Pediatric Rheumatology Board ReviewSimona Nativ, MDPediatric RheumatologyGoryeb Childrens Hospital

Juvenile Rheumatoid Arthritis (JRA)Synovial inflammation leading to bone/joint erosionMorning stiffness, limp, or falling oftenEasy fatigabilityJoint swellingMinimal painJoint NEVER red or exquisitely tenderAlteration of activitiesLoss of function

JRA: ACR Classification CriteriaAge: < 16yo at time of onsetDuration: at least 6 weeksArthritis in one or more joints Exclusion of other rheumatologic d/oSubgroup named after 6 monthsSystemic: arthritis with feverPauciarticular: 4 or fewer jointsPolyarticular: 5 or more joints

Juvenile Idiopathic Arthritis (JIA)OligoarticularPersistent Extended (>4 joints after 6 months)RF Positive PolyarticularRF Negative PolyarticularSystemic OnsetPsoriatic ArthritisEnthesitis-related ArthritisOther

Pauci JRA4 or fewer jointsLarge joints: knees, ankles, wrists NOT HIPSerologyPositive ANANegative RFMain morbidityASYMPTOMATIC ANTERIOR UVEITIS (assoicated with positive ANA)Can lead to blindness

Poly JRA5 or more involved jointsSmall and large jointsPIP, MCP, wristRheumatoid nodulesANA may be positiveRF may be + or If + then worse prognosis

Systemic JRAMales = FemalesQuotidian feverArthritisVisceral involvementHSMLADSerositisLeukocytosisRashEvanescent, salmon coloredANA and RF negative

Fleeting salmon-color rashMacular or wheal-likeNot pruriticIrregularMay coalesce with fever

Quotidian Fever Pattern

SpondyloarthritisEnthesitis-related JIAEnthesis: insertion of ligaments and tendons into boneAsymmetrical arthritis affected 4 or fewer jointsMale predominance

Ankylosing spondylitisEnthesitis of axial skeleton and sacroiliac joints. Present with back painLoss of lumbosacral mobilityOligoarthritis of joints of lower extremitiesCommon presentationMale with back pain, morning stiffness that is relieved w/ exerciseLabs HLA-B27 positiveIncreased ESRANA and RF are NEGATIVERadiologyBamboo SpineTreatmentNSAIDS, Sulfasalazine, Mtx

JRA TreatmentNSAIDs, NaproxenDMARDS (some examples)MethotrexateAnti-TNF agentsAbatacept Low dose steroids as bridging agents

Systemic Lupus ErythematosusMultisystemic autoimmune disease of unknown etiologyMore common in femalesPrepubertal 4:1Postpubertal 8-9:1

SLE Criteria 4/114 SkinMalar RashDiscoid RashPhotosensitivityOral Ulcers2 Immunologic ANAdsDNA, anti-Smith, antiphospholipid antibodies5 Organ Systems CNSSeizurePsychosisSerositisKidneyProteinuriaArthritisNon erosiveHematologicLymphopenia (

Discoid LupusWell-circumscribed, red-purplish, elevated plaques

Malar RashSpares nasolabial folds

Oral Ulcers

TreatmentNSAIDSHydroxychloroquine (Plaquenil)Ototoxic, ocular side effectsSteroidsImmunosuppressantsCyclophosphamideAzathioprineCellceptSunscreen

Neonatal LupusMaternal Transfer of AntibodiesAnti-Ro (SS-A)Wane at 6 moEven with asymptomatic moms

ComplicationsRashHeart block usually 3rd degree50 % of babies born to moms with SLEDamage and scarring during 2nd trimesterNot reversible HepatitisNeutropenia/thrombocytopeniaHydrops fetalis

TreatmentSupportiveMay need cardiac pacing

Neonatal LupusAnnular plaquesRaccoon EyesAnnular Scaling

Congenital Heart Block

Drug Induced LupusD-SLED = Drugs for the Heart (procainimide)S = SulfonamidesL = LithiumE = Epilepsy medications (anticonvulsants)OthersINHMinocyclineMost often reversibleANAAnti-histone Ab

Juvenile Dermatomyositis (JDM)Myopathy and Vasculopathy

MyopathySymmetrical proximal muscle weakness

Vasculopathy Skin Manifestations

JDM: Clinical ManifestationsInsidious in onsetConstitutional SymptomsFatigueFeverWeight lossMuscle weaknessPhysical FindingsHeliotrope Rash Photosensitive rash upper torso, extensor surfaces of arms/legsNail fold telangiectasiasGottron papulesGowers signDysphagia/dysphonia/dyspneaNodular calcifications

Heliotrope RashViolaceous hueMalar rashPeriorbital edema

Gottrons SignPathognomonic for JDMRed,thickened, scaly skin overlying PIPs

CalcinosisNail fold dilation and loopsStriaePhotosensitive Rash

JDM: Work Up & TreatmentLabsIncreased CK, Aldolase, LDH, AST, ALTIncreased vWF AntigenUsually nl ESR/CRP+ ANA at timesRadiologyIncreased T2 signal on MRI b/l thighsEMGNormal NCS, increased muscle irritability and dischargeTreatmentSunscreen SteroidsMethotrexateIVIGComplicationsAt high risk of gastric perforation

Henoch-Schonlein Purpura (HSP)

IgA mediated leucocytoclastic vasculitisMost common small vessel vasculitis in childrenUsually preceded by URI or Strep infectionAge: 2-13 years oldUsually self limited

HSP: Clinical ManifestationsRashPalpable purpuraAngioedemaAbdomen Colicky pain (may precede skin rash)Intussusception- currant jelly stoolIleoilealArthritis Large joints: knees, ankles, wristsPeriarticular therefore no damage to jointRenalHematuriaProteinuria

Palpable PurpuraMay have some superficial ulcerationsConcentrated on buttocks and lower extremities

HSP: Laboratory EvaluationNORMAL PLATELETSMild/mod WBCUrinalysis Range from normal to nephritic picture ESRANA/RF negativeC3, C4 normalANCA negative

HSP: Clinical CourseUsually self-limited disease in childhood

Resolution of symptoms in 6-8 weeks

Recurrence in 33% within the first few months

Prognosis dependent upon renal involvementMassive GI hemorrhage in 2% of patientsModerate to severe glomerulonephritisRenal Insufficiency in 1%

HSP: TreatmentSupportive therapy for joint and abdominal complaints

NSAIDs may aggravate abdominal complaintsAvoid in pts with renal manifestations

Controversial role of steroids

Scleroderma

Linear SclerodermaLinear bands of hard,translucent, shiny skinMuscle atrophyFlexion contracture

Morphea Flesh colored, erythematous or purplish patches Ivory plaqueFirm Hyperpigmented plaque

Raynauds PhenomenonSharp demarcation

CRESTSclerodactylyCalcinosisRaynaudTelangiectasia

Kawasaki DiseaseFever 5 days plus 4/5 Rash (not vesicular)b/l non exudative bulbar conjunctivitis (limbic sparing)Oral mucus membrane changesSingle unilateral anterior cervical lymph node enlargement 1.5 cmHand/foot changes (edema, erythema, peeling)

KD: Laboratory StudiesInc WBC (PMN predominance)Inc Platelet count > 7 daysAnemia for ageInc AST and bilirubinLow AlbuminHyponatremiaInc ESR/CRPSterile pyuria

Question #1A 6 year old boy with recent strep pharyngitis presents to his pediatricians office with intermittent cramping abdominal pain for the past 2 days. He has had decreased po intake secondary to abdominal pain, and his mother reports that he has been complaining of leg pain. On examination, he is well appearing with a rash as shown below, and has a left swollen and tender ankle and knee. Of the following the most important laboratory investigation to order next is:A. CBCdiffB. IgA levelC. ANCA levelsD. Urinalysis with microscopyE. BMP

Question #2You are called to evaluate a full term newborn born three days ago to a healthy 27 year old G1P1 mother, who developed the following rash after treatment for hyperbilirubinemia with phototherapy. What is the most appropriate management of the rash?A. Referral to dermatology for KOH scrapingB. Treatment with steroid topical creamC. Advice the family on sun protection and reassure them that this is self limitedD. Refer to hematology

Question #3A 9 year old girl presents with fevers, progressive fatigue and proximal muscle weakness. She has the following rashes on presentation. The test most likely to confirm the diagnosis is:A. Slit lamp examinationB. Lab testingC. MRI thighsD. Chest X rayE. Muscle Biopsy

Question #4A 16 year old Hispanic female presents to your office after returning from summer vacation in the Caribbean for the past 2 months. She notes that over the past 2 months she has developed diffuse joint pains and swelling around her ankles which have progressed to involved her mid calves. She also notes the development of an erythematous rash on her face and neck, as well as generalized fatigue and tactile temperatures. On examination, her heart rate is 96, her temp is 37 degrees C, and her BP is 140/80. She has a malar rash, oral ulcers and 2+ pitting edema to her mid calf. Initial labs reveal:Sodium 137 mEq/LPotasium 4.7mEq/LBUN 40 mg/dLCreatinine 2.1mg/dLAlbumin 1.8 g/LHgb 8.7 g/dLUA: 3+ protein 2+bloodANA 1:2560dsDNA 1:1280

The most important subsequent test to help guide treatment is:A. MRI brainB. Kidney biopsy24 hour urine collectionEMGBone marrow aspiration

Question #5A 2 year old boy presents with 6 days of fevers to 40 degrees C, significant irritability, conjunctival injection, and diffuse maculopapular rash on his torso and lower extremities. On physical examination, he is noted to be irritable, febrile to 39 degrees, and with a strawberry tongue, unilateral cervical adenopathy, injected conjunctivae that are non-exudative and limbic sparing. Laboratory investigations reveal mild anemia, elevated ESR and CRP, and mildly elevated transaminases. He is admitted to the floor for treatment. The intervention most likely to prevent the most common and dreaded morbidity related to this disease is:A. Aspirin therapyB. AntibioticsC. IVIG therapyD. MotrinE. Steroids

*Good evening everyone. My name is Simona Nativ and I am one of the pediatric rheumatologists at Goryeb Children;s Hospital. Tonight we are going to review the most common and most commonly tested rheumatologic disorders. *What is arthritis? Arthritis is defined as swelling in a joint, tenderness upon palpation or manipulation of a joint, and restriction of range of motion of a joint. Arthritis is a clinical descriptive term and does not necessarily indicate the etiology. Juvenile rheumatoid arthritis is an autoimmune disorder in children which leads to chronic synovial inflammation leading to bone and joint erosion. Classic clinical features that occur in kids with chronic arthritis include morning stiffness, limp and clumsiness. Parents will often describe their kids are falling often, with loss of function and alteration of activities due to pain and swelling. Chronic inflammation may lead to fatigue, weight loss, and poor growth. Important to note, that while these children have swollen joints, with tenderness on manipulation and restriction, these joints are NEVER red or exquistively tender, and children should NOT report bone pain or night time wakening. The pain is described as aching and is not severe. Redness, severe pain, bone pain or nighttime wakening are key words that should imply a process other than JRA. JRA is an older classification system which defines arthritis as occuring in patients less than 16 years of age, with duration of findings >6 weeks, with arthritis in 1 or more joints, and exclusion of other rheumatologic disorders. In this classification system, the subtype is defined after 6 months of symptoms and includes only 3 categeories which are Systemic arthritis, Pauciarticular disease defined as 4 or fewer joints, and polyarticular disease defined as 5 or more joints. *The newer and more commonly used classification system is broader and includes more subtypes such as enthesitis related arthritis, psoriatic arthritis, systemic onset disease, polyarticular JIA divided into RF positive and negative, as well as oligoarticular arthritis which is divided into persistent oligoarticular and extended disease-meaning that after 6 months of symptoms patients developa more polyarticular course. **PauciJRA or oligoarticular JIA classically occurs in Caucasian females ages 2-6 years old, and typically involves larger joints such as the knees, ankles and wrists. The hips are never involved. These patients are commonly ANA positive which confers an increased risk for asymptomatic anterior uveitis. The ANA does not have any indication as to the prognosis of the arthritis, and will dictate the frequency of ophthalmology visits. The uveitis is the major morbidity and because it is asymptomatic may lead to blindness. This requires evaluation with slit lamp evaluation by an ophthalmologist. The above picture demonstrates bilaterally swollen knees with bony hypertrophy, and muscular atrophy on the left side secondary to disuse. The lower picture is an unfortunately consequence of uveitis: irregularity of the pupil due to This radiograph depicts the classic findings evident in joints of patients with ongoing arthritis: there is osteopenia, joint space narrowing and bony overgrowth of the right knee. Ongoing inflammation can also lead to erosions. *This is a classic picture of a child with olioJIA: an overall happy child, which goes back to the point that these children are not in overwhelming pain. However, he is standing with his left knee extended and flexed, a position of comfort to avoid full extension because of swelling of the knee. **Polyarticular JRA/JIA involves 5 or more joints. The joints involved are both large and small and include PIPs, MCPs and wrists. These patients may be ANA+-more likely if they are younger at onset. Patients in this category tend to be either RF positive or negative. Typically those that are RF- are younger `5-10 years old. Those that are RF positive tend to have disease that more closely mimics the destructive nature of adult RA course: with a prolonged, difficult to treat course, along with nodules, and need for more aggressive treatment. The pictures above depicte PIP swelling, and the lower right hand picture depicts rheumatoid nodules in an adult that may also occur in pediatric patients with RF+ JIA. This is a typical radiograph of a patient with polyJIA, the right carpal bones are osteopenic, with crowding, joint space narrowing and with erosions. The MCPs and PIPS are swollen, and have some ulnar deviation, and maybe some subluxation visible. *Also common to kids with polyJIA is TMJ involvement. One of the forgotten joints, TMJ involvement puts patients at risk for micrognathia if left untreated which can cause both cosmetic and medical issues due to small jaw size. **Systemic JIA is a unique subgroup in that the etiology is more common to that of Crohns disease than of the other subgroups of JIA. This is considered an autoinflammatory disease, and is treated with other types of medications than the other subgroups. Males are as commonly affected as females, and the peak ages of onset are 2-6 years of age. As its name implies, in addition to arthritis, there are systemic features which predominate and may precede arthritis features by days, weeks and sometimes even months. This can make diagnosis very difficult and patients often undergo fever of unknown origin workups prior to a diagnosis of systemic disease. They may undergo bone marrow biopsies, and other invasive procedures. Hallmarks are quotidian fevers, an evanescent, salmon colored rash which is linear or circular ~2-5mmin size, and typically located over the trunk and proximal extremities. In addition, patients may have visceral involvement such as hepatosplenomegaly, lymphadenopathy, and serositis. These patients are typically ANA, and RF negative. These are pictures of the evanescent salmon colored rash that is typically fleeting, usually with febrile spikes. The rash is not pruritic, but may be wheal like. Important to note that in patients with dark pigmentation, the rash may be difficult to discern. *The quotidian fever pattern is depicted below. Typically there are fever spikes in the morning and evening, with return to baseline in between, and occassionally mild hypothermia between febrile episodes. *Spondyloarthritis, or enthesitis related JIA represents a subgroup which has a male predomionance, and typically presents as asymmetric arthritis with enthesitis. Enthesitis is inflammation of the sites of insertion of ligaments and tendon into bone. Depicted are two schematics of entheseal points: plantar facial insertion points, patellar insertion points, and not depicted Achilles tendon insertion points into the calcaneous. These sites may be visibly swollen and painful. **Ankylosing spondylitis is the most severe form of ERA. There is typically enthesitis of the axial skeleton and SI joint involvement. These patients typically present with progressive back pain that is relieved by exericse and loss of lumbosacral mobility. There is also commonly oligoarthritis of joints of lower extremities. These patients are typically ANA and RF negative, but will have HLAB27+. Radiographic evaluation may demonstrate a bamboo spine. *This is a classic radiographic film of a bamboo spine with fusion of the vertebral bodies and often of the posterior vertebral elements as well.A bamboo spine typically involves the thoracolumbar and or lumbosacral junctions and predisposes to unstable vertebral fractures, as well as loss of lumbosacral mobility. *The knowledge of specific treatments is not necessary for the pediatric boards, and treatment plans are tailored both to the subtype, aggressiveness of disease, accompanying symptoms such as prescence of uveitis, as well as family wishes and dynamics. However, I would like to point out that over the past 20 years significant achivements have been made in terms of advancement in medications which have allowed these patients to live relatively normal lives without disabilities and wheelchairs. The biologic medications, such as the anti-TNF medications have revolutionized the forefront of the treatment of JIA. *In most basic terms lupus is an autoimmune disease with autoantibodies to self nuclear antigen in various tissue leading to organ damageMore common in females: prepuberty 4:1, after puberty 8:1*In order to make the dx must have 4 of the 11 criteria. The criteria include cutaneous findings, immunologic findings, as well as organ specific manifestations. Malar rash fixed erythema, flat or raised, spares nasolabial foldsSerositis pericarditis, pleuritis, peritoneal surfaces leading to abdominal painNON-erosive arthritisRenal: persistent proteinuria or cellular casts

*Discoid lupus may be part of the systemic form of SLE, or may be the hallmark of DLE (discoid lupus erythematosus where patients have cutaneous manifestations in absence of systemic findings). These are Well circumscribed, elevated plaques with advancing borders of scale.May show some depigmentationMost frequently on face and scalp (especially behind ears)

*The malar rash typically occurs in the Photosensitivity distributionThe rash is typically Erythematous, sometimes scaly patchNot specific for SLE-also seen in dermatomyositis*Gingivitis, mucosal hemorrhage, erosions, and ulcerationsMost commonly found on the hard palate and are painless! 10-15% of SLE patients*Treatment of SLE is complicated and again depends on many factors including organ manifestations. In addition to medications such as hydroxhycloroquine, steroids, and immunosuppressive medications, these patients must adhere to lifestyle modifications such as daily use of sunscreen. *Neonatal lupus is the one of the rare occassions you will see a pediatric rheumatologist in the NICU. This is a condition that is noted in neonates due to maternal transfer of antibodies, specifically anti-RO (SSA). Interestingly, these mothers are often healthy and without any autoimmune symptomology. The transplancental passage of this antibody, whose levels tend to wane at 6 months, may lead to significant complications. The most important of these are 3rd degree heart block which will require cardiac pacing and is due to the attack of fetal cardiac myocytes. Typically, this complication occurs in the end of the 1st-2nd trimester of fetal development, such that this is an irreversible process. Other complications, include rash (which I will show you in th next slide), heptatiis, neutropenia/thrombocytopenia, and hydrops fetalis. Typically these patients are treated supportively and in the case of the rash are given sun protection advise as the rash is photosensitive. Mothers with known SLE, and with previous infants with heart block are monitored throughout prgnancy with fetal echocardiography. *The mean age of onsetof rash is 6weeks,but can be as late as 3 monthswith new lesions rarely occur after 3 monthsThe rash, and antibodies will typically clear by 6-12 months and there are no lasting effects bc maternal IgG antibodies are cleared by the infantApprox 1/4 have lasting scarring/atrophy/depigmentation/telangiectasias*NLE is the most frequent cause of congenital heart block!Occurs in 25-30% of affected patients*Important to know are medications which may cause drug induced SLE. These drugs include procainadmide, sulfonamides, lithium, anticonvulsants, INH, and monocycline. These patients will have indistinguishable features from patients with SLE, and may even have similar serologies, butwill typically have anti-histone antibodies. The removal of the offending agent will lead to reversibility in the majority of these patients. *Another interesting, and rare disorder is JDM. This is a myopathy which presents as symmetrical proximal muscle weakness, as well as a vasculopathy typically with cutaneous manifestations. *The onset is typically insidious, and patients will present with constitutional symptoms such as fever, fatigue, weight loss, and muscle weakness. Muscular wekaness may also lead to dysphagia/dysphonia and dyspnea in severe cases. On physical examination, heliotrope rash, photosensivie rashes, nail fold telangiectasias, Gotrrons papules, and nodular calcifications are presents. *The heliotrope rash presens as a violaceous rash on the upper and lower eyelids There may be periorbital edema as well. The malar rash associated with JDM may or may not spare the nasolabial folds. *Pathognomonic for JDM is the Gotrons signs which presents as red, thickened scaly skin that overlies the PIPs, and MCPs. Othe cutaneous manifestations include a photosensitive rash, and calcinosis. These are subcutenaous calcium deposits, which are disfiguring and may also lead to contractures depending on their location. They are very difficult to treat, and may be the nidus for infections when they rupture leading to oozing of a white toothpaste like material. Surrgical removal often leads to recurrence and medications are not usually helpful. A simple way to evaluate for vasculopathy is manification of the capillaries surrounding the nailbed using a device known as a dermatoscope. Typical findings may include capillary dilation and loops. **Typically these patients will have elevated muscle markers, and depending on their presentation may have normal inflammatory markers. Myopathy may be present on specially protocolized MRIs which show increased T2 signals within the thighs. However, the GOLD standard remains findings of necrosis, edema and inflammation on muscle biopsy. Treatment includes suncreen, and immunosuppressive medications. *Remember that purpura blanch on pressure and then can progress to petechiae, can occur in crops, last 3-10 daysEdema occurs in dependent areas LE, buttocks, scrotum, eyelidsComplications of HSP include: nephrotic sydrome, bowel perforation, testicular torsion from scrotal edema*****Literally means hardened skinAlthough pathophysiology between two categories are similar as well as skin findings,They are two separate entities with respect to prognosis.Only rare cases of localized scleroderma have shown any evidence of visceral involvement. *Sclerotic areas occuring in linear distribution often on limbsLimbs often indurated with associated indentation or puckeringMay lead to contracturesWasting of muscle and bone**-Characterized by pallor, cyanosis, and hyperemia with pain, burning, numbness, tingling, swelling, and hyperhidrosis of the affected fingers and toes. -Precipitated by cold or emotional stress-All pts with scleroderma, 10-30% of patiens with SLE, or primary disorder-Recent review, 69% of patients had primary form. *