PERSPECTIVES OPINION

The coming of age of adolescent rheumatology Despina Eleftheriou, David A. Isenberg, Lucy R. Wedderburn and Yiannis Ioannou Abstract | The goal of planned adolescent health-care transition procedures is to optimize functioning and well-being for all young people, including those who have special health-care needs. In this regard, the transitioning of young people with childhood-onset rheumatic diseases to adult health care is increasingly important, particularly as many of these patients might continue to have active disease or considerable sequelae well into their adult lives. Key components of a successful plan for health-care transition include encouragement of patient self-advocacy, tailoring of the process to each individuals’ needs, family adaptation, and readiness and training of relevant health-care providers. Improving outcomes in patients with serious rheumatic diseases presenting in adolescence will be achieved by increasing our understanding of the aetiopathogenesis of these disorders, identifying accurate predictors of the development and/or course of disease and better defining long-term outcomes. In this article, we discuss transitional health-care models, as well as the benefits and challenges of providing transitional care to adolescents with rheumatic diseases. We also highlight the need to ensure that research is integral to transitional care pathways. Eleftheriou, D. et al. Nat. Rev. Rheumatol. 10, 187–193 (2014); published online 7 January 2014; doi:10.1038/nrrheum.2013.202

Introduction Young people (aged 10–24  years) now account for nearly half of the population worldwide, representing the largest generation of adolescents that has existed throughout history. 1 Thus, in the past decade, increasing emphasis has been placed on the particular health needs of teenagers and young people, putting adolescents at the centre of global health policies.1,2 In 2007, the UK Chief Medical Officer’s report 3 recog­nized that the effects of poor health during the teenage years can last a lifetime and that keeping adolescents healthy is a valu­able investment to ensure the future of the nation. Young people entering adoles­cence demonstrate distinct sets of behaviours, capa­cities, resources and vulnerabilities, which might complicate transi­tions in family, peer and educational domains, as well as in health behaviours.4 These transitions can all modify the childhood passage towards health and wellbeing, and are Competing interests The authors declare no competing interests.

influenced by societal norms and economic factors that change over the generations and vary between countries.2,4,5 The biological transition from adolescence to adulthood is a normal aspect of ageing; however, considerable uncertainty often exists regarding the optimal ways for health-care providers to support this transition, particularly in those with chronic health problems.6,7 Advances made in the field of rheumatology over the past decade, in particular, have led to substantial decreases in long-term morbidity and mortality rates.8,9 Paediatric patients with rheumatic diseases now frequently survive into adulthood, and therefore often have to face the many challenges imposed by ongoing chronic illness. 10–12 Furthermore, unmet needs of adolescents with chronic rheumatic diseases and gaps in the care of this patient group, particularly at transfer to adult health-care provision, are still reported, despite the solid evidence base supporting the need for, the practical approaches to, and the positive outcomes of planned and individualized

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transitional care.7,13,14 In a commissioned UK Department of Health review of this topic, Kennedy 15 highlighted some of the problems underlying these issues, stating that “a main cultural obstacle for young people is the lack of recognition of them as distinctly different to children as well as adults”, and that adolescents represent “a forgotten group, caught between child and adult, and therefore the bureaucratic bar­ riers and professional spheres of influence”. Another important aspect complicating the implementation of health-care transition programmes is the lack of research into how patients in the adolescent age group and their developmental milestones should be evaluated. Moreover, the ability to study adolescents and young adults with chronic diseases at clinical and basic science levels is necessary to better understand these conditions and increase the prospects of ­optimizing treatment and outcomes. In this article, we discuss the principles and challenges of providing tailored, adolescent-­friendly transitional health-care services for young people with rheumatic diseases; existing transition models and barriers to implementation of transition services are outlined. We also highlight the need for development of a research agenda aimed at optimizing clinical care and outcomes focused specifically on this age group.

Adolescents as a unique group The WHO defines adolescence as the period of life between the ages of 10 and 19 years.16 This interval represents a critical and unique period of growth and development between childhood and adulthood, when biological, psychological and social changes occur at a tremendous pace;17 in addition to sexual and physical maturation during this time, individuals acquire the skills needed to engage in adult relation­ ships, carry out responsible roles in society, develop the capacity for abstract reasoning and generally become more independent. 17 Neurocognitive development during adolescence is important and, in particular, involves the prefrontal region of the brain, where ‘executive’ functions such as abstract and long-term reasoning are co­ordinated.18,19 These changes are not fully established until after the second VOLUME 10  |  MARCH 2014  |  187

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PERSPECTIVES decade of life, whereas the brain centres responsible for impulsive and rewardseeking behaviours are fully developed by early-adolescence.20 This developmental pattern therefore results in a ‘neuro­ cognitive’ disconnect during adolescence that renders young people vulnerable to impulsive and reward-seeking behaviour and susceptible to peer pressure.20,21 Thus, adolescence is not only a peak period of physical development, but is also a time of considerable vulnerability.

Rheumatic disease in adolescence Long-term outcomes The burden of musculoskeletal disease continues to increase throughout childhood and adolescence, with approximately 70% of all patients with JIA not achiev­ing treatment free remission within 10 years of diagnosis.22,23 Further­more, auto­immune and autoinflammatory diseases of childhood or adolescent onset are increasingly recognized to have major health con­sequences that affect mental health, education, and social and family life through­out the teen­ age years and well into adulthood. 23,24 Examples of such disorders include juvenile idiopathic arthritis (JIA), inflammatory myositis (juve­nile dermatomyositis [JDM]), juv­enile systemic lupus erythematosus (JSLE) and juvenile-onset vasculitis, as well as systemic sclerosis, autoinflammatory syndromes, chronic pain and noninflammatory conditions. For example, depression is more common in adolescents with arthritis, and although educational outcomes in young adults with JIA are similar to those of the general population, the rate of employment among patients with JIA are lower than expected, mostly due to disease-­associated reduced physical functioning.23 The propor­tion of inflammatory disease cases that onset during adolescence is substantial: around 15–20% of all patients with SLE develop the disease before the age of 16 years and the median age of onset of JSLE is around 12 years, roughly coincident with puberty;25 in addition, one-third of patients present with JIA during adolescence.26 Interestingly, Packham et al.10,11,27,28 examined the long-term outcomes of a large, well-documented cohort of adults with JIA (n = 246; mean age of 35.4 years) and found that a considerable proportion of these patients continued to have persisting pain, with only 7% of adults with JIA being pain free; 27 functional dis­ability, 10 mood dis­turbances11,27 and unemployment 28 were also common in this cohort. In this 188  |  MARCH 2014  |  VOLUME 10

cohort of older adults with JIA,10,11,27,28 a key predictor of pain was depression during young adult years (15–25 years). In keeping with these findings, Foster et al.12 reviewed 16 studies of disease outcomes in JIA and showed that about one-third of patients had disease-related disability and a substantial proportion (10–45%) had persistent disease activity long into their adult lives. With the advent of biologic therapies leading to more effective control of disease during adolescence, additional studies are now needed to establish how these agents have affected long-term outcomes in patients with JIA and rheumatic diseases presenting in young people. Nevertheless, the findings discussed above support the need for effective health-care transition procedures to ensure adequate treatment and support of young patients during what seems to be an important period with regard to the ­long-term o­utcomes of chronic disease.

Influence of adolescence on disease Adolescence is a time of pubertal maturation controlled largely by complex inter­ actions between the brain, the pituitary gland and the gonads, which in turn are influenced by environment factors (that is, social, cultural and ambient influences).18 As a result of the activation of hormones controlling physical development, most children undergo a growth spurt, develop primary and secondary gender characteristics, and become fertile during early adolescence. Interestingly, a number of studies have suggested that immunological responses and steroid sex hormones are linked at physio­ logical and cellular levels.29 For instance, T cells and macrophages express intra­ cellular and extracellular receptors for oes­ tro­gens and androgens, implying that such hormones could have direct effects on the immune system.30 In fact, oestrogen (speci­ fically 17β-oestradiol [E2]) has effects on T‑cell immunity, causing fluctuations in the activity of cytotoxic T lymphocytes (CTLs) in the human endometrium during the menstrual cycle;31 CTL activity is high­ est in the pre-ovulatory phase and reduces in the post-ovulatory phase.31 Androgens secreted at higher levels during male and female puberty might also influence immune responses.32 Testosterone might, for instance, suppress the stress response to infection. Evidence supporting this effect comes from observations that adrenal and immune corticosterone responses to endotoxin are inhibited by testosterone in animal models.33 Furthermore, in a study in adults,34



psychological stress has been associated with a reduction in gluco­corticoid sensitivity and a propensity for worsening rhinovirus infection. Anecdotal experiences indicate that flares in disease activity in adolescents with an auto­i mmune rheumatic disease also tend to occur coincident with stressful experiences, such as exams or leaving home, and non-adherence to therapy is not always a clear cause of these flares. How­ ever, whether the presence of psychological stress is associated with changes within the innate and adaptive immune response and gluco­corticoid sensitivity in adolescents with rheumatic disease, and there­ fore accounts for increased disease severity in patients within this age group, currently remains unclear. This possibility warrants further study. Several childhood-onset rheumatic dis­ ease have different incidence, prevalence or clinical phenotypes in teenagers compared with cases in pre-adolescent children or adults.13,23,25 For example, genetic risk conferred by specific HLA alleles varies consider­ably with age of disease onset in JIA (now confirmed by complete haplotype analysis), and age of disease onset is a key factor that contributes to variations in gene expression and clinical course in this disease.35 These findings indicate that the pathogenetic mechanisms under­lying juvenile rheumatic disease might vary depending on age at disease onset, which is an important consideration for selecting the most appropriate treatment in young people, and highlight the requirement for additional research in young patients.

Managing disease in adolescents Many specific challenges complicate the management of adolescent individuals with chronic rheumatic diseases as they transition towards adult life. Such complications include variable clinical presentations and the influence of disease and treatments on physical development, as well as effects of the sexual and psychological developmental changes associated with puberty. Of note, the long-term toxicities of biologic and nonbiologic DMARDs, apart from cortico­steroids, used to treat rheumatic dis­e ases during childhood are not well established at present. However, we anticipate that the consolidated registries for biologic therapies, will provide evidence that demon­strate the long-term safety profile of DMARDs and biologic agents. To date, no conclusive data support an increased risk of malignancy or cardiovascular complica­tions www.nature.com/nrrheum

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PERSPECTIVES in adults with juvenile-onset rheumatic ­diseases ir­respective of treatment. The burden of chronic disease that starts in childhood or adolescence and remains active throughout the teenage years can influence all aspects of life.14,36 In addition, changing lifestyles, the need of adolescents to develop independence from their parents, and difficulties in accepting chronic dis­ ease and its treatment have marked effects on adherence to therapy, and thus disease manage­ment and outcomes.36,37 Litt et al.36 found that decreased adherence to treatment among 38 adolescents with JIA was asso­ciated with younger age at disease onset, longer disease duration, shorter duration of subspeciality care, greater delay between disease onset and first subspeciality clinic visit, and fewer clinic visits. Importantly, reports from studies in children with other chronic diseases, such as cystic fibrosis and diabetes mellitus, have suggested that poor adherence and gaps in medical follow‑up dur­ing the transition from paediatric to adult health-care services are directly related to adverse clinical outcomes.37–40 Hence, effective subspeciality input within a planned programme of transitional care throughout adolescence (that is, within both the paediatric and adult health-care environments), with the aim of establishing independent management of health care, is necessary to optimize adherence. Parents also need to come to terms with their changing roles as their children reach adolescence and begin independent manage­ ment of their health care in parallel with their evolving social independence. 41 Parents of young people with chronic diseases can sometimes be overprotective, disturbing the adolescent’s pursuit of independence and self-advocacy, and thus influencing the transition from paediatric to independent adult health care.14,41–43 Interestingly, Chaney et al.41 discovered that dysfunctional family interactions and high levels of family stress were predictive of lower adherence to medications among 18 children and adolescents with JIA. This finding underlines the importance of cohesive family relationships, at a time of considerable change, in ensuring an effective transition of adolescent patients to adult health care. The inability of young people with rheumatic disease to participate fully in all physical activities might also lead to isolation, which could in turn have adverse effects on their health or their use of health-care systems. Developing friendships and intimate relationships is in fact a key component

Table 1 | Key features of paediatric and adult health-care provision Feature

Paediatric health care

Adult health care

Patient management

Multidisciplinary, involving larger teams of health-care professionals

Physician-orientated, involving smaller teams of health-care professionals

Care approach

Parent-orientated

Patient-orientated

Clinic appointment duration

Allows time to extract varied and detailed information

Short, relative to those for paediatric patients, limiting information that can be obtained

Psychological support

Good access

Access is often limited

Follow-up

Active follow-up at regular intervals

The large numbers of adult patients under clinical care place pressure on resources and can result in less stringent follow-up

of adolescent development, but several studies of young adults with JIA have identified difficulties in this area, particularly in men. Of young adults with JIA, 37.6% reported that they were sexually active before transfer to adult rheumatology care by the age of 18 years. 11 Importantly, however, young people with rheumatic disease might not receive adequate counselling for sexual health.44 Indeed, Suris et al.44 reported that young people with chronic illnesses are as sexually active as their healthy peers, but have a higher risk of negative out­comes, including sexually transmitted infect­ions and sexual abuse. These issues can further complicate the management of chronic disease and should be addressed in planned health-care transition protocols aimed at adolescents. In general, all of the factors discussed above can increase the risk of adolescent patients with chronic rheumatic disease becoming noncompliant with health-care procedures and thus putting their health at risk. Findings from a number of studies suggest that poor adherence with healthcare protocols directly influences clinical outcomes specifically in patients with rheumatic diseases.26,36,45,46 For example, Petri et al.46 recorded patient adherence to treatment and planned clinical visits in a cohort of 198 patients with SLE and concluded that nonadherence was an important factor in determining renal morbidity (renal disease was defined as serum creatinine levels ≥1.5 mg/dl [132.6 μmol/l], renal failure or nephrotic syndrome). The bidirectional relationships between the diseases and/or their treatments and developmental and/ or psychological changes occurring during adolescence, as well as the personal and/or social circumstances affecting adolescents and young people, are now well recognized. Consideration of these relationships during transition of health care is fundamental to

NATURE REVIEWS | RHEUMATOLOGY

ensuring adherence, managing disease in young people and maximizing their quality of life.13,14

Care transition services Defining transitional health care Many—perhaps the majority of—­individuals navigate through adolescence without expe­ ri­encing extensive or lasting personal difficulty; however, their behaviours during this period can be challenging for families and carers, as well as for health-care profes­sionals.21,47 Furthermore, discharging children with chronic diseases from paedi­atric clinical care and enrol­ling them in adult health services has the potential to cause disengagement of young people from their health care, and creates the risk that such patients might fall in the existing gap between paediatric and adult care—­literally lost in transition during this vulnerable time. 7,14,47–49 These challenges are compounded by the distinct differences between the paediatric and adult health-care environments (Table 1). The recog­nition that young people require a tailored approach to health care is well established,7 hence the need for the planned process of transition to facilitate the transfer of care between services. With regard to health care, ‘transition’ is defined herein as the young-person-centred process of addressing the medical, psychological, educational and vocational issues as young patients with chronic disease move from child-focused to adult-focused clinical care.50 The process of transition is not complete until the young adult patient is participating fully in an adult health-care programme, which is different to the notion that transition is complete upon transfer of care.51 Models of transitional health care Despite universal agreement that good transitional health care is necessary, currently no VOLUME 10  |  MARCH 2014  |  189

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PERSPECTIVES single model, representing the ‘gold standard’, has been demonstrated as the most effective method of transitioning adolescents to adult health-care systems. Transi­tion programmes vary considerably and are dependant on the structure and fund­ing of the local health-care system.14,48 Sawyer et al.52 have recognized three general models of transitional care for adolescents with chronic illness: disease-focused transition from paedi­atric care to an adult sub­specialist; primary care–coordinated care spanning the period from adolescence to adulthood; and generic adolescent health services, with care coordi­nated by dedicated adolescent healthcare providers. A majority of the existing transition services in rheuma­tology both in the UK and the USA are disease-focused and thus speciality-based rather than generic, and thus adhere to the first model; primarycare physicians and other specialists, such as endocrin­ologists, can still be involved, but the rheumatology services tend to coordi­ nate the care of ­adolescent patients with rheumatic diseases. The first evaluation of an evidencebased transitional care programme in any childhood-onset disease was conducted in rheumatology and reported positive outcomes.43,53 The approach taken was based on the work of Janet McDonagh and the British Society of Paediatric and Adolescent Rheumatology, and involved a multi­centre trial to study the implementation of a co­ordi­nated transitional care programme built around certain core principles aimed at providing comprehensive, coordinated and uninterrupted health care that is developmentally appropriate for patients approaching transition from paedi­atric to adult health care.43,53 The translational health-care protocol resulted in improvement at follow-up in documentation of transitional issues, disease-specific educational needs, adolescent readiness and parental needs, with the exception of dental care, dietary calcium, and home exercise programmes.43,53 The age at which the concept of an independent clinic visit was introduced to young patients was lower in the patients exposed to the transitional procedure than those who were not (P = 0.01), but no other changes in age-related transitional milestones were reported.43,53 Importantly, an increase in the proportion of participants who had prepar­ atory visits to the adult clinic, had a transition plan and had joint injections while awake at follow-up was also associated with the transitional health-care programme.43,53 Interestingly, Shaw et al.54 also reported a 190  |  MARCH 2014  |  VOLUME 10

marked overall improvement in satisfaction scores for both adolescents with JIA and parents at 12 months after entering a structured programme of transitional care. In this study,54 three key aspects, in particular, considerably improved the young patients’ satisfaction with transition services: having a named member of staff to coordi­n ate care; planning for the move to adult care; and having opportunities to meet other young people with JIA. These studies have facili­tated identi­fication of the key components around which a transitional service should be built; written policy should be available, and the service should comprise an early, planned and well-documented process delivered by trained professionals and geared towards helping young people develop their resilience, which is audited and frequently modified based on input from young people.55 Skills that should be imparted to young people so that they can negotiate their own health care, independently, during transition have also been recognized, and include communication, decision making, creative problem solving, assertiveness, self-care, self-­determination and self-advocacy.55 Tucker et  al. 14 have also described a transi­t ional health-care model based on a dedicated clinic for young people aged 18–24 years, a ‘young adults with rheumatic disease’ (YARD) clinic, involving both paedi­atric and adult rheumatologists, with established links to physiotherapy, occupational therapy and other youth-friendly subspecialities.This care model was designed to encourage independence and self-advocacy in a gradual way, through a process that begins in the paediatric rheuma­t ology clinic several years before transition to adult care, and is aimed at eventual transfer to adult care at age 22 to 24 years.14 This model of shared clinical care involves paedi­ atric and adult rheumatologists in the same clinic setting, together with a clinical nurse trained in transitional care, a social worker, established links with physiotherapy, occupational therapy, vocational and sexual counselling services, and a developing network of subspecialists in youth-friendly adult medicine.14 In addition, within our own practice we have developed a transitional care pathway involving rheumatologists with an interest and training in both adolescent and adult rheumatology. These clinicians undertake transitional inflammatory arthritis, JSLE and JDM clinics within the paediatric setting, then transfer to a tertiary adolescent



rheumatology centre (when their patients are between the ages 13 and 15 years) where they continue to provide care, before transferring care to a young adult inflammatory arthritis, SLE and myositis clinic when the patients reach around 18–19 years of age. Using this system, continuity of patient care by the lead clinician is maintained into adulthood from around 13 years of age, and transition is planned within a multi­ disciplinary framework and individualized to the patient’s specific needs. Further­more, the rheumatologists are fully integrated into both the paediatric and adult rheumatology departments. Crucially, interwoven into this clinical framework is the infrastructure supporting transition of research, along with the patient’s clinical care, across these clinical health-care environments. Importantly, this service was developed within the needs and capabilities of the local health-care and academic systems. Our own experience, in keeping with the findings of other groups, suggests that the development of youngadult clinics is also needed to facilitate provision of health care to adolescents within the available adult facilities and to encourage potential paediatric–adult collaborations in terms of clinical service, education, train­ ing and research.14,51 Although coordinated transition efforts initiated in early adoles­ cence could be beneficial, whether these efforts translate into long-term improve­ ments in disease control or vocational suc­ cess remains unclear at present, and further studies are needed to clarify this issue.

Barriers to transition of care Barriers to successful transition of patients with rheumatic disease from paediatric to adult health care can, in general terms, be considered as patient-related, parent-related and/or protocol-related. Poor adherence, limited understanding of the disease and thus the need to comply with treatment, isolation and inadequate self-advocacy skills, as well as a reluctance to leave services with known and trusted staff represent patientdependent factors that might hamper effective transitioning.7,13,14 On the other hand, parents are not always willing to relinquish control when adolescent patients are transferred to adult health-care systems. 7,13,14 Likewise, paediatric care providers can have difficulty in ‘letting go’ of their patients. In addition, adult health-care providers might have limited knowledge of childhood-onset rheumatic disease and outcomes,7,13,14 and could, potentially, provide care to young people that is less than ideal. Thus, these www.nature.com/nrrheum

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PERSPECTIVES care providers might be reluctance to take on patients until they reach adulthood. Smooth transfer of medical records between paedi­atric units and adolescent and/or young adult services, as well as coordinated support for patients with complex diseases, is essential for effective transition of health care.7,13,14 In the era of biologic therapy, additional complexities centre around financing of treatment as patients move across services. The timing of transition might be further com­plicated in countries with an insurance-based health-care system, where insurance policies can dictate that young people are covered by their parents in­surance until the age of 26 years.

Ensuring an effective transition Notably, many different health-care transition models identify common key features of an effective transitioning process that might help overcome these potential bar­riers, such as individualized plan­ning involving the young person and their families. 7,13,14 Written transition policies are advocated, and should incorporate the views of both paediatric and adult healthcare teams as well as the wider multi­ disciplinary team. 7,13,14 Flexibility within the health-care transition protocol is key, appreciating that the transition process varies from individual to individual on the basis of social and cognitive maturity, current disease status and the preparedness of both the family and the patient.7,13,14 Pro­moting skills in self-advocacy and the ability to independently navigate within health-care systems are critical for effective transition of young people with chronic dis­ eases between care providers.7,13,14 Of the upmost importance, the transition process needs to include parents or guardians, enabling them to support their children with appropriate levels of protectiveness while also allowing them to develop their independence.7,13,14 Furthermore, administrative transfer and exchange of information between health-care providers is always a concern for families and could be addressed by providing young patients with copies of any documentation or the development of information platforms to facilitate online data transfer.13,14,43 Inclusion of transitional research A dearth of research exists regarding adoles­c ent rheumatic disease. 49 The few research efforts relating to this topic tend to focus on clinical research, and translational basic science research with an emphasis on

Transitional research Maintain engagement with cohort studies Ensure access to clinical trials Clinical AND translational basic science research Education for researchers and health-care providers

Paediatric rheumatology health care and research

10

13

16

19

20

Adolescent rheumatology (age)

Adult rheumatology health care and research

Communication and transition care plans Paediatric and adult health-care providers working together Parent orientated

Transitional care

Dependent

Clinical care

Management of health care

Patient orientated

Independent

Figure 1 | Schematic demonstration of the key concepts that should be considered to ensure a smooth transition of clinical care and the continuation of high-quality research during the transfer of patients between paediatric and adult health-care and research environments. The timing and duration of this transition depends on the patient’s cognitive development and therefore needs to be individualized; thus, the age range provided is an approximation. Importantly, clinical care should continue to be patient-orientated throughout and beyond the transition period. Smooth transitioning of patients from paediatric to adult health-care systems requires appropriate training and/or education of, and communication between, all groups and individuals involved, including the patients and their parents, particularly as paediatric patients become more independent. As multiple factors are likely to influence the phenotype and management of childhood-onset disease during adolescence, scientific and clinical research programmes should include patients undergoing this transition.

disease in adolescents is particularly scarce. Research into rheumatic diseases affecting the young is focused mainly on paediatric patients, with a relative paucity of data or studies addressing changing incidence, clinical phenotypes or mechanisms of these diseases during adolescence. Similarly, clini­cal trials of new treatments usually involve young children or older adults. The logistics of transferring patients across different health-care settings into adult care while the patient is participating in a clinical trial can be a bureaucratic minefield. Hence, older adolescents are rarely recruited into clinical trials; if such patients are successfully recruited into interventional studies, transfer of care is often delayed until completion of trials involving paediatric or adolescent patients, which might not be in the patient’s best interests. This situation means that the evidence base supporting biologic therapy in adolescents and young adults is poor, despite the fact that these periods of life represent times of phenotypic change in many inflammatory diseases, such as JIA, JDM and SLE.25 Likewise, almost no basic science data on how pathogenesis and responses to treatment are affected by

NATURE REVIEWS | RHEUMATOLOGY

physiological changes during this time are available at present. Therefore, adolescents overall are a largely forgotten group, overlooked and under­served by the research community. Clearly, however, top-quality transla­tional basic science research must be linked to a sub­stantive research-driven clinical service, with the aim of building and expand­ ing patient cohorts as the underpin­ning resource supporting efforts to improve tran­sitional health care. Integrated systems, for instance collecting long-term data in patients participating in cohort and other research studies as they transition from paediatric to adolescent care and beyond, are essential. Currently, important data on disease course, response to treatment, adverse effects of new medications and long-term outcomes are not recorded in many patients, and, if collected, would enable disease activity trajectories to be better defined in young people with rheumatic diseases. In addition, studies are needed that aim to establish whether timing of transitioning, patient and/or parent readi­ness, preparation of adult providers, or specific transitional health-care processes VOLUME 10  |  MARCH 2014  |  191

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PERSPECTIVES are important to improve outcomes such as quality of life, and physical, social and mental aspects of health. This area is extremely challenging to study because of the multiplicity of interactions between behaviours (of patients, families and care providers), the variation in approaches between health-care settings (Table 1) and the lack of standardized evaluative tools. Such integrated research initiatives would, however, provide a great opportunity to address these issues, not only in rheumatic diseases but also in many other chronic illnesses. In the UK, two initiatives have been developed with the aim of filling this research gap. Firstly, a partnership has been formed between two major UK funding bodies (Arthritis Research UK [ARUK] and the Great Ormond Street Hospital Children’s Charity [GOSHCC]), paediatric and adult health-care organizations (Great Ormond Street Hospital [GOSH] and University College London [UCL] Hospital) and a university (UCL) to establish a jointly funded research centre dedicated to adolescent rheumatology, the ARUK Centre for Adolescent Rheumatology. Secondly, a UK‑wide network of clinicians and researchers with expertise in paediatric and adult rheumatic diseases, the Barbara Ansell National Network of Adolescent Rheumatology (BANNAR) has been newly established. The ARUK Centre for Adolescent Rheumatology will work closely with BANNAR, with the primary goal of furthering research within the area of adolescent rheumatology. Through such efforts, basic science translational platforms are being developed that connect paediatric and adult rheumatology and are fully integ­ rated within a clinical and research infrastructure, thus encouraging age-appropriate participation of adolescents and young adults. Nevertheless, adolescent rheumatology research will only thrive if the perspectives of the young people, as voiced by themselves, are considered when setting key priorities for research agendas. This model of integrating transitional clinical care with transitional research is illustrated ­schematically in Figure 1.

Conclusions Adolescent health is an equal concern alongside existing worldwide health priori­ties, recognizing that young people represent the future of the human race. 2 Chil­dren with rheumatic diseases naturally and inevit­a bly become adolescents and 192  |  MARCH 2014  |  VOLUME 10

then young adults, many still with active disease or with accumulated damage due to disease.13,14,49 Engagement of young people and their families during their health-care transition is critical to ensure the smooth completion of this process. A well-timed, well-planned and well-executed transition enables young people to undertake adult activities and roles, promoting their independence and self-advocacy, and thus encouraging them to eventually manage their own health. By focusing attention on understanding how and why rheumatic diseases are different in adolescents, and the course and outcomes of such diseases as young people enter adult life, we hope that the current research efforts in adolescent rheumatology will dramatically improve treatment and care for young people. Department of Paediatric Rheumatology and Arthritis Research UK Centre for Adolescent Rheumatology, University College London Institute of Child Health, 30 Guilford Street, London WC1N 3JH, UK (D. Eleftheriou, L. R. Wedderburn). Centre for Rheumatology, University College London, 46 Cleveland Street, London W1T 4JF, UK (D. A. Isenberg). Arthritis Research UK Centre for Adolescent Rheumatology, University College London, 5 University Street, London WC1E 6JF, UK (Y. Ioannou). Correspondence to: Y. Ioannou [email protected] 1. UNICEF. Progress for children: A report card on adolescents (No. 10) [online], http://www. unicef.org/publications/index_62280.html (2012). 2. Sawyer, S. M. et al. Adolescence: a foundation for future health. Lancet 379, 1630–1640 (2012). 3. Donaldson, L. & Banatvala, N. Health is global: proposals for a UK Government-wide strategy. Lancet 369, 857–861 (2007). 4. Viner, R. M. et al. Adolescence and the social determinants of health. Lancet 379, 1641–1652 (2012). 5. Catalano, R. F. et al. Worldwide application of prevention science in adolescent health. Lancet 379, 1653–1664 (2012). 6. Rosen, D. S., Blum, R. W., Britto, M., Sawyer, S. M. & Siegel, D. M. Transition to adult health care for adolescents and young adults with chronic conditions: position paper of the Society for Adolescent Medicine. J. Adolesc. Health 33, 309–311 (2003). 7. McDonagh, J. E. Transition of care from paediatric to adult rheumatology. Arch. Dis. Child. 92, 802–807 (2007). 8. Hayward, K. & Wallace, C. Recent developments in anti-rheumatic drugs in pediatrics: treatment of juvenile idiopathic arthritis. Arthritis Res. Ther. 11, 216 (2009). 9. Tucker, L. B. Controversies and advances in the management of systemic lupus erythematosus in children and adolescents. Best Prac. Res. Clin. Rheumatol. 16, 471–480 (2002). 10. Packham, J. C. & Hall, M. A. Long-term follow-up of 246 adults with juvenile idiopathic arthritis:



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Acknowledgements D. Eleftheriou and Y. Ioannou acknowledge research support from Arthritis Research UK (grant 20164). Y. Ioannou also acknowledges support from the National Institute for Health Research University College London Hospitals Biomedical Research Centre. Author contributions D. Eleftheriou and Y. Ioannou contributed equally to researching data for the article and writing the manuscript. D. Eleftheriou, L. R. Wedderburn and Y. Ioannou made substantial contributions to discussion of content. All authors reviewed and/or edited the manuscript before submission.

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