Systemic Lupus Erythematosus
The Basics…
• SLE is a multisystem, chronic but often episodic,
autoimmune disease
• Epidemiology
– 20% of patients are diagnosed in childhood
• Uncommon before age 5
– Female predominance
• 3:1 in children
• 9:1 after puberty
– Prevalence higher in Native Americans African
Americans, Asians, Hispanics, and Filipinos
• Disease more severe in African Americans and Hispanics
The Basics (con’t)…
• Etiology
– Exact cause unknown
• Multigenic
– Environmental trigger in a genetically predisposed individual
Question #1
• All of the following are possible clinical
manifestations of SLE, EXCEPT:
– A. Chorea
– B. Raynaud’s Syndrome
– C. Oral ulcers
– D. Libman-Sacks endocarditis
– E. Myositis
Clinical Manifestations
• Constitutional
– Fever*
– Weight loss
– Myalgias
• Mucocutaneous
–
–
–
–
–
Butterfly rash or malar erythema*
Photosensitive discoid lesions/ maculopapular lesions
Vasculitic lesions palmar erythema
Alopecia
Oral ulcers*
Malar Erythema
Discoid Rash
Vasculitic Lesions
Oral Ulcers
Clinical Manifestations
• Cardiovascular
– Pericarditis
• Chest pain (worse when lying down or taking deep breaths)
• Friction rub
– Myocarditis
• CHF
• Arrhythmia
– Endocarditis
• Libman-Sacks endocarditis
– Sterile verrucous vegitations
– Can lead to SBE
– Raynaud Phenomenon
Raynaud’s Syndrome
Clinical Manifestations
• Cardiovascular (con’t)
– Premature atherosclerosis
•
•
•
•
•
Glucocorticoids
Dislipoproteinemia
Nephrotic syndrome
Increased expression of adhesion molecules
Antiphospholipid Abs
Clinical Manifestations
• Pulmonary
– Pleural effusion
– Abnormal PFTs
• 60% of adolescents with SLE with subclinical pulmonary dz
– Shrinking lung syndrome
– (Pneumonitis, pulmonary hemorrhage, pulmonary
HTN)
• Gastrointestinal
– Pancreatitis
– Mesenteric vasculitis
– Peritonitis, hepatitis
Question #2
• Of the following, which is the most correct
statement regarding renal disease in SLE:
– A. It is not common but is a major cause of
morbidity
– B. It is common and a major cause of morbidity
– C. It is common but not a major cause of
morbidity
– D. It is not common and is not a major cause of
morbidity
– E. There is no renal disease associated with SLE
Clinical Manifestations
• Renal
– Lupus nephritis
•
•
•
•
Occurs in 75% of patients within 2 yrs of diagnosis
Major cause of morbidity
Early evidence: microscopic hematuria, proteinuria
WHO classification:
–
–
–
–
–
–
Class I: Normal
Class II: Mesangial proliferation
Class III: Focal segmental glomerulonephritis
Class IV: Diffuse proliferative glomerulonephritis*
Class V: Membranous nephritis
Class VI: Glomerulosclerosis
Clinical Manifestations
• Musculoskeletal
– Arthralgias/ arthritis*
• Usually nonerosive/ non-deforming
• Both large and small joints
• Painful!!
– Myalgias/ weakness
• CNS
– Second leading cause of morbidity/ mortality
– Most common manifestations
• Psychiatric symptoms
• Seizures
• HA
Clinical Manifestations
• CNS (con’t)
– Can also see:
•
•
•
•
•
Chorea
Neuropathies
Transverse myelitis
Stroke
Infection
• Hematologic
– Cytopenias (all lines can be affected!)
• Leukopenia
• Anemia
– 50% of patients affected
• Thrombocytopenia
– Consider SLE in women with chronic ITP
Classification Criteria for Diagnosis
Question #3
• A 14 yo F presents to your clinic with a several
week h/o fevers, arthralgias and rash. She has
been worked up extensively for infection and
malignancy and all testing was negative. You
suspect SLE. Which of the following laboratory
tests is the best SCREENING test for SLE?
–
–
–
–
–
A. Anti-ds DNA
B. ANA
C. Anti-SSA (Ro) and anti-SSB (La)
D. Anti-Smith
E. Anti-RNP
Laboratory Evaluation
• ANA
– Best SCREENING test
– Non-specific
• Anti-ds DNA
– High SPECIFICITY.
– Helpful for monitoring disease activity
– Predictive of disease flares
• Other specific antibodies
– anti-Sm (Smith) and anti-RNP (ribonucleoprotein)
– anti-Ro (SS-A) and anti-La (SS-B)
• Serologic markers of active disease
– Reduced levels of C3 or C4
– Elevated titers of anti-ds DNA antibodies
Laboratory Evaluation
Treatment
Antiphospholipid Antibody Syndrome
• May be primary or secondary
– 66% pediatric SLE patients with + anticardiolipin Abs,
62% with lupus anticoagulants
• Affected patients at risk for:
–
–
–
–
–
–
Arterial and venous thrombosis
Recurrent fetal loss
Raynaud phenomenon
Thrombocytopenia
Neurologic involvement
Libman-Sacks endocarditis
Antiphospholipid Antibody Syndrome
• Laboratory features
– Presence of anticardiolipin Abs
– Prolonged PTT
– Circulating lupus anticoagulant
• Abnormal mixing study
Question #4
• A 39wga M is born via NSVD with no complications.
On PE the day after birth, he is found to have
erythematous, circular skin lesions on his face and
chest, along with mild hepatomegaly. His platelets are
low at 142k, otherwise his CBC is normal. He is feeding
well with normal voids and stools. Of the following,
maternal labs would MOST LIKELY show:
–
–
–
–
–
A. Anti-SSA(Ro) and/or anti-SSB(La) Ab positive
B. Anti-cardiolipin Ab positive
C. Anti-RNP Ab positive
D. Anti-Smith Ab positive
E. ANA negative
Neonatal Lupus Erythematosus
 Due to transplacental transfer of
maternal antibodies (Anti Ro &La)
 Most common manifestations
 Hematologic
 Cutaneous
 Hepatic
 Cardiac
 Most manifestations resolve
without sequelae after an average
of 6 months
 Exception: congenital heart
block
Neonatal Lupus Erythematosus
Question #5
• A 6 year old female come to clinic with an evanescent
generalized rash, fever for 2 weeks, and a swollen left knee.
Mom states the knee has been swollen for 2 months and
sometimes feels warm. She has given the girl ibuprofen for
the past 3 days without relief of fever or knee swelling.
When asked about previous illness, mom states that the
whole family had colds and sore throats about 3 months
ago, but everyone else is now feeling fine. Labs reveal a
positive ASO titer and negative anti-DNAse B.
• Which of the following is the MOST likely diagnosis?
–
–
–
–
–
A. Poststreptococcal arthritis
B. Lyme disease
C. Acute rheumatic fever
D. Juvenile idiopathic arthritis
E. Septic arthritis
JUVENILE IDIOPATHIC ARTHRITIS
Definition
• JIA is the presence of objective signs of
arthritis in at least one joint for more than 6
weeks in a child younger than age 16 after
other types of childhood arthritis have been
excluded
– Arthritis = swelling of the joint or 2 or more of the
following: limitation of motion, tenderness, pain
with motion, or joint warmth
Often a Diagnosis of Exclusion
Clinical Features
• Eight Categories
– 1) Systemic
– 2) Oligoarthritis persistent
– 3) Oligoarthritis extended
– 4) Polyarthritis RF-negative
– 5) Polyarthritis RF-positive
– 6) Enthesitis-related arthritis
– 7) Psoriatic arthritis
– 8) Other
*Systemic JIA
•
•
•
•
10% of all cases
Onset peaks between 1 and 6 years old
Boys = Girls
Daily or twice-daily high spiking fevers
(>102.2)
• Other features: faint pink maculopapular rash,
LAD, HSM, pericarditis
• With persistent disease: osteoporosis, growth
abnormalities, brachydactyly, micrognathia
Systemic JIA
Brachydactyly
Micrognathia
Systemic JIA
Question #6
• You are following a patient that you suspect has
systemic JIA. You have sent off blood work and
are waiting for the results. Which of the following
lab results are you LEAST likely to see?
–
–
–
–
–
A. Anemia
B. Leukocytosis
C. Positive ANA
D. Thrombocytosis
E. Positive Rheumatoid Factor
Systemic JIA (cont’d)
• Systemic features may precede arthritis by weeks to
months
• Life-threatening complications: pericardial tamponade,
systemic vasculitis, macrophage activation syndrome
(MAS)
• *Lab findings
–
–
–
–
–
–
–
Leukocytosis
Thrombocytosis
Anemia
Elevated acute phase reactants
ANA (5 to 10%)
*RF (<2%)
Elevated ferritin
Question #7
• You have referred a 4 year old female patient of
yours to a pediatric rheumatologist due to
swelling, pain, and limited range of motion in her
knees bilaterally and left ankle. You have just
received her lab results which include ESR of 80
mm/hr, CRP of 5 mg/dL, and a positive ANA.
• Which of the following complications is she MOST
at risk for?
–
–
–
–
–
A. Leg length discrepancy
B. Uveitis
C. Pericarditis
D. Erosive arthritis
E. Macrophage activation syndrome
*Oligoarthritis JIA
•
•
•
•
Arthritis in 4 or fewer joints in first 6 months
40% of cases
Persistent = no more than 4 joints
Extended = more than 4 joints (after 6
months)
• Onset age 1 to 5
• Girls > Boys
– Girls are ANA positive 75 to 85%
• *ANA (+) are at greatest risk of developing uveitis
*Ocular Complications
• Granulomatous chronic inflammatory process
in anterior chamber
• 80% of kids are asymptomatic
• Morbidity includes:
– Corneal clouding
– Cataracts
– Glaucoma
– Visual loss
• Frequent evaluations may prevent serious
complications
Ocular Complications
Oligoarthritis JIA (cont’d)
• Affects large joints
– Knees
– Ankles
• Children present with swollen, warm joint,
and limp worse in morning
• Leg length discrepancy
– Due to increase in blood flow to the growth plate
following chronic inflammation
• Constitutional symptoms are rare
Oligoarthritis JIA
JIA vs Septic Arthritis
• *Joint aspiration
– If WBC >100,000 and 90% are polys, then infection
is likely
– Culture should always be obtained
Polyarthritis JIA
•
•
•
•
5 or more joints in first 6 months
25% of JIA
Girls > Boys
Occurs at any time during childhood
– RF (+) are girls in later childhood (>8 yr) with
symmetric small joint arthritis, poorer prognosis
• 40 to 50% are ANA (+)
Enthesitis-related JIA
• Inflammation of the enthesis, where tendon
attaches to bone, and arthritis
• Children tend to have 2 of the following:
–
–
–
–
–
–
Sacroiliac joint tenderness
Inflammatory spinal pain
Presence of HLA B27
Positive family history
Acute anterior uveitis
Onset of oligoarthritis or polyarthritis in a boy >8
years
Psoriatic JIA
• Chronic arthritis and
definite psoriasis or 2 of
the following criteria:
– Dactylitis
– Nail pitting or
onycholysis
– Family history of
psoriasis
Question #8
• A 9-year-old male reports during his well child check
that he has been having morning stiffness, limited
mobility, and swelling in his proximal interphalangeal
joints for the past 6 weeks. He sometimes has trouble
writing in school. You order some lab testing and plain
films. His rheumatoid factor comes back positive.
• Of the following treatment modalities, which one has
been shown to slow the radiologic progression of his
joint disease?
–
–
–
–
–
A. Physical therapy
B. NSAIDS
C. TNF-alpha antagonists
D. Intra-articular corticosteroids
E. DMARDs (ex: methotrexate)
Treatment
• *Pharmacologic
– 1) NSAIDS
– 2) Disease-modifying Anti-rheumatic drugs
(DMARDS)
– 3) Biologics
– 4) Corticosteroids
• *Multidisciplinary team
– Physical and occupational therapy, social work,
rheum nurse, primary care physician
• With team approach, children with JIA function better
and surpass peers
Pharmacologic Treatment
• NSAIDS
– First line
– Inhibit COX-1 and COX-2 that are involved in the
inflammatory response
– Ibuprofen, naproxen, tolmetin, choline magnesium
trisalicylate, and aspirin are FDA approved
– Average time to symptomatic improvement is 1
month
– *Adverse effects are: abdominal pain, anorexia,
bleeding gastritis, increased bruising, increased liver
enzymes, encephalopathy, Reye syndrome
– Take with food and antacids, H2-blockers, or PPIs
Pharmacologic Treatment
• DMARDs
– Slow the radiologic progression of disease
– Ex: methotrexate, sulfasalazine, penicillamine,
hydroxychloroquine
• Biologics
– TNF-alpha antagonists, cytokine inhibitors
– Ex: entanercept, infliximab, adalimumab
• Corticosteroids
– Used for serious systemic manifestations
– Intra-articular for those with limited joint involvement