SECTION 4 pain in specific populations and diseases 220 Speci \201 c medications NSAIDs are the mainstay of pain treatment in pediatric patients w ith rheumatic diseases ( Table 22.2 ) providing rapid and eff ec- tive analgesia in a varie ty of well-tolerated oral preparations (liq- uid, chewable tablets, tablets, capsules). NSA IDs work peripherally inhibiting cyclo-oxygenase (COX), which reduces prostaglandin product ion and subsequently pain (see also Anderson, Chapter 43, this volume). Analgesia from NSAI Ds may be additive to that of opioids and other adjuvant medications. NSAIDs have a ceiling eff ect (i.e. increased doses have no further benefi t). COX-2 selec- tive inhibitors (mel oxicam and celecoxib) are approved by the US Federal Drug Administration (FDA) for use in J IA and are eff ec- tive and safe (Foeldvari et al., 2009 ; Ruperto et al., 2005 ), although there is little information regarding long-term cardiovascular risks in children taking ei ther selective or non-selective NSAIDs. suffi cient to eliminate pain and other symptoms. Further goals of treatment in children an d adolescents are to alleviate pain, improve or preserve function, and restore normal growt h. Unfortunately, no clinical trials in JIA have addressed pain management as a primary end point. Even the original studies of non-steroidal anti-infl am- matories (NSAIDs) in childr en with JIA used disease activity out- comes that included pain, rather than pain alone, to prove effi cacy (Giannini et al., 1990 ; Laxer et al., 1988 ; Nicholls et al., 1982 ; Stea ns et al., 1990 ). Initial treatment of pain related to infl ammatory arthritides is NSAIDS, adding acetaminop hen for acutely painful events. Th erapy may be escalated based on disease severity, sympto m intensity, functional disability or lack of effi cacy, to include: corticoster- oids (sys temic or intra-articular injections); disease modifying antirheumatic drugs (DMARDs) such a s methotrexate, sulfasala- zine, hydroxychloroquine, or lefl unomide; and biological therap ies such as TNF blockers (etanercept, infl iximab, adalimumab, goli- mumab, certolizumab ), interleukin-1 blockade (anakinra, rilona- cept, canakinumab), B-cell depletion (rituxima b), interleukin-6 inhibition (tocilizumab) and T-cell costimulation blockade (abata- cept). Recently, studies of early aggressive treatment (Tynj l et al., 2011 ; Wallace et al ., 2012 ) have led to development of algorithms and treatment protocols for various subtype s of JIA (Beukelman et al., 2011 ; DeWitt et al., 2012 ; Tynj l et al., 2011 ; Wallac e et al., 2012 ). Table 22.2 shows the dosing of agents commonly used to treat pain in JIA. Signifi cant potential adverse eff ects from NSAIDs and COX-2 inhibitors include gastrointe stinal toxicity (dyspepsia, gastri- tis, ulcers, constipation and diarrhea), renal toxicity (interstitial nephritis, papillary necrosis, decreased blood fl ow, hypertension), hepatot oxicity (hepatocellular injury, cholestasis); cardiovascular toxicity has thus far been rep orted only in adults. Platelet inhibition occurs with most NSAIDs and needs to be considere d in patients with a coexisting bleeding diathesis or prior to a surgical proce- dure. NSAI Ds (especially naproxen) have also been associated with pseudoporphyria, which can cause si gnifi cant scarring (Lang and Finlayson, 1994 ). Typically, fair-skinned children are at gr eatest risk for pseudoporphyria with sun exposure. Th e skin lesions present as small linea r scratches in sun-exposed areas such as the face or arms. Sunscreen use is encouraged whil e on NSAIDs. Intra-articular injection of long-acting corticosteroids can be a highly eff ective means o f immediately reducing joint infl am- mation and pain, especially for monoarticular or olig oarticular JIA, as well as persistently symptomatic joints in polyarticular disease (Wallen and Gillies, 2006 ). Because of wide ranging and distressing side eff ects, as well as con cerns about obscuring a diagnosis of cancer, the routine use of systemic corticosteroids to reduce pain is discouraged, except in cases of severe systemic JIA following a bone marrow biopsy to rule out cancer, when arthritis is so severe the child will otherwise become bed rid- den or wheelchair-bound, or for short-term use while starting a new agent or intervent ion with delayed eff ect (Connelly and Schanberg, 2006 ). Acetaminophen is an appropriate analgesic for mild to moder- ate pain and can be used in co mbination with NSAIDs. Patients must be cautioned not to take more than the recommended dos age (10 \200\22315 mg/kg/dose every 4 \200\2236 h, maximum of 4 g in 24 h). Larger doses, e specially taken chronically, can cause signifi cant hepatotox- icity and are an important c ause of liver failure. It is important to remember that many analgesics contain acetaminoph en as well as the principal analgesic (e.g. Percocet contains acetaminophen in addition to oxycodone) in order to avoid overdosing patients with acetaminophen. As one of the oldest and most potent anti-infl ammatory medica- tion available, systemic co rticosteroids have historically been used by practitioners to reduce pain in rheumatic dise ase even with- out overt evidence of active infl ammation. While corticosteroids immediatel y reduce infl ammation and may secondarily decrease pain with substantial symptom relief, c orticosteroids unfortunately do not change the long-term course of arthritis and are not re mit- tive agents so the actual benefi t is limited. Corticosteroids can also mask the prese nce of malignancy or other rheumatic disease and should not be used in the absence of a cle ar diagnosis or without consultation with a pediatric rheumatologist. In addition, chronic use of systemic corticosteroids has many undesired side eff ects (e.g. growth retardation, osteoporosis, avascular necrosis, cataracts, and immunosuppression), which are especially d evastating for chil- dren. Nevertheless, 27% of pediatric rheumatologists surveyed about pa in treatment in JIA preferentially prescribed systemic cor- ticosteroids over analgesics to treat residual pain in children with arthritis because of discomfort and lack of training in the use of opioid pain medications (Kimura et al., 2006 ). Opioids (see also Strassels, Chapter 45, this volume) which act as agonists blocking princi pally and less commonly recep- tors in the central nervous system, are gaining accept ance to treat chronic, non-malignant pain in adults and children (Kalso et al., 2004 ; Slat er et al., 2010 ). However, a recent Cochrane systematic review did not fi nd strong eviden ce for long-term use in adult RA (Whittle et al., 2011 ). Opioids may be better tolerated, have more rapid onset of action, and are potentially less toxic than aggressive immunosuppr ession. Tramadol is a weak opioid that provides fairly eff ective relief of mild to moderat e pain when NSAIDs and aceta- minophen have failed. While there is fair evidence of its eff i cacy in osteoarthritis (Manchikanti et al., 2011 ), it has not been studied specifi cally in children with arthritis. Additional choices for acute pain include various oxycodone pr eparations, and for long-term pain management methadone (which also acts as an antagonist o f NMDA receptors) may be useful. Methadone is not well studied in children but several stud ies suggest dosing only two to three times per day may be eff ective (Berde et al., 1991 ; Brown et al., 2004 ; Shir et al., 1998 ). CHAPTER 22 inflammatory arthritis and arthropathy 221 Table 22.2 Medications used to treat pain in rheumatic diseases Name Dosage Max. dose/day How supplied NSAIDs Aspirin 60 \200\223100 mg/kg/day 20 \200\22330 mg/dl level Chewable tablet, tablet Divided 3 times/day Ibuprofen 30 \200\22340 mg/kg/day 2400 mg Liquid, chewable tablets, tablets Divided 3 times/day Naproxen 10 \200\22320 mg/kg/day 1000 mg Liquid, tablet Divided 2 times/day Indomethacin 2 \200\2234 mg/kg/day 200 mg Liquid, capsule, tablet Divided 2 \200\2233 times/day Meloxicam 0.125 \200\2230.25 mg/kg 7.5 mg Liquid, tablet Once daily 100 mg/dose (>25 kg) 200 } 2 times/day 400 mg Capsule Celecoxib 50 mg/dose (12 \200\22325 kg) mg/dose (>50 kg) Tolectin 40 mg/kg/day 1600 mg Tablet Divided 3 times/day Etodolac SR 20 \200\22330 mg/day (by age) 1000 mg Tablet Once daily Nabumetone 30 mg/kg/day 2000 mg Tablet Divided 1 \200\2232 times/day Analgesics, including opioids Acetaminophen 10 \200\22315 mg/kg/dose 2 \200\2234 g Liquid, chewable tablet, tablet Every 4 \200\2236 h Hydrocodone 0.15 mg/kg Limited by side e \200 ects Liquid, tablet Every 3 \200\2236 h Oxycodone 0.005 \200\2230.2 mg/kg Limited by side e \200 ects Liquid, capsule, tablet Every 3 \200\2236 h Tramadol 25 \200\223100 mg 300 mg Tablet Every 6 \200\2238 h Methadone 0.2 \200\2230.4 mg/kg Limited by side e \200 ects Liquid, tablet Every 6 \200\22312 h Hydromorphone 0.03 \200\2230.08 mg/kg/dose Limited by side e \200 ects Liquid, tablet Every 4 h Other agents Gabapentin 8 \200\22335 mg/kg/day 3600 mg Tablet Divided 3 times/day Amitriptyline 10 \200\22330 mg/day 75 mg Tablet At bedtime Pregabalin a 150 \200\223300 mg/day 450 mg Tablet Divided 2 times/day b Duloxetine a 30 \200\22360 mg/day 60 mg Tablet Once daily c a Not FDA approved in children <18 years. b Trials in children 12 \200\22317 have starting dose of 25 mg with slow titration until e \200 ect achieved. c Trials in children from 13 \200\22317, starting dose of 30 mg. SECTION 4 pain in specific populations and diseases 222 Despite potential benefi ts, pediatric rheumatologists rarely use opioids to treat JIA-rela ted pain with nearly 60% expressing refusal to use opioids for chronic pain management in a recent survey even though more than 75% of respondents reported caring for patients with s ignifi cant arthritis-related pain despite adequate medical treatment (Kimura et al., 2006 ). Side eff ect concerns such as drowsiness, fatigue, and constipation as well as respirato ry depression strongly infl uenced pediatric rheuma- tologists \200\231 attitudes toward op ioid use, but those opposed to opi- oid use were most concerned about addiction and depende nce ( \207 2 5.51, p = 0.019). Most side eff ects, including sedation, nausea, and pruriti s are reversible and short term. Additional complica- tions such as respiratory distress ca n be avoided by starting at low dose and titrating to eff ect. A pre-emptive bowel regimen, including a stool soft ener and stimulant, can prevent constipation (Connelly and Schanber g, 2006 ). Cognitive-behavioral therapy (CBT) aims to manage pain by improving self-reliance and facil itating normal activities through the use of coping skills, decreasing cognitive responses to pain, and using behavioral strategies including progres- sive muscle relaxation, distrac tion, and guided imagery (see also Logan et al., Chapter 50, this volume). Addressing copin g strategies through CBT is integral to pain management in JIA, as pain coping accounts for a large amount of the variance in self-reported pain intensity over and above the effect o f disease activity (Sawyer et al., 2004 ; Schanberg et al., 1997 ; Thastum et al., 2005 ).T wo published studies demonstrated improvement in self-reported pain ratings of children wit h chronic arthritis after CBT both immediately after treatment and at 6-month follow-up (La vigne et al., 1992 ; Walco et al., 1992 ). The stud- ies are limited by small sample size, abbreviated scope of the CBT intervention, and the lack of functional outcome variables. Al though future studies of CBT are necessary to understand fully its role in treatment of chi ldren with JIA, a systematic review of controlled trials of psychological therapy for chron ic pain concluded that there is evidence to support the use of CBT to treat headaches and o ther types of recurrent and chronic pain in children and adolescents (Palermo et al., 2010 ). The lack of side effects and the generalizability of the skills make CBT an attractive a djunctive intervention. Adjuvant medications oft en are useful for managing chronic pain in children with JIA. Th e most commonly used medication of this type is amitriptyline, a tricyclic antidepressant us ed in low doses at night for generalized chronic pain associated with sleep distur- bance. However, in an N of 1 Bayesian trial in six children with JIA, Huber found low-dose amitrip tyline did not improve pain scores (Huber et al., 2007 ). Selective serotonin re-uptake inh ibitors (SSRIs) may be used to treat comorbid mood disorders in children and adolescents wi th JIA. Given FDA-mandated black box label- ling for SSRIs, these medications should only b e used with close follow-up and extensive parent education about the increased risk of suic idality. Adding medications that address neuropathic pain has been advocated in adult arthr itis (e.g. gabapentin, pregabalin, duloxetine), but there are no published studies looking specifi cally at their usage to treat chronic pain in JIA or other childhood-onset rheumati c diseases. Physical therapy and exercise programs can help reduce pain in children with arthritis, who tend to be less physically active and more deconditioned than their peers (Takken et al., 2008 ). Decreased physical activity as a result of disease symptoms leads to decreased aero bic capacity and endurance, decreased exercise time, and decreased peak workload as compare d with healthy con- trols (Giannini and Protas, 1991 ; Klepper and Giannini, 1994 ). Kleppe r et al . studied the eff ect of an exercise regimen in 25 chil- dren with arthritis, showi ng that improved aerobic conditioning was achieved and was associated with decreased pain, without dis- ease exacerbation (Klepper 1999 , 2008 ). Several other studies have demonstra ted decreases in active joint count and disease sever- ity with initiation of a therapeutic exercise program, as well as decreased pain and improved cardiovascular fi tness, but note d diffi culty in motivating patients to continue achieving aerobic goals (Singh-Grewal et a l., 2006 , 2007 ; Takken et al., 2008 ). Future studies are necessary to delineate the most appropriate exercise for children with arthritis. Surgical interventions Th e role of surgery in treating pain and disability in children wit h chronic arthritis is not straight forward; although several studies suggest children expe rience marked pain reduction aft er surgery (Dell \200\231Era et al., 2008 ; Iesaka et al., 2006 ; Parvizi et al., 2003 ). Surgical interventions including synovectomy, soft -tissue release, and arthroplasty are generally limited to children with marked functional impairme nt, severe disabling pain, or deform- ity. Whenever possible, the age and skeletal maturity of the child should be considered, and surgery should be delayed until growth plate closur e. Surgical interventions should be performed in spe- cialized clinics at tertiary centers with awareness of the presence of arthritis in the cervical spine and temporomandibular joi nts, if intubation is planned. Pharmacological advances in treating chil- dren with chronic arthritis have brought into question the role of surgical interventions and likely will be an increasingly rare occur- rence in the future. Improving sleep quality often is overlooked in the treatment of pain. One study described f requent night waking, parasomnias, sleep anxiety, sleep-disordered breathing, and daytime f atigue in children with arthritis compared with controls and disturbed sleep was associated with increased pain (Bloom et al., 2002 ). Bromberg and colleagues found that self-reporte d nightly sleep quality was highly predictive of pain the following day, with bet- ter mood attenuating the effect (Bromberg et al., 2012 ). Thus, even simple measures to improve sle ep, including use of a sup- portive but soft mattress and sleeping in warm pajamas (e.g. sw eat clothes), should be recommended to children with JIA. Physical therapists also can sugg est sleep positions that maxi- mize level of comfort depending on the unique combination of active joints. Relaxation techniques, such as progressive muscle relaxation or guided imag ery taught within the context of cogni- tive behavioral therapy, also can be useful in impr oving sleep hygiene. Non-pharmacological interventions Th e growing acceptance of the biopsychosocial model of p ain has prompted the development and study of non-pharmacological interventions for JIA-rel ated pain. Research on non-pharmacolog- ical interventions has included programs for improv ing physi- cal conditioning and sleep hygiene, massage therapy, and, perhaps most important ly, cognitive behavioral therapy. CHAPTER 22 inflammatory arthritis and arthropathy 223 Other interventions, including integrative approaches (see Zeltzer, Chapter 60, this volume ) to improve pain in children with JIA have not been well studied; however, limited researc h includes studies of the use of massage and orthotics in children with JIA and several int erventions in adult RA. Field and col- leagues evaluated the eff ectiveness of massage in d ecreasing pain in a sample of 20 children with mild to moderate arthritis (Field et al., 19 97 ). Children were randomly assigned to either a mas- sage therapy or relaxation technique s control group. Immediately aft er treatment, children who received massage had lower leve ls of anxiety and decreased salivary cortisol levels. Th ey also reported less present pain , less pain during the past week, and fewer painful locations than children in the control condition. A controlled trial of 40 children investigating the eff ectiveness of custom ort hotics showed signifi cant improvements in pain, ambulation speed, and self-related functio nality and activity, when compared to chil- dren using over-the-counter inserts and support ive athletic shoes (Powell et al., 2005 ). Lal et al., 2011 ; Palermo et al., 2004 ). Tong and colleagues \200\231 recent systematic r eview of qualitative studies about the experiences of children with JIA identifi ed six maj or themes: aversion to being diff erent, striving for normality, stigma and understanding, suspen- sion in uncertainty, managing treatment, and desire for knowledge (Tong et al., 201 2 ). Of note, pain from JIA, its impact and manage- ment were pervasive within all themes a nd the author \200\231s conclusions reinforce the concepts and framework of the biopsychoso cial pain model. Chronic recurrent pain in children, which likely includes those with JIA, is known to have negative short-term impact including poorer social and peer relationships, missed school an d decreased functionality, and emotional and psychological distress (Connelly et al., 2012 ; Eccleston and Crombez, 2007 ; Haverman et al., 2012 ; Palermo, 2000 ; Roth-Isigkeit et al ., 2005 ). Without properly address- ing pain as a standard part of JIA treatment, long-ter m disability and increased medical expenditures may result (Arkela-Kautiainen et al., 2006 ; Foster et al., 2003 ). Understanding relationships between pain, school attendance, sleep , stress, emotion regulation, and mood will guide development of interventions designed to enhance the functionality and productive coping of children and adolescents with JIA. An evidence based review of non-pharmacological treatments for adults with rheumatoid arthr itis found that aerobic physical exercise, sports, and muscle-strengthening exercises demon - strated positive benefi t in pain and health related quality of life; however, there was little evidence that dietary measures, nutri- tional supplements and elimination diets were eff ective (Gossec et al., 2006 ).Further controlled studies on these and other non- pharm acological interventions are required before reaching conclusions relating to the eff ectiv eness of these approaches in children with JIA-related pain. To improve routine care of children with JIA, pain assessment and control are included in p roposed standards for health care delivery quality measurements (Lovell et al., 2011 ). Con sensus assessment and treatment plans addressing pain in children with JIA are being develo ped through CARRA and will provide recommendations regarding use of various treatment modal i- ties to manage the multifactorial nature of pain in rheumatic conditions. Additionally, validation and standardization of out- come measurements for the assessment of pediatric rh eumatic conditions, which includes pain intensity assessment, are being addressed through w orldwide eff orts through organizations such as Pediatric Rheumatology INternational Trials Organization (PRINTO) and Pediatric Rheumatology Collaborative Study Group (PRCSG). With t he advent of newer agents introduced earlier in the disease course to quickly limit infl am mation, new studies are needed to investigate if shift s in the treatment paradigm result i n fewer pain complaints and less pain related functional limitation. Consensus derived algo rithms will stand- ardize assessment and treatment of JIA-related pain in clinical settings . Th rough comparative eff ectiveness research studies using the CARRA network, we can eval uate the best modalities to approach pain. Outcomes More comprehensive assessment and tracking of pain in chil- dren with rheumatic co nditions are needed upon which to base future treatment considerations. Currently, there is no generally accepted, standardized method of assessing pain for children with rheumatic c onditions and pain improvement is not considered independently in either pharmaceutical or investigator-initiated medication effi cacy trials, despite a call from the international p ediatric pain community to perform more comprehensive pain assessments in children particip ating in clinical trials (McGrath et al., 2008 ). A Childhood Arthritis and Rheumatology Re search Alliance (CARRA) initiative has sought to formalize pain assess- ment as part of the routine evaluation of children and adolescents presenting to pediatric rheumatology clinic s (Stinson et al., 2012 ). Additionally, more in depth understanding of the context of pain in JIA is needed to guide development of more eff ective interventions. Symptom tracking u sing electronic diaries or other mobile technologies can reveal the ecological momentary im pact of pain in JIA, demonstrating hourly as well as daily variability not apparent in cros s sectional pain assessments during routine clinic visits (Connelly et al., 2007 ; Schanber g et al., 2003 ; Stinson et al., 2006 , 2008 ). Conclusion Pain is common in children with infl ammatory arthritis despite aggressive treat ment of JIA with contemporary medications. Pain is an important, but oft en neglected, aspe ct of care for children with arthritis, negatively impacting well-being and function. Furth er research is needed to prospectively identify patients and families early in the course o f disease who would benefi t from additional support to optimize pain management and limit distress. In addi- tion, future clinical trials should assess the impact of study inter- ve ntions on pain as a primary endpoint, assessed independently from other response variables. Extremely important in any assessment of pain is gathering infor- mation directly from chil dren themselves as studies show a lack of concordance between provider, parent, and patient perceptions of pain, especially as children get older and depression or other psy- chologi cal distress is more common (Garcia-Munitis et al., 2006 ; SECTION 4 pain in specific populations and diseases 224 Case example is more frequent in males than females and is not associated with autoantibodies such as rh eumatoid factor or antinuclear antibod- ies. Because arthritis may be limited to the axial skeleton, overt joint abnormalities may not be present. Entheseal tenderness can overlap or be in similar locations as fi bromyalgia tender points ( Figure 22.3 ), for example, as no ted in the gluteal region and hip girdle (Fitzcharles and Esdaile, 1997 ). TNF- blockade (such as etanercept, infl iximab, golimumab, or adalimumab) treats the infl ammatory compo nent of this form of JIA extremely well, even helping heal destructive changes noted in the axial skeleton. A 15-year-old adolescent female presents for evaluation of diff use musculoskeletal pain, w hich has been ongoing for 2 years. In the past, she was able to cope with the pain and keep playing basketball, her favorite sport. Over the past 6 months, she stopped playing basket ball due to swollen knees and lower back pain. Every morning she is stiff for 2 h. Physical exam shows arthritis of both knees, but also exquisite tenderness at bilateral sacroiliac joints with poor fl exion of the lumbar spine. She also has enthesitis (tenderness at the b ony insertion points of tendons and ligaments) at bilateral Achilles tendons, greater troch anteric heads, tibial tuberosities, and anterior superior iliac crests (see Figure 22.2 ). Laboratory evaluation includes normal blood counts with elevated ESR of 50. HLA B27 is posi tive but antinuclear antibody, rheumatoid factor, and anti-citrullinated cyclic peptide are negative. MRI and plain fi lms reveal erosions at her sacroiliac joints. Her primary care provider has started ibuprofen 600 mg three times daily. Since starting the medica- tion, s he is moving better with morning stiff ness lasting only an hour. Her knee swelling is unch anged. Secondary fi bromyalgia is common in adult patients with rheumatic conditions, but also occ urs in children and adoles- cents. Treatment of pain should incorporate a biopsychosocial m odel addressing all elements that may be contributing to her current health status: anti-in fl ammatories and immune modula- tors for infl ammation, physical exercise for fatigue and functional limitations, and counseling to improve pain coping and address psychological and emotional confounders. For this teen, initia- tion of amitriptyline to improve sleep quali ty, graduated aerobic exercise in addition to adjunctive treatment with a TENS unit or mass age therapy, as well as cognitive behavioral therapy will help manage residual pain. Escala tion of arthritis treatment such as using courses of oral or parenteral corticosteroids do not treat the central pain processing changes underlying diff use persistent pain or impact factors moderating pain in the case of this teen. Given the clinical picture, she was diagnosed with enthesitis- related juvenile idiopathic arthritis, also known as a seronegative spondyloarthropathy, by a pediatric rheumatologist. Because of the severity of joint fi ndings on imaging, she immediately was started on a TN F- blocker and underwent intra-articular joint injections for her knees. With initiation of treatment, her infl ammatory lab markers normalized, her knee swelling fully resolved a nd she resumed most normal daily activities. Unfortunately in follow-up, she still complain ed of back pain, which she now characterized as extending up her entire back into her neck, shoulder blades and including her lower back. She is worried that the newly diagnosed arth ritis is worsening since her pain has changed, and is now sharper, more stabbing in nature and seems to aff ect more body parts including hips, knees, shoulders and elbows. She also is fatigued, oft en miss- ing school. A short course of oral prednisone does not provide re lief or improvement in her symptoms. On further history, she endorses non-restorative sleep and multiple psychosocial and emotio nal stressors, including recently breaking up with her boyfriend. Previously, she was physi cally active but has not engaged in aerobic activity since onset of the knee arthritis. She expresses desperation to get to back to feel- ing normal. Re-examination shows no obvious joint abnormali- ties but she has diff use musculoskeletal tenderness at her gluteal insert ions and other tender points. To address the current con- cerns, she was started on low-dos e amitriptyline to help with sleep and provided a regimented physical therapy program inclu ding range of motion and core strengthening exercises, as well as a conditioning program to work on aerobic capac- ity for eventual resumption of her previous physical activities. Ad ditionally, she is referred to a therapist for counseling regard- ing pain coping strategie s. In the setting of enthesitis-related JIA (also known as juve- nile spondyloarthropathy), fi bromyalgia overlay can occur, especially in females, making the diagnosis and assessment o f current health status especially challenging (Aloush et al., 2007 ; Fitzcharles and Boulo s, 2003 ). Characteristically, this form of JIA Figure 22.2 Entheseal insertion sites. Entheses are the sites where ligaments and tendons i nsert into bone. Reproduced from Annals of the Rheumatic Diseases , M. Mander et al., Studi es with an enthesis index as a method of clinical assessment in ankylosing spondylitis, Vol ume 46, Issue 3, p. 198, Copyright 1987, with permission from BMJ Publishing Group Ltd, http://ard.bmj.com/. CHAPTER 22 inflammatory arthritis and arthropathy 225 Connelly , M. , Anthony , K. K. , Sarniak , R. , Bromberg , M. H. , Gil , K. M. , and Schan berg , L. E. ( 2010 ). Parent pain responses as predictors of daily activities and mood in children with juvenile idiopathic arthritis: the utility of electronic diaries . J Pain Sym ptom Manage , 39 (3), 579 \200\223590. Connelly , M. , Bromberg , M. H. , Anthony , K. K. , Gil , K. M. , Franks , L. , and Schanberg , L. E. ( 2012 ). Emotion regulation predicts p ain and functioning in children with juvenile idiopathic arthritis: an electronic diary stu dy . J Pediatr Psychol , 37 (1), 43 \200\22352. Tenderness of skin overlaying trapezius Low cervical spine Midpoint of trapezius Supraspina tus Pectoralis, maximal lateral to the second costochondral junction Lateral epicondyle of the elbow Upper gluteal area Low lumbar spine Medial fat pad of the knee Connelly , M. , Keefe , F. J. , Affl eck , G. , Lumley , M. A. , Anderson , T. , and Waters , S. ( 2007 ). Eff ects of day-to-day aff ect regulation on the pain experience of patient s with rheumatoid arthritis . Pain , 131 (1 \200\2232), 162 \200\223170. Connelly , M. and Schanberg , L. ( 2006 ). Opioid therapy for the treatment of refractory p ain in children with juvenile rheumatoid arthritis . Nat Clin Pract Rheumatol , 2 (12), 636 \200\223637. Figure 22.3 Fibromyalgia tender points. Tender points are a hallmark of the generalized mus culoskeletal pain of patients with \201 bromyalgia. Adapted from Hakim, A., Clunie, G., a nd Haq, I. 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