Lupus Flashcards
ACR Lupus Criteria 1997
Malar Rash Discoid rash Photosensitivity Serositis Hematological d/o Neurological d/o Arthritis Renal disease Autoantibodies ANA Oral Ulcers
Need four of 11
Pathways involved in clearing apoptotic materials
Complement and receptors PD1 BCL1 Fas/Fas ligand Immunoglobulin receptors
What are NETs rich in?
- DNA
- LL37
- High mobility group protein B1 (HMGB1)
Adaptive Immunity pathology of lupus
IC are formed and activate pDC
pDC produce IFNa
Fc gammaR IIa on the pDC membrane delivers IC to TLR7 (if RNA) and TLR9 ( if DNA)
TLR induced production of IFNa leads to differentiation of monocyte to DCs and activation of immature myeloid DCs
myeloid DCs activate auto reactive T and B cells, leading to increased autoantibody production
mDCs also cause CD8T cells to differientate into cytotoxic T cells
Risk of a sibling of a patient with lupus having lupus
20 fold increased compared to general population
Which single gene mutations can cause lupus?
homozygous c1q deficiency (90%) C2 deficiency (1/3), higher association with Ro antibodies C4 (increased risk)
Name a disease in which hormones play a role in the development of lupus
Klinefelter syndrome has an increased risk of lupus but they generally have milder disease as compared to XY adult men with SLE (higher risk of nephritis)
Viruses implicated in lupus
EBV
CMV
Drugs implicated in DIL
Hydralazine (HIGH) Procainamide (HIGH) Isoniazid Methyldopa Quinidine (Moderate) Minocycline Chlorpromazine
In children-anti epileptics meds are commonly implicated
TNFi can cause signs suggestive of SLE (anti ds DNA, low complement etc)
Anti histone ab
Suggestive of DIL but not diagnostic
Pathogenesis of LN
Formation of ICs lead to activation of complement and FC gamma receptors
DNASE I
Major renal nuclease
Found to be down regulated in LN leading to impaired clearance of apoptotic cells leading to further exposure of chromatin fragments
What is a full house?
Deposition of IgA, IgM, IgG, C3, C1q, and kappa and lambda light chains
Acute nephritic syndrome
Microscopic hematuria (occ macro)
HTN
Proteinuria (mild to nephrotic)
*Commonly a manifestation of Class III or IV
What to consider if you notice gross hematuria in a lupus patient
Renal vein thrombosis
Thrombotic microangiopathy
Clotting factor deficiency (PT deficiency)
Nephrotic Syndrome
Nephrotic range proteinuria
Hyperlipidemia
hypoalbuminemia
Edema
*Commonly seen in class V
Complications associated with Class V
Thrombosis
CV events
Predictors of poor renal outcomes
African American race low GFR (<60 mL/min/1.73m2 Nephrotic range proteinuria at presentation
Recurrence of SLE after transplantation
20-30% though recurrence is generally mild and not associated with decreased patient survival
Leading cause of death in pediatric LN patients before and after ESRD
Infection
Cardiovascular complications
Which antibody triggers neutrophils to become apoptotic?
RNP
Percentage of first degree relatives of patients with SLE who also have the disease
10%
Percentage of children with a mother with lupus who have a positive ANA
27%
Pathology of acute cutaneous lupus
Disruption of the dermal-epidermal junction, infiltration of T cells and fibrinoid degeneration
Pathology of chronic cutaneous lesions
Thickening of the keratotic layer, epidermal atrophy, follicular plugging, and fibrosis of the elastic tissues
Most common sign of neuropsychiatric disease in cSLE
Headache –> described as a migraine or unrelenting, severe headache requiring narcotic analgesia
Most common cardiac manifestation of lupus
Pericarditis
- Chest x ray may show an enlarged cardiac silhouette
- EKG shows elevated ST segments and peaked t waves
- Treatment if mild is usually steroids and NSAIDs
- May require IV steroids pulse
Signs of myocarditis
- Elevation in CK mB and troponin
- Enlarged silhouette
- EKG shows nonspecific ST and T wave changes and arrythymias
- Echo shows global hyperkinesis, reduced LV EF, regional wall motion abnormalities
Most common valvular disease in lupus
Libman Sacks endocarditis
- Sterile, small, verrucous value lesions typically on the mitral valve but also found on other valves, chordae tendineae and endocardium
- most common in longer disease activity, with APLs, high disease activity
- Usually asymptomatic
Most common PFT finding in lupus
restrictive disease and or impaired diffusion.
Bronchoscopy findings supportive of PAL
Frank blood in airways
serosangionous BAL fluid, hemosiderin laden macrophages, absence of purulent sputum, lack of infectious organisms
Cause of Autoimmune hemolytic anemia
Warm agglutinins
Signs of anemia of chronic disease
Low Hg, normocytic, normochromic, low iron, low relic count, high ferritin
Signs of HUS
MAHA, thrombocytopenia, acute kidney injury
–look for schistocytes
Signs of TTP
MAHA, thrombocytopenia, fever, AKI, neurological deficits
-look for schistocytes
Leukocytoclastic vasculitis
Erythematous or violaceous punctate, non blanching less of the fingertips or palms
Cause of thrombocytopenia associated with ITP
Antibodies against GP11B/IIa and thrombopoietin receptor TPOR
Most common areas to clot with positive LAC
Legs
Cerebral veins
Pulmonary vasculature
Anti Ro/SS-A
Strongly associated with neonatal lupus and subacute cutaneous lupus
Anti- C1q
Good marker of LN activity and correlates with severity of nephritis and proteinuria
- also associated with angioedema symptoms
What can be tested to find those at risk of AZA toxicity ?
Thiopurine methyltransferase (TPMT)
Most often causes of death
Infection, renal failure, cardiopulmonary
Findings suggestive of lupus in lymphoid tissue
Hematoxylin bodies
What can be found in patients with transverse myelitis?
- APls
When do clinical manifestations of drug induced lupus resolve?
- 6 months after the drug is removed
When do ds DNA antibodies go away?
- 12 to 24 months
