Systemic Lupus Erythematosus

Question 1

Highest prevalance in African-American and Afro-Caribbean women

Answer 1

5.5-6.5 times more prevalent in women

Question 2

An autoimmune disease in which organs and cells undergo damage initially mediated by tissue-binding autoantibodies and immune complexes

Answer 2

Systemic lupus erythematosus

Question 3

SLE autoimmunity may begin with

Answer 3

activation of innate immunity through binding of DNA,RNA and proteins by Toll-like receptors in plasmacytoid dendritic cells and monocytes/macrophages

Question 4

Tissue damage begins with

Answer 4

Deposition of autoantibodies and or immune complexes followed by destruction mediated by complement activation and release of cytokines/chemokines

Question 5

Sclerosis/fibrosis with irreversible tissue damage occur in

Answer 5

Kidney
Lung
Blood vessels
Skin

**Each processes depends on the individual’s genetic background, environmental influences and epigenetics

Question 6

Multigenic disease

Answer 6

1. single-gene defects
2. IFN production or function
3. Polymorphisms influence clinical manifestation: genes related to end organ dysfunction
4. Multiple epigenetic changes

Question 7

Single gene defects

Answer 7

1. Homozygous deficiencies of early components of complement (C1q,r,s; C2, C4)
2. Mutation in TREX 1 (encoding DNAse) on the X chromosome

Question 8

IFN production or function

Answer 8

Most characteristic increased gene expression pattern of SLE patients

Question 9

Polymorphisms influence clinical manifestations

Genes related to end-organ dysfunction

Answer 9

1. MYHA9/APOL1: associated with ESRD in all ancestries
2. APOL1G1/G2: ESRD(but not SLE) only in African americans

Question 10

Multiple epigenetic changes

Answer 10

1. Hypomethylation of DNA encoding genes, promoter regions
2. Transcription factor in CD4+ T cells, B cells, and monocytes

Question 11

Risk factors for SLE

Answer 11

1. Female (exposure to estrogen pills; Estradiol binds to T and B lymphocytes)
2. Genes expressed on the X chromosome (TREX1, XXY karyotype/Klinefelter’s syndrome)
3. Exposure to UV light
4. EBV virus
5. Tobacco smoking
6. Prolonged exposure to crystalline silica (soap powder dust or soil)
7. Exposure to pesticides during childhood

Question 12

Biopsy of affected skin

Answer 12

1. Deposition of Ig at the dermal-epidermal junction (DEJ)
2. Injury to basal keratinocytes
3. Inflammation dominated by T lymphocytes in the DEJ and around blood vessels and dermal appendages

**clinically unaffected skin: may show Ig deposition at the DEJ

Question 13

Lupus skin lesions are characterized by

Answer 13

Expression of IFN-regulated cytokines and chemokines and by IFN-producting pDCs and keratinocytes

**not specific but highly suggestive of dermatologic SLE

Question 14

Classes of lupus nephritis that should be aggressively given immunosuppresion

Answer 14

Class III and class IV disease
Class V accompanied by III or IV

Question 15

Treatment for lupus nephritis is not recommended in patients with

Answer 15

Class I disease
Class II disease
Extensive irreversible changes (class VI)

Question 16

Classification of Lupus Nephritis

Class I: MINIMAL mesangial lupus nephritis
Normal glomeruli by light microscopy
Mesangial immune deposits by immunofluorescence

Class II: Mesangial PROLIFERATIVE lupus nephritis
Purely mesangial hypercellularity of any degree OR
Mesangial matrix expansion by light microscopy with mesangial immune deposits
Subepithelial or subendothelial deposits maybe visible by immunofluorescence or EM

Class III
Active OR inactive FOCAL, segmental or global endo-or extracapillary glomerulonephritis involving <=50% of all glomeruli TYPICALLY WITH FOCAL subendothelial immune deposits, with or without mesangial alterations

Class III A: active lesions- focal proliferative lupus nephritis

Class III (A/C): active and chronic lesions, focal proliferative and sclerosing lupus nephritis

Class III C: chronic inactive lesions with glomerular scars: focal sclerosing lupus nephritis

Answer 16

Class IV: DIFFUSE Lupus nephritis

Active or inactive diffuse, segmental, or global endo- or extracapillary glomerulonephritis involving >=50% of all glomeruli, typically with DIFFUSE SUBENDOTHELIAL immune deposits with or without mesangial alterations.

Class is divided into:
Diffuse SEGMENTAL (IV-S) lupus nephritis when >=50% of the involved glomeruli have segmental lesions

Diffuse GLOCAL (IV-G) lupus nephritis when >=50% of the involved glomeruli have global lesions

*Class includes cases with DIFFUSE WIRE LOOP DEPOSITS but with little or no glomerular proliferation.

Class V: Membranous Lupus nephritis
Global or Segmental SUBEPITHELIAL immune deposit or their morphologic sequelae by light microscopy and by IF or EM with or without mesangial alterations

Class V lupus nephritis may occur in combination with class III or IV in which case both will be diagnosed
Class V lupus nephritis: may show advanced sclerosis

Class VI: advanced sclerotic lupus nephritis
>=90% of glomeruli globally sclerosed WITHOUT residual activity

Question 17

Patterns of vasculitis
But may indicate ACTIVE disease

Answer 17

Leukocytoclastic vasculitis is the most common

Question 18

Diagnosis of SLE is based on clinical features AND autoantibodies

Answer 18

Two classification systems:
1. SLICC
-for evaluating an individual patient
-any combination of 4 or more well-documented criteria at any time of history with at least one in the clinical and one in the immunologic category
-specificity 97%, sensitivity 84%

2. 2019 Eular/ACR classification
   -more current
   -must have a positive ANA >=1:80 by IF and a score of 10
   -specificity 97, sensitivity 93%

**Please see tables

Question 19

High titer IgG antibodies to double-stranded DNA and antibodies to the SM antigen
(anti-dsDNA and anti-Smith)

Answer 19

Both specific for SLE therefore, favor the diagnosis in the presence of compatible clinical manifestations

Question 20

Polyarthritis

Answer 20

Soft tissue swelling and tenderness in joints and or tendons

Most commonly in hands, wrists and knees

Question 21

Erosions on joint X-ray

Answer 21

Rare
indentified by ultrasound in 10-50% of patients

**Individuals with erosions may fulfill criteria for both RA and SLE (rhupus)

Question 22

Ischemic necrosis of bone

Answer 22

If pain persists in a single joint, such as a knee, shoulder or hip

Prevalence is increased in patients with SLE treated with systemic glucocorticoids

Question 23

Other musculoskeletal manifestations

Answer 23

Myositis with clinical muscle weakness
Elevated creatinine kinase levels
Postive MRI scan
Muscle necrosis and inflammation on biopsy

Question 24

Drugs that can cause muscle weakness

Answer 24

Glucocoritcoid therapy (common)
antimalarial therapies (rare)

Question 25

Most common CHRONIC dermatitis in lupus

Answer 25

Discoid lupus erythematosus (DLE) -roughly CIRCULAR with slightly raised, SCALY, HYPERPIGMENTED ERYTHEMATOUS rims and DEPIGMENTED ATROPIC CENTERS in all dermal appendages disfiguring 5% with DLE have SLE patients with SLE, 20% may have DLE

Question 26

Most common ACUTE SLE rash

Answer 26

"Butterfly rash" Photosensitive, slightly raised occasionally SCALY ERYTHEMA on the face (cheeks and nose) Worsening of this rash often accompanies flare of systemic disease

Question 27

SUBACUTE cutaneour lupus erythemaotosus (SCLE)

Answer 27

Consists of: SCALY RED PATCHES, similar to psoriasis OR CIRCULAR, FLAT, RED-rimmed (annular_ lesions