RCC REVIEW:

RHEUMATOLOGY AND MSK

Muhammed Dhalla
December 5, 2019
• 2.1.18.1. Anatomy, structure and function of bone, joint and connective tissues, normal and abnormal 
OBJECTIVES
• 2.1.18.2. Physiology of normal bone growth and function
• 2.1.18.3. Recognition of non-inflammatory connective tissue diseases, e.g. Marfan's syndrome, Ehlers Danlos syndrome 
• 2.1.18.4. Mechanisms of immune responses in rheumatic disease 
• 2.1.18.5. Indications for, and interpretation of laboratory tests on blood and synovial fluid 
• 2.1.18.6. Pharmacology of common anti-inflammatory drugs, corticosteroids and immunosuppressive drugs 
• 2.1.18.7. Effects of chronic rheumatic diseases on physical growth and social development 
• 2.1.18.8. Common radiographic abnormalities in musculoskeletal diseases
•
2.1.18.9.1. Congenital abnormalities 
• 2.1.18.9.2. Joint and limb pain 
• 2.1.18.9.3. Common fractures, dislocations or injuries 
• 2.1.18.9.4. Joint deformities 
• 2.1.18.9.5. Septic arthritis and osteomyelitis 
• 2.1.18.9.6. Common gait disorders (limp, torsional and angular deformities of lower limbs) 
• 2.1.18.9.7. Scoliosis 
• 2.1.18.9.8. Acute / chronic arthritis 
• 2.1.18.9.9. Systemic rheumatologic diseases, e.g. systemic lupus erythematosis, juvenile idiopathic (rheumatoid) arthritis 
• 2.1.18.9.10. Bone tumors  
 2.1.18.9.9.
SYSTEMIC RHEUMATOLOGIC DISEASES
• Broad categories of Rheumatologic Disease:
• “Autoimmune”
• Juvenile Idiopathic Arthritis
• Connective Tissue Diseases
• Systemic lupus erythematosus
• Juvenile Dermatomyositis
• Mixed / Undifferentiated connective tissue disease
• Vasculitis
• Systemic (large, medium, and small-vessel)
• Localized (cutaneous PAN, CNS vasculitis)
• “Autoinflammatory”
• Periodic Fever Syndromes
• Chronic Recurrent Multifocal Osteomyelitis (CRMO/CNO)
JUVENILE ARTHRITIS
 2.1.18.9.9.
SYSTEMIC RHEUMATOLOGIC DISEASES
• Juvenile Idiopathic Arthritis: Basic Definitions
• Arthritis: inflammation of a joint, characterized by an effusion, or by the presence of at least 2 of:
swelling, erythema, painful range of motion/tenderness.
• Chronic Arthritis: arthritis lasting in a single joint for at least 6 weeks.
• Juvenile Idiopathic Arthritis: chronic arthritis with onset before age 16.

• Oligoarticular: involvement of no more than 4 joints within the first 6 months (accumulated).
• Can be classified as “persistent” if never more than 4, and “extended” if eventually includes more than
4 total joints.
• Polyarticular: involvement of at least 5 joints within the first 6 months
 2.1.18.9.9.
SYSTEMIC RHEUMATOLOGIC DISEASES
• Differential Diagnosis Infectious Mechanical
Septic Arthritis Traumautic
• Fracture
Osteomyelitis
• Hemarthrosis
Transient Synovitis
Developmental
• Slipped Capital Femoral Epiphysis
• Legg-Calve-Perthes (AVN)
• Osgood-Schlatter Disease
• Sindig-Larsen-Johansson Disease

Inflammatory
Bone/Muscle
Reactive Arthritis
Post-Strep Reactive Arthritis Malignancy
Viral Arthropathy • Bone (osteosarcoma, Ewings)
Juvenile Arthritis: • Muscle (rhabdomyosarcoma)
• Juvenile Idiopathic • Synovium (PVNS)
• IBD-associated Cerebral Palsy
• CF-associated Muscular Dystrophy
Systemic Lupus Erythematosus
Vasculitis
Sarcoidosis
 2.1.18.9.9.
SYSTEMIC RHEUMATOLOGIC DISEASES
• Classification:
**Exclusions:
A)  Psoriasis or history of psoriasis in patients or first-
degree relatives (formally diagnosed).
B) Arthritis in HLA B27 positive males beginning after
the age of 6 years.
C) Ankylosing spondylitis, ERA, sacroilitis with IBD,
Reiter's syndrome, acute anterior uveitis, or history of
any in first-degree relative.
D) Presence of IgM RF on at least 2 occasions 3
months apart.
E) Presence of systemic-onset JIA in patients.
 2.1.18.9.9.
SYSTEMIC RHEUMATOLOGIC DISEASES
• Epidemiology:
• Incidence: 7-21 / 100 000 || Prevalence ~ 200 / 100 000
• ~ 10% systemic, 10% psoriatic, 10-15% ERA, 20% polyarticular, 40% oligoarticular
• Multiple genetic markers associated with each of the different subtypes. Most important
things to remember:
• HLA-B27 associated with enthesitis-related arthritis
• Other HLAs are associated with other subtypes of JIA
 2.1.18.9.9.
SYSTEMIC RHEUMATOLOGIC DISEASES
• Presentation: depends on subtype (but strong similarities)
• Oligoarticular: typically presents with asymmetric large joint arthritis of a lower extremity (knee
89%, ankle 36%), usually in a young child (peak age 1-3 years).
• Polyarticular:
• RF positive: presents in adolescent females, typically with multiple joints simultaneously, usually as
symmetric small joint.
• RF negative: bimodal peaks in childhood (1-3 years, F > M) and adolescence (F >> M)
• Psoriatic: bimodal peak in infancy (peak 3 years) where it mimics oligoarticular JIA, and in late
childhood (10-14 years) where it mimics RF negative or ERA.
• Enthesitis-related arthritis: typically presents as either oligoarthritis of a lower extremity in a
preadolescent male, or with chronic insidious lower back pain in an adolescent male (can affect
both genders).
• Characterized by the presence of Enthesitis, or tenderness at entheseal insertions.
 2.1.18.9.9.
SYSTEMIC RHEUMATOLOGIC DISEASES
 2.1.18.9.9.
SYSTEMIC RHEUMATOLOGIC DISEASES
• Systemic JIA: will likely soon be reclassified as an autoinflammatory disease.
• Typically presents in early childhood (age 1-5 years) with fever and arthritis.
• Fever: Quotidien fevers (i.e. qD-BID, rapid rise / fall, high peaks above 39C)
• Arthritis: typically large joint polyarticular, but highly variable.
• Historically the most destructive arthritis when present, particularly in the hips.
• Arthritis present in ~ 90% at onset (compared to fever at 98%).
• Rash: evanescent (meaning comes and goes, usually with fever), salmon colored rash of varying
distribution and symptoms. Non-vesicular. Occasionally urticarial.
• Other: lymphadenopathy, HSM, pleural effusion, hepatitis, pericarditis.

• Macrophage Activation Syndrome: a severe potential complication of sJIA most easily

distinguished by extreme hyperferitinemia and hepatitis. Will discuss later.
 2.1.18.9.9.
SYSTEMIC RHEUMATOLOGIC DISEASES
• Presentation: What defines inflammatory joint pain?
• Worse in the morning, improves throughout the day.
• Worse with rest and better with activity.
• Stiffness tends to be worse than pain, and may cause functional issues.
• Symptoms tend to be either constant or ebb and flow over weeks (i.e. several weeks of
symptoms, then few weeks of no symptoms).
• IE the patients who have pain a few nights a week here and there are not JIA
• Involved joints tend to follow certain patterns, at least in many cases.
 2.1.18.9.9.
SYSTEMIC RHEUMATOLOGIC DISEASES
• Major complications:
• MSK: chronic (untreated) arthritis leads to growth asymmetry* and leg length discrepancy, short
stature, chronic deformity, chronic osteoarthritis, and osteoporosis (and subsequent fracture risk).
• Uveitis: most important associated complication of JIA; accounts for up to 40% of all childhood
uveitis, and occurs in 10-15% of all children with JIA (30% of oligo)
• In majority of cases is ASYMPTOMATIC until complications develop.
• Ultimate complication is blindness: on the way there, can develop keratopathy, synechiae, glaucoma,
cataracts, and cystoid macular edema.
• Other: poor joints lead to poor sports participation and social exclusion, which can have
numerous metabolic and mental health effects throughout childhood.
 2.1.18.9.9.
SYSTEMIC RHEUMATOLOGIC DISEASES
• Investigations (2.1.18.5. Indications for, and interpretation of laboratory tests)
• ANA: is a risk factor for uveitis in the context of JIA.
• ANA does not change the risk of JIA whatsoever; whether titer is 1:40 or 1:4000, the likeliehood of JIA is unaffected.
• ANA in high titers may suggest the presence of a connective tissue disease such as SLE. In teenage females it is
helpful to consider whether SLE should be thought of.
• Rheumatoid Factor: unlike adults, 95% of children have RF negative disease. Should order it in adolescents
or those with polyarticular small joint disease.
• RF is only positive if it persists for beyond 3 months. There are many causes of transiently positive RF, most
commonly infection.
• HLA-B27: is seen in 10% of the HEALTHY population; given the incidence of JIA is low, a positive HLA-
B27 affects post-test probability but does not give a diagnosis. It is used for classification and risk
stratification.
• Bloodwork for work-up: ANA, RF, HLA-B27, celiac screen, CBC, albumin, ESR/CRP, iron studies (for IBD
arthropathy), TSH, FT4
 2.1.18.9.9.
SYSTEMIC RHEUMATOLOGIC DISEASES
• Investigations: Joint aspiration and Injection.
• Joint aspirate is NOT part of the work-up for juvenile arthritis; it is done when considering
alternate conditions as a way to rule them out.
• The most common (and in common practice, only) reason to consider a joint aspiration is to rule
out septic arthritis – i.e. in the context of acute arthritis.
• Most often seen in adult medicine, because gout is a common differential and on exam can be
indistinguishable from septic arthritis.

• In the context of chronic arthritis, a joint aspirate is rarely necessary or helpful.

 2.1.18.9.9.
SYSTEMIC RHEUMATOLOGIC DISEASES
• However… because they like to ask it sometimes…
 2.1.18.9.9.
SYSTEMIC RHEUMATOLOGIC DISEASES
• Management:
1. Corticosteroid Injection: direct injection with steroid (typically TA) results in rapid
improvement or resolution of arthritis, with effects lasting 3-24 months. Is rapid and
inexpensive.
In younger children, will require sedation. Will only target the joints you choose (i.e. will miss
subclinical joints). Can make infections worse if wrong diagnosis.
Complications can include local / cosmetic, infection, bleeding, anesthesia.
 2.1.18.9.9.
SYSTEMIC RHEUMATOLOGIC DISEASES
• Management
2. NSAIDs: inhibit COX, which converts arachidonic acid into proinflammatory molecules
(prostaglandin, thromboxanes, prostacyclins).
Most commonly recommend Naproxen because T1/2 allows for BID dosing. Anti-inflammatory
treatment requires high doses in a sustained manner.
Naproxen: 15-20 mg/kg/d divided BID for at least 2 months
Ibuprofen 30-40 mg/kg/d divided TID or QID for at least 2 months
Celecoxib 50-100 mg daily or BID for at least 2 months.
Adverse effects are uncommon and usually preventable. Can see dyspepsia/GI ulcer, renal
injury, and pseudoporphyria.
 2.1.18.9.9.
SYSTEMIC RHEUMATOLOGIC DISEASES
• Management:
3. Systemic Corticosteroids: highly effective for short term management, extremely poor long-
term monotherapy. Long list of adverse effects. Will sometimes be used to induce remission
while awaiting proper treatment.
**Please do NOT use without d/w rheumatology, as it will mask/treat joints**
4. Methotrexate: Disease modifying anti-rheumatic drug (DMARD). First line therapy for all
extensive JIA or disease refractory to NSAID/injection. Used in low doses – is well tolerated,
safe, and efficacious in 80% of patients.
Adverse effects include immunosuppression (minor degree), transaminitis (reversible in vast
majority), GI intolerance / oral ulcers (manageable). Is extremely teratogenic while using it.
Should avoid alcohol.
Cannot have LIVE vaccinations per current recommendations.
5. Other DMARDS: Leflunomide, Sulfasalazine, Thalidomide, +/- Plaquenil.
 2.1.18.9.9.
SYSTEMIC RHEUMATOLOGIC DISEASES
• Management: Biologics
• Biologics are a category of synthesized antibodies that range from fully-human to chimeric.
Within each category they share adverse effect profiles.
• The most common ones to be aware of are the Anti-TNF agents, which include:
Enbrel (Etanercept) / Erelzi
Remicaide (Infliximab)
Humira (Adalimumab)
The main differences are in method of delivery (IV vs. SC), frequency (q1w-q8w), and
immunogenicity (ability to induce other autoimmune disease).
Main adverse effects are immunosuppression (moderate risk), latent disease reactivation
(hepatitis/TB), injection/infusion reaction, demyelinating disease*, and autoimmune disease*

Cannot have live vaccinations.

 2.1.18.9.9.
SYSTEMIC RHEUMATOLOGIC DISEASES
• Management: Other Biologics
• Rituximab: anti-CD20, used in refractory arthritis and SLE
• Abatacept: anti-CTLA4, used in refractory arthritis
• Anakinra: anti-IL1R antagonist, used in systemic JIA, MAS, fever syndromes.
• Canakinumab: anti-IL1 agent, used in systemic JIA and fever syndromes.
• Tocilizumab: anti-IL6 agent, used in systemic JIA and refractory polyarticular JIA
 2.1.18.9.9.
SYSTEMIC RHEUMATOLOGIC DISEASES
• Management: Role of the Pediatrician:
• Encourage families to follow directions for regular labwork. Ensures complications can be
caught early and prevented.
• See patients on immunosuppressants who have fever – may need throat swab, cultures, and
consideration for empiric antibiotics.
• Encourage those on methotrexate to use double contraception and avoid / abstain from alcohol.
• Do not prescribe sulfa antibiotics to those on methotrexate.
RELATED CONDITIONS
 2.1.18.9.9.
SYSTEMIC RHEUMATOLOGIC DISEASES
• Septic Arthritis: acute monoarthritis (usually), most often caused by gram positive
organism such as Staph or Strep. Consider K. Kingae as a gram negative organism, seen in
up to 10% of cases. Other organisms based on risk factors. Typically will be acute in onset
with a hot, red, swollen joint and accompanying systemic illness. Diagnosis ideally through
joint aspiration for fluid and culture and blood counts. Etiologic agent only found in 2/3 of
cases. Managed with antibiotics and aspiration / drainage. \
• Transient Synovitis: Most often a condition of the hip, and primary differential for young
children with limp. Typically less painful (can weightbear with difficulty) and less
systemically unwell. Use the Kocher criteria to distinguish between TS and septic arthritis.
 2.1.18.9.9.
SYSTEMIC RHEUMATOLOGIC DISEASES
• Lyme Disease: read the CPS statement! Arthritis is a “late disease” manifestation, typically
manifesting ~ 4 months after tick bite (though can be seen sooner). Is indistinguishable from
oligoarticular JIA – usually a monoarthritis of a knee; joint fluid typical for inflammation not
infection, and spirochetes not seen on joint fluid in general.
Diagnosis through serologic testing in at-risk individuals. Always ask about a history of tick
exposure / travel to Lyme endemic areas.
Even with treatment, a significant minority can have chronic inflammatory arthritis and
ultimately a diagnosis of JIA.

• Chronic Lyme Disease: this is not a thing; do not refer this to us. Please.
 2.1.18.9.9.
SYSTEMIC RHEUMATOLOGIC DISEASES
• Reactive Arthritis: currently this term encompasses several former diagnoses: typical
reactive arthritis, Reiter syndrome, and post-strep reactive arthritis:
• Typical: the typical description of reactive arthritis is a peripheral arthritis involving one or
several joints that follows a few weeks after an infection with a dysentery-like illness
(salmonella, yersinia, etc…). Other agents include chlamydia and mycoplasma. Can also cause
dactylitis and enthesitis. Will see elevated inflammatory makers; joint fluid similar to
inflammatory. Typically resolves within few weeks to months, and can be managed with
NSAIDs. Some proportion go on to have chronic or recurrent arthritis and may be reclassified as
JIA/ERA. Sulfasalazine favored over methotrexate.
• Reiter Syndrome: described a triad of arthritis, conjunctivitis/uveitis, and urethritis. No longer an
independent term.
 2.1.18.9.9.
SYSTEMIC RHEUMATOLOGIC DISEASES
• Post-Strep Reactive Arthritis: a peripheral arthritis that follows soon after a GAS infection
(typically < 10 days). Is additive, typically lasting ~ 2 months, with some cases lasting up to
6 months or having recurrences. Has been associated with erythema nodosum in some cases.
Has moderate response to ASA / NSAIDs, but is typically self-limited. Throat swab often
positive given the latency from diagnosis. Management is NSAIDs.
• Rheumatic Fever: a systemic disease typified by carditis, arthritis, and typical rash. Usually
occurs several weeks after strep infection. Diagnosis is clinical using the Jones Criteria. Key
note is the arthritis is migratory and highly responsive to ASA and NSAIDs. Treatment is
supportive and with antibiotics (clearance -> prophylaxis).
 2.1.18.9.9.
SYSTEMIC RHEUMATOLOGIC DISEASES
• IBD-Associated Arthropathy: one of the most common extraintestinal manifestations of CD >
UC. Most common manifestation is arthropathy and arthralgias without true arthritis. 2 major
patterns are described:
• Peripheral: this tends to follow a pattern of oligoarticular JIA involving large, more proximal joints
(though can involve any / all joints). Follows the course of the disease and management is by
improving control of underlying CD. If arthritis like this flares, it is likely there is a subclinical CD
flare in the bowel.
• Axial: this tends to mimic ERA / AS, and is more common in those who are HLAB27 positive. Tends
to be independent from IBD course and often requires treatment independent of IBD (though
treatments tend to overlap).
• CF-Associated Arthropathy: seen in up to 8% of patients with CF. Typical presentation is
transient arthritis lasting 1-10 days with full resolution and relapses. NSAIDs usually sufficient.
• Celiac Disease: It is known that celiac patients can have an inflammatory arthropathy that
responds to GFD; however, also higher risk of JIA. If there is likely JIA, should screen for
Celiac, and if positive, treat before diagnosing JIA formally.
SYSTEMIC LUPUS
 2.1.18.9.9.
SYSTEMIC RHEUMATOLOGIC DISEASES
• The prototypic autoimmune disease, caused by a loss of Tolerance.
• An antibody mediated disease (at it’s most simple level of comprehension).
• There are some subtypes of “congenital” SLE that are related to direct defects in the complement
pathway.
• The most common of these is homozygous anti-C1q deficiency, wherein 90% of affected patients
will have SLE. Also seen in C2 and C4 deficiencies.
• Typified by the Anti-dsDNA Antibody (more antibodies will be discussed).
• Typified by involvement of skin, blood/marrow, and kidneys in majority.

• Unlike adults, pediatric SLE tends to have more frequent / severe organ manifestations, less
commonly has sicca symptoms / arthritis, and can have a more defined genetic basis.
 2.1.18.9.9.
SYSTEMIC RHEUMATOLOGIC DISEASES
• Classification Criteria*
• ACR Criteria (for classification) - most recently modified in 1997. Classification requires any 4 criteria, and has
a 76.6% sensitivity, and 93.4% specificity in children.
• Malar rash (fixed erythema, flat or raised, sparing nasolabial folds)
• Discoid rash (raised erythematous patches with keratotic scaling and follicular plugging)
• Photosensitivity (rash from exposure to sunlight)
• Oral or Nasopharyngeal ulceration (usually painless)
• Arthritis (non-erosive, involving at least 2 peripheral joints)
• Serositis (pleuritis, pleural effusion, pericarditis, pericardial effusion)
• Renal disorder (proteinuria > 0.5 g/d, or cellular casts)
• Neurologic disorder (seizures or psychosis, without other explanation)
• Hematologic disorder (hemolytic anemia, leukopenia (< 4.0), lymphopenia (< 1.5), or thrombocytopenia)
• Immunologic disorder (dsDNA, Sm, LAC, ACl, or false positive RPR)
• Positive ANA
 2.1.18.9.9.
SYSTEMIC RHEUMATOLOGIC DISEASES
• Epidemiology:
• Incidence ~ 1 / 100 000; Prevalence ~ 2-25/100 000
• Typical (pediatric) age of onset in early adolescence (5:1 F to M ratio)
 2.1.18.9.9.
SYSTEMIC RHEUMATOLOGIC DISEASES
• Typical Manifestations: The ACR criteria are common manifestations.
• Systemic: fevers, malaise, fatigue, lymphadenopathy, weight loss.
• Rashes: malar, photosensitive, discoid, others (many types; any rash can be SLE), oral / nasal
ulceration.
• Sicca Symptoms: dry mouth (excessive cariogenesis), dry eyes (ulcerations).
• MSK: myositis, arthralgia, arthritis (typically non-erosive, symmetric, small joint).
• End-Organ:
• Neuropsychiatric (seizures, psychosis || anxiety, depression, headaches*)
• Cardiopulmonary (effusions, hemorrhages, endocarditis)
• Vascular (vasculitis, Raynaud phenomenon)
• Thromboembolic (stroke, coronary sinus venous thrombosis, DVT/PE) – related to APLs
• Glomerulonephritis (5 subtypes; affects 20-75%, with 20-50% developing ESRD).
 2.1.18.9.9.
SYSTEMIC RHEUMATOLOGIC DISEASES
• Note on Cutaneous Lupus: it is seen in pediatrics, and does not necessitate a referral to rheumatology in
all cases.
• Myriad of cutaneous manifestations of SLE, most of which can be seen in systemic and cutaneous SLE.
• Malar rash, photosensitivity, discoid, tumid, subacute cutaneous, RP
• Bullous, livedo, vasculitic, alopecia, oral/nasal ulcers.
• The first half of these are seen in both systemic and cutaneous, while the latter are seen in systemic (or
in other conditions).
• In general if you have a patient with isolated cutaneous features:
• Do full set of SLE labs (will discuss shortly)
• Refer to Dermatology for biopsy to confirm
• If anything positive on labs – refer to rheumatology; if work-up negative, consider repeating annually or as
needed and refer if becomes positive.
 2.1.18.9.9.
SYSTEMIC RHEUMATOLOGIC DISEASES
• Investigations: Antibodies
• ANA: Highly sensitive, poorly specific. Excellent screening tool.
• 99% of patients will be positive for ANA (usually at titer above 1:80, not always).
• Up to 20% of healthy pediatric population positive for ANA at 1:40-1:80.
• This means you only order an ANA if you suspect SLE* – if it is negative there is almost NO reason to refer
/ work-up further, unless there is a manifestation so pathognomonically SLE that you suspect false negative
(GN, APLS, etc…)
• dsDNA: Highly sensitive and extremely specific. Excellent diagnostic tool.
• Will be positive in > 90% of SLE (bit less than ANA though); < 5% of SLE patients negative with active
disease. Can be used as a marker of activity in some patients.
• ENA: The types of ANA. Each ENA is associated with certain manifestations of disease, and can be
seen in other diseases as well. In general this can be interpreted by the rheumatologist if positive
(though please only order it in the correct context, as it is notorious to have low titer false positives).*
 2.1.18.9.9.
SYSTEMIC RHEUMATOLOGIC DISEASES
• Investigations: Equally important:
• CBC: Any/all cell lines can be down; can mimic malignancy; can present as an isolated chronic
ITP that later involves other cell lines.
• Creatinine, Urea, Urinalysis: The most important test for SLE; even more important than
dsDNA/ANA, should always evaluate for renal disease if you ever mention the word lupus.
• Prefer a first AM sample to rule out orthostatic proteinuria.
• If positive can refer to nephrology and complete work-up as they await triage.
• Complements: Low C4 is notoriously common in SLE; Low C3 also common, but has a much
broader differential so in isolation is harder to interpret.
• General chemistries: screening for end organ function, MAS, and differentials (malignancy,
infection) depending on presentation.
 2.1.18.9.9.
SYSTEMIC RHEUMATOLOGIC DISEASES
• Management: Guided by the manifestations; Kidneys take priority.
• Corticosteroids: used almost universally in all types of SLE with end-organ disease. Topical used
for cutaneous SLE. Not as helpful for systemic manifestations.
Renal disease (excluding the uncommon class I/II) typically get steroid pulse.
• Cytotoxic Agents: used primarily for renal disease (class II-V), end-organ disease, or refractory
manifestations.
• Cyclophosphamide: the best treatment for SLE in terms of length of study and efficacy. Many adverse
effects, including nausea/vomiting, SIADH, hair loss, and long-term infertility (up to 10% in pubertal
females). Gold standard for NPSLE. Advantage is it only needs to be given for 6 months (IV) then can
switch to Imuran.
• Mycophenolate Mofetil: will likely be the universal gold standard in a few years, has shown non-
inferiority to IV cyclophosphamide in even severe SLE, excluding NPSLE (because of low CNS
penetrance). Given orally, and main AE are cytopenias and GI intolerance.
 2.1.18.9.9.
SYSTEMIC RHEUMATOLOGIC DISEASES
• Management: Other Agents.
• Plaquenil: The gold standard for maintenance therapy – used in almost every flavor and variety of SLE. Has
been shown to decrease flare rates and severity of flares when they occur. Considered in many a life-long
therapy. Only significant adverse effect is Bulls-Eye Maculopathy, which can develop in those taking it for
more than 5 years, and presents as reversible loss of color vision. Can be detected prior to onset with
ophthalmologic screening and reversed with adjustment or discontinuation of plaquenil.
• Sun Safety: UV light can trigger DNA release and cause an SLE flare, even in those without cutaneous
disease. All patients with SLE should be counselled on sun safety / clothing, and to use sunscreen liberally and
regularly.

• Rituximab: used mostly in refractory SLE or in isolated / severe hematologic SLE.

• Imuran: used for milder disease, particularly class I/II GN, systemic disease, cutaneous disease, or vasculitic
disease. Also used as a maintenance agent and stepdown from cyclophosphamide. Main AE is cytopenia and
intolerance. Can cause critical neutropenia in patients with TMPT deficiency.
• ASA: sometimes used alongside other agents in the management of APLA.
NEONATAL LUPUS
 2.1.18.9.9.
SYSTEMIC RHEUMATOLOGIC DISEASES
• The prototype of a vertically transmitted autoimmune disease.
• Is due to the passage of maternal anti-Ro antibodies across the placenta and into the fetal
circulation. There are some fetal factors at play.
• Is NOT a permanent condition; lasts as long as antibodies do. Typically the onset of
manifestations will be in-utero (cardiac) and within first month or so (remainder) and will tend
to fade over the course of 6 months along with antibodies.
• Some slightly higher long term risk for JIA and SLE, but low enough that a referral is not warranted
for screening. We will discharge these patients after 1 year of life and they will be re-referred as any
patient would be if they develop disease.
• Most often, mothers do not know they have the pathogenic antibody (they may have
subclinical disease). Always refer mother to rheumatology if baby has NLE formally
diagnosed. Can prevent majority of manifestations with maternal treatment with plaquenil.
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SYSTEMIC RHEUMATOLOGIC DISEASES
• Manifestations:
• Cardiac: Congenital Heart Block is the most common and severe manifestation of NLE, and the
reason we attempt to diagnose and treat it.
• Can present as any degree of heart block, though third degree quite common.
• No good evidence that it progresses through stages; it is unclear.
• NLE accounts for > 90% of cases of congenital heart block.
• Risk of CHB in Anti-Ro positive mother is 1-2%; increases to 15% if previous baby CHB.
• Other manifestations (primary and as sequelae) are EFE and DCM. Mortality if these develop in
childhood is > 10%.
• Screening protocols for mothers with Ro antibody are serial echocardiograms from weeks 18-30, with
administration of tapering Dexamethasone from time of diagnosis to delivery at first sign of CHB (low
FHR, abnormal echo). With severe low FHR, may add IVIG and Beta agonist (terbutaline, salbutamol)
 2.1.18.9.9.
SYSTEMIC RHEUMATOLOGIC DISEASES
• Manifestations:
• Cutaneous: typically manifests as discrete, round papules with fine scale. Usually annular and
usually on the face and upper chest. More specific is the “racoon eyes”. May also see bullous,
targetoid, or other lesions – ddx is broad.
• Rarely present at birth; peak onset ~ 6 weeks, resolution by 6 months (average 17 weeks of rash).
• Does not require any treatment. Can use topical steroids but is purely cosmetic. Should not scar.
• Hematologic: seen in up to 30%; most common is isolated thrombocytopenia (first week) or
neutropenia (weeks 2-6), though aplastic anemia also seen.
• Self-limited and requires no treatment; if symptomatic, may consider IVIG / steroids.
• Liver: transaminitis seen in up to 25%; case reports of fulminant liver failure.
• Neurologic: Case reports of hydrocephaly / macrocephaly and seizures.
JUVENILE
DERMATOMYOSITIS
 2.1.18.9.9.
SYSTEMIC RHEUMATOLOGIC DISEASES
• Disease of chronic, progressive muscle inflammation that is (likely) based on small vessel
vasculopathy / vasculitis.
• Manifests with progressive proximal muscle weakness (not pain usually) that may result in
corticobulbar weakness, and pathognomonic rashes.
• Incidence ~ 0.02-3.2 / 1 million children; childhood peak 4-9 years, F > M.
 2.1.18.9.9.
SYSTEMIC RHEUMATOLOGIC DISEASES
• Manifestations:
• MSK Disease: Proximal muscle weakness, particularly hips and shoulders.
• In younger children, often manifests as motor regression; older is loss of ADLs.
• On exam will appreciate proximal muscle weakness (using MMT, Trendelenberg) and can be seen clinically by appreciating the Gower
sign.
• Always ask about the Dangerous D’s (Dysphagia, Dyspnea, Dysphonia). If any are positive, they warrant an Urgent referral /
admission and should be kept NPO.
• Other MSK manifestations include osteoporosis, arthritis (up to 65%), and contractures.
• Mucocutaneous Disease: Pathognomonic rashes (see next slides)
• Calcinosis is another common (?) manifestation, though in general can be hard to detect for non-rheumatologist and is usually a
sequelae of chronic disease.
• Other:
• Lipodystrophy: loss of subcutaneous fat, accompanied by metabolic syndrome.
• Vasculopathy: GI vasculopathy ranges on a spectrum from abdominal pain to ischemic bowel (with perforation and ulceration
described).
• Cardiopulmonary: With active disease may have weakness due to inflammation of intercostal muscles; with certain subtypes (Jo-1,
MDA-5) can see ILD.
 2.1.18.9.9.
SYSTEMIC RHEUMATOLOGIC DISEASES
 2.1.18.9.9.
SYSTEMIC RHEUMATOLOGIC DISEASES
 2.1.18.9.9.
SYSTEMIC RHEUMATOLOGIC DISEASES
 2.1.18.9.9.
SYSTEMIC RHEUMATOLOGIC DISEASES
 2.1.18.9.9.
SYSTEMIC RHEUMATOLOGIC DISEASES
 JUVENILE DERMATOMYOSITIS
• What is this?
 2.1.18.9.9.
SYSTEMIC RHEUMATOLOGIC DISEASES
 2.1.18.9.9.
SYSTEMIC RHEUMATOLOGIC DISEASES
 2.1.18.9.9.
SYSTEMIC RHEUMATOLOGIC DISEASES
 2.1.18.9.9.
SYSTEMIC RHEUMATOLOGIC DISEASES
 2.1.18.9.9.
SYSTEMIC RHEUMATOLOGIC DISEASES
 2.1.18.9.9.
SYSTEMIC RHEUMATOLOGIC DISEASES
 2.1.18.9.9.
SYSTEMIC RHEUMATOLOGIC DISEASES
• Bonham and Peter Diagnostic Criteria: 
1. Symmetric proximal muscle weakness.
2. Characteristic cutaneous changes (heliotrope rash, extensor (Gottron) papules).
3. Elevation of CK, AST, LDH
4. EMG changes characteristic of myopathy and denervation (polyphasic/short/small motor potentials,
fibrillations/sharp waves/insertional irritability, high-frequency repetitive discharges).
5. Muscle biopsy showing compatible findings (necrosis, fiber size variation, perifasicular atrophy,
degeneration with regeneration, mononuclear inflammatory infiltrate).

6. MRI IS BEST DIAGNOSTIC TEST--> gold standard

7. Biopsy only done if no rash
 2.1.18.9.9.
SYSTEMIC RHEUMATOLOGIC DISEASES
• Investigations
• Muscle Enzymes: at least one is elevated in 80-98% of patients at time of diagnosis
• CK, AST, ALT, and LDH are main ones we order || Aldolase helpful but not done in most institutions
• CK typically elevated to the 1.5-15x range (contrast DMD typically much higher)
• Does not necessarily correlate with disease activity
• Can be falsely normal with progressive inactivity or severely delayed diagnosis
• vWF Antigen: marker of endothelial injury, and elevated in vasculopathy / vasculitis
• Is the best marker of disease activity and early flare (Guzman et al)
• Other Biomarkers: ESR > CRP; low complements on occasion; high IgG on occasion
• Other Rheumatology Things: ANA, dsDNA, ENA, UA, etc…
• ANA elevated in 40-70% || ENA positive in up to 75% (RNP, SSA, PM-Scl)
 2.1.18.9.9.
SYSTEMIC RHEUMATOLOGIC DISEASES
• Key points in management:
• Disposition: JDM can be a medical emergency. Consider admission, NPO with IV fluids, 1:1 or
1:2 nursing care, and full CRM to assess cardiopulmonary weakness
• Remember that they may have respiratory muscle weakness; as such they may be unable to manifest
tachypnea and will drop their minute ventilation rapidly. Strongly consider a baseline gas and reassess
as needed to prevent need for intubation.
• Other Services: early involvement of OT/PT for rehabilitation, SLP for swallowing assessment
(clinical determination), and nursing for support / care.
• General measures: Don’t forget sun protection in community – like with SLE, sun can trigger
cutaneous disease, which can activate systemic disease.
• Corticosteroids: typically give a pulse in all but the most mild of cases, followed by a very slow
taper. Very good evidence that tapering quickly (faster than 6 months) has higher likelihood of
disease flare.
 2.1.18.9.9.
SYSTEMIC RHEUMATOLOGIC DISEASES
• Management:
• Methotrexate: Gold standard for the management of JDM, recommended in all cases that don’t
require more aggressive treatment. Minimum of 2-3 years. SQ is preferred due to concerns of
absorption with subclinical GI vasculopathy.
• IVIG: Gold standard for severe cutaneous disease; used in addition to methotrexate and steroids,
not in lieu of.

• Cyclophosphamide: used for the more severe or refractory disease manifestations, particularly
those requiring ICU admission or with progression while on methotrexate.
• Rituximab: considered at same level (or as next step, depending on algorithm) to
cyclophosphamide; may be more useful in antibody-positive disease.
• Other: Anti-TNF biologics, Imuran, MMF, and Cyclosporine are all considered for multiple
refractory disease states.
THE OTHER CTDS
 2.1.18.9.9.
SYSTEMIC RHEUMATOLOGIC DISEASES
• Raynaud Phenomenon: can be primary (most common) or secondary. It is likely Raynauds
if it is (1) induced by cold, and (2) results in a well demarcated area of biphasic color change
(usually white -> blue -> red). In general RP affects fingers (+/- toes, noes, ears)
asymmetrically, is well demarcated, and causes paresthesias. Occurs with relative change in
temperature and with emotional distress. Can take 10-40 minutes to revert to normal when
rewarmed.
Risk factors for secondary RP: male, young age, ANA, abnormal nailfolds.
Management: avoid vasoconstrictors (i.e. ADHD meds, smoking), core temperature
maintenance, extremity warmth, “windmilling”.
Main DDx: Vasomotor instability / acrocyanosis, Erythromelalgia.
 2.1.18.9.9.
SYSTEMIC RHEUMATOLOGIC DISEASES
• Sjogren Syndrome: typically manifests as dry mouth and dry eyes; very uncommon in pediatrics,
and when present is often very atypical in presentation and picked up while screening for SLE.
Serology is typically highly positive for ANA, RF, Ro, and La, and notably negative for dsDNA.
Treatment is topical (drops, drinking water) +/- plaquenil in some.
• Linear Scleroderma: see photos; typically manifests as a slowly growing patch of abnormal skin or
subcutaneous tissue; usually manifests with skin hypopigmentation, and over time will develop loss
of fat / muscle, atrophy of site, hyperpigmentation, and change in skin to a hard, shiny appearance.
ANA often positive. Clinical + pathologic diagnosis. Treated with topical therapy, prednisone, and
methotrexate.
• Systemic Sclerosis: very rare; manifestations highly variable in childhood, but include
sclerodactyly (tightening of skin around hands and mouth) and interstitial lung disease. Can also
have arthritis as a common manifestation. Treatment depends on disease, but notably steroids are
avoided, as it can cause renal disease.
 2.1.18.9.9.
SYSTEMIC RHEUMATOLOGIC DISEASES
• Mixed CTD: essentially is a diagnosis given to patients who have some features of multiple
CTDs (usually combination of SLE, JDM, and RP) but who have abnormally high anti-RNP
levels. Treated same as SLE.
• Undifferentiated CTD: essentially MCTD without high levels of RNP.
• Overlap Syndrome: when patient meets diagnostic criteria for more than one connective
tissue disease.
VASCULITIS
 2.1.18.9.9.
SYSTEMIC RHEUMATOLOGIC DISEASES
HENOCH-SCHONLEIN
PURPURA
 2.1.18.9.9.
SYSTEMIC RHEUMATOLOGIC DISEASES
• The prototypical leukocytoclastic vasculitis, also referred to as IgA vasculitis).
• Second-most common pediatric vasculitis (after KD); mean age 7 years.
• Classification: PReS/EULAR criteria confer a sensitivity of 100% and specificity of 87%.
Requires (A) and one of (B)
• (A) Palpable purpura, with a lower limb distribution (*if atypical distribution, MUST also have
biopsy findings of B)
• (B) Any one of the following:
• Diffuse abdominal pain
• Arthritis or arthralgia
• Renal involvement (hematuria, proteinuria)
• Biopsy demonstrating leukocytoclastic vasculitis (skin) or IgA proliferative GN (renal)*
 2.1.18.9.9.
SYSTEMIC RHEUMATOLOGIC DISEASES
• Etiology: remains unclear; thought to be a reaction to an infection given seasonality is
described, but multiple agents have been implicated.
• Manifestations:
• Cutaneous: palpable purpura (95-100%), in dependent distribution (*don’t forget to check the
buttocks). Lesions occur in crops, and can recur over the course of 6 months from diagnosis
(though each episode less severe / shorter in duration).
• Gastrointestinal: abdominal pain (70%) or GI bleeds (30%) are most common. Typically occurs
within 7 days of rash (always within 1 month; rarely precedes). Intussusception is seen, and can
be a cause of either manifestation.
• Renal: glomerulonephritis seen in 30%; 20 % will have it at onset*
• Other: arthritis (50-80%; oligoarticular, transient), pulmonary hemorrhage, seizure, parotitis,
scrotal edema, urethritis, carditis.
 2.1.18.9.9.
SYSTEMIC RHEUMATOLOGIC DISEASES
• Investigations: not necessary for diagnosis (which is clinical) except for a CBC (need to
prove purpura in presence of normal platelets).
• Inflammatory markers typically elevated
• IgA may be elevated in ~ 70% of cases (non-specific, not useful for diagnosis).
• ANCA should be negative; consider checking in atypical cases.
• Management: In acute phase management is supportive care alone. Main management is to
monitor for development of renal disease, and refer to nephrology if proteinuria / hematuria
develop.
• Corticosteroids are useful for short-term relief. Can improve arthritis and abdominal pain. If
giving Rx, should do 1 mg/kg/d, tapering over 4 weeks (otherwise symptoms return).
• Steroids do not influence the development of GN.
• NSAIDs can be used for arthritis, depending on severity of bowel involvement.
KAWASAKI DISEASE
 2.1.18.9.9.
SYSTEMIC RHEUMATOLOGIC DISEASES
• The most common vasculitis of childhood, involving small-to-medium vessel with a
predilection for coronary arteries.
• Everything you need to know is in the updated AHA 2017/2018 guidelines.
 2.1.18.9.9.
SYSTEMIC RHEUMATOLOGIC DISEASES
• Diagnosis: Requires (A) and at least 4/5 (B)
• (A) Fever for > 5 days (4 if IVIG eradicates fever)
• (B) Any 4 of the following:
• Bilateral nonpurulent bulbar conjunctivitis (80-90%)
• Oropharyngeal changes (80-90%) - red/fissured lips, strawberry tongue, pharyngeal erythema
• Extremity changes (80%) - erythema / edema (acute phase), desquamation (convalescent phase)
• Polymorphous rash (>90%) - nonvesicular (AHA clarifies to maculopapular, erythroderma, or EM like)
• Cervical LN (50%) - at least one node > 1.5 cm.
 2.1.18.9.9.
SYSTEMIC RHEUMATOLOGIC DISEASES
• Diagnosis: Incomplete KD - Requires use of an algorithm based on above criteria. 
• Diagnosis may be made in the presence of (A) and 2-3 (B) if the following scenario are met:
• Elevated ESR (40) / CRP (30) and at least 3 supplementary criteria* confirm diagnosis
• *Anemia, albumin < 31, elevated ALT, sterile pyuria, leukocytosis, thrombocytosis (after day 7)
• *Positive echocardiogram (alone) is sufficient
• If ESR/CRP not high enough, clinical observation warranted; if high enough, check labs and treat
accordingly.
• Incomplete KD is alternatively diagnosed in any patient with fever and any feature, who then
develops CA dilatation. In infants < 6 months, consider with fever alone.
 2.1.18.9.9.
SYSTEMIC RHEUMATOLOGIC DISEASES
• Differential Diagnosis:
• Infection (Measels, other viral illness, RMSF, scarlet fever, toxic shock syndrome)
• Drug hypersensitivity (serum-sickness like reaction, SJS)
• Systemic JIA
• Polyarteritis nodosa
• Investigations: see the supplementary criteria for incomplete KD
• Chemistries: elevated ESR/CRP/platelet/WBC, low hemoglobin, sterile pyuria, transaminitis,
elevated triglycerides/LDL, 
• Neutropenia and thrombocytopenia may be seen, which are markers of severity/MAS.
• Platelets typically begin to rise after 5-7 days, peaking in the second week.
• Sterile fluids: CSF pleocytosis; synovial leukocytosis
• Antibodies: ANCA and anti-endothelial antibodies occasionally seen.
 2.1.18.9.9.
SYSTEMIC RHEUMATOLOGIC DISEASES
• Management: Initial treatment...
• IVIG: given as a single dose 2g/kg, within 10 days of onset, but as  soon as possible after diagnosis.
• AHA states it is reasonable to give after 10 days, if (1) ESR/CRP elevated, AND (2) CA abnormalities, OR persistent
unexplained fever.
• Even with treatment, 20% will develop transient CA abnormalities, 5% CAA, and 1% giant aneurysm (in Japan, at least). 
• Approximately 10-20% of patients will not respond to IVIG; no good risk stratification for non-Japanese populations.
• ASA: given at moderate (30-50 mg/kg/d) or high (80-100 mg/kg/d) is reasonable until patient afebrile.
• AHA states it does not appear to lower the risk of CAA; however, recent publications suggest it may decrease risk of IVIG
resistance.
• May consider the risk of Reye syndrome when using moderate-high dose (not reported with low dose) if patient has
Influenza/varicella. May skip ASA here.
• Corticosteroids: multiple conflicting studies; AHA recommendations are that it may be considered when given as
a 2-3 week taper, along with IVIG and ASA, for high-risk patients.
• Should not use single, high dose pulse IVMP; should not use steroids after primary treatment with IVIG/ASA unless
refractory *see below*
 2.1.18.9.9.
SYSTEMIC RHEUMATOLOGIC DISEASES
• Management: Refractory disease...defined as recurrence of fever > 36 hours after the end of
the first IVIG.
• IVIG: standard of care is to administer second dose (2g/kg) of IVIG.
• Corticosteroids: high dose IVMP (20-30 mg/kg x 3 days, +/- oral taper) may be considered as an
alternative to second-dose IVIG, or for double-refractory disease.
• May also/instead use a tapering (2-3 week) course of prednisone alongside second-dose IVIG/ASA.
• Infliximab: given at 5 mg/kg, may be considered for refractory/double refracory disease (level C;
steroids / IVIG level B)
• Cyclosporine: may also be considered where other options have failed.
• Other: in highly refractory disease, TNFi, cytotoxics (CYP), and PLEX have all been used with
some success.
 2.1.18.9.9.
SYSTEMIC RHEUMATOLOGIC DISEASES
• Management: Subacute phase...
• ASA: low dose (3-5 mg/kg) should be given for 4-6 weeks in those without CA abnormalities
until echocardiogram normal. 
• Anticoagulants: warfarin (target INR 2-3) for those with giant or rapidly expanding aneurysms;
in less severe cases, triple therapy (ASA, clopidogrel, warfarin) may be used.
• Should avoid inhibitors of ASA (including ibuprofen).
OTHER VASCULITIS
 2.1.18.9.9.
SYSTEMIC RHEUMATOLOGIC DISEASES
• Takayasu Arteritis: Essentially the only primary large vessel vasculitis of childhood.
Involves the aorta and it’s major branches, and manifestations are related to the areas of
obstruction. Common manifestations include systemic (fever, weight loss), arthralgia,
myalgia, claudication, headaches (80%), stroke, chest pain, hypertension (> 80%),
abdominal pain (ischemic). Inflammatory markers are typically elevated, but diagnosis is
based on imaging (MRA/angiography, but echocardiogram often gives an idea).
DDx: fibromuscular dysplasia, Marfan/Loeys-Dietz, Kawasaki, other vasculitis
Treatment: corticosteroids are used for induction; standard of care has typically been
methotrexate, but relapse rates > 50%. New evidence favoring Tocilizumab and is Calgary
standard of care.
Clinical Pearl: high overlap with TB (as etiology vs. differential).
 2.1.18.9.9.
SYSTEMIC RHEUMATOLOGIC DISEASES
• Polyarteritis Nodosa: affects medium and small vessels, typically manifesting as
constitutional symptoms, hypertension and vasculitic rash (nodular, livedo) with
manifestations based on where vasculitis is occurring (myalgia, nephropathy, neuropathy).
Most commonly triggered by Strep. Diagnosed either radiographically or histologically
(usually both). Management is with antibiotics, steroids, and immunomodulation (Imuran).
• Cutaneous PAN: a subtype of PAN which does not seem to be related (i.e. very rarely
evolves into systemic disease). Manifests as typical cutaneous manifestations of PAN with
systemic symptoms. Episodic and seems to be related to streptococcal infections.
Clinical Pearl: If you have weird, “rheum” looking rashes, always check an ASOT before
referring (even if you will refer anyway).
 2.1.18.9.9.
SYSTEMIC RHEUMATOLOGIC DISEASES
• Granulomatosis with Polyangiitis (GPA): formally called Wegener’s disease, is the most
common ANCA-associated vasculitis. Affects small and medium arteries, particularly in the
skin, kidney, and airways.
• Major manifestations:
• Upper airway (chronic bloody nasal discharge, sinusitis, septal perforation)
• Lower airway (LTB stenosis, pulmonary nodules/infiltrates/hemorrhage)
• Renal (necrotizing pauci-immune glomerulonephritis)
• Investigations: typically c-ANCA (PR3) positive; may have p-ANCA (MPO) too. Will have
elevated inflammatory markers and inflammatory CBC.
• Diagnosis: clinical + histologic + serological
• Management: steroids + cyclophosphamide/Rituximab/PLEX
 2.1.18.9.9.
SYSTEMIC RHEUMATOLOGIC DISEASES
• Microscopic Polyangiitis: another necrotizing small vessel ANCA vasculitis, distinguished from
GPA in several ways (though there is overlap):
• Clinically more likely to have GI and cutaneous manifestations; that said all manifestations with GPA
do overlap.
• Serologically more associated with p-ANCA (MPO).
• Histologically lacks granulomas (still necrotizing) versus EGPA and GPA.
• Management: identical to GPA in vast majority of cases.
• Eosinophilic Granulomatosis with Polyangiitis: formerly called Churgg-Strauss, this is the
rarest ANCA vasculitis (overall incidence ~ 1 / million). Much overlap with GPA, this entity is
distinct due to presence of eosinophils in tissue (infiltrate) and serum (eosinophils should account
for > 10% total WBC). Often associated with eosinophilic asthma and chronic sinusitis. Can have
either ANCA subtype. Importantly can result in carditis (major mortality). Treatment is similar to
GPA, but new trial in 2018 showed promise for a drug called Mepolizumab (anti-IL5 biologic).
 2.1.18.9.9.
SYSTEMIC RHEUMATOLOGIC DISEASES
• Behcets Disease: vasculitis involving any size vessels (unique). Major manifestation is
recurrent oral and genital ulcers, with uveitis and typical skin lesions. Most common in those
of Silk-Route ancestry, and some association with HLA-B51. In addition to common
manifestations, CNS disease is important (in children most common is CSVT; in adults
encephalomyelitis). Very often associated with arthritis, and common to have
thrombophlebitis and DVT (10%). Diagnosis is notoriously challenging. Management is
based on organ-system involvement [ulcers = conservative, colchicine, TNFi; other
manifestations usually require immunomodulation].
• Sarcoidosis: very uncommon in childhood. 2 main variants:
• Adolescent: mimics adult disease with hilar adenopathy, elevated ACE, arthritis, pulmonary
hypertension, and myriad of other manifestations.
• Blau Syndrome: infantile onset with triad of arthritis, uveitis, and typical rash.
AUTOINFLAMMATORY
 2.1.18.9.9.
SYSTEMIC RHEUMATOLOGIC DISEASES
• General Principles of Fever Syndromes:
• Internal Consistency: every patient will have different manifestations, and some may not even
have fevers. The key is that the “episodes” tend to be identical every time. They don’t necessarily
need to be like clockwork in schedule (except PFAPA), but in each case the majority of
symptoms should be the same.
• Manifestations: common manifestations are fever (usually high grade), rashes, myalgias,
conjunctivitis, headaches, and abdominal pain.
• History: the best history you can take is a fever diary. Consider using the AIDAI.
• Always ask for a family history. Most of the time you will be diagnosing the first member in a family,
so questions to consider: Sensorineural hearing loss, unexplained renal failure (amyloidosis),
childhood tonsillectomy (PFAPA), childhood fevers.
• Demographics / consanguinity.
• Family history suggestive of immunodeficiency.
PFAPA
 2.1.18.9.9.
SYSTEMIC RHEUMATOLOGIC DISEASES
• Periodic Fever, Aphthous Stomatitis, Pharyngitis, Rash
• The most common periodic fever syndrome of childhood
• Unique from the other fever syndromes in several respects:
• Self-limited*
• Exquisitely responsive to single doses of prednisone
• No clear genetic basis*
• Only one that can be managed surgically to resolution*
 2.1.18.9.9.
SYSTEMIC RHEUMATOLOGIC DISEASES
• Manifestations:
• General: age < 5 at onset (typically); episodes are “like-clockwork”; episodes are internally
consistent and child is well between episodes.
• Fever: typically high spiking (> 39C); mean duration 2-5 days every 28 days.
• Aphthous ulcers: seen in ~ 70%; non-scarring and last 3-5 days.
• Pharyngitis: seen in ~ 70%; usually erythema/exudate and GAS negative.
• Adenitis: seen in ~ 90%; usually cervical (if generalized, consider malignancy).
• Other: arthralgia, abdominal pain, headaches, malaise.
• Investigations:
• May see elevated WBC, ESR, CRP, and elevated IgGAM*
 2.1.18.9.9.
SYSTEMIC RHEUMATOLOGIC DISEASES
• Diagnosis: clinical diagnosis after more likely/pathologic diagnoses ruled out (especially
immunodeficiency, infection, and malignancy). 
• Marshall Criteria: initial criteria, though not used religiously (many will make clinical
diagnosis based on age and characteristic periodicity of fever). For criteria, should meet all of
following:
• Onset of disease in early childhood
• Regularly recurring episodes of fever
• Presence of aphthous stomatitis, pharyngitis, and/or cervical adenitis during flares
• Asymptomatic intervals between flares, with normal growth
• Absence of URTI symptoms during episode
• Exclusion of cyclical neutropenia, other periodic fever syndromes, immunodeficiency, and
autoimmune diseases
 2.1.18.9.9.
SYSTEMIC RHEUMATOLOGIC DISEASES
• Management:
• Conservative: PFAPA is not a life-threatening illness; fevers are not harmful medically. A wait-
and-see approach may be desired by the parents.
• Ensure that parents are considering best interest of the child. Though the fevers are not medically
harmful, the child often misses school and feels miserable. This alone is indication enough for
treatment, given the lack of AE with treatment.
• Natural history: most children outgrow over 4-8 years, usually before age 10.
• NSAIDs: anti-inflammatory dosing of Ibuprofen during episodes is safe / effective.
• Steroids: arguably the gold-standard of pharmacotherapy; by definition, PFAPA responds
exquisitely well.
• Initial dose 0.6-1 mg/kg q12-24h [at first sign of episode]; can increase to 2 mg/kg.
• In almost all cases, prednisone will abort fever within 24h and markedly diminish the rest of the
symptoms (if they develop at all).
• In about 50% of cases, episodes will become more frequent.
 2.1.18.9.9.
SYSTEMIC RHEUMATOLOGIC DISEASES
• Management:
• Colchicine: rarely used, but in select cases can be given as prophylaxis.
• Cimetidine: used with variable efficacy, mostly in US; fallen out of favor.
• Tonsillectomy: alternate gold-standard in the management of PFAPA
• Cochrane meta-analysis in 2014 of 2 studies demonstrated remission or dramatic reduction in episode
severity / frequency.
• 4-fold increased likeliehood of becoming symptom-free; in those who do not become symptom free,
average interval increases to 2 months-2 years.
 2.1.18.9.9.
SYSTEMIC RHEUMATOLOGIC DISEASES
FMF
 2.1.18.9.9.
SYSTEMIC RHEUMATOLOGIC DISEASES
• Familial Mediterranean Fever: the most common monogenic fever syndrome
• Autosomal recessive mutations in the MEFV gene on chromosome 16p
• Most common in Ashkenazi Jewish, Arab, Turkish, and Italian populations.
• Onset of disease typically in adolescence or childhood (> 90% start before 20y)
• Diagnosis: typically clinical (recurrent short fevers in right demographic, accompanied by
abdominal/chest/skin/joint manifestations.
• Tel Hashomer Criteria: diagnosis with > 2 major criteria, or 1 major and > 2 minor:
• Major: recurrent fever with serositis, AA-Amyloidosis without predisposing disease, favorable
response to colchicine treatment.
• Minor: recurrent febrile episodes, erysipelas-like erythema, FMF in a first-degree relative.
 2.1.18.9.9.
SYSTEMIC RHEUMATOLOGIC DISEASES
• Manifestations: episodes are typically short (6-72h), occur every 4-12 weeks
• Fever: typically abrupt onset, > 38C, lasting 6-72 hours.
• Serositis: peritonitis >> pleuritis >> pericarditis.
• Peritonitis often severe and can mimic appendicitis; multiple case series.
• Arthropathy: arthralgia or arthritis, typically oligoarticular, usually self-limited but can linger for
a few days after episode terminates.
• Myalgia: seen in up to 20%; usually exertional and responsive to NSAIDs
• Cutaneous: a macular, erysipeloid rash is common, usually during fever, most often affecting the
foot and leg. May rashes are, however, described.
 2.1.18.9.9.
SYSTEMIC RHEUMATOLOGIC DISEASES
• Investigations: As before, investigations are mostly to rule out other diseases.
• Inflammatory markers and CBC suggest inflammation; SAA usually high.
• SAA can be elevated between episodes, and is a marker of severity. CRP can also be, but this is
quite uncommon in NA populations.
• Genetic testing highly reliable; in practice will often do a gene panel however.
• Management:
• Colchicine is the gold standard first line treatment, has extremely few side-effects, and is limited
in dosing only by GI intolerance. Marked improvement in 95%, and near-remission in 75%.
• Anti-IL1 Biologics are successful in refractory disease (Anakinra, Canakinumab).
• Long Term: life-long disease / treatment; in pre-colchicine era, rate of amyloidosis was ~
40%, with majority requiring renal transplant by age 40.
OTHER FEVER
SYNDROMES
 2.1.18.9.9.
SYSTEMIC RHEUMATOLOGIC DISEASES
• TNF-Receptor Associated Periodic Syndrome (TRAPS): autosomal domintant mutation
of the TNFRSF1A gene on chromosome 12, seen in multiple ethnicities but most common in
Northern Europeans and Irish populations. Manifests with prolonged fevers (1-4 weeks) of
variable intensity, and a distinctive migratory macular erythema with myalgia. Mimics
cellulitis. Often also have conjunctivitis, and can have serositis and arthritis.
• Hyper IgD Syndrome / Mevalonic Aciduria: autosomal recessive condition of the MVK
gene, resulting in decreased synthesis of MK, which results in inability to convert mevalonic
acid. Total lack of function results in the metabolic disorder of MA (rarely have fevers; often
have neurodevelopmental phenotype). Partial function results in fever syndrome. Onset
before 6 months, with moderate fever duration (3-7 days) every 1-2 months. Often
accompanied by variable rash, LN/Splenomegaly, and headaches. In spite of name, IgD not
specific – diagnosed genetically and (during episodes) by urine organic acid profile showing
elevation in level of mevalonic acid.
 2.1.18.9.9.
SYSTEMIC RHEUMATOLOGIC DISEASES
• Cryopyrinopathies: set of 3 distinct diseases all caused by autosomal dominant mutations in
NLRP3 gene.
• FCAS: Familial cold autoinflammatory syndrome; most common; manifests with recurrent, self-
limited episodes of (non-prutitic) cold-induced urticaria, fever, arthralgia and (sometimes)
conjunctivitis. Onset ~ 1-2 hours after exposure, lasts < 24 hours. Unlike cold-induced urticaria,
response is generalized.
• MWS: Muckle-Wells Syndrome; more severe variant; manifests with recurrent fever, (non-pruritic)
urticaria, arthralgia, and (sometimes) conjunctivitis. Major distinction is this subset develops
SNHL** and has 25% risk of amyloidosis.
• This is extremely important in real life – the SNHL is reversible, if treated early. This single condition is
why you always ask about FHx of SNHL. You can diagnose it early and treat and save their hearing for
life.
• NOMID: Neonatal onset multisystem inflammatory disorder; most severe; presents in neonatal
period as episodic fevers, rashes, severe neurologic disease (meningitis, hydrocephaly, uveitis, optic
disc edema, SNHL). Up to 2/3 develop a severe deforming arthritis. Mortality is high.
• Consider this diagnosis in a neonate with refractory, culture-negative sepsis and high CRP.
 2.1.18.9.9.
SYSTEMIC RHEUMATOLOGIC DISEASES
• DIRA: Deficiency of the IL-1 Receptor Antagonist; relatively newly described fever
syndrome that presents in neonatal period, manifesting with multifocal sterile osteolytic
bone lesions (which cause pain, irritability, poor feeding). May also develop pustular rashes
and fevers. Inflammatory markers high. Can achieve full remission with Anakinra.
• DADA2: Deficiency of Adenosine Deaminase 2; relatively newly described
autoinflammatory syndrome, this one mimics PAN and results in infantile strokes, along
with recurrent fevers and livedoid rash.
• Aicardie-Goutieres Syndrome: disease resulting in chilblains, CNS calcifications, and
progressive neurodevelopmental decline.
CRMO
 2.1.18.9.9.
SYSTEMIC RHEUMATOLOGIC DISEASES
• Chronic Recurrent Multifocal Osteomyelitis
• Sometimes referred to as CNO (chronic non-bacterial osteomyelitis) to denote the fact that it is
not, necessarily, recurrent or multifocal in all cases.
• Peak age of diagnosis 7-12 years, often with protracted pre-diagnostic phase.
• Associated with several other diseases including:
• Severe acne
• Psoriasis
• Spondyloarthropathy
• IBD
• May be a limited phenotype of SAPHO, and adult diagnosis with similar lesions.
 2.1.18.9.9.
SYSTEMIC RHEUMATOLOGIC DISEASES
• Manifestations: Bone pain or pathologic fracture (less often, incidental).
• Bone lesions are most common in the tibia, fibula, femur; less common (though still > 20%) and
more specific are pelvis, clavicle, and mandible.
• Bone lesions can present as unifocal or multifocal; in the world of whole body scans, it is not
uncommon to find additional asymptomatic lesions.
• Bone lesions in the vertebrae often present as pathologic compression fracture (unless they are
picked up incidentally).
• Some patients may have constitutional symptoms and low grade fevers; however, these patients
unequivocally need to be seen by oncology and orthopedics, and have a histologic evaluation for
malignancy.
 2.1.18.9.9.
SYSTEMIC RHEUMATOLOGIC DISEASES
 2.1.18.9.9.
SYSTEMIC RHEUMATOLOGIC DISEASES
• Imaging: lesions can be seen on any modality.
• Plain Films: shows a mixed osteolytic and sclerotic lesion (though goes through phases) with
cortical thickening; occasionally see periosteal reaction. Can be indistinguishable from leukemia.
Will evolve over years.
• Bone Scan: lesions always have increased uptake and this is an excellent modality to pick up
asymptomatic sites.
• MRI: local MRI is the gold-standard to diagnose CRMO on imaging; whole-body MRI is used in
selective institutions in Canada (including Calgary) to identify asymptomatic sites.
• There is debate as to whether it is necessary to look for asymptomatic sites. Most people
would agree that checking the spine is critical, as presence of lesions here often indicates
more aggressive therapy. Other treatments are all systemic, so argument to be made for less
investigation.
 2.1.18.9.9.
SYSTEMIC RHEUMATOLOGIC DISEASES
• Investigations:
• Labs: typically have elevated ESR, CBC, +/- platelets. Mainly look for cytopenia to help in
evaluation for malignancy.
• Histology: it is not uncommon for a bone biopsy to be required in these patients to definitively
rule out infiltrative and primary bone tumors. Clinical criteria have been developed to help save
on biopsies. In general the things that make CRMO more likely than malignancy or infection are:
• Presence of multiple, non-contiguous lesions.
• Presence in the clavicle or mandible.
• Particular radiographic features (marginal sclerosis).
• Normal CBC and elevated CRP.
• Absence of a fever.
 2.1.18.9.9.
SYSTEMIC RHEUMATOLOGIC DISEASES
• Differential Diagnosis: this the most likely thing they will test you on.
• Infection: osteomyelitis (particularly chronic – TB, etc…)
• Malignancy: leukemia, osteosarcoma, Ewings, LHC
• Other: Hypophosphatasia, Immunodeficiency (CGD)
 2.1.18.9.9.
SYSTEMIC RHEUMATOLOGIC DISEASES
• Management:
• NSAIDs: at anti-inflammatory doses this is first-line therapy for CRMO. Not clear it necessarily
modifies the natural history, but most people advocate for chronic use. Provides relief in > 80%
of patients. Variable remission rates in studies.
• Immune Modulation: variable degree of evidence for induction of remission with sulfasalazine,
methotrexate, and TNF inhibitors.
• Bisphosphonates: approaching the gold-standard of care, with protocols developed by local
expertise and now used worldwide. Pamidronate preferred. Multiple protocols. Main indications
are for vertebral lesions, or refractory pain.
• Natural History: in a single lesion, the process (from onset to radiographic resolution) takes
~ 3 years. There are a subset who have chronic disease.
NON-RHEUMATOLOGIC
MSK DISEASES
MARFAN SYNDROME
 2.1.18.3. NON-INFLAMMATORY
CONNECTIVE TISSUE DISEASES
• The prototypic inherited connective tissue disease.
• **There is an AAP Article on this**

• Epidemiology: the most common inherited connective tissue disease.

• Incidence ~ 1 : 5000-10000 live births
• Etiology: caused by an autosomal dominant mutation in Fibrillin-1 (FNB1).
• 75% of cases are inherited directly; 25% are de novo mutations.
 2.1.18.3. NON-INFLAMMATORY
CONNECTIVE TISSUE DISEASES
• Clinical Manifestations:
• Cardiovascular: aortic root dilatation is the most common manifestation, and the most common
cause of morbidity and mortality. ~ 50% develop in childhood and over 80% lifetime risk. High
risk of aortic root dissection.
• Second-most common manifestation is mitral valve prolapse; ~ 40% lifetime risk.
• Less commonly can affect more distal segments of the aorta, particularly abdominal.
• Ocular: ectopia lentis (superior dislocation of the lens) is the most common and pathognomonic
feature of MD, manifesting as quickly progressive myopia. Even without this, MD patients often
have myopia due to shape of eye.
• MSK Features: many; the key features are a “marfanoid” habitus of tall stature, long limbs /
fingers, with multiple deformities.
 2.1.18.3. NON-INFLAMMATORY
CONNECTIVE TISSUE DISEASES
• Diagnosis with the "Modified Criteria" are more clinical, classified based on presence or absence of parent with the
disease.
• Negative FMHx: root dilatation PLUS extra criteria (ectopia lentis, FNB-1 mutation, systemic score > 7).
• Positive FMHx: aortic root dilatation OR ectopia lentis OR systemic score > 7.
• Non-MSK Features:
• Spontaneous pneumothorax.
• Dural ectasia (widening of dural sac around spinal cord).
• MSK Features:
• Arachynodactyly (manifests as positive wrist sign and positive thumb sign).
• Chest wall deformity (pectus kerinatum, pectus excavatum).
• Foot deformity (hindfood deformities, pes planus).
• Spine deformity (scoliosis, kyphosis).
• Facial features (dolicocephaly, enophthalmos, malar hypoplasia, downslanting fissures, retrognathia).
• Other (reduced elbow extension, protucio acetabulae, long limbs [low US:LS ratio, high AS:ht ratio]).
• Skin striae (not better explained by something else).
 2.1.18.3. NON-INFLAMMATORY
CONNECTIVE TISSUE DISEASES
• Management: general principles are below. The AAP has an exhaustive summary which I
have synthesized in the “notes” section.
• Cardiac Assessment: when suspecting MD, patient requires an echocardiogram. If a diagnosis is
made, echocardiogram is done at least annually.
• Ophthalmologic Assessment: when suspecting MD, patient requires eye exam, and if a diagnosis
is made, annual (or q6 monthly) follow-ups.
• Anticipatory Counselling: counsel them on symptoms of pneumothorax and above, to know they
should seek care.
• Family Counselling: if patient is formally diagnosed, particularly with genetic diagnosis, should
be sent to genetics and all first degree relatives should have echocardiogram pending genetic
testing.
EHLERS DANLOS
SYNDROME
 2.1.18.3. NON-INFLAMMATORY
CONNECTIVE TISSUE DISEASES
• Heterogeneous group of disorders [currently 11 + 8 subtypes] with fairly disparate
manifestations and genetics.
• Type I: is the classic, severe form that manifests with severe joint laxity, easy bruising, and poor
wound healing (caused by mutation in COL5A1)
• Type III: is the most common (and irritating) form, causing generalized hypermobility. This is the
one most commonly thought of when discussing EDS. Multiple genes implicated, none with any
consistency.
• Type IV: the vascular (and severe) subtype that results in vessel and bowel wall rupture,
translucent skin, and mortality (mutations in COL3A1 or COL1A1)
• Remaining slides pertain exclusively to Type III
 2.1.18.3. NON-INFLAMMATORY
CONNECTIVE TISSUE DISEASES
• Assessment: the key thing you are attempting to delineate is as follows:
• Do they have hypermobility, or is there another cause for their symptoms?
• If they are hypermobile, are they so hypermobile they are developing other complications (i.e.
dislocations)?
• Are they exhibiting other features of connective tissue disease (involving the skin, usually) in
addition to their hypermobility (if present)?
• History: mostly pertains to the above – specifically ask about dislocation, sprains, and
injuries. Don’t forget family history and infantile history.
• Physical Exam: primarily trying to rule out other pathology (tarsal coalition, inflammatory
arthritis) and to establish hypermobility using Beighton Score.
 2.1.18.3. NON-INFLAMMATORY
CONNECTIVE TISSUE DISEASES
 2.1.18.3. NON-INFLAMMATORY
CONNECTIVE TISSUE DISEASES
• In adults, Type III EDS can be diagnosed by the presence of hypermobility (Beighton score
> 6/9) and at least 2 of the following 3 categories of features:
• (A) systemic manifestations of CTD [soft skin, hyperextensible skin, unexplained striae, bilateral
piezogenic papules of heel, recurrent abdominal hernias, atrophic scarring, pelvic/uterine/rectal
prolapse, dental crowding/high arched palate, arachnodactyly, high AS:h ratio, MVP, aortic root
dilation)
• (B) positive family history [first-degree relative with formal diagnosis of EDS].
• (C) MSK complications [MSK pain in 2 or more limbs daily for > 3 months, chronic widespread
pain for > 3 months, recurrent joint dislocation / instability in the absence of trauma].
 2.1.18.3. NON-INFLAMMATORY
CONNECTIVE TISSUE DISEASES
• Benign Joint Hypermobility: this condition is essentially the term favored for adolescents
or children with hypermobility who do not have the features of EDS. Marks the end of a
normal flexibility spectrum.
• Different sources use different Beighton cut-offs ranging from 4-6.
• The Beighton, notably, is not the be-all and end-all of assessment. It does not look at every joint.
The bones, ligaments, and tissues all grow and mature at different rates, and children can have
pain in a few joints.
• Best way to assess this is to check the Beightons, but also do a full joint exam and attempt to
appreciate whether there is relative hypermobility.
• Management: treatment for this and EDS type III are the same – physiotherapy and pain
control. Prefer pediatric phyiostherapy.
 2.1.18.3. NON-INFLAMMATORY
CONNECTIVE TISSUE DISEASES
• Fibromyalgia: a term that is used with variability in pediatrics; depending on school of
training, may refer to it as central sensitization, functional pain syndrome, or diffuse
idiopathic widespread pain.
• All terms means the same: the patient has diffuse, non-organic mechanical pain.
• We no longer use trigger points in diagnosis (though picture attached).
• The key way to delineate this from joint hypermobility or JIA is by physical exam:
• People with FM are tender pretty much everywhere – over joints, entheses, bones, muscles, all with
varying degrees.
• The “stress muscles” always seem more affected – i.e. the neck and shoulders.
• As a “functional” syndrome, it often occurs alongside anxiety/mood disorder, recurrent
headaches, chronic abdominal pain, and dysmenorrhea.
• Management is with a multidisciplinary team, management of comorbid mental health issues,
sleep management, and a regimented health / exercise program.
 2.1.18.3. NON-INFLAMMATORY
CONNECTIVE TISSUE DISEASES
• There are literally dozens of other “connective tissue” diseases or metabolic / genetic
conditions that can mimic them. You do not need to learn them (as far as I know) but in the
notes section is just a small list that I learned for my rheumatology exam. Can keep for
future reference.
• 2.1.18.1. Anatomy, structure and function of bone, joint and connective tissues, normal and abnormal 
REVIEW
• 2.1.18.2. Physiology of normal bone growth and function
• 2.1.18.3. Recognition of non-inflammatory connective tissue diseases, e.g. Marfan's syndrome, Ehlers Danlos syndrome 
• 2.1.18.4. Mechanisms of immune responses in rheumatic disease 
• 2.1.18.5. Indications for, and interpretation of laboratory tests on blood and synovial fluid 
• 2.1.18.6. Pharmacology of common anti-inflammatory drugs, corticosteroids and immunosuppressive drugs 
• 2.1.18.7. Effects of chronic rheumatic diseases on physical growth and social development 
• 2.1.18.8. Common radiographic abnormalities in musculoskeletal diseases
•
2.1.18.9.1. Congenital abnormalities 
• 2.1.18.9.2. Joint and limb pain 
• 2.1.18.9.3. Common fractures, dislocations or injuries 
• 2.1.18.9.4. Joint deformities 
• 2.1.18.9.5. Septic arthritis and osteomyelitis 
• 2.1.18.9.6. Common gait disorders (limp, torsional and angular deformities of lower limbs) 
• 2.1.18.9.7. Scoliosis 
• 2.1.18.9.8. Acute / chronic arthritis 
• 2.1.18.9.9. Systemic rheumatologic diseases, e.g. systemic lupus erythematosis, juvenile idiopathic (rheumatoid) arthritis 
• 2.1.18.9.10. Bone tumors  
 SPECIFIC QUESTIONS THAT WE DEFINITELY DID NOT GET
FROM OLD EXAMS BECAUSE THAT WOULD BE WRONG
AND WE AREN’T ALLOWED TO DO THAT, RIGHT GUYS?
• Remember: in all likeliehood the questions you are struggling to find answers for are mis-
remembered. Alternatively they were poorly written “test” questions, and their Ankgoff
score would not hit the cut-off to be rated.
• There were no questions I can recall on my exam that were as poorly worded or confusing as
any question we are about to discuss.
• I mean, other things – I’m not discussing my exam because I’m not allowed to…
 SPECIFIC QUESTIONS THAT WE DEFINITELY DID NOT GET
FROM OLD EXAMS BECAUSE THAT WOULD BE WRONG
AND WE AREN’T ALLOWED TO DO THAT, RIGHT GUYS?
• Most likely this is a RLL pneumonia (an
A 6 year old Greek girl presents with a high fever,
tachypnea, and RUQ pain.  On exam, there is no
answer in other iterations). The main hint
guarding in the abdomen.  What is the most likely seems to be the lack of guarding in the
diagnosis?  abdomen.
a.      Bacterial pneumonia  • “FM” likely stands for “FMF” as seen in other
b.      Pleurodynia iterations – this is a serositis / peritonitis, and
c.      FM
would cause guarding.
• The “Greek” is likely there to throw you off.
 SPECIFIC QUESTIONS THAT WE DEFINITELY DID NOT GET
FROM OLD EXAMS BECAUSE THAT WOULD BE WRONG
AND WE AREN’T ALLOWED TO DO THAT, RIGHT GUYS?
• Again a difficult question because we don’t
Girl with JDM, what is the best diagnostic test
a) EMG
know when it was written first, and we don’t
b) CK know the other answers.
• From the actual diagnostic criteria (from the
70’s) MRI is not included, even though it is the
gold standard.
• Muscle biopsy would be the best answer if it is
asking for “best” test.
• Between these two, EMG is more specific and
sensitive, so pick it. CK can be up in many
conditions, and in severe JDM may not be
elevated. In most severe cases they have
burned away so much muscle they have none
left to produce a CK.
 SPECIFIC QUESTIONS THAT WE DEFINITELY DID NOT GET
FROM OLD EXAMS BECAUSE THAT WOULD BE WRONG
AND WE AREN’T ALLOWED TO DO THAT, RIGHT GUYS?
• The questions that discuss priority are always
2 year old has fever of 40 degrees and is irritable. He
refuses to move his left hip.  What is the first thing you
challenging – often you are deciding between
do?  practicality and accuracy.
a. Aspirate the left hip with needle  • Because of the presence of fever, B and C are
b. X-ray  definitely wrong. This is a case of septic
c. Bone scan arthritis until proven otherwise.
d. Admit, do blood culture and start antibiotics
• I would choose D. Because of the age and
presentation, I would want coverage as I am
working up, knowing that yield of aspirate is
60% overall. A is not wrong however, and
could be done simultaneously in practice.
 SPECIFIC QUESTIONS THAT WE DEFINITELY DID NOT GET
FROM OLD EXAMS BECAUSE THAT WOULD BE WRONG
AND WE AREN’T ALLOWED TO DO THAT, RIGHT GUYS?
• This is trying to make you think of PANDAS.
Boy with recurrent pharyngitis. Episodic jerking of
shoulders and head over past 6 weeks. Most likely
This is hard… because Nelsons itself
diagnosis? disagrees.
a. Rheumatic fever • In the psychiatry chapter there is a small
b. Transient tic disorder section about it being an organic cause of tic
c. Tourettes disorders.
d. Some sort of seizure disorder • In the ID section, they say it’s not real.
• It may be a form of autoimmune encephalitis
(per Susa).
• Based on this, the answer is B. They are
unlikely to give you a red herring like
pharyngitis.
• It is not Rheumatic fever – this is not
Syndenham Chorea.
 SPECIFIC QUESTIONS THAT WE DEFINITELY DID NOT GET
FROM OLD EXAMS BECAUSE THAT WOULD BE WRONG
AND WE AREN’T ALLOWED TO DO THAT, RIGHT GUYS?
• Of these the most likely is SLE (A).
12 yo girl – fever, malaise, arthralgia for 3 weeks.
ESR 50, WBC 3 (leukocytes 10%, neutrophils 90%). • Main reason is the elevated ESR.
Trace proteinuria/hematuria. BUN/Cr normal. What is • As an interesting learning point, ESR is elevated
your diagnosis? in active lupus disease (and flare), CRP suggests
a. lupus either serositis (from SLE), infection, or MAS.
b. systemic JIA Both being raised often means you have active
c. PSGN SLE being triggered by infection, causing
serositis, or causing MAS.
• Not B because they state arthralgia and they don’t
define fever. I’d imagine if you are to answer sJIA
you’d be given a clear picture of quotidien.
• Not C because of only trace protein and blood,
and you should NOT have fever with this (it’s
POST-strep, so your infection is passed long ago).