Pathology-RA and Scleroderma Flashcards Preview

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Type of synovitis associated with rheumatoid arthritis?

Chronic, non-suppurative because predominant cells are macrophages, lymphocytes and minimal neutrophils.



The acute and chronically inflamed synovium in rheumatoid arthritis with synovial cell hyperplasia. Note that you will see PMNs in synovial fluid, but no crystals or organisms.


Most common age when rheumatoid arthritis presents



What type of hypersensitivity is involved in rheumatoid arthritis?

Type IV hypersensitivity: activation of CD4+ T-cells are responding to synovial peptides. These T-cells produce cytokines that induce macrophages and synovial lining cells to release TNF-alpha. CD4+ cytokines also up regulate endothelial adhesion molecules to bring more inflammatory cells into the synovium. B cell response is also potentiated by the CD4+ cytokines and B cells produce rheumatoid factor ( and CCP antibodies (against citrulline-modified peptides).


Genetic associations with rheumatoid arthritis

HLA-DRB1 alleles in MHC II and arthritogenic antigen (enzymatic conversion of arginine to citrulline in peptides), however, note that there is only a 30% concordance rate in monozygotic twins and environmental factors play a large role in triggering disease.


How does the pannus of rheumatoid arthritis mediate joint and bone damage?

1) Pannus spreads directly into cartilage and bone, neutrophils and synoviocytes release protease and elastase that degrades cartilage and bone 2) Pannus releases cytokines: IL-1 and TNF-alpha from macrophages and synoviocytes stimulate osteoclast activating factor, endothelial cell adhesion molecule expression and collagenases that break down cartilage and bone. Either pathway results in fibrous ankylosis that eventually fills in with bone and the joint is deformed with loss of function.


The section below is from a normal synovium with a single layer of cells and loose connective tissue. What would you expect to see on a similar biopsy in a patient who has rheumatoid arthritis?

Note large amounts of acute and chronic inflammatory cells, B-cell follicles and pale connective tissue indicating edema. The inflammation can become so intense that papillary germinal centers form and synovial cells proliferate.


3 stages of rheumatoid arthritis

1) Gradual onset of fatigue, weight loss, weakness and vague MSK discomfort 2) Small joints of hand and feet in a symmetrical distribution 3) Wrists, ankles, elbows, knees and cervical spine pain, tenderness and swelling.


Radiological manifestations of rheumatoid arthritis

Osteopenia and bone erosions around the affected joint space. Narrowed joint space from loss of cartilage. Extra-articular destruction of tendons, ligaments and the joint capsule. Late deformities like ulnar deviation, flexion-hyperextension of fingers and bony ankylosis.


What is rheumatoid factor?

IgM that recognizes Fc portion of IgG in 80% of patients with RA. It forms immune complexes and circulates in serum and deposit in places around the body, augmenting joint inflammation and vasculitis. Note that high titers are associated with severe disease and it is not specific for rheumatoid arthritis.


Patient prognosis with rheumatoid arthritis and no rheumatoid factor

Better than when RF is present


What subcutaneous lesion is present in patients with rheumatoid arthritis, SLE and rheumatic fever? Where can they be found outside of the subcutaneous tissue?

Rheumatoid nodules: these are firm, moveable, non-tender lesions that result from pressure and central fibrinoid necrosis that becomes surrounded by histiocytes, lymphocytes and plasma cells to form a granuloma. The can also be found in the heart, causing arrhythmias by disturbing the conduction system and lungs, causing fibrosis and respiratory failure.


A patient presents with rheumatoid nodules and high RF titers. Where would you expect to see vasculidities and this patient?

Small to medium arteries (possibly causing an MI or stroke), digital arteries (peripheral neuropathy, gangrene and ulcers) and leukocytoclastic venulitis (purpura, skin ulcers and splinter hemorrhages) all result from rheumatoid factor complex deposition.


Common causes of death in patients with rheumatoid arthritis

Amyloidosis (SAA deposition from chronic inflammation), vasculitis, GI bleed (aspirin and NSAIDs), infection (corticosteroids, anti-TNF-alpha) and nodules in heart and lungs.


Features of systemic sclerosis

Intimal thickening of blood vessels from endothelial injury and vasospasm that causes vasospasm. Excessive collagen in skin from fibroblast activation.


Genetic factors in systemic sclerosis

ANA and other autoimmune diseases in relatives. MHC II associations.


A 50 year old woman presents with widespread tightening of the skin beginning at the fingers and toes that have moved past the knees and elbows. She also complains of ischemic bowel pain, Raynaud's and chest angina. Labs show anti-topoisomerase antibody. What is the likely diagnosis?

Diffuse scleroderma. This involves large portions of the skin and has extensive, often fatal, visceral involvement. Note that Raynaud’s is the presenting factor in 70% of patients with diffuse scleroderma.


A 50 year old woman presents with tightening of the skin confined to the fingers, forearms and face. Labs show anti-centromere antibody. What is the likely diagnosis and what other physical findings might you look for?

Limited scleroderma. You would look for the sub-type CREST syndrome: Calcinosis, Raynaud’s, Esophageal dysfunction, Sclerodactyly, Telangectasia. Note that all of these findings are typical of vascular injury.


How does the immune response in the skin of a patient with scleroderma evolve from the early to the late phase?

Early: CD4 and macrophage inflammatory cells w/swelling of fingers and hands. Late: Dense fibrosis and atrophy as inflammatory infiltrates disappear.


What blood vessels are affected in patients with systemic sclerosis?

Small arteries and arterioles not only show vasospasm, but also endothelial proliferation and intimal fibrosis that can cause multiple organ ischemia. Microvasculature shows decreased capillary loops and dilated capillary loops (nail fold shown below)


A 50 year old woman presents with widespread tightening of the skin beginning at the fingers and toes that have moved past the knees and elbows. She also complains of ischemic bowel pain, Raynaud's and chest angina. Labs show anti-topoisomerase antibody. What serious renal complication could she develop and how would you treat her?

Intimal thickening of the interlobular arteries results in hyper-reninemia in 10% of patients with scleroderma. This results in scleroderma renal crisis (malignant hypertension) and rapid renal failure if not treated with ACE-I.


Major cause of mortality of patients with systemic sclerosis

Pulmonary hypertension with cor pulmonale from interstitial fibrosis.


GI symptoms in patients with systemic sclerosis

Sclerosis causes neural dysfunction, smooth muscle atrophy and fibrosis. This results in GERD + Barrett esophagus, dysphagia, malabsorption in the small bowel, functional obstruction and bacterial overgrowth from obstruction.


Treatment for systemic sclerosis

Supportive care is the only current option