Chapter 19: Autoimmune Diseases, Sjogren’s Syndrome and Progressive Systemic Sclerosis
Definition: – This is a chronic inflammatory condition mainly affecting lacrimal and salivary glands, characterized by:-
- Dry eyes – Keratoconjunctivitis sicca.
- Dry mouth – Xerostomia.
Types:- SS is of two types.
- Primary SS – When disease occurs alone.
- Secondary SS – When it is associated with rheumatoid arthritis, SLE and less frequently with systemic sclerosis.
Age: It involves middle-aged females 40 to 60 years of age.
Sex: It is more common in females with a male: female ratio of 1:9.
Major Immunologic Features
- There is an infiltrate of lymphocytes and plasma cells in the involved tissue.
- There is an increased level of Ig and also the presence of RF & ANA.
- Presence of autoantibody against salivary duct cell antigen.
Etiology and Pathogenesis
- HLA-association:- There is a strong association between HLA-B8 and HLA-DR3.
- The damage to tissue is not clear whether due to T-L or B-L.
- There may be functional defects in:
- Macrophagic cells.
- The activation of the above cells may start because of:
- Genetic defect.
- Viruses-like EBV.
- Deranged immune regulatory system.
- The inflammatory cells are mainly T-L and-B-lymphocytes, with the predominance of CD4+ There may be few CD8+ cells. All these express markers of activation and these Th-2 cells may stimulate B-L.
- There is the presence of other autoantibodies in SS:
- 70% shows RF.
- 50-80% shows ANA.
- 25% LE cell Positive.
- SS-A (anti- Ro) against the extractable nuclear antigen.
- SS-B (anti-La) against the extractable nuclear antigen.
All these autoantibodies may be due to activation of-B-L because there is also hypergammaglobulinemia.
Signs & Symptoms
- There is blurred vision, burning, and itching of the eyes.
- There is difficulty in swallowing due to thick secretions (Xerostomia).
- Oral mucosa may show atrophy.
- There is an enlargement of the parotid gland in 50% of the cases.
- 25% show extraglandular involvement like kidney, lung, CNS, and muscles.
- Sometimes they have fatigue, low-grade fever, arthralgias, and myalgias.
It shows periductal and perivascular lymphocytic infiltrate in the early stages.
Then there is epithelial hyperplasia which leads to obstruction. Lymphocytic infiltrate increases with the appearance of fibrosis. There is atrophy of mucosa. The lymphocytic infiltrate sometime give a picture of Pseudolymphoma.
- There is mild anemia and raised ESR.
- SS-A and SS-B are considered serological markers.
- Schirmer’s test to demonstrate decrease in tear flow.
- Eye-Slit lamp examination of the eye with Bengal staining shows typical punctate corneal ulcer and these are highly diagnostic.
Sjogren’s syndrome gives 40 fold increased risk for lymphomas and mostly these are B-cell lymphoma.
Systemic sclerosis (Scleroderma) is a chronic disabling condition of unknown etiology, characterized by fibrosis of the skin, blood vessels and internal organs e.g. lung, heart, kidney, and gastrointestinal tract.
Types: It has two types:
- Localized-(morphea)- It is a limited cutaneous form in which skin thickening is limited to the distal extremities and face.
- Diffuse progressive systemic sclerosis (PSS)-there is more severe diffuse cutaneous involvement and the internal organs.
Age: Third and fourth decades of age, but no age is immune.
Sex: This is more common in females with Male: Female ratio of 1:2-5.
Etiology and Pathogenesis
- The exact cause is unknown.
- The basic problem is the increased deposition of collagen.
This may be because of:
- Microvascular injury.
|Microvascular Injury||Humoral Serologic Abnormalities||Altered collagen synthesis|
1. Recurrent injury to
2. There is a serum factor
3. cytotoxic to endo-
4. Auto Ab damage the
5. Endothelial injury à
6. Platelets aggregation.
8. ischemia is a stimulus for fibroblastic proliferation and leads to Fibrosis.
1. Ig is raised by 50%.
2. ANA—present in
3. R.Factor—present in
4. Scl-70—present up to
5. Anti centromere
All these indicate a humoral disorder.
1. It is increased
collagen synthesis but
It is all normal form.
2. Abnormal CMI and
attract and activate
fibroblast and leads
to increase collagen
3. TL and IL1 & FNF-α
attract and activate
4. The end result is fibrosis
Table XXV – Pathogenesis of Progressive Systemic Sclerosis
Signs and Symptoms
- Most of the time first presentation is Raynaud’s phenomenon preceding other systems by months or years. It is typically triggered by cold, and the patient will have pallor and/or cyanosis of fingers followed by redness.
- Skin involvement leads to a limitation of movements as an extension of digits. The involvement of the face shows the loss of wrinkles and microstomia. There is a loss of hair.
- Arthritis symptoms sometimes resemble rheumatoid arthritis.
- Pulmonary fibrosis is frequent and pulmonary hypertension only appears in 10% of the patients.
- The patient may have pleuritis, pericarditis and cardiac fibrosis.
- Renal involvement is rare but is fatal.
Virtually all organs are involved.
Bundles of the collagen bind the skin to the underlying tissue.
Changes take place in three stages.
Stage I: There is edema which is non-pitting and microscopically there is edema, perivascular lymphocytic infiltrate, capillaries and small arteries are thickened, and there is collagen deposition.
Stage II: Due to an increase in collagen formation, wrinkles disappear. Epidermis becomes thin.
Stage III: This is the atrophic stage where claw-like hand, the face is drawn and mask. Microscopically there is atrophy of epidermis and increase collagen. Calcification may be seen.
In the late stages due to loss of blood supply ulceration may take place.
Skin involvement may be a part of CREST syndrome. Where:
C = Calcinosis.
R = Raynaud’s phenomenon.
E = Esophageal involvement.
S = sclerodactyly (localized sclerosis of the finger).
T = Telangiectasia.
Gastrointestinal involvement is seen >50% of the cases. Esophagus show thin mucosa, frequently ulcerated, covers abundant collagen deposition in the lamina propria, submucosa and serosa. Esophagus will show rubber-hose appearance and is inflexible. There is mononuclear cells infiltrate. Similar changes are seen in other segments of gastrointestinal tract.
3. Musculoskeletal system
There is inflammatory synovitis and fibrosis in the muscles.
Sometime may see primary biliary cirrhosis.
There is diffuse fibrosing alveolitis.
There may be involvement in 2/3 of the cases. There is thickening of the intima of interlobular arteries and fibrinoid necrosis of the intima and media of afferent arterioles. Patient may show hypertension in 30% of the cases.
7. Blood vessels
These may show vasculitis.
- There is normochromic and normocytic anemia. Also, there are raised ESR.
- Increased Ig.
- The biopsy of the skin and muscles is diagnostic.
- The synovial fluid shows mainly neutrophils.
- Radiological findings show a narrowing of the joint spaces.
- One-fourth show low titer of rheumatoid factor.
- Also, show scl-70 (Ab against DNA-topoisomerase 1).
- Antinuclear autoantibodies are considered to be specific for systemic sclerosis.
50% die in 2-3 years.
- It is symptomatic.
- For Raynaud’s phenomenon, keep hand warm and reduce stress.
- Renal hypertension may be controlled by drugs blocking the Renin-Angiotensin system (captopril, enalapril).
- Esophagus and intestinal hypomotility can be improved with metoclopramide.