Download Overview of Systemic Lupus Erythematosus

Overview of Systemic
Lupus Erythematosus
Pediatric Rheumatology
Red Team Resident
Teaching Series
Systemic Lupus Erythematosus
• Episodic, heterogeneous, multisystem autoimmune disease
• Widespread inflammation of vessels and connective tissues
• Variable clinical manifestations and course
• characterized by remissions and relapses
• Incidence in children: 0.5-0.6/100,000 children/year
• 20% of adults have onset in childhood (<19 years old)
• Female to male ratio: 9:1
• Uncommon before 4 years of age
• More common in African American and Hispanic children
• Children have more aggressive disease with more organ
involvement than adults
• 30% may progress to renal insufficiency depending on
treatment
• 10 year survival 80-90%
Current Theories Of Pathogenesis
In SLE
• Etiology unknown
• Multiple genes are associated with a predisposition towards
developing lupus
• Immune dysregulation of B and T cell responses
• Immune complex deposition
• Abnormalities of complement
• Decreased clearance of apoptotic debris
• Hormonal imbalance
• Environmental triggers including UV B light, infection
• Loss of tolerance to chromatin and other autoantigens
• Cross reactivity between bacterial and mammalian DNA
• Abnormal response to DNA?
These factors, acting alone or together, may trigger onset of
disease in a genetically predisposed host.
Immune complex disease
• Antibodies can be against self (e.g. nuclear components in
SLE) or foreign antigens (i.e. drugs or microorganisms in serum
sickness)
• Antibodies and antigens combine to form immune complexes
• Immune complexes deposit in blood vessels and tissues and
activate inflammatory response leading to tissue destruction
ACR 1997
Revised
Lupus
Criteria
Need 4 of 11 criteria for a
diagnosis of lupus
(sensitivity of 96%
and a specificity of 100%
in children). If a patient
has lupus nephritis, then
only a total of 3 of 11
criteria are needed.
2012 SLICC Criteria
Click on this link for further details on individual
criteria: http://www.rheumtutor.com/2012-sliccsle-criteria/
Clinical Features of SLE
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Constitutional symptoms
Musculoskeletal disease
Mucocutaneous manifestations
Renal Disease
Central nervous system disease
Cardiopulmonary disease
Hematologic abnormalities
Gastrointestinal involvement
Musculoskeletal Disease
• Incidence: 76%
• Arthralgias
• Arthritis
• Non-erosive
• Involves small joints of the hands, wrists, elbows, shoulders, knees,
ankles
• Can be migratory, lasting 24-48 hours
• Myalgias/ muscle weakness
• Usually proximal
Mucocutaneous Manifestations
• Frequency: 76%
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Malar rash
Discoid lupus
Vasculitis (purpura, petechiae)
Raynaud’s phenomenon
Nail involvement
Alopecia
Periungual erythema/ Livedo reticularis
Photosensitivity
Oral/ nasal ulcers
Malar rash: classic butterfly rash,
symmetric, sparing nasolabial folds. Can
also include the chin and forehead. One
third to one half of children have this at
presentation. Can be photosensitive.
Chronic discoid-type malar rash. Discoid
lesions tend to be coin-shaped, red and
raised with a scaly, sometimes
hypopigmented center. This type of
lesion can occur in both purely
cutaneous (discoid) and systemic lupus.
This is a typical photosensitive eruption
involves the face, neck, and "V" of the
chest. It occurs after exposure to UV
light, and is found in 17-58% of patients
with lupus. Crusting has developed
following the breakdown of vesicular
and bullous lesions.
This is livedo reticularis. While not
a diagnostic criteria, it is a
vasculitic-type rash often seen in
individuals with lupus and other
vasculitides. Note the mottled,
lacey-type pattern.
This is a palatal ulcer. Oral and nasal
ulcers occur in 30-40% of lupus patients.
Oral ulcers tend to occur on the hard
palate, but can occur on the buccal
mucosa. They start as hyperemic areas
that ulcerate. In the nose, they can
precipitate nose bleeds. They are often
painless, and are an indicator of active
disease.
Raynaud’s (single digit): characterized
by triphasic color change in an
extremity to cold temperature or
emotional upset: blanching (white),
then cyanosis (blue), then reactive
hyperemia (red), accompanied by
ischemic pain. To meet a diagnosis of
Raynaud’s, the blanching white phase
and one other color phase need to be
present. Primary Raynaud’s = patients
without known autoimmune disease;
Secondary Raynaud’s = with
autoimmune disease.
Neuropsychiatric Manifestations
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Frequency: 20-40%
Difficult to diagnose and treat
Second to nephritis as most common cause of morbidity & mortality
Can occur at any time; even at presentation
Standard lab examinations have not been helpful in diagnosing or
managing CNS symptoms
• COMMON: Depression, organic brain syndrome, functional
psychosis, headaches, seizures, cognitive impairment, dementia,
coma
• OCCASIONAL: Cerebral vascular accidents (thrombosis or vasculitis),
aseptic meningitis, peripheral neuropathy, cranial nerve palsies
• RARE: Paralysis, transverse myelopathy, chorea
Cardiovascular Findings
• Pericarditis
• Most common cardiac manifestation in children
• Can be asymptomatic, or represented by chest pain worsened by
lying down or deep breathing that is relieved by sitting up and
leaning forward. Tamponade is rare but does occur.
• Myocarditis
• Sterile valvular vegetations (Libman-Sacks endocarditis – see
photo below)
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• Less common in children than in adults.
• Subclinical, it is a sterile nodule of fibrinoid necrosis of the
collagenous tissue of the valve.
• Risk of bacterial endocarditis
Arrhythmias
Cor pulmonale
Vasculitis (small vessels)
Atherosclerosis/ Coronary Heart disease
Dyslipoproteinemias
Pulmonary Findings
• Incidence: 5-67%
• May be subclinical (abnormal PFTs)
• Pleuritis
• unilateral or bilateral chest pain, exacerbated by deep inspiration
• Pleural effusion
• Usually small, can be asymptomatic
• Pneumonitis
• Pulmonary infiltrates, atelectasis, or rales; occurs in 10-15% of
children
• Pulmonary hemorrhage
• Chest pain, hemoptysis, pallor, anemia
• Pulmonary hypertension
• Restrictive lung disease & diffusion defects most commonly
observed abnormalities on PFTs
GI Involvement
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Mild LFT elevation--not significant clinically--BUT NEED TO
EXCLUDE AUTOIMMUNE HEPATITIS
Colitis
Mesenteric vasculitis
Protein-losing enteropathy
Pancreatitis
Exudative ascites
Hematologic Findings
• Leukopenia, especially lymphopenia
• Neutropenia is rare except in the case of anti-neutrophil
antibodies, or in the case of infections
• Anemia
• mild to moderate, common, due to chronic disease and mild
hemolysis
• Severe anemia is uncommon (5%), due to immune mediated
hemolysis (Coombs +)
• To meet lupus criteria, the anemia needs to be Coombs positive
• Thrombocytopenia
• Due to immune mediated damage
• mild (100-150K) is common
• severe (<20K) is uncommon (5-10%)
• Bone marrow suppression/arrest (aplastic anemia)--very
rare, due to antibodies against bone marrow precursors
Coagulopathy
• Hypocoagulable states:
• Anti-platelet antibodies--decreased numbers of platelets or
decreased function (increased bleeding time)
• Other platelet dysfunction and thrombocytopenia
• Anti-clotting factor antibodies
• Hypercoagulable states:
• Antiphospholipid Antibody Syndrome (APS)
• Presence of antiphopholipid antibodies detected by one of the
following tests:
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Anticardiolipin antibodies
Beta 2-glycoprotein antibodies
Direct Russel Viper Venom Test
Lupus Anticoagulant
• Protein C and S deficiencies
• Thrombotic thrombocytopenic purpura
Renal Disease
• More common and more severe in children than in adults
• Most common cause of morbidity & mortality
• Can present as proteinuria (including nephrotic range),
hematuria, cellular casts, hypertension, decreased GFR <->
renal failure
• Glomerulonephritis – occurs in at least 75%
• Glomerulonephritis class based on inflammation location and
amount, and is predictive of potential for renal damage
• Class I+II, III and IV GN (mesangial, focal and diffuse proliferative):
result from immune complex deposition from the circulation
• Class V GN (membranous): results from in situ formation of immune
complexes
• Microscopic or gross hematuria
• Renal failure (up to 30-50% of children prior to 1980)
Laboratory Findings
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Cytopenias (anemia, thrombocytopenia, leukopenia)
Elevated ESR, CRP, Immunoglobulins (particularily IgG)
Hypoalbuminemia
Proteinuria; RBCs, casts in urine
Decreased creatinine clearance
Low complement levels (C3/ C4)
• C4 depression is more specific than C3 depression
• Autoantibodies (ANA, APL, Coombs, anti-platelet Ab,
rheumotoid factor, etc.)
• (Immune complexes)
Antinuclear Antibodies (ANA)
• Sensitive but not specific, 95-98% patients positive
• Against nuclear components of the cell
• Titer specific- up to 10% of population have +ANA w/o
disease; also see with infections, medications, malignancy
• Subtypes:
• dsDNA: high specificity for lupus (over 80%)
• ENA (extractable nuclear antigens)
• Smith: specific for SLE
• U1RNP: associated with MCTD
• SSA/SSB: Sjogren’s, neonatal lupus
• Histone: drug induced lupus
SLE - Treatment
• Treatment is usually based on organ system involvement and
the severity of involvement
• MILD DISEASE: Rashes, arthritis, leukopenia, anemia, arthritis, fever,
fatigue
• MODERATE DISEASE: Mild disease + mild organ system involvement
such as: mild pericarditis, pneumonitis, hemolytic anemia, mild renal
disease
• SEVERE DISEASE: Severe, life-threatening organ system involvement
• Sunscreen and UV avoidance
• Immunizations and infections
• Patients on immunosuppressive medications should avoid ALL LIVE
VACCINES
• Infections should be treated promptly due to immunosuppression and
risk of disease flair
• Unvaccinated patients exposed to VZV or measles should receive VZIG
or IVIG
• Physical and occupational therapy
Medications Used in Lupus
• NSAIDs
• Naproxen – often used with arthritis, mild serositis
• Ibuprofen – can cause aseptic meningitis in lupus patients
• Antimalarials (usually Hydroxychloroquine)
• Used in all patients
• Aspirin for patients with APLs
• Corticosteroids
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Used in all patients except those with very mild disease
Pulse dose
High dose (1-2 mg/kg/day)
Low maintenance dose (5-7.5 mg/day)
Medications Used in Lupus
• DMARDs and Immunosuppressives
• Azathioprine – hematologic disease, mild NP disease, general
steroid-sparing agent
• Methotrexate – arthritis, skin disease, general steroid-sparing
agent
• Cyclosporine/Prograf - nephritis
• MMF – nephritis, general steroid-sparing agent
• Cytoxan – nephritis, cerebritis, pulm HTN
• Biologics
• Rituximab
• Benlysta
• Theurapeutic Plasmaphresis
• Stem Cell Transplantation
Emergencies in SLE
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Fever: always rule-out infection
Renal disease: uremia, hypertension
Cytopenias: acute hemolytic anemia, thrombocytopenia
CNS: seizures, coma
Pleural effusion (symptomatic)/ pneumonitis/ pulmonary
hemorrhage
Pericarditis/ myocarditis/ tamponade
Peritonitis/ pancreatitis/ GI bleed
Raynaud's: digital necrosis
Ocular: retinal vein thrombosis, retinal vasculitis, hemorrhage,
edema
Thrombotic events, catastrophic antiphospholipid antibody
syndrome (CAPS), thrombotic thrombocytopenic purpura
“Lupus Crisis”
Practice Question
•10-year-old girl with SLE for a health supervision visit. Initially
presented at 8 years with ITP, found to have positive ANA, then
arthritis and dsDNA. She is currently doing well in school. Malar
rash noted on exam.
•The MOST useful screening test for other organ involvement is:
A. Coombs test
B. ESR
C. Brain MRI
D. Urinalysis
E. VDRL