O14 Transitions in diagnosis and between services in juvenile idiopathic arthritis: living and learning

Abstract Case report - Introduction Juvenile Idiopathic Arthritis (JIA) is a lifelong condition in over 50% but there is limited knowledge of JIA in adulthood. We discuss C, who presented in childhood with polyarticular JIA which evolved into systemic lupus erythematosus (SLE). After careful transition she defaulted on care and had a life-threatening SLE flare. In adult services axial symptoms became dominant. Adult rheumatologists queried a third diagnosis of axial spondyloarthropathy, not recognising axial disease as a feature of JIA. This case highlights that knowledge sharing is needed to improve care of adults with JIA and reminds us that transfer can be a risky time. Case report - Case description C presented age 11 with pain and swelling in the small joints of her hands and feet. She was treated for polyarticular JIA with methotrexate and etanercept. At the point of transfer and having had early, detailed transition planning, C developed mouth ulcers, and Raynaud’s with lymphopenia, positive ANA, DsDNA, Ro, Sm, and RNP antibodies, low C4 and an elevated ESR, resulting in a diagnosis of evolving SLE/JIA. Treatment with methotrexate and etanercept continued but C’s adherence became poor. She stopped taking methotrexate due to nausea and ceased etanercept some months previously. C had extra transition support to enhance adherence and transferred into the young adult clinic (YAC) re-established on treatment. After transfer, her SLE became more complex so there was further transition into the adult connective tissue disease (CTD) service. Azathioprine was prescribed but failed to control symptoms and was stopped, although adherence was a significant issue again. C was admitted to hospital with an SLE flare causing rash, inflammatory arthritis, and nephritis with strongly positive DsDNA and low C3 and C4. She also had hyperferritinaemia, anaemia, leucopoenia, neutropenia, a raised CRP, and haemophagocytosis on bone marrow trephine due to haemophagocytic lymphohistiocytosis (HLH). This flare was a life-threatening culmination of poor adherence. C commenced mycophenolate and rituximab during this admission. Engagement improved significantly but C developed back pain associated with a raised CRP. An MRI scan revealed evidence of bilateral sacroiliitis, interpreted by the adult SLE team as possible axial spondyloarthropathy, as she has a history of psoriasis. Referral back to the adolescent team highlighted that axial disease is a feature of polyarticular JIA. Close liaison between the two led to a revision of her diagnosis away from SLE to polyarticular JIA/SLE crossover syndrome with axial disease. C is currently managed with tocilizumab and mycophenolate. Case report - Discussion Paediatric and adolescent rheumatologists recognise that inflammatory disease in young people may evolve: C went from a diagnosis of polyarticular JIA to SLE to possible axial spondyloarthropathy to polyarticular JIA/SLE crossover. C transitioned into the YAC and then into the adult CTD service. There may have been a conflict here between focusing on generic young adult care, as opposed to specialist disease-related care. Defaulting on medical care is a normal phenomenon in adolescent development. For C this resulted in a life-threatening SLE flare. In adolescents, it is crucial to recognise transfer as a high-risk time, to remain alert to potential non-adherence and to chase up non-attendance especially immediately after seemingly successful transfer. Therefore, extra appointments and support may be needed in adult services. JIA is a small yet significant part of general adult rheumatology workload. In Sheffield, JIA comprises 4% of the adult inflammatory arthritis service (compared with 39% for rheumatoid arthritis (RA), the commonest adult inflammatory arthritis). There is little in the literature about the phenotype or treatment of JIA in adults leading to the relative invisibility of JIA in adult rheumatology and relabelling of JIA as RA. Management of adolescent and adult JIA is further complicated by the differing definition and distributions of active joints between JIA and adult inflammatory arthritis. Both recognise tender and swollen joints as active, but in paediatrics, restricted joints are also ‘active’. Paediatric joint counts include all joints, not just selected joints as in, for example, DAS28 in RA. The burden of adolescent and adult JIA may be under-recognised and under-treated. For C this led to delayed recognition of axial disease in adult services, but early and close working of adolescent and adult specialists led to the correct diagnosis and reinforces the importance of taking a life course approach to JIA. Case report - Key learning points C was managed in a seamless service where child-to-adult pathways are well developed. Despite this, she had significant non-adherence to medication, causing a life-threatening disease flare. The period immediately after transfer may be one of particular vulnerability and should be a target for extra support in adult services. Adult rheumatology is often super-specialised and just as transition from child to adult services may risk information being lost and a failure of developmentally appropriate care, transition within adult services (here from the YAC to the specialist CTD clinic) may also be challenging for patients and professionals alike. What worked well here was referral back to the YAC when axial disease was recognised and the shared approach to diagnosis and appropriate management. The optimum way to assess JIA activity in adults is not established. There is evidence that using scores for rheumatoid arthritis such as DAS28 risks underestimating JIA activity and denying young people access to treatment but there are no validated scores for adult JIA. This is a key area for future research. JIA persists into adult life in at least half of those with childhood onset disease. It is important that all rheumatologists appreciate the course, impact, and phenotypes of JIA in adults, to ensure the best outcomes and treatment. Young adult clinics are an ideal way to ensure developmentally appropriate care, but may not be feasible in all services, making education about JIA for adult rheumatologists (which paediatric and adolescent rheumatologists are ideally placed to deliver) all the more necessary. Young people with JIA need to be continually educated about their disease especially at transfer to adult services so they can remind adult rheumatologists that they have JIA. Good collaboration across all areas of rheumatology improves care for children, adolescents, and adults with rheumatic disease


1
The Medical School: The University of Sheffield, Sheffield, United Kingdom, and 2 Rheumatology: Sheffield Teaching Hospitals NHSFT, Sheffield, United Kingdom Case report -Introduction: Juvenile Idiopathic Arthritis (JIA) is a lifelong condition in over 50% but there is limited knowledge of JIA in adulthood. We discuss C, who presented in childhood with polyarticular JIA which evolved into systemic lupus erythematosus (SLE). After careful transition she defaulted on care and had a life-threatening SLE flare. In adult services axial symptoms became dominant. Adult rheumatologists queried a third diagnosis of axial spondyloarthropathy, not recognising axial disease as a feature of JIA. This case highlights that knowledge sharing is needed to improve careof adultswith JIA and reminds us that transfer can be arisky time.
Case report -Case description: C presented age 11 with pain and swelling inthesmalljointsofherhands andfeet.She wastreatedfor polyarticular JIA with methotrexate and etanercept. At the point of transfer and having had early, detailed transition planning, C developed mouth ulcers, and Raynaud's with lymphopenia, positive ANA, DsDNA, Ro, Sm, and RNP antibodies, low C4 and an elevated ESR, resulting in a diagnosis of evolving SLE/JIA. Treatment with methotrexate and etanercept continued but C's adherence became poor. She stopped taking methotrexate due to nausea and ceased etanercept some months previously. C had extra transition support to enhance adherence and transferredinto the young adult clinic (YAC) re-established on treatment. After transfer, her SLE became more complex so there was further transition into the adult connective tissue disease (CTD) service. Azathioprine was prescribed but failed to control symptoms and was stopped, although adherence was a significant issue again. C was admitted to hospital with an SLE flare causing rash, inflammatory arthritis, and nephritis with strongly positive DsDNA and low C3 and C4. She also had hyperferritinaemia, anaemia, leucopoenia, neutropenia, a raised CRP, and haemophagocytosis on bone marrow trephine due to haemophagocytic lymphohistiocytosis (HLH). This flare was a life-threatening culmination of poor adherence. C commenced mycophenolate and rituximab during this admission. Engagement improved significantly but C developed back pain associated with a raised CRP. AnMRIscan revealed evidence of bilateralsacroiliitis, interpreted by the adult SLE team as possible axial spondyloarthropathy, as she has a history of psoriasis. Referral back to theadolescentteam highlighted thataxialdiseaseisafeatureofpolyarticular JIA. Close liaison between the two led to a revision of her diagnosis away from SLE to polyarticular JIA/SLE crossover syndrome with axial disease. C is currentlymanaged with tocilizumaband mycophenolate. Case report -Discussion: Paediatric and adolescent rheumatologists recognise that inflammatory disease in young people may evolve: C went from a diagnosis of polyarticular JIA to SLE to possible axial spondyloarthropathy to polyarticular JIA/SLE crossover. C transitioned into the YAC and then into the adult CTD service. There may have been a conflict here between focusing on generic young adult care, as opposed to specialist disease-related care. Defaulting on medical care is a normal phenomenon in adolescent development. For C this resulted in a life-threatening SLE flare. In adolescents, it is crucial to recognise transfer as a high-risk time, to remain alert to potential non-adherence and to chase up non-attendance especially immediately after seemingly successful transfer. Therefore, extra appointments and support maybe needed inadult services. JIA is a small yet significant part of general adult rheumatology workload. In Sheffield, JIA comprises 4% of the adult inflammatory arthritis service (compared with 39% for rheumatoid arthritis (RA), the commonest adult inflammatory arthritis). There is little in the literature about the phenotype or treatment of JIA in adults leading to the relative invisibility of JIA in adult rheumatology and relabelling of JIA as RA. Management of adolescent andadult JIAis furthercomplicatedbythe differing definition anddistributions of active joints between JIA and adult inflammatory arthritis. Both recognise tender and swollen joints as active, but in paediatrics, restricted joints are also 'active'. Paediatric joint counts include all joints, notjustselectedjointsas in,forexample,DAS28inRA.Theburdenofadolescent and adult JIA may be under-recognised and under-treated. For C this led to delayed recognition of axial disease in adult services, but early and close working of adolescent and adult specialists led to the correct diagnosis and reinforces the importance of taking a life course approach to JIA. Case report -Key learningpoints . C was managed in a seamless service where child-to-adult pathways are well developed. Despite this, she had significant nonadherence to medication, causing a life-threatening disease flare.
The period immediately after transfer may be one of particular vulnerability and should be a target for extra support in adult services.
. Adult rheumatology is often super-specialised and just as transition from child to adult services may risk information being lost and a failure of developmentally appropriate care, transition within adult services (here from the YAC to the specialist CTD clinic) may also be challenging for patients and professionals alike. What worked well here was referral back to the YAC when axial disease was recognised and the shared approach to diagnosis and appropriate management. . The optimum way to assess JIA activity in adults is not established.
There is evidence that using scores for rheumatoid arthritis such as DAS28 risks underestimating JIA activity and denying young people access to treatment but there are no validated scores for adult JIA. This is a key area for future research. . JIA persists into adult life in at least half of those with childhood onset disease. . It is important that all rheumatologists appreciate the course, impact, and phenotypes of JIA in adults, to ensure the best outcomes and treatment. Case report -Introduction: Macrophage Activation Syndrome (MAS) affects approximately 10% of patients with Systemic Juvenile Idiopathic Arthritis (sJIA) which left untreated can have fatal consequences. MAS in sJIA often occurs in the context of uncontrolled disease or following a concurrent infectious trigger. Overactive T lymphocytes and macrophages produce a cytokine storm of pro-inflammatory cytokines including TNF-a, IL-1b, IL-6, IL-18, IFN-c and IFN-c induced chemokines. Tocilizumab (TCZ), an anti-IL6 receptor monoclonal antibody, can be used in the treatment of sJIA. Research has shown that patients receiving Biologicaltherapiesmayhavefewersymptomsandlesspronounced biochemical changes than Biological-naïve patients at presentation with MAS. Case report -Case description: We highlight the case of a 12-year-old female diagnosed with sJIA complicated by MAS. Her initial presentation fulfilled the 2016 EULAR/ACR criteria for MAS in sJIA with daily fever, rash, hyperferritinemia (19058 ng/ml), hypertriglyceridemia (362 mg/dl) and raised aspartate aminotransferase (230 U/l) with a marrow demonstrating haemophagocytosis. She was treated with pulsed Methylprednisolone (MP), oral Prednisolone (PNL), and fortnightly IV Tocilizumab 8 mg/kg. Once controlled, she switched to weekly subcutaneous Tocilizumab 162 mg and weaned Prednisolone. Several months after diagnosis, following a tooth abscess and shingles, the patient represented with intermittent fever, pruritic rash, myalgia, generalised arthralgia, and a rapid onset of enlarging organomegaly. MRI identified cervical, axillary, and inguinal lymphadenopathy and marked hepatosplenomegaly (Spleen 17 cm). Lymphoproliferative disorders were excluded through marrow aspiration and lymph node biopsy. During this presentation, the biochemistry did not meet the 2016 EULAR/ ACR criteria. However, she was treated for suspected MAS due to the Tocilizumab therapy. After switching from Tocilizumab to subcutaneous Anakinra (ANA) 2 mg/kg/d with three days IV Methylprednisolone 30 mg/ kg, her symptoms and biochemical parameters improved (Table1). Case report -Discussion: IL-6 is a key player of immune activation and is involved in the generation of the acute phase response. The use of Tocilizumab, an IL-6 inhibitor, masks the febrile picture of MAS and it is therefore unsurprising to see an altered representation of MAS biochemically. Alterations seen in this case study included a delayed rise in acute phase reactants (ESR, CRP), with absence of hyperferritinemia and hypertriglyceridemia. However, the ongoing hemophagocytic process with increased cell turnover within the reticuloendothelial system still caused marked organomegaly with significant biochemical changes seen via a steadilyrising LDH and transaminases. Biological treatment for sJIA therefore alters the traditional clinical presentation and inflammatory biochemical profile resulting in patients who may not necessarily fulfil the 2016 EULAR/ACR criteria forMAS in sJIA. Functional assays were performed looking at the perforin-cytolytic pathway during both MAS presentations ( Table 1). The first test during the initial diagnosis of sJIA reported a defective granular release assay and perforin deficiency, but a relative normal sCD25. However, this followed treatment with steroids. The latter test showed normal expression of both NK cell and perforin. The normal repeat functional assays following a year of Tocilizumab makes a genetic aetiology unlikely. This suggests an acquired form of a functional deficiency of both NK cells and perforin activity, with dysfunction of both, can be seen in the background of active sJIA. This function is often restored once systemic inflammation is controlled. Infectious aetiology for Leishmania was considered but as the histology of the marrow lacks histiocytes infiltration, no further DNA PCR testing was offered. Case report -Key learning points: The occurrence of MAS in sJIA is often presumed in the context of a background of uncontrolled inflammation or following concurrent infectious triggers. The use of biologics with cytokine directed therapies have revolutionized the treatment of sJIA and remarkably shortened the time to achieve inactive disease. In this case study we learn that achieving disease control does not necessarily prevent MAS as this complex phenomenon has multiple aetiologies which drive the pathway towards a cytokine storm. This case study as well as data from phase III clinical trials of Tocilizumab, report that treatment using Tocilizumab does not confer protection against the development of MAS. This observation concludes that subtle deterioration of a sJIA patient receiving biologics should prompt additional investigation to exclude a subclinical MAS presentation. Absence of fever and a normal ferritin level does not negate the possibility of a partially treated MAS. Patients receiving Tocilizumab, an IL-6 inhibitor, are less likely to be febrile, and have lower ferritin, CRP, and triglycerides levels, thus makinginterpretation of MAS biochemical resultsdifficult. This indirectly validates the presence of other cytokines orchestrating the pathogenesis of MAS in the context of a systemically controlled sJIA on IL-6 inhibitor. Emerging evidence have reported disproportionately elevated levels of circulating IL-18, IFN-c and IFN-c chemokines in sJIA patients who develop MAS.