1. Pediatric Rheumatology Board Review
Simona Nativ, MD
Pediatric Rheumatology
Goryeb Children’s Hospital
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.

2. Juvenile Rheumatoid Arthritis (JRA)
Synovial inflammation leading to bone/joint erosion
Morning stiffness, limp, or falling often
Easy fatigability
Joint swelling
Minimal pain
Joint NEVER red or exquisitely tender
Alteration of activities
Loss of function
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.

3. JRA: ACR Classification Criteria
Age: < 16yo at time of onset
Duration: at least 6 weeks
Arthritis in one or more joints
Exclusion of other rheumatologic d/o
Subgroup named after 6 months
Systemic: arthritis with fever
Pauciarticular: 4 or fewer joints
Polyarticular: 5 or more joints
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.

4. Juvenile Idiopathic Arthritis (JIA)
Oligoarticular
Persistent
Extended (>4 joints after 6 months)
RF Positive Polyarticular
RF Negative Polyarticular
Systemic Onset
Psoriatic Arthritis
Enthesitis-related Arthritis
Other
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.

5. Pauci JRA 4 or fewer joints Serology Main morbidity
Large joints: knees, ankles, wrists
NOT HIP
Serology
Positive ANA
Negative RF
Main morbidity
ASYMPTOMATIC ANTERIOR UVEITIS
(assoicated with positive ANA)
Can lead to blindness
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

6. 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.

7. 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.

8. Poly JRA 5 or more involved joints Rheumatoid nodules
Small and large joints
PIP, MCP, wrist
Rheumatoid nodules
ANA may be positive
RF may be + or –
If + then worse prognosis
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.

9. 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.

10. Also common to kids with polyJIA is TMJ involvement
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.

11. Systemic JRA Males = Females Quotidian fever Arthritis
Visceral involvement
HSM
LAD
Serositis
Leukocytosis
Rash
Evanescent, salmon colored
ANA and RF negative
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.

12. “Fleeting salmon-color rash” Macular or wheal-like Not pruritic
Irregular
May coalesce with fever
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.

13. Quotidian Fever Pattern
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.

14. Spondyloarthritis Enthesitis-related JIA
Enthesis: insertion of ligaments and tendons into bone
Asymmetrical arthritis affected 4 or fewer joints
Male predominance
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.

15. Ankylosing spondylitis
Enthesitis of axial skeleton and sacroiliac joints.
Present with back pain
Loss of lumbosacral mobility
Oligoarthritis of joints of lower extremities
Common presentation
Male with back pain, morning stiffness that is relieved w/ exercise
Labs
HLA-B27 positive
Increased ESR
ANA and RF are NEGATIVE
Radiology
Bamboo Spine
Treatment
NSAIDS, Sulfasalazine, Mtx
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.

16. 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.

17. JRA Treatment NSAIDs, Naproxen DMARDS (some examples)
Methotrexate
Anti-TNF agents
Abatacept
Low dose steroids as bridging agents
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.

18. Could it Be lupus?

19. Systemic Lupus Erythematosus
Multisystemic autoimmune disease of unknown etiology
More common in females
Prepubertal 4:1
Postpubertal 8-9:1
In most basic terms lupus is an autoimmune disease with autoantibodies to self nuclear antigen in various tissue leading to organ damage
More common in females: prepuberty 4:1, after puberty 8:1

20. SLE Criteria  4/11 Malar Rash Discoid Rash Photosensitivity
5 Organ Systems
CNS
Seizure
Psychosis
Serositis
Kidney
Proteinuria
Arthritis
Non erosive
Hematologic
Lymphopenia (<4,000)
Lymphopenia (<1,500)
AIHA
Thrombocytopenia (<100,000)
4 Skin
Malar Rash
Discoid Rash
Photosensitivity
Oral Ulcers
2 Immunologic
ANA
dsDNA, anti-Smith, antiphospholipid antibodies
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 folds
Serositis – pericarditis, pleuritis, peritoneal surfaces leading to abdominal pain
NON-erosive arthritis
Renal: persistent proteinuria or cellular casts

21. Discoid Lupus Well-circumscribed, red-purplish, elevated plaques
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 depigmentation
Most frequently on face and scalp (especially behind ears)

22. Malar Rash Spares nasolabial folds
The malar rash typically occurs in the Photosensitivity distribution
The rash is typically Erythematous, sometimes scaly patch
Not specific for SLE-also seen in dermatomyositis
Spares nasolabial folds

23. Oral Ulcers Gingivitis, mucosal hemorrhage, erosions, and ulcerations
Most commonly found on the hard palate and are painless!
10-15% of SLE patients

24. Treatment NSAIDS Hydroxychloroquine (Plaquenil) Steroids
Ototoxic, ocular side effects
Steroids
Immunosuppressants
Cyclophosphamide
Azathioprine
Cellcept
Sunscreen
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.

25. Neonatal Lupus Maternal Transfer of Antibodies Complications Treatment
Anti-Ro (SS-A)
Wane at 6 mo
Even with asymptomatic mom’s
Complications
Rash
Heart block – usually 3rd degree
50 % of babies born to moms with SLE
Damage and scarring during 2nd trimester
Not reversible
Hepatitis
Neutropenia/thrombocytopenia
Hydrops fetalis
Treatment
Supportive
May need cardiac pacing
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.

26. Neonatal Lupus Raccoon Eyes Annular Scaling Annular plaques
The mean age of onsetof rash is 6weeks,but can be as late as 3 months…with new lesions rarely occur after 3 months
The rash, and antibodies will typically clear by 6-12 months and there are no lasting effects bc maternal IgG antibodies are cleared by the infant
Approx 1/4 have lasting scarring/atrophy/depigmentation/telangiectasias
Annular plaques

27. Congenital Heart Block
NLE is the most frequent cause of congenital heart block!
Occurs in 25-30% of affected patients

28. Drug Induced Lupus D-SLE Others Most often reversible ANA
D = Drugs for the Heart (procainimide)
S = Sulfonamides
L = Lithium
E = Epilepsy medications (anticonvulsants)
Others
INH
Minocycline
Most often reversible
ANA
Anti-histone Ab
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.

29. Juvenile Dermatomyositis (JDM)
Myopathy and Vasculopathy
MyopathySymmetrical proximal muscle weakness
Vasculopathy  Skin Manifestations
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.

30. JDM: Clinical Manifestations
Insidious in onset
Constitutional Symptoms
Fatigue
Fever
Weight loss
Muscle weakness
Physical Findings
Heliotrope Rash
Photosensitive rash – upper torso, extensor surfaces of arms/legs
Nail fold telangiectasias
Gottron papules
Gower’s sign
Dysphagia/dysphonia/dyspnea
Nodular calcifications
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.

31. Heliotrope Rash Violaceous hue Periorbital edema Malar rash
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.
Malar rash

32. Gottron’s Sign Pathognomonic for JDM
Pathognomonic for JDM is the Gotrons signs which presents as red, thickened scaly skin that overlies the PIPs, and MCPs.
Red,thickened, scaly skin
overlying PIPs

33. Nail fold dilation and loops
Calcinosis
Striae
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.
Photosensitive Rash
Nail fold dilation and loops

34. JDM: Work Up & Treatment
Labs
Increased CK, Aldolase, LDH, AST, ALT
Increased vWF Antigen
Usually nl ESR/CRP
+ ANA at times
Radiology
Increased T2 signal on MRI b/l thighs
EMG
Normal NCS, increased muscle irritability and discharge
Treatment
Sunscreen
Steroids
Methotrexate
IVIG
Complications
At high risk of gastric perforation
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.

35. Henoch-Schonlein Purpura (HSP)
IgA mediated leucocytoclastic vasculitis
Most common small vessel vasculitis in children
Usually preceded by URI or Strep infection
Age: 2-13 years old
Usually self limited
Remember that purpura blanch on pressure and then can progress to petechiae, can occur in crops, last 3-10 days
Edema occurs in dependent areas – LE, buttocks, scrotum, eyelids
Complications of HSP include: nephrotic sydrome, bowel perforation, testicular torsion from scrotal edema

36. HSP: Clinical Manifestations
Rash
Palpable purpura
Angioedema
Abdomen
Colicky pain (may precede skin rash)
Intussusception- currant jelly stool
Ileoileal
Arthritis
Large joints: knees, ankles, wrists
Periarticular therefore no damage to joint
Renal
Hematuria
Proteinuria

37. Palpable Purpura May have some superficial ulcerations
Concentrated on buttocks and lower extremities

38. HSP: Laboratory Evaluation
NORMAL PLATELETS
Mild/mod  WBC
Urinalysis
Range from normal to nephritic picture
 ESR
ANA/RF negative
C3, C4 normal
ANCA negative

39. HSP: Clinical Course Usually self-limited disease in childhood
Resolution of symptoms in 6-8 weeks
Recurrence in 33% within the first few months
Prognosis dependent upon renal involvement
Massive GI hemorrhage in 2% of patients
Moderate to severe glomerulonephritis
Renal Insufficiency in 1%

40. HSP: Treatment Supportive therapy for joint and abdominal complaints
NSAIDs may aggravate abdominal complaints
Avoid in pts with renal manifestations
Controversial role of steroids

41. Scleroderma Literally means hardened skin
Although 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.

42. Linear Scleroderma Linear bands of hard, translucent, shiny skin
Flexion contracture
Muscle atrophy
Sclerotic areas occuring in linear distribution often on limbs
Limbs often indurated with associated indentation or puckering
May lead to contractures
Wasting of muscle and bone

43. Morphea Flesh colored, erythematous or purplish patches
Firm Hyperpigmented
plaque
Ivory plaque

44. Raynaud’s Phenomenon Sharp demarcation
-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.

45. CREST
Calcinosis
Sclerodactyly
Raynaud
Telangiectasia

46. Kawasaki Disease Fever ≥ 5 days plus 4/5 Rash (not vesicular)
b/l non exudative bulbar conjunctivitis (limbic sparing)
Oral mucus membrane changes
Single unilateral anterior cervical lymph node enlargement ≥ 1.5 cm
Hand/foot changes (edema, erythema, peeling)

50. KD: Laboratory Studies
Inc WBC (PMN predominance)
Inc Platelet count > 7 days
Anemia for age
Inc AST and bilirubin
Low Albumin
Hyponatremia
Inc ESR/CRP
Sterile pyuria

51. Question #1
A 6 year old boy with recent strep pharyngitis presents to his pediatrician’s 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. CBCdiff
B. IgA level
C. ANCA levels
D. Urinalysis with microscopy
E. BMP

52. Question #2
You 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 scraping
B. Treatment with steroid topical cream
C. Advice the family on sun protection and reassure them that this is self limited
D. Refer to hematology

53. Question #3
A 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 examination
B. Lab testing
C. MRI thighs
D. Chest X ray
E. Muscle Biopsy

54. The most important subsequent test to help guide treatment is:
Question #4
A 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/L
Potasium 4.7mEq/L
BUN 40 mg/dL
Creatinine 2.1mg/dL
Albumin 1.8 g/L
Hgb 8.7 g/dL
UA: 3+ protein 2+blood
ANA 1:2560
dsDNA 1:1280
The most important subsequent test to help guide treatment is:
A. MRI brain
B. Kidney biopsy
24 hour urine collection
EMG
Bone marrow aspiration

55. Question #5
A 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 therapy
B. Antibiotics
C. IVIG therapy
D. Motrin
E. Steroids