SC(NHS)FT Reg. I.D. No. 346 Medical Guidelines for Paediatric Medicine RHEUMATOLOGY
13.1. JUVENILE IDIOPATHIC ARTHRITIS
13. RHEUMATOLOGY 13.1. JUVENILE IDIOPATHIC ARTHRITIS A. INTRODUCTION B. PRESENTATION AND DIAGNOSIS C. CLASSIFICATION D. INVESTIGATIONS E. TREATMENT F. FURTHER READING
A. INTRODUCTION Juvenile idiopathic arthritis (JIA) is the most common autoimmune disease in childhood and affects approximately 1 in 1000 children. By definition, onset of disease occurs before the age of 16 years and causes joint swelling, stiffness and pain for greater than 6 weeks. Aetiology remains unknown and curative treatment continues to prove elusive. Despite this, great advances in treatment have occurred over the past 10 years. Currently, paediatric rheumatologists advocate a „zero tolerance‟ approach to joint inflammation in patients with JIA. Traditional treatments such as steroids and methotrexate, together with newer biologic therapies make this approach to management achievable today.
B. PRESENTATION AND DIAGNOSIS Children and young people typically present with persistent joint swelling and stiffness. If joints of the lower limbs are affected, children may present with a limp. Difficulties dressing are frequent at presentation when upper limb joints are involved. Often at presentation, patients and families may have noticed a single joint swelling (eg. knee) but when careful examination is performed other subtle involvement at other joints (eg. temporomandibular joint) is found [Further Reading Item 1]. JIA is a diagnosis of exclusion; Accurate diagnosis rests on taking a detailed history from the patient and their family and, most importantly, performing a thorough musculoskeletal (MSK) examination. Other tools (blood tests, imaging investigations) are more useful in excluding other diagnoses. pGALS (paediatric Gait, Arms, Legs, Spine) is a well established screening examination tool and should form the foundation of a thorough MSK examination [Further Reading Item 2]. Abnormalities found on pGALS screening are then examined in more detail, with pREMS (paediatric Regional Examination of the Musculoskeletal System), which provides a standardised approach to more detailed MSK examination [Further Reading Item 3]. Diagnosis of JIA is often reached with clinical examination demonstrating the importance of a thorough MSK examination. [Further Reading Items 1,4].
C. CLASSIFICATION Historically, various phenomenological-based classification systems have evolved over time. In 2001 the International League of Associations for Rheumatology (ILAR) proposed the most widely used system in current use, which subdivides childhood arthritis based on number of joints involved, serological findings and systemic disease manifestations, within the first 6 months of diagnosis.
SC(NHS)FT Implemented November 2015 Review Aug 2017 (do not use after this date) Page 333 of 511
SC(NHS)FT Reg. I.D. No. 346 Medical Guidelines for Paediatric Medicine RHEUMATOLOGY
13.1. JUVENILE IDIOPATHIC ARTHRITIS
[Further Reading Item 5]. This classification system orders JIA into the following subtypes: Oligoarthritis (affecting 4 or fewer joints) Polyarthritis (affecting 5 or more joints) Systemic onset arthritis Psoriatic arthritis Enthesitis-related arthritis Undifferentiated
Uveitis Approximately 30% of patients with JIA will develop uveitis at some point during their illness (either before or after the onset of joint symptoms). Children with oligoarthritis are most likely to be affected. Patients may have symptoms of red or sore eyes, but frequently are asymptomatic (this is especially the case in younger children). It is therefore vital that all patients with suspected JIA are referred promptly for assessment by an experienced ophthalmologist. Untreated, uveitis causes blindness and remains one of the leading causes of acquired blindness in children.
Systemic JIA Systemic JIA (sJIA) is a subtype of JIA (constituting 10-20% of all JIA) which, in many respects behaves differently to other subtypes [Further Reading Item 6]. Some clinicians suggest it is best thought of as a distinct condition. Extra-articular features (regular spiking fevers, hepatosplenomegaly, vasculopathy, serositis, rash) are more prominent than the arthritis (which may not be present at presentation). The clinical course of sJIA is highly variable. Most patients with sJIA gradually recover over a period of 1-2 years during which systemic features fade. Occasionally, patients have a more aggressive illness in which systemic features persist and arthritis affects an increasing number of joints. Treatment strategies for sJIA vary depending on which symptoms (systemic features or arthritis) predominate. Interleukin blockers (IL-1 & IL-6) have been particularly effective in treating sJIA; Tocilizumab (an IL-6 blocker) recently gained NICE approval for treatment of sJIA.
D. INVESTIGATIONS Diagnosis of JIA is a CLINICAL diagnosis, and investigations are usually performed early in history of joint swelling to exclude other causes of joint swelling. If considering a diagnosis of JIA, please refer to paediatric rheumatology team, whom do not require any investigations to be performed prior to seeing the patient. However, tests you may consider useful if needing to perform investigations, are as follows:
FBC: may help to exclude leukaemia; White cell count and platelets may be especially high in sJIA.
SC(NHS)FT Implemented November 2015 Review Aug 2017 (do not use after this date) Page 334 of 511
SC(NHS)FT Reg. I.D. No. 346 Medical Guidelines for Paediatric Medicine RHEUMATOLOGY
13.1. JUVENILE IDIOPATHIC ARTHRITIS
ESR and CRP: both are non specific markers of inflammation, but doing BOTH at same time is helpful if considering an inflammatory disease. ANA: Anti-nuclear antibody: as a risk assessment for eye disease in oligoarthritis.
Rheumatoid factor: positive in Rheumatoid factor positive arthritis. Usually high levels. VZV IgG: to look for antibodies to varicella zoster infection prior to immunosuppressants being used. X-rays are helpful in excluding other causes, rarely specific or abnormal in early JIA. If there is doubt about whether a joint is swollen or what structures are actually swollen an ultrasound scan may be a more useful test.
E. TREATMENT Steroids Corticosteroids remain the treatment of choice for quick-acting suppression of inflammation. Direct injection of steroid into affected joints provides definitive treatment, and may be sufficient treatment for single affected joints (eg. Oligoarthritis affecting 1 joint). Occasionally a single steroid joint injection will induce long-term remission. For widespread joint involvement, steroids may be given systemically; intravenously, orally, occasionally intramuscularly. Conventionally „pulses‟ of three consecutive days of intravenous steroids are given and repeated as frequently as required. Long term corticosteroid use can have side effects (weight gain, growth suppression, osteopenia and associated fractures). Steroid use for inflammatory conditions is generally used to induce remission of “active” disease, with more definitive treatment, or immunosuppression being added in while steroids are weaned.
Methotrexate Methotrexate remains the first line disease modifying drug for patients with JIA. It has been used in children for more than thirty years and has an excellent long-term safety record. It is given once weekly and although it may be administered enterally it is most efficacious when given by subcutaneous injection. Methotrexate is potentially hepatotoxic and can cause bone marrow suppression. These effects are extremely rare however, their seriousness warrants regular blood test monitoring for all patients on methotrexate. Nausea and vomiting are a less severe, but more frequently troubling. National guidance for use of methotrexate in JIA can be found via the BSPAR website [www.BSPAR.org.uk].
Biologics Over the past decade a new generation of biologic treatments have become available for patients with JIA. These drugs have been developed to specifically target pro- inflammatory molecules involved in the inflammation cascade. These treatments include anti-Tumour Necrosis Factor (anti-TNF) agents (etanercept, infliximab and adalimumab). All biologics for patients in Sheffield Children‟s Hospital and in the region are prescribed by the Paediatric Rheumatology Consultants.
SC(NHS)FT Implemented November 2015 Review Aug 2017 (do not use after this date) Page 335 of 511
SC(NHS)FT Reg. I.D. No. 346 Medical Guidelines for Paediatric Medicine RHEUMATOLOGY
13.1. JUVENILE IDIOPATHIC ARTHRITIS
Table to illustrate current biologics in use for paediatric rheumatology patients in SCH.
Drug Method of Administration Method of action
Tocilizumab IV infusion IL-6 blockade Every 2 -4 weeks Etanercept Subcutaneous Injection Anti-TNF Twice weekly OR once weekly Abatacept IV infusion Inhibits co-stimulation of T-cells Every 4 weeks after initial doses at 0, 2 and 4 weeks Adalimumab Subcutaneous injection Anti-TNF Every 2 weeks Infliximab IV infusion Anti-TNF every 4-8 weeks after initial doses at 0, 2 and 4 weeks Anakinra Subcutaneous injection IL-1 blockade Once Daily Rituximab IV infusion Monoclonal B cell antibody 6-12 months
F. FURTHER READING 1. Hawley DP, Foster HE. Paediatric musculoskeletal examination – a case-based review. Paediatrics and Child Health 2011 Dec;21(12):527-33. 2. Foster HE, Kay LJ, Friswell M, Coady D, Myers A. Musculoskeletal screening examination (pGALS) for school-aged children based on the adult GALS screen. Arthritis Rheum 2006 Oct 15;55:709-16 3. Pediatric regional examination of the musculoskeletal system: a practice and consensus-based approach. Arhtritis Care Res (Hoboken). 2011 Nov;63(11):1503-10. doi: 10.1002/acr.20569. 4. McMahon AM, Tattersall R. Diagnosing Juvenile Idiopathic Arthritis. Paediatrics and Child Health 2011 Dec;21(12):552-7. 5. Petty RE, Southwood TR, Manners P, Baum J, Glass DN, Goldberg J, He X, Maldonado-Cocco J, Orozco-Alcala J, Prieur AM, Suarez-Almazor ME, Woo P, International League of Associations for Rheumatology: International league of associations for rheumatology classification of juvenile idiopathic arthritis: second revision, Edmonton, 2001. J Rheumatol 2004, 31:390-92. 6. Ramanan AV, Grom AA. Does systemic-onset juvenile idiopathic arthritis belong under juvenile idiopathic arthritis? Rheumatology 2005;44:1350-1353.
(Section 13.1. reviewed by Dr A McMahon, May 2015)
SC(NHS)FT Implemented November 2015 Review Aug 2017 (do not use after this date) Page 336 of 511
SC(NHS)FT Reg. I.D. No. 346 Medical Guidelines for Paediatric Medicine RHEUMATOLOGY
13.1. JUVENILE IDIOPATHIC ARTHRITIS
Performing a Musculoskeletal Examination
A musculoskeletal examination should be part of the general examination of children, when performing a systemic examination.
Certainly there are some red flags indicating when an MSK or pGALS should be performed.
If in doubt, or you have concerns raised by either history or examination please refer to your paediatric rheumatology team.
Red Flags Red flags raise concern about infection, malignancy or non-accidental injury
Fever, mlaise, systemic upset (reduced appetite, weight loss, sweats) Bone or joint pain with fever Refractory or unremitting pain, persistent night waking Incongruence between history and presentation (such as the pattern of the physical findings and a previous history of neglect)
When to perform pGALS in the assessment
Child with muscle, joint or bone pain Unwell child with pyrexia Child with limp Delay or regression of motor milestones The “clumsy” child in the absence of neurological disease Child with chronic disease and known association with MSK presentation
If in doubt, or you have concerns raised by either history or examination please refer to your paediatric rheumatology team.
SC(NHS)FT Implemented November 2015 Review Aug 2017 (do not use after this date) Page 337 of 511