Systemic Lupus Erythematosus (SLE) is an autoimmune disease characterized by autoantibodies that can cause injury to multiple organs. The exact cause is unknown but involves genetic, immunological, and environmental factors. Key aspects include the presence of various nuclear and cytoplasmic autoantibodies, defective B and T cell tolerance, and exposure to environmental triggers. The autoantibodies can cause direct tissue damage or form immune complexes that activate complement pathways. This leads to manifestations in various organs like the kidneys, blood vessels, skin, and joints. Renal involvement is a major cause of morbidity and mortality in SLE patients.
2. Overview
1) Defination
2) Etiopathogenesis-
Etilogy
Spectrum of antibodies positive
Pathogenesis
3) Morphology -in Vessels / Kidney/ Skin /Joints/ Pericarditis/ CNS/ CVS/ Spleen.
4) Clinical Features
5) ACR Criteria for diagnosis of a case of SLE
6) Updates in criterias
7) Just to end up Pearls
8) Referances
3. Definition
SLE is an autoimmune disease involving multiple organs,
characterized by vast array of autoantibodies, (particularly ANAs)
in which injury is caused by-
mainly deposition of immune complexes and
binding of antibodies to various cells and tissues.
4. Forms to describe
1) Systemic /
Disseminated form
2) Discoid form
Acute and chronic inflammatory
lesions
Chronic lesion
Lesions are widely scattered in
body
Localised skin lesion involving bridge
of nose and adjacent cheeks
without any sytemic manifestation
There is presence of various
nuclear and cytoplasmic
autoantibodies in plasma.
Autoantibodies may or may not
present
5. Etio-Pathogenesis
The exact etiology of SLE is not known.
1) However spectrum of autoantibodies against nuclear and cytoplasmic components of
cells are demonstrable in plasma by immunofloroscence tests in almost all cases.
2) Genetic Predisposition/ Factors
3) Immunological factors
4) Environmental factors
Etiology-
6. Spectrum of autoantibodies in SLE
Specificity of Autoantibody % positive Association with specific disease features
ANA 95-98 Found against DNA and RNA antigen, used as screening test
ds- DNA 40-60 Nephritis, specific for SLE
U1 RNP 30-40 more often in Sjogren's syndrome
SMITH (Sm) antigen 20-30
Sm antigen is a Core protein of small ribonucleoprotein
particle, and is specific for SLE
Ro (SS-A)/(SS-B)
nucleoprotein
30-50 congenital heart block, neonatal lupus
Phospholipid protein
complex (anti- PL)
30-40
Antiphospholipid syndrome (a thrombotic complication) in
10% of SLE patient
Multiple nuclear antigen
(generic ANA)
95-100 not specific
Histone In drug induced lupus
Anti ribosomal P antibody in CNS lupus
7. Etio-Pathogenesis
1) The source of these spectrum of autoantibodies and hypergamaglobunemia is –
mainly Polyclonal activation of B cells,
brought about by
- Genetic Predisposition/ Factors
- Immunological factors
- Environmental factors
Etiology-
8. Etio-Pathogenesis
1) Genetic Predisposition/ Factors
eg * Increase risk in first degree relative
* higher rates of concordance in monozygotic twins
* Inherited deficiency of early complement component eg C2, C4 or C1q.
(Lack of complements impair removal of circulating immune complex
favoring tissue deposition.)
* Deficeincy of C1q results in defective pahocytic clearance of apoptatic cells----
2) Immunological factors
3) Environmental factors
Etiology-
9. Etio-Pathogenesis
1) Genetic Predisposition/ Factors
2) Immunological factors
Eg * Failure of self tolerance of in B cells, due to
- defective elimination of self reactive B cells in bone marrow before maturation or
defective self tolerance mechanisms.
- defect in peripheral tolerence mechanism
* T helper (CD4+) specific for nucleosomal antigen escapes tolerance and
contributes in production of autoantibodies.
* TLR gives signal of detection of microbial products like nucleic acid to B cell
(which are specific for nuclear antigen), leading increase production of Anti
Nuclear autoAb.
3) Environmental factors
Etiology-
10. Etio-Pathogenesis
1) Genetic Predisposition/ Factors
2) Immunological factors
3) Environmental factors Eg. * Exposure to UV light
- induces apoptosis in cells and may alter DNA in such a
way to make it more immunogenic.
* Drugs like Hydralazine, procainamide, and
D-penicillamine induces SLE like response.----
* Certain viral infections like EBV infection and
Hormones like ostrogen with unknown pathogenesis.
Etiology-
11. Pathogenesis
1) UV radiations leads to apoptosis of cells.
2) Inadequate clearance of these nuclear
antigen creates increased burden of
nuclear Ag in all organs.
3) B and T cells with defective tolerance,
stimulated by nuclear Ag, start to form
Ab against it , even though these are self
Ag.
4) The Ag-Ab complexes formed binds to Fc
portion of dendritic cell and B cell.
5) The nucleic acid component engages TLR
leading
1) Bcell to produce more autoantibodies
2) Dendritic cell to produce more Ty 1 IFN
stimulating more apoptosis.
And continuing the vicious cycle.
12. Pathogenesis
1) UV radiations leads to apoptosis of cells.
2) Inadequate clearance of of nuclear
antigen creats increased burden of
nuclear Ag in all organs.
3) B and T cells with defective tolerance
stimulated by nuclear Ag, giving Ab
againts it.
4) The Ag-Ab complexes formed binds to Fc
portion of dendritic cell and B cell.
5) The nucleic acid component egages TLR
leading
1) B cell to produce more autoantibodies
IgG
2) Dendritic cell to produce more ty 1 IFN
stimulating more apoptosis
13. Pathogenesis
2) * Now these types of autoantibodies are formed against blood cells (RBC, platelet
and leucocyte) ,which leads to promoting their phagocytosis and lysis, and
accordingly showing haematological derangement/cytopenia in SLE.
* Autoantibodies against phospholipids - increased thrombosis in patients, with
recurrent spontaneous abortion and
thrombotic episodes. (part of the antiphospholipid
syndrome.)
* Autoantibodies are also produced against clotting factors such as thrombin-
clotting disorders.
* Autoantibodies against CNS receptors and neurons leading neuropsychiatric
complications like psychosis and seizures.
14. Pathogenesis
2) * Now these types of autoantibodies are formed against blood cells (RBC, platelet
and leucocyte) ,which leads to promoting their phagocytosis and lysis, and
accordingly showing haematological derangement/cytopenia in SLE.
* Autoantibodies against phospholipids - increased thrombosis in patients, with
recurrent spontaneous abortion and
thrombotic episodes. (part of the antiphospholipid
syndrome.)
* Autoantibodies are also produced against clotting factors such as thrombin-
clotting disorders.
* Autoantibodies against CNS receptors and neurons leading neuropsychiatric
complications like psychosis and seizures.
This is an example of TYPE 2 Hypersensititvity in SLE.
15. Pathogenesis
3) LE cell Phenomenon
Principle -ANAs cannot penetrate the intact cells and thus cell
nuclei should be exposed to bind them with the ANAs. The binding of
exposed nucleus with ANAs results in homogeneous mass of nuclear
chromatin material which is called LE body or haematoxylin body.
For demonstration of LE cell phenomenon in vitro, the blood sample
is traumatized to expose the nuclei of blood leucocytes to ANAs. This
results in binding of denatured and damaged nucleus with ANAs. The
ANA-coated denatured nucleus is chemo tactic for phagocytic cells.
*If this mass is engulfed by a neutrophil, displacing the nucleus
of neutrophil to the rim of the cell, it is called LE cell .
*If the mass is phago-cytosed by a monocyte, it is called Tart cell.
16. Pathogenesis
3) LE cell Phenomenon
Principle -ANAs cannot penetrate the intact cells and thus cell
nuclei should be exposed to bind them with the ANAs. The binding of
exposed nucleus with ANAs results in homogeneous mass of nuclear
chromatin material which is called LE body or haematoxylin body.
For demonstration of LE cell phenomenon in vitro, the blood sample
is traumatized to expose the nuclei of blood leucocytes to ANAs. This
results in binding of denatured and damaged nucleus with ANAs. The
ANA-coated denatured nucleus is chemo tactic for phagocytic cells.
*If this mass is engulfed by a neutrophil, displacing the nucleus
of neutrophil to the rim of the cell, it is called LE cell .
*If the mass is phago-cytosed by a monocyte, it is called Tart cell.
17. Pathogenesis
3) LE cell Phenomenon
Principle -ANAs cannot penetrate the intact cells and thus cell
nuclei should be exposed to bind them with the ANAs. The binding of
exposed nucleus with ANAs results in homogeneous mass of nuclear
chromatin material which is called LE body or haematoxylin body.
For demonstration of LE cell phenomenon in vitro, the blood sample
is traumatized to expose the nuclei of blood leucocytes to ANAs. This
results in binding of denatured and damaged nucleus with ANAs. The
ANA-coated denatured nucleus is chemo tactic for phagocytic cells.
*If this mass is engulfed by a neutrophil, displacing the nucleus
of neutrophil to the rim of the cell, it is called LE cell .
*If the mass is phago-cytosed by a monocyte, it is called Tart cell.
18. Pathogenesis
3) LE cell Phenomenon
Principle -ANAs cannot penetrate the intact cells and thus cell
nuclei should be exposed to bind them with the ANAs. The binding of
exposed nucleus with ANAs results in homogeneous mass of nuclear
chromatin material which is called LE body or haematoxylin body.
For demonstration of LE cell phenomenon in vitro, the blood sample
is traumatized to expose the nuclei of blood leucocytes to ANAs. This
results in binding of denatured and damaged nucleus with ANAs. The
ANA-coated denatured nucleus is chemo tactic for phagocytic cells.
*If this mass is engulfed by a neutrophil, displacing the nucleus
of neutrophil to the rim of the cell, it is called LE cell .
*If the mass is phago-cytosed by a monocyte, it is called Tart cell.
D/Ds for LE test Rheumatoid arthritis, lupoid hepatitis, penicillin
sensitivity etc.
19. Pathogenesis
4) * The Ag-Ab complexes (DNA Anti-DNA complex or some times Ig Anti-Ig)
deposited at sites such as renal glomeruli, wall of small blood vessels etc giving a
systemic involvement.
20. Pathogenesis
4) * The Ag-Ab complexes (DNA Anti-DNA complex or some times Ig Anti-Ig)
deposited at sites such as renal glomeruli, wall of small blood vessels etc giving a
systemic involvement.
* These Ag-Ab complexes activate classical complement pathway leading to
consumption of serum C3 and C4 at the time of SLE flares.
* This leads to low levels of complements being activated and are consumed faster
than it can be produced.
21. Pathogenesis
4) * The Ag-Ab complexes (DNA Anti-DNA complex or some times Ig Anti-Ig)
deposited at sites such as renal glomeruli, wall of small blood vessels etc giving a
systemic involvement.
* These Ag-Ab complexes activate classical complement pathway leading to
consumption of serum C3 and C4 at the time of SLE flares.
* This leads to low levels of complements being activated and are consumed faster
than it can be produced.
This is an example of TYPE 3 Hypersensititvity in SLE.
25. Morphology
1) In Blood Vessels
* An acute necrotizing vasculitis affecting small
arteries and arterioles.
* Arteritis is characterized by necrosis and by fibrinoid
deposits within vessel walls containing antibody, DNA,
complement fragments, and fibrinogen;
* A transmural and perivascular leukocytic infiltrate is
also frequently present.
* In chronic stages, vessels show fibrous thickening
with luminal narrowing.
27. Morphology
2) In Kidney
* Kidney involvement is one of the most important clinical features of SLE, with renal failure
being the most common cause of death.
* A kidney biopsy is essential in the renal assessment of patients with SLE and is indicated in all
patients having abnormalities of urine sediment or abnormal renal function. Because
1) it is not possible to accurately predict the histopathology based on the clinical presentation even
though in general - more severe histology tends to correlate with more severe clinical disease.
2) it has been shown that in untreated patients the histopathologic features of the renal disease can
provide an indication of the subsequent clinical course, thus the renal biopsy can aid in planning
treatment.
The pathologic findings of lupus nephritis are extremely diverse can involve :
glomeruli,
tubules,
interstitium, and blood vessels.
28. Morphology
In Kidney International Society of Nephrology (ISN)/Renal Pathology
Society (RPS) classification of lupus nephritis 2004
CLASS
I Minimal mesangial lupus nephritis least common
II Mesangial proliferative lupus nephritis
III Focal lupus nephritis (<50% of glomeruli)
III (A) Active lesions
III (A/C) Active and chronic lesions
III (C) Chronic lesions
IV Diffuse lupus nephritis (=50% of glomeruli) most common
IV (A) Active lesions
IV (A/C) Active and chronic lesions
IV (C) Chronic lesions
V Membranous lupus nephritis
VI
Advanced sclerosing lupus nephritis (=90% globally
sclerosed glomeruli without residual activity)
29. Morphology
1) In Kidney
Minimal mesangial lupus nephritis (class I)
- is rarely encountered in renal biopsies.
- Immune complexes are present in the mesangium,
- but there are no concomitant structural alterations
detectable by light microscopy.
- usually manifest as- mild microscopic hematuria
and/or mild proteinuria, and renal function is typically
normal.
30. Morphology
1) In Kidney
Mesangial proliferative lupus nephritis
(class II)
- is seen in 10% to 25% of cases and is associated with
mild clinical symptoms demonstrated by an inactive
urinary sediment. Less than 50% of the patients have
mild hematuria and/or proteinuria, which usually
does not exceed 1 g per 24 hours.
31. Morphology
1) In Kidney
Mesangial proliferative lupus nephritis
(class II)
- is seen in 10% to 25% of cases and is associated with
mild clinical symptoms demonstrated by an inactive
urinary sediment. Less than 50% of the patients have
mild hematuria and/or proteinuria, which usually
does not exceed 1 g per 24 hours.
- Immune complexes deposit in the mesangium on
electron microscopy, with a mild to moderate
increase in the mesangial matrix and cellularity, as
seen by light microscopy.
- The nephrotic syndrome is exceedingly rare and,
when present, it may be a manifestation of
concomitant minimal change disease.
32. Morphology
1) In Kidney
Mesangial proliferative lupus nephritis
(class II)
- is seen in 10% to 25% of cases and is associated with
mild clinical symptoms demonstrated by an inactive
urinary sediment. Less than 50% of the patients have
mild hematuria and/or proteinuria, which usually
does not exceed 1 g per 24 hours.
- Immune complexes deposit in the mesangium on
electron microscopy, with a mild to moderate
increase in the mesangial matrix and cellularity, as
seen by light microscopy.
- The nephrotic syndrome is exceedingly rare and,
when present, it may be a manifestation of
concomitant minimal change disease.
33. Morphology
1) In Kidney
Focal lupus nephritis (class III)
- is seen in 20% to 35% of cases.
- Lesions are visualized in less than half the total
glomeruli of kidney, and they may be segmentally
or globally distributed within each glomerulus.
- Active lesions are characterized by swelling and
proliferation of endothelial and mesangial cells,
infiltration by neutrophils, and/or fibrinoid deposits
with capillary thrombi .
- The clinical presentation may range from only mild
microscopic hematuria and proteinuria, to a more
active urinary sediment with red blood cell casts
and acute severe renal insufficiency.
34. Morphology
1) In Kidney
Focal lupus nephritis (class III)
- is seen in 20% to 35% of cases.
- Lesions are visualized in less than half the total
glomeruli of kidney, and they may be segmentally
or globally distributed within each glomerulus.
- Active lesions are characterized by swelling and
proliferation of endothelial and mesangial cells,
infiltration by neutrophils, and/or fibrinoid deposits
with capillary thrombi .
- The clinical presentation may range from only mild
microscopic hematuria and proteinuria to a more
active urinary sediment with red blood cell casts
and acute severe renal insufficiency.
35. Morphology
1) In Kidney
Focal lupus nephritis (class III)
- is seen in 20% to 35% of cases.
- Lesions are visualized in less than half the total
glomeruli of kidney, and they may be segmentally
or globally distributed within each glomerulus.
- Active lesions are characterized by swelling and
proliferation of endothelial and mesangial cells,
infiltration by neutrophils, and/or fibrinoid deposits
with capillary thrombi .
- The clinical presentation may range from only mild
microscopic hematuria and proteinuria to a more
active urinary sediment with red blood cell casts
and acute severe renal insufficiency.
36. Morphology
1) In Kidney
Diffuse lupus nephritis (class IV)
- is the most serious and most commonly
encountered in renal biopsies, occurring in 35%
to 60% of patients.
- It is distinguished from focal lupus nephritis
(class III) by involvement of half or more of
glomeruli.
- Most of the glomeruli show endothelial and
mesangial proliferation, leading to diffuse
hypercellularity of these structures
- and producing in some cases epithelial
crescents that fill Bowman’s space.
37. Morphology
1) In Kidney
Diffuse lupus nephritis (class IV)
- is the most serious and most commonly
encountered in renal biopsies, occurring in 35%
to 60% of patients.
- It is distinguished from focal lupus nephritis
(class III) by involvement of half or more of
glomeruli.
- Most of the glomeruli show endothelial and
mesangial proliferation, leading to diffuse
hypercellularity of these structures
- and producing in some cases epithelial
crescents that fill Bowman’s space.
38. Morphology
1) In Kidney
Diffuse lupus nephritis (class IV)
- is the most serious and most commonly
encountered in renal biopsies, occurring in 35%
to 60% of patients.
- It is distinguished from focal lupus nephritis
(class III) by involvement of half or more of
glomeruli.
- Most of the glomeruli show endothelial and
mesangial proliferation, leading to diffuse
hypercellularity of these structures
- and producing in some cases epithelial
crescents that fill Bowman’s space.
39. Morphology
1) In Kidney
Diffuse lupus nephritis (class IV)
- The extensive, subendothelial immune complexes create a circumferential thickening of the
capillary wall, resembling rigid “wireloops” on routine light microscopy
40. Morphology
1) In Kidney
Diffuse lupus nephritis (class IV)
- The extensive, subendothelial immune complexes create a circumferential thickening of the
capillary wall, resembling rigid “wireloops” on routine light microscopy
41. Morphology
1) In Kidney
Diffuse lupus nephritis (class IV)
- The extensive, subendothelial immune complexes create a circumferential thickening of the
capillary wall, resembling rigid “wireloops” on routine light microscopy
42. Morphology
1) In Kidney
Diffuse lupus nephritis (class IV)
- On Electron microscopy- reveals prominent electron-dense subendothelial
immune complexes (between endothelium and basement membrane),
43. Morphology
1) In Kidney
Diffuse lupus nephritis (class IV)
- Electron microscopy- reveals prominent electron-dense subendothelial
immune complexes (between endothelium and basement membrane),
44. Morphology
1) In Kidney
Diffuse lupus nephritis (class IV)
- Immune complexes can be visualized by
staining with fluorescent antibodies
directed against immunoglobulins or
complement, resulting in a granular
fluorescent staining pattern .
- Most affected patients have hematuria
with moderate to severe proteinuria,
hypertension and renal insufficiency.
45. Morphology
1) In Kidney
Diffuse lupus nephritis (class IV)
- Immune complexes can be visualized by
staining with fluorescent antibodies
directed against immunoglobulins or
complement, resulting in a granular
fluorescent staining pattern .
- Most affected patients have hematuria
with moderate to severe proteinuria,
hypertension and renal insufficiency.
46. Morphology
1) In Kidney
Diffuse lupus nephritis (class IV)
- Immune complexes can be visualized by
staining with fluorescent antibodies
directed against immunoglobulins or
complement, resulting in a granular
fluorescent staining pattern .
- Most affected patients have hematuria
with moderate to severe proteinuria,
hypertension and renal insufficiency.
47. Morphology
1) In Kidney
Membranous lupus nephritis (class V)
- It occurs in 10% to 15% of cases , characterized
by widespread thickening of the capillary wall
due to deposition of subepithelial immune
complexes.
- Thickening of capillary walls is caused by
increased deposition of basement membrane
like material, as well as accumulation of immune
complexes.
- Patients with this histologic change almost
always have severe proteinuria with overt
nephrotic syndrome.
48. Morphology
1) In Kidney
Membranous lupus nephritis (class V)
- It occurs in 10% to 15% of cases , characterized
by widespread thickening of the capillary wall
due to deposition of subepithelial immune
complexes.
- Thickening of capillary walls is caused by
increased deposition of basement membrane–
like material, as well as accumulation of immune
complexes.
- Patients with this histologic change almost
always have severe proteinuria with overt
nephrotic syndrome.
49. Morphology
1) In Kidney
Advanced sclerosing lupus nephritis
(Class VI)
- It’s a global glomerulosclerosis affecting over
90% of the glomeruli without residual activity.
- In less advanced lesions, mesangial and
endocapillary hypercellularity may be seen .
- Severe tubular atrophy, interstitial fibrosis,
inflammation, and atherosclerosis are usually
present.
- Patients have significant proteinuria and
severe renal insufficiency, and are unlikely to
respond to therapy.
51. Morphology
2) In Kidney
- While most cases of lupus nephritis fall into already mentioned six categories,
some overlap between classifications also exists.
- The most common involves classes III and V, and IV and V, and have been
designated as combined classes III + V, and IV + V, respectively.
- The transformation of lupus nephritis lesions from one class to another is not
uncommon during the course of the disease.
- It has been reported in 10–50% of patients who undergo successive renal
biopsies and it has occurred between all morphologic types:
- focal to diffuse,
- focal to membranous,
- diffuse to membranous,
- membranous to diffuse proliferative, and
- membranous to membranous with focal proliferative lesions.
52. Morphology
3) Skin
- The skin is involved in a majority of
patients;
- A characteristic erythematous or
maculopapular eruption over the malar
eminences and bridge of the nose
(“butterfly pattern”) is observed in
approximately half of the cases.
- Exposure to sunlight (UV light) exacerbates
the erythema (so-called photosensitivity),
and a similar rash may be present
elsewhere on the extremities and trunk,
frequently in sun-exposed areas.
53. Morphology
3) Skin
- The skin is involved in a majority of
patients;
- A characteristic erythematous or
maculopapular eruption over the malar
eminences and bridge of the nose
(“butterfly pattern”) is observed in
approximately half of the cases.
- Exposure to sunlight (UV light) exacerbates
the erythema (so-called photosensitivity),
and a similar rash may be present
elsewhere on the extremities and trunk,
frequently in sun-exposed areas.
54. Morphology
3) Skin
- Histopathologic findings include liquefactive degeneration of the basal layer of the
epidermis,
- edema at the dermoepidermal junction, and mononuclear infiltrates around blood
vessels and skin appendages.
55. Morphology
3) Skin
- Histopathologic findings include liquefactive degeneration of the basal layer of the
epidermis,
- edema at the dermoepidermal junction, and mononuclear infiltrates around blood
vessels and skin appendages.
56. Morphology
3) Skin
- Histopathologic findings include liquefactive degeneration of the basal layer of the
epidermis,
- edema at the dermoepidermal junction, and mononuclear infiltrates around blood
vessels and skin appendages.
59. Morphology
3) Skin
- Immunofluorescence microscopy reveals
déposition of immunoglobulin and
complement at the dermoepidermal
junction;
- similar immunoglobulin and complement
deposits may also be present in apparently
uninvolved skin. (Ref- Robbins)
- Clinically uninvolved areas will show
deposition of immunoglobulins in about
half of the patients with systemic lupus
erythematosus but no deposition of the
membrane attack complex (ie
complements) (Ref-Ackerman)
60. Morphology
4) Joints
- It consists of swelling and a nonspecific mononuclear cell infiltration in the
synovial membranes.
- Erosion of the membranes and destruction of articular cartilage, such as in RA, are
exceedingly rare.
61. Morphology
4) Joints
- It consists of swelling and a nonspecific mononuclear cell infiltration in the
synovial membranes.
- Erosion of the membranes and destruction of articular cartilage, such as in RA, are
exceedingly rare.
5) CNS
- CNS disease often is ascribed to vascular lesions causing ischemia or multifocal
cerebral microinfarcts.
- Small vessel angiopathy with noninflammatory intimal proliferation is the most
frequent pathological lesion; frank vasculitis is uncommon.
- The angiopathy may result from thrombosis caused by antiphospholipid antibodies.
Premature atherosclerosis occurs and may contribute to CNS ischemia.
62. Morphology
6) Pericarditis with other serosal cavity involvment
- Pericardium and pleura, in particular, are serosal membranes that show a variety of
inflammatory changes in SLE ranging (in the acute phase) from serous effusions to
fibrinous exudates
- that may progress to fibrous opacification in the chronic stage.
63. Morphology
7) CVS
- Involvement of the heart is manifested
primarily in the form of Pericarditis.
- Myocarditis (in the form of a nonspecific
mononuclear cell infiltrate) and valvular
lesions (called Libman-Sacks endocarditis)
also occur but are less common in the current
era of aggressive corticosteroid therapy.
64. Morphology
7) CVS
- This nonbacterial verrucous endocarditis
takes the form of irregular, 1- to 3-mm warty
deposits, seen as distinctive lesions on either
surface of the leaflets (i.e., on the surface
exposed to the forward flow of the blood or
on the underside of the leaflet) .
65. Morphology
7) CVS
- This nonbacterial verrucous endocarditis
takes the form of irregular, 1- to 3-mm warty
deposits, seen as distinctive lesions on either
surface of the leaflets (i.e., on the surface
exposed to the forward flow of the blood or
on the underside of the leaflet) .
66. Morphology
7) CVS
- This nonbacterial verrucous endocarditis
takes the form of irregular, 1- to 3-mm warty
deposits, seen as distinctive lesions on either
surface of the leaflets (i.e., on the surface
exposed to the forward flow of the blood or
on the underside of the leaflet) .
68. Morphology
7) CVS
- The basis of accelerated atherosclerosis in SLE is not
fully understood, but the process seems to be
multifactorial; certainly, immune complexes can
deposit in the coronary vasculature, leading to
endothelial damage by that pathway.
- Moreover, glucocorticoid treatment causes alterations
in lipid metabolism, and renal disease (common in SLE)
causes hypertension; both of these are risk factors for
atherosclerosis.
69. Morphology
7) Spleen
- The spleen may be moderately enlarged.
- Capsular fibrous thickening is common, as is
follicular hyperplasia with numerous plasma
cells in the red pulp.
- Central peni cilliary arteries characteristically
show thickening and perivascular fibrosis,
producing onion-skin lesions.
71. Clinical features
- ...SLE is a multisystem disease that is highly
variable in clinical presentation.
- Its diagnosis relies on combination of clinical,
serological and morphological changes.
73. as per ACR ie American College of Rheumatology in 1997.
For a person said to have SLE,
4 of these 11 criteria are to be present serially or
simultaneously.
74. as per ACR ie American College of Rheumatology in 1997.
For a person said to have SLE,
4 of these 11 criteria are to be present serially or
simultaneously.
75. Some of the scientist raises concerns about the ACR criteria eg.
1) Concerns about many patients without any immunologic criteria being
classified as SLE,
2) Duplication of highly correlated cutaneous lupus terms (malar rash and
photosensitivity) and missing out on many other lupus cutaneous
manifestations,
3) Many of the SLE specific neurologic manifestations were not included.
4) Quantification of urine protein had to be modified utilizing new standards,
5) Omission of low serum complement levels
6) Inclusion of new knowledge on antiphospholipid antibodies in the immunologic
criteria
7) Patients with biopsy proven lupus nephritis may not be classified as SLE
according to ACR criteria
76. To over come these lacunae New SLICC* 2012 Revision of
the ACR Classification Criteria - Clinical
77. New SLICC* 2012 Revision of the ACR
Classification Criteria - Clinical
SO finally classify a patient as having
SLE if,
a) The patient satisfies four of the
criteria,
including at least one clinical
criterion and one immunologic criterion
OR
b) The patient has biopsy-proven
nephritis compatible with SLE AND with
(+) ANA or (+) anti-dsDNA antibodies.
78. Variants
1) Chronic discoid Lupus
erythematosus
- Skin manifestation may mimic SLE,
but systemic manifestation are rare.
- Manifested as skin plaques with
edema, erythema, scaliness, follicular
plunging and skin atrophy,
surrounded by elevated
erythematous border.
- Skin biopsy shows Ig and C3 at
dermoepidermal junction similar to
SLE.
79. Variants
1) Chronic discoid Lupus
erythematosus
- Skin manifestation may mimic SLE,
but systemic manifestation are rare.
- Manifested as skin plaques with
edema, erythema, scaliness, follicular
plunging and skin atrophy,
surrounded by elevated
erythematous border.
- Skin biopsy shows Ig and C3 at
dermoepidermal junction similar to
SLE.
80. Variants
1) Chronic discoid Lupus
erythematosus
- Skin manifestation may mimic SLE,
but systemic manifestation are rare.
- Manifested as skin plaques with
edema, erythema, scaliness, follicular
plunging and skin atrophy,
surrounded by elevated
erythematous border.
- Skin biopsy shows Ig and C3 at
dermoepidermal junction similar to
SLE.
81. Variants
2) Subacute cutaneous Lupus
erythematosus
- Skin rash tend to be wide spread,
superficial, and non scarring.
- There is a strong association with
antibodies to the SS-A Ag and with
HLA DR3 genotype.
82. Variants
2) Subacute cutaneous Lupus
erythematosus
- Skin rash tend to be wide spread,
superficial, and non scarring.
- There is a strong association with
antibodies to the SS-A Ag and with
HLA DR3 genotype.
84. Variants
3) Drug induced lupus erythematosus
- A lupus erythematosus like syndrome may
develop in patients receiving drugs like………
85. Variants
3) Drug induced lupus erythematosus
- A lupus erythematosus like syndrome may
develop in patients receiving drugs like………
- These drugs are associated with
development of ANA, but most patient do
not have symptoms of lupus (one third
have symptoms like Arthralgia, fever
serositis)
- Anti-histone antibody are specific here
compared to ANAs.
86. Variants
3) Drug induced lupus erythematosus
- A lupus erythematosus like syndrome may
develop in patients receiving drugs like………
- These drugs are associated with
development of ANA, but most patient do
not have symptoms of lupus (one third
have symptoms like Arthralgia, fever
serositis)
- Anti-histone antibody are specific here
compared to ANAs.
- Person with
- HLA DR4 – given with Hydralazine
- HLA DR6 – given with Procainamide, are
at shown to be at greater risk for lupus
erythematosus like symptoms.
87. Just to sum up Myths vs Reality-
1
The major cause of death in SLE
patients is: active lupus ?/
complications of renal failure?/
infection?
Correct answer is non of the above
In the 1970s, Urowitz and Gladman reported on the bimodal pattern of mortality in
SLE. Whereas “early” deaths were caused predominantly by active SLE, “later”
deaths were
2
Lymphadenopathy must be
investigated aggressively to rule
out lymphoma.
Lymphadenopathy occurs in approximately 40% of lupus patients
The involved lymph node chains are found usually in the cervical, axillary, and
inguinal areas.
Pathological features include the absence of tenderness in the nodes; enlargement
greater than three centimeters; induration; age older than 40, and a location above
the clavicle . Additional indicators of concern are splenomegaly and a monoclonal
expansion of CD19+/CD22+ B lymphocytes in the peripheral blood.
Lupus patients have a slightly increased risk for both Hodgkin’s (3.6%) and non-
Hodgkin’s(3.1%) lymphoma.
88. Just to sum up Myths vs Reality-
3
Autoimmune liver
disease is common
in SLE.
Autoimmune liver disease is relatively uncommon in SLE. It affects only about 2% of
patients.
Positive ANA assays are the norm in both conditions. However, Anti SM Ab and AMA
antibodies occur in fewer than 30% of SLE patients and, when present, are usually
found in low titers.
Elevations of the serum hepatic aminotransferases tend to be lower in lupus-
associated hepatitis when compared with autoimmune liver disease.
Histopathology may resolve the question. Autoimmune hepatitis is associated with a
characteristic periportal hepatitis and piecemeal necrosis.
89. Just to sum up Myths vs Reality-
4
Autoimmune
hemolytic anemia is
the most common
cause of anemia in
lupus.
AIHA is found in approximately 10% of patients with SLE.
The most common causes of anemia in SLE are chronic disease and iron deficiency.
For lupus patients with stage 4 CKD, the KDOQI guidelines recommend maintaining a target
hemoglobin of 11–12 mg/dL through the use of erythropoietin . (National Kidney
Foundation produces clinical practice guidelines through the NKF Kidney Disease Outcomes
Quality Initiative (NKF KDOQI))
5
Serum creatinine is a
reliable indicator of
renal function.
Measurement of the serum creatinine level is a practical but relatively insensitive indicator
of abnormalities in GFR as level is affected by variables with little direct relationship to renal
function, including sex, muscle mass, and age.
90. Just to sum up Pearls-
Pearls : Comment:
1
Up to one-third of lupus patients have one or more additional
autoimmune diseases.
Other autoimmune disorders often linked to SLE
include Sjögren’s syndrome, autoimmune
thrombocytopenia, hypothyroidism, and polymyositis
.
2
Lupus is associated with the production of type I interferon
and a peripheral blood interferon “signature.” The fact that
type I and type II interferons are powerful inhibitors of
osteoclasts is one likely explanation for the fact that only a
small subset of lupus patients has bony erosions.
3
In a pregnant lupus patient, substantial renal dysfunction can
be present despite the finding of a normal serum creatinine
level.
91. Just to sum up Pearls-
4
Proteinuria is a better
indicator of lupus
nephritis than is
hematuria.
Hematuria is one of the renal manifestations of lupus listed on the (SLEDAI) . However,
sound clinical judgment is essential before ascribing hematuria to active lupus. SLE
patients may have hematuria from a variety of causes, including menses, trauma, renal
calculi. (SLEDAI = SYSTEMIC LUPUS ERYTHEMATOSUS DISEASE ACTIVITY INDEX)
In the SELENA studies, the investigators amended the SLEDAI to require that hematuria
only be used in the presence of proteinuria as a manifestation of lupus .
5
“ANA-negative lupus”
still exists.
The sensitivity of ANA assays is suboptimal. Depending on which type of assay is used and
the quality of the laboratory in which it is performed, the sensitivity of ANA testing can be
less than 70% in patients who have SLE.
In addition, assays for other autoantibodies such as those directed against Ro, La, Sm,
RNP.
Biopsies of skin and kidney lesions are required in selected cases.
92. Just to sum up Pearls-
5
“ANA-negative lupus”
still exists.
Biopsies of skin and kidney lesions are required in selected cases.
6
Lupus patients are
immunosuppressed,
even without our help.
SLE patients have difficulty with multiple viral infections, especially herpes zoster,
cytomegalovirus, and papillomaviruses
Perhaps because of splenic dysfunction, SLE patients have difficulty with encapsulated
organisms such as the pneumococcus and meningococcus.
All SLE patients must be vaccinated.
7
Diffuse or focal
myocarditis can mimic
myocardial infarction.
In a lupus patient with chest pain, regardless of the patient’s age, exclude active coronary
ischemia. Patients with SLE can and do develop coronary arteritis, leading to myocardial
infarction.
8 Cigarette smoking is associated with an increased risk of cutaneous lupus for unknown reason.
94. References
1) Robbins and Cotran pathologic basis of disease." APA (9th ed.) Kumar,
V., Abbas, A. K., Fausto, N., Robbins, S. L., & Cotran, R. S. (2014)
2) Rosai and Ackerman’s Surgical Pathology - (2011) Peter A. Humphrey,
Louis P. Dehner, John D. Pfeifer-The Washington Manual of Surgical
Pathology-LWW (2012)
3) https://cmijournal.files.wordpress.com/2015/10/slicc-criteria-
article.pdf last date of access 16/07/17
4) https://en.wikipedia.org/ last date of access 16/07/17
5) http://www.merriam-webster.com/medical/le%20cell last date of
access 16/07/17
6) A Presentation “Pearls and Myths in SLE”, By Ahmed Mohammed Abd El
Wahab Lecturer of Internal Medicine (Nephrology)
Hinweis der Redaktion
This topic will be discussed under heading like
It derived its name from
1) Systemic – as it is non organ specific, but virtually involves every other organ of the body.
2) Lupus- from latin word Lupus = wolf , because it was initially believed to affect skin only and eat away skin like wolf.
3) Erythematosus- Rash malar/discoid.
RNP= Ribonucleoprotein
------Many cells normally undergo apoptosis, and if they are not cleared their nuclear components may elicit immune responces
TLR= Toll like receptors
------------ theses drugs causes demethylation of DNA, which could influence the expression of genes involved in the development of autoimmunity, or the ability of DNA to activate host cells.
This was first diagnostic laboratory test for SLE. Positive in about 70% cases but it now of historical significance only.
Dia 1 There are two LE cells having rounded masses of amorphous nuclear material (LE body) which has displaced the lobes of neutrophil to the rim of the cell.
Dia 2 Tart cell - Macrophage that has phagocytized a lymphocyte.
IC= Immune complex
The morphologic changes in SLE are extremely variable and depend on the nature of the autoantibodies, the tissue in which immune complexes deposit, and the course and duration of disease.
The most characteristic morphologic changes resulting from the deposition of immune complexes in a variety of tissues are………
Now about the morphology……..
So vasculitis affecting small arteries and arterioles results in-
ISN/RPS classification is based entirely on the evaluation of glomerular alterations seen by light microscopy, immunofluorescence, and electron microscopy,
A proliferative, A/C necrotizing, C sclerosing lesions
Now we will look for the detailed morphology…………..
Fig: Here in the photograph shown, is mild diffuse mesangial hypercellularity and an increase in matrix.
Mesangial deposits may be identified by immunofluorescence and electron microscopy
Fig: 1- Here is photograph which shows two necrotizing lesions in a glomerulus (segmental distribution) (H&E stain)
Fig: 2- There is focal and segmental glomerulonephritis characterized by segmental necrosis, adhesions to the Bowman capsule, and leukocytic infiltration.
Fig: 1- there is marked global increase in cellularity throughout the glomerulus (H&E stain).
Fig: 2- Glomerulus with an epithelial crescent showing two hyaline thrombi
Fig: 1 and Fig: 2- Lupus nephritis showing a glomerulus with several “wire loop” lesions representing extensive subendothelial deposits of immune complexes (periodic acid Schiff stain).
Similar photograph showing “wire loop” lesions representing extensive subendothelial deposits of immune complexes (H & E stain).
End- endothelium,
Ep- Epithelial cells with foot process
Mes- Mesangium
RBC- In capillary lumen
US- Urinary space
Fig: 1- Immunofluorescence preparation for IgG showing large amounts of immune complex deposits not only in the mesangium and along the glomerular capillary loops, but also around tubular basement membranes, interstitium, blood vessels, and in the Bowman capsule.
Fig: 2- Deposition of IgG antibody in a granular pattern, detected by immunofluorescence.
Fig: The capillary walls are thickened and the mesangial matrix increased.
Just to sum up these morphology in tabular form……………….
This is a classical photograph of patient with malar or butterfly rash, involving area mainly above nasolabial fold.
Fig 1 : Lesion of chronic discoid lupus erythematosus - showing hyperkeratosis and hydropic degeneration of basal layer.
Fig 1 : Lesion of chronic discoid lupus erythematosus - showing hyperkeratosis and hydropic degeneration of basal layer.
Fig 2 : An H&E-stained section shows liquefactive degeneration of the basal layer of the epidermis and edema at the dermoepidermal junction
Fig: An immunofluorescence micrograph stained for IgG reveals deposits of immunoglobulin along the dermoepidermal junction.
Membrane attack complex- C5b, C6, C7
.
.
.
Fig 2 : Libman sac endocarditis of mitral valve in lupus erythematosus. The vegetation attached to the margin of thickened valve leaflet are in reddish in color.
Fig 1 : Vegetations of RHD Rheumatic heart disease- many small (Aschoff bodies with anitschkow cells), IE infective endocarditis- large destructive, NBTE Non bacterial thrombotic endocarditis- medium thrombotic, LibmanSacEno Lupus – mixed and present on either side.
.
.
.
.As we have already discussed…………..
Clinical features ie signs and symptoms in Easy to remember format…………..
The preliminary criteria for classification of SLE was published in 1971, and was popularly known as the ARA (American Rheumatism Association) Criteria,
which were then modified in 1982 (The ACR/American College of Rheumatology Criteria)
And in 1997 ACR given these 11 criteria to diagnose a case of SLE.
Antibodies against phospholipid B2 glycoprotein complex also bind to cardiolipn antigen, which is used in serologic diagnosis of syphilis. There for false positive .
The antibodies from syphilis clear from serum over the period of 3-4months and if even after they are present means that are due to SLE and not from syphilis.
SLICC (Systemic Lupus International Collaborating Clinics) is an international research group that is over 30 years old, which is dedicated to SLE and has contributed much to this field, including development of the ACR/SLICC Damage Index.
SLICC given total of 17 points or criteria with compulsory 1 clinical and 1 immunological for a diagnosis of SLE.
12. ANA (antinuclear antibody) above laboratory reference range
13. Anti-dsDNA above laboratory reference range (except ELISA: twice above laboratory reference range)
14. Anti-Sm (anti-Smith) antibody
15. APS abs: LAC, false-positive test for syphilis, anticardiolipin IgG, IgM, or IgA Abs, at least twice normal or medium-high titer, same for anti-B2 glycoprotein 1
16. Low complement: low C3, low C4, low CH50
17. Direct Coombs test in the absence of hemolytic anemia
Skin rash tend to be wide spread, superficial, and non scarring.
theses drugs causes demethylation of DNA, which could influence the expression of genes that are involved in the development of autoimmunity, or the ability of DNA to activate host cells.