disease, which was not examined in this study, or to sociocultural influences that may influence feelings, attitudes, and emotions.

Given that Türkiye has approximately 180 school days (36 school weeks) per year for primary and secondary education, we report a 10% annual loss of school days (approximately 18 days equivalent to 3.5 school weeks/year) among our participants who were in school, which is comparable to that reported in an international survey and retrospective chart review-based study of the burden of PoSD [28].

In the present study, most parents were unaware of PoSD prior to their children being diagnosed with the disease. This highlights the importance of supplying parents with reliable sources of information. Pediatric rheumatologists should provide parents with all necessary information about the disease, encourage them to ask any questions they may have, and agree with them on the treatment plans. Digital tools were also common sources used by parents seeking information about PoSD. Nevertheless, more than two-thirds of parents were unable to recall any website or social media platform that specifically addressed PoSD. It is important to understand the reasons for this, as digital tools are an effective means of reaching large populations, which may facilitate the dissemination of accurate and standardized information to patients and their caregivers, as well as increasing awareness among the public.

Modica et al. [29] reported that the social media use of parents of children with PoSD changed during the diagnostic journey and that an increase in the frequency of Facebook posts and visits to disease-specific websites was observed following diagnosis. It is therefore important to consider the quality of the information provided and the appropriateness of the reading level [30]. Referring parents to digital platforms where they can access up-to-date, credible information could reduce their anxiety, particularly in the period following diagnosis. A randomized controlled study conducted in England involving parents of children recently diagnosed with juvenile idiopathic arthritis (JIA) demonstrated that a web-based intervention comprising information about the disease and its treatment and a cognitive behavioral therapy toolkit to assist in coping with JIA was effective in reducing illness-related parental stress [31].

In the current study, fear, cautious optimism, which includes both hope and worry about the future, and denial of the disease were the key emotions that parents experienced upon the diagnosis of PoSD in their children. Although sociocultural contexts are important determinants of the expression of feelings, a study from Canada that evaluated the emotional journeys of parents with children with JIA reported a similar emotional pattern of mixed emotions, which included shock, disbelief, fear, denial, sorrow, hope, regret and anxiety [32].

Limitations

This study has several limitations. As a limitation inherent to the study, parent- or patient-reported data can be subject to recall bias, particularly in cases where patients were diagnosed with PoSD a long time ago. Although the investigators were instructed to enroll all consecutive eligible patients with PoSD who attended the clinic during the study period, a selection bias might have occurred due to patients or their relatives who declined to participate in the study. The study did not consider the severity of disease as we were primarily focused on the diagnostic journey. But we acknowledge that severity of initial signs and symptoms may prompt the diagnosis and need to be investigated in future studies. In view of the potential impact on patient journeys as well as parental experiences and perceptions, assessment of the influence of parental demographics such as educational level, income status, and residential place on survey responses will also be beneficial in forthcoming studies. The incorporation of a comprehensive qualitative element within the study questionnaire could have facilitated the acquisition of more profound insights into patients’ perceptions, as well as the contextual factors that informed their responses. Indeed, several qualitative studies conducted in adolescents with JIA have enhanced the value of questionnaire-based research in pediatric rheumatology by offering insights into various aspects of JIA, particularly relevant to patients [33,34,35]. We acknowledge that incorporating a qualitative component in future research could enrich the interpretation of results and enhance the patient-centeredness of the tool. Considering that a Delphi panel of pediatric rheumatologists estimated that the number of new cases of PoSD was 55 per year in Türkiye [36], this 39-patient study, which collected data primarily from Western Türkiye may not be representative of the entire country, causing a sampling bias. Nevertheless, this survey-based study can provide a basis for future large-scale studies that will identify regional differences in PoSD diagnosis and management, as well as in parents’ and patients’ perceptions.

Conclusion

This study, which was the first of its kind to collect data on PoSD patient journeys in Türkiye, highlighted several key points that require attention for more effective disease management. Physicians must be well informed about the signs and symptoms of PoSD, ensuring that this rare disease is considered a potential diagnosis, particularly in patients with fever of unknown origin. This should be a priority in the context of continuous medical education. Given parents’ limited knowledge of PoSD, pediatric rheumatologists should provide them with pertinent information about this disease in comprehensible language following the diagnosis. This can serve to alleviate their concerns and enable them to become responsible, well-informed partners of healthcare professionals in the management of their children’s healthcare. Furthermore, improving the utilization of credible information sources and engaging parents in the activities of patient associations are vital.