Derm #10: Pathology Of Rheum

Front 1

Which antibody found in patients with lupus is associated with a hypercoagulable state, involving venous and arterial thromboses?

On average, how many different circulating antibodies may be present in typical SLE?

Back 1

Anti-phospholipid antibody --> associated with thrombosis

On average, 3 different antibodies present simultaneously in lupus

Front 2

Direct vs. Indirect Immunofluorescence

What 3 things can Indirect Immunofluorescence tell you?

Back 2

Direct- useful for tissue samples, antibody to specific antigen

Indirect- 1) If someone has +/- ANA, 2) Quantify the amount of antibodies, 3) pattern of antibody (specific to certain syndromes) ---> here a secondary antibody to the immune complexes is employed

Front 3

What is this characteristic pattern seen in lupus nephritis?

Back 3

Lumpy Bumpy (granular pattern)

From Immune Complex deposits (sub endo, sub epi, and mesangial) in the glomerulus

Front 4

Rapid recognition-

ANA pattern?

Associated with what condition?

Back 4

Homogeneous (diffuse) pattern.

Abs to chromatin, histone, and DNA. Associated with SLE (non specific)

Front 5

Rapid recognition-

ANA pattern?

Associated with what condition?

Back 5

Speckled pattern

Abs to non-DNA (ex: Sm, RNP, SS-A, SS-B)

Seen in SJOGRENs, and SLE

Front 6

Rapid recognition-

ANA pattern?

Associated with what condition?

Back 6

Nucleolar pattern

Abs to DNA topoisomerase I (scl-70)

Diffuse Scleroderma (dc-SSc)

Front 7

Rapid recognition-

ANA pattern?

Associated with what condition?

Back 7

Centromere pattern (note some have 46 dots, some have more- because they have duplicated)

Abs to centromere

Limited Scleroderma (CREST)

Front 8

The following changes shown in this image are indicative of what condition?

Back 8

CREST. C= calcinosis
R= Raynaud's phenomenon
E= esophageal dysfunction
S= serodactyly
T= telangiectasia

Front 9

What are the six classifications of Lupus Nephritis?

Which is the most severe? Which is the most common?

Back 9

Class I- minimal mesangial
Class II- mesangial proliferative
Class III- Focal proliferative
Class IV- Diffuse proliferative ***
Class V- Membranous
Class VI- Advancing Sclerosis

(Diffuse Proliferative is the most severe and also the most common)

Front 10

What class of Lupus Nephritis is seen here? How can you tell? What Immune deposits are present?

Back 10

Class II- Mesangial proliferative

Mesangial pattern on Immunostain and when seen in Electron microscopy. "Full House"- IgG, M, A, C3,4,1q

Front 11

What type of imaging would you use to diagnose Class I Lupus nephritis? Why?

Back 11

Use Immunologic or EM. You can't diagnose it on Light Microscopy because it appears normal.

Class I= Minimal mesangial lupus (very mild hematuria/proteinuria)

Front 12

What is this type of Lupus Nephritis? How can you tell?

What is the PREDOMINANT type of Immune complex (IC) deposit here?

Back 12

Class III- Focal Proliferative GN (Focal because not all parts of kidney affected), Segmental = not all glomerulus affected (like FSGS)

*Sub endothelial IC deposits

Front 13

What type of lupus nephritis is shown here?

What is the predominant type of IC deposit?

Back 13

Diffuse proliferative GN.

Subendothelial deposits predominate. The ENTIRE glomerulus has a WIRE LOOP pattern (thick capillary wals from deposits). You also see Crescents.

Front 14

What type of deposit is predominant in this image? Based on the presentation, what type of Lupus Nephritis do you think this is?

Back 14

Subendothelial deposits are predominant (see in EM)

This pattern looks granular and non-mesangial. Affecting whole glomerulus. Likely Class 4- Diffuse proliferative GN

Front 15

What is this type of lupus nephritis?

What type of deposits are predominant in this?

Back 15

Class V: Membranous GN

You can tell because basement membrane is thickened and there are SUBEPITHELIAL deposits.

Front 16

What type of Lupus Nephritis is seen here?

Back 16

Class VI: Advanced Sclerosing
Diffuse global glomerulosclerosis

Sclerosed glomeruli, no active glomerular disease. Renal failure occurs --> pts need dialysis.

Front 17

What is the most common cause of death in patients with Lupus?
What percentage of Lupus patients have renal involvement?

Back 17

Renal failure = most common cause of death

Renal involvement seen in 50-70% of patients with SLE

Front 18

What can you see in terms of skin involvement in SLE?

Back 18

Damage to skin cell --> release antigen --> produce complex and deposit in the DEJ (basement membrane)

- there is edema and lymphoid infiltrates in the skin (can be seen in uninvolved skin too!). Extravasation of RBCs, purpura- might lead to malar rash

Front 19

T or F

The changes seen in this individual are associated with other organ damage?

Back 19

Discoid Lupus Erythematosus (NOT involving other organs).

SLE might develop many years later.

Front 20

What is unique about this lesion, seen in SLE?

What other insults to this organ are seen in SLE?

Back 20

It is sterile- i.e. if you culture the area there will be no bacteria found! The vegetation forms from fibrin deposits on the valve. (Libman-Sacks endocarditis).

Other insults= myocarditis, pericarditis (most common)

Front 21

What are the strange cells seen in this image?

Back 21

LE Bodies (neutrophil/mac that engulfs aggregates of DNA + immunoglobulins). Stain a characteristic dark blue (for DNA).

Hematoxylin body= LE body

Front 22

What is the main problem seen in RA and shown in this biopsy

Describe the pathogenesis.

Back 22

Chronic Synovitis (inflammation of the synovium lining the joints)

CCP or exogenous stimulus will cause cell hyperplasia, neovascularization, fibrin organization coating the synovial space.

Front 23

What is the name for this? What is made up of?

Back 23

Rice bodies- organized fibrin found on the surface of synovium and in joint space.

*this happens in response to Ag stimulation and inflammation in RA.

Front 24

Which is the most non-specific serological test for SLE?

What are more specific tests for SLE? Which one is associated with Drug-induced lupus (procainamide, hydralazine, INH, etc.)

Back 24

ANA = least specific (lots of people have it)

More specific: AntiS-Sm, and Anti-dsDNA

*anti-histone associated with Drug-induced Lupus

Front 25

What is Pannus?

Back 25

Pannus- abnormal layer of fibro-CT with synovial cells and inflammatory cells admixed.

Covers articular cartilage.

Front 26

What is this structure is called? What condition is it associated with?

Back 26

Rheumatoid Nodule- most commonly in subcutis (but may be seen in distal structures)

Contains fibrinoid necrosis core. Surrounded by palisade of histiocytes. Seen in zones of high pressure.

Front 27

Osteoarthritis vs. Rheumatoid Arthritis

Back 27

Osteo- older individuals, M<45, Oligoarthritis, hips, knees, NOT MCP. NON INFLAMMATORY

Rheumatoid- younger onset (30s), Polyarthritis, small, symmetric, PIP affected. INFLAMMATORY

*note: no inflammation, pannus, of ankylosis of joint. Just progressive erosion of cartilage.

Front 28

What serologic tests can be done for RA? Which one is better at catching early RA?

Back 28

Rheumatoid Factor= IgM to the Fc portion of IgG

Cyclic Citrullinated peptide (anti-CCP)= seen in EARLY RA

Front 29

What syndrome is referred to as an "Autoimmune exocrinopathy" and why?

What is the Primary and Secondary form of the syndrome?

Back 29

Sjogren's: Affects exocrine glands (lacrimal and salivary)

Primary: just sicca, destruction of the lacrimal and salivary glands
Secondary: associated with other autoimmune diseases (ex: SLE, RA, scleroderma). More common- 60%

Front 30

What does this biopsy show? What syndrome would this likely be a result of?

What type of cells do we see infiltrates of (be specific)?

Back 30

Biopsy of salivary gland--> Sialadenitis (inflammation of salivary gland)

There are lymphocytic infiltrates and predominantly CD4+ T CELLS!

Front 31

This is an advanced lesion of a disease we learned about. What does it show?

What is the most dangerous outcome in these patients?

Back 31

Sjogren's : Infiltrates of lymphocytes are destroying the gland (replacing functional tissue). Benign lymphoepithelial lesions are seen as are Myoepithelial islands.

The involvement of immune cells gives these patients an increased risk for developing B-cell Lymphoma (MALT)

Front 32

If a patient had this alone (along with keratoconjunctivitis sicca), what type of disease would you suspect?

Back 32

PRIMARY Sjogren's (just the sicca)

This is xerostoma (atrophic tongue, deeply fissured). The nose is also dry, crusting, and ulcerated.

Front 33

What are the two most common Antibodies that are found in Sjogren's syndrome?

Back 33

Ss-A (Ro), Ss-B (La) --> directed against ribonuclear proteins

*note, they are also positive for Rheumatoid Factor

Front 34

What is seen in this picture? Would it be considered Localized or Systemic Scleroderma?

Back 34

Localized-

This is Morphea- or circumscribed patches of cutaneous fibrosis. Limited to the skin!

Front 35

The skin seen in this patient shows characteristic changes of a particular condition. What do you see?

Back 35

This shows Systemic sclerosis (increased production of collagen in the dermis).

The artery becomes thick and narrowed (preventing blood flow). This can manifest as Raynaud's phenomenon. Skin changes= sclerodactyly and tight skin.

Front 36

What type of collagen is seen here? What condition is this?

Back 36

Systemic Sclerosis- Collagen type I

Collagen has lost its basket weave appearance and there are no adnexal structures seen (no hair follicles or dermal sweat glands seen)

Front 37

Describe the following GI manifestations and what condition are they seen in?

Back 37

Esophageal hypomotility, Watermellon stomach (telangiectasia), There is fibrosis in the muscularis of the stomach, preventing peristalsis. Loss of villi => malabsorption.

These are extracutaneous manifestations of Scleroderma (Lc-SSc upper GI, Dc-SSc all of GI).

Front 38

This individual has developed malignant hypertension. What condition that we learned might this be associated with?

Back 38

Systemic Sclerosis (kidney's are affected due to vascular change- intimal thickening and narrowing of the arteries).

Front 39

What are important features of this condition depicted in these two images?

What do you have to worry about with these patients?

Back 39

Dermatomyositis: Inflammation of skin and muscle.

- lilac or heliotrope eyelid discoloration
- PERIMESIAL inflammation (around the muscle)

*risk of cancer is increased!

Front 40

Dermatomyositis vs. Polymyositis?

What antibody is present in the inflammatory myopathies?

Back 40

Polymyositis- lack of cutaneous involvement. ENDOMYSIAL inflammation (within the muscle fiber itself).

Jo-1

Front 41

In order to be diagnosed with a "Mixed Connective Tissue Disease" what would need to be present?

These patients manifest with lupus like, scleroderma-like, and dermatomyositis changes. What system of the body is relatively spared?

What is one positive thing about this diagnosis?

Back 41

Antibody to U1RNP seen in all of these patients!

Surprisingly, little RENAL involvement!

*responds very well to CORTICOSTEROIDS