Systemic connective tissue disease - rheumatoid arthritis, dermatomyositis, systemic sclerosis (scleroderma).
Rheumatoid arthritis
- Autoimmune disease that affects joints causing them to become warm, swollen and painful, often worse following rest
- Most commonly wrist and hands are involved. Can also cause anemia, pericarditis and tiredness
- Cause is a combination of genetic and environmental factors, underlying mechanism is cytokine-mediated inflammation with CD4 T cells being the source, with production of antibodies against cyclic citrullinated peptides which cause lesions on the joints. Antibodies are further directed against citrullinated fibrinogen, type II collagen, alpha-enolase and vimentin.
- On histology, chronic papillary synovitis is visible with dense perivascular inflammatory cell infiltrates and increased vascularity along with neutrophil aggregates and increased osteoclast activity
Remember: the destructive lesion of RA is the pannus, inflamed proliferating synovium with granulation tissue that grows over and erodes cartilage and bone, ending in fibrous or bony ankylosis (ulnar deviation, swan-neck and boutonnière fingers). Rheumatoid nodules, central fibrinoid necrosis rimmed by palisading histiocytes, form under the skin over pressure points.
Dermatomyositis
- Is the most common inflammatory myopathy in children, although it can occur in adults where it may be a paraneoplastic disorder. In both cases it is autoimmune.
- It is an example of a primary inflammatory myopathy.
- The disease sees perivascular mononuclear cell infiltrates with tubuloreticular inclusions in endothelial cells and myofiber damage .
- Type 1 interferon-induced gene produces are upregulated in affected muscles.
- It causes skin rash, muscle weakness and inflammatory myopathy
H&E, dermatomyositis: perifascicular atrophy, small damaged fibres at the edges of the fascicles along the septa, the hallmark of the disease.
Image: “Dermatomyositis muscle biopsy HE” by Jensflorian, CC BY-SA 4.0, via Wikimedia Commons.
Scleroderma
- A systemic immunological disorder characterised by excessive fibrosis in multiple tissues, obliterative vascular disease and evidence of autoimmunity.
- Scleroderma is somewhat of a misnomer as while the skin is it’s main target, lesion are present throughout the body.
- Two groups:
- Diffuse scleroderma - early widespread skin involvement and rapid progression
- Limited scleroderma - generally confined to skin of face and fingers, involvement of rest of the body occurs later
- Pathogenesis is uncertain, but thought to go like this:
- Injury to endothelial cells by unknown mechanisms causes T-cell migration and activation
- T-cells respond to some self antigen, which activate macrophages
- Macrophages and T-cells release cytokines that stimulate fibroblasts
- B-Cell activation also occurs, directed against DNA topoisomerase I
- Morphologic changes - can affect any organ:
- Skin