Systemic Lupus Erythematous

Erythema of light exposed area

SLE produce painless oral ulcers.

The risk is higher in patients with disseminated DLE (22%) than in DLE confined to the head and neck (1.2%).

Females developing DLE before the age of 40 years,with HLA-B8 in their histocompatibility type, have an increasedrisk of ‘converting’ to SLE. Neither immunological nor biochemical abnormalities appear to alter the patient’s progress.

Antibodies to the Ro/SS-A antigen are usually always found in SCLE.

A wide variety of autoantibodies can be seen in systemic lupus erythematosus, including all of those listed. However, high titers of anti-double-stranded DNA and anti-Sm (not listed above) are considered to be the most specific for systemic lupus erythematosus.

MUST KNOW:

• Anti-Jo-1 is associated with inflammatory myopathies.
• Anti SS-A and anti-SS-B  are associated with Sjögren syndrome.

Neonatal lupus erythematosus (NLE) is a disorder caused by the transplacental passage of maternal antibodies.

First, what type of anemia is it? It must be a hemolytic form, since it is associated with unconjugated hyperbilirubinemia (hence the yellow sclerae), resulting from increased destruction of red blood cells.

Increased erythrocyte destruction is the cause (not the effect) of splenomegaly.

Furthermore, a positive Coombs test implies that hemolysis is mediated by antibodies attached to red blood cells. Thus, the correct choice must be either IgG or IgM. Since the Coombs test is positive at warm temperature (37 C), the antibody is a warm agglutinin.

Warm agglutinins are virtually always of IgG type and may be triggered by a variety of disorders, including lymphomas, drugs, and autoimmune diseases such as SLE. IgG-coated red cells are then sequestered by the spleen, where hemolysis occurs, thus explaining splenomegaly.

By contrast, cold agglutinins are IgM and can be demonstrated by Coombs test at cold temperature (0-4 C).

Cold agglutinins are usually triggered by Mycoplasma pneumoniae infection or lymphomas.

Systemic lupus erythematosus (SLE) predominantly affects younger women, and so the question of lupus and pregnancy may arise frequently in clinical practice. Patients with SLE have an increased incidence of spontaneous abortion, fetal death in utero, and prematurity. The mother may experience an exacerbation in the activity of her disease in the third trimester or peripartum period, and it may be difficult to distinguish between active SLE and preeclampsia. Therapy of pregnant patients with SLE is problematic, and the generalist should consult the literature or a specialist when such a patient is encountered.Congenital malformations (choices B, C, and D) are not a complication of pregnancies in patients with SLE.

Ref: Cunningham F.G., Leveno K.J., Bloom S.L., Hauth J.C., Rouse D.J., Spong C.Y. (2010). Chapter 54. Connective-Tissue Disorders. In F.G. Cunningham, K.J. Leveno, S.L. Bloom, J.C. Hauth, D.J. Rouse, C.Y. Spong (Eds), Williams Obstetrics, 23e.

Ans. is ‘c’ i.e., Diffuse proliferative

Ans. is ‘d’ i.e., Complete heart block

o Maternal lupus erythmatosus has been associated with a high incidence of congenital heart block in offspring.

Answer is C (Polyserositis):

Polyserositis is included as a diagnostic criteria for SLE and is the most characteristic feature of SLE amongst the options provided.

Uveitis is not a characteristic feature of SLE

Ocular manifestation include sicca syndrome, non specific conjunctivitis, episcleritis, retinal vasculitis and optic neuritis. Uveitis is not mentioned as an ocular manifestation of SLE.

Ocular manifestations are not characteristic of SLE and are not included in the diagnostic criteria for SLE.

Joint Deformity is not a characteristic feature of SLE

Arthritis is included amongst the diagnostic criteria for SLE, however arthritis in SLE is typically nor erosive and does not lead to joint deformities.

Cavitatory Lesion in lungs are not characteristic of SLE 

Cavitatory Lesion in lungs are not characteristic of SLE

Diagnostic Criteria for Systemic Lupus Erythematous

Answer is D (Joint Deformity)

SLE is characterized by non erosive arthritis. Joint deformities may occur but these are rare and limited to hands & feet.

Presence of joint deformities should rasie the suspicion of a non lupus inflammatory arthropathy like RA, and hence joint deformities is the single best answer amongst the options provided.

Answer is C (Wire loop lesions):

Wire loop lesions are characteristic of SLE

Wire loop lesions:

• Wire loop lesions represent local PAS – Positive thickening of glomerular capillary walls and are characteristically sen in Lupus Nephritis (SLE)
• These lesions result from subendothelial deposits between endothelium and basement membrane. When extensive and confluent, these subendothelial deposits create a homogenous thickening of the capillary wall which can be seen in light microscopy as ‘Wire loop lesion’
• Wire loop lesions are most characteristic of Lupus Nephritis Class IV or Diffuse Lupus Nephritis These may however also be seen in Class III (Focal Lupus Nephritis) and Class V (membranous) Lupus Nephritis.

Answer is B (Endocarditis) :

Ans. C: Type III hypersensitivity

Type III hypersensitivity response (Immune-complex mediated response) Examples are:

• Some form of glomerulonephritis
• Serum sickness
• Arthus reaction
• SLE

Antinuclear antibody (ANA) testing and anti-extractable nuclear antigen (anti-EN A) form the mainstay of serologic testing for SLE.

Several techniques are used to detect ANAs. Clinically the most widely used method is indirect immunofluorescence. The pattern of fluorescence suggests the type of antibody present in the patient’s serum.

ANA screening yields positive results in many connective tissue disorders and other autoimmune diseases, and may occur in normal individuals.

Subtypes of antinuclear antibodies include anti-Smith and anti-double stranded DNA (dsDNA) antibodies (which are linked to SLE) and anti-histone antibodies (which are linked to drug-induced lupus).

Anti-dsDNA antibodies are highly specific for SLE; they are present in 70% of cases, whereas they appear in only 0.5% of people without SLE.

The anti-dsDNA antibody titers also tend to reflect disease activity, although not in all cases.

Ans. is ‘c’ i.e., SLE

The characterisitc histopathologic picture of the spleen in SLE is periaterial fibrosis or anion skin lesion.

• First described by Libman and Sacks, this lesion is defined as the presene of 3 to as many as 20 seperated layers of the normally densely packed periarterial collagen of the penicillary or follicular arteries producing the appearance of concentric rings (anion peel).

Ans. is ‘b’ i.e., SLE

Both ESR and CRP are markers of inflammation

• Erythrocyte sedimentation rate or ESR is used to separate inflammation from non-inflammation.
• Another sign of inflammation is the rise in blood level of number of proteins called as acute phase proteins.
• One of the proteins is C-reactive protein (CRP).
• Like ESR and other acute phase proteins, CRP also goes up in inflammation.
• In systemic lupus however the level does not rise unless there is infection associated.
• The normal response to active inflammatory disease is an increase in plasma CRP concentration. o For reasons that remain unclear tht response is either significantly lower in magnitude or entirely absent in a few inflammatory conditions.
• This has proven diagnostically useful because there are very few inflammatory conditions in which ESR is significantly raised (reflecting an inflammatory process) but plasma CRP is only slightly raised or even normal.
• One ofthese conditions is systemic lupus erythematosus (SLE or lupus), a relatively common chronic autoimmune disease that predominantly affects women of child-bearing age.
• When this inflammation occurs in the lupus patient it is accompanied as expected by a marked increase in ESR. However in contrst to most other inflammatory condition, the plasma CRP remains resolutely normal. The combination of raised ESR and normal CRP is a useful diagnostic feature of SLE.

Other disorders where CRP is not increased

• Osteoarthritis, leukemia, anemia
• Polycythemia, viral infection
• Ulcerative colitis, pregnancy, estrogen

Ans. d. Immune complex deposits

Ans. is ‘d’ i.e., All are true

SLE (sytemic lupus Erythematosus)

• Autoimmune disorder
• Inflammation of blood vessel
• Childhood SLE had poor pnognosis than adult SLE

Hall mark of SLE is presence of antinuclean antibody (ANA)

• More common in female.
• Malar rash in pathognomic of SLE
• Non – erosive arthritis
• Nephritis
• Encephalopathy
• Pleuritis / Pericarditis
• Cytopenia

Ans. is ‘c’ i.e., SLE 

Ans. is ‘b’ i.e., SLE 

Band test (Lupus band test)

• Lupus band test is done upon skin biopsy, with direct immunofluorescence staining, in which, if positive, IgG and complement depositions are found at the dermoepidermal junction. This test can be helpful in distinguishing systemic lupus erythematosus (SLE) from cutaneous lupus, because in SLE the lupus band test will be positive in both involved and uninvolved skin, whereas with cutaneous lupus only the involved skin will be positive.
• The minimum criteria for positivity are:
• In sun-exposed skin : Presence of a band of deposits of IgM along the epidermal basement membrane in 50% of the biopsy, intermediate (2+) intensity or more.
• In sun protected skin : Presence of interrupted (i.e. less than 50%) deposits of IgM along the epidermal basement membrane, intermediate (2+) intensity or more.
• The presence of other immunoglobulins (especially IgA) and/or complement proteins (especially C4) increases the specificity of a positive test.

Ans. is ‘d’ i.e., Class V 

KIDNEY INVOLVEMENT IN SLE (LUPUS NEPHRITIS)

A. Glomerular disease

T1. here are several versions of WHO classification of lupus nephritis ‑

• Minimal or no detectable abnormalities (class 1) 
• It occurs in less than 5% of patients.
• Has best prognosis.

2. Mesangial lupus glomerulonephritis (class II)

1. Focal proliferative glomerulonephritis (class III)
2. Diffuse proliferative glomerulonephritis (class IV)
3. Membranous glomerulonephritis (class V) 

B. Tubulointerstitial disease

• Though glomeruli are involved primarily in lupus nephritis, interstitium and tubules can also be involved especially in association with diffuse proliferative glomerulonephritis.
•  Granular deposition of immunoglobulin and complement in tubular basement membrane are seen.

Anti-DNA antibodies is usually associated with active lupus nephritis 

Also know

• Nephritis is the most serious manifestation of SLE.
• Most common cause of death is renal failure due to nephritis.

Ans. is ‘a’ i.e., Anti ds DNA 

Ans. is ‘d’ i.e., Class V

Ans. is ‘b’ i.e., Anti-Ro & Anti-LA 

Most sensitive                         Antinuclear antibody (ANA)

Most specific                            Antidouble stranded anitbody and the antibody against smith (Sm)

Associted with neonatal            Anti Ro, AntiLA antibody

lupus and congenital

heart block

Associated with lupus               Anti P antibody

psychosis

Ans. is ‘b’ i.e., SLE