SYSTEMIC LUPUS ERYTHEMATOSUS (Davidsons 18th pp 855)
Epidemiology: F:M = 9:1
Aetiology / Pathogenesis: T lymphocyte function defect + polyclonal B lymphocytes activation --> uncontrolled production of antibodies + immune complexes. Genetics plays a part (HLA-B8 / DRE3), environmental agents (drugs, sunlight, oestrogen). Its an Type II direct antibody cytotoxic reaction as well as a Type III immune complex deposition disease.

Clinical features:
1) Arthralgia, Arthritis, Fevers
2) Skin Lesions: rashes
3) Cardiopulmonary: endocarditis, myocarditis, pericarditis, pleurisy, fibrosing alveolitis, 'shrinking lung syndrome'
4) Renal: haematuria (red cell casts) --> renal failure or nephrotic syndrome
5) CNS: seizures and pyschosis (these account for 50% of CNS signs)
6) Other: Abdominal: pain (peritonitis, pancreatitis, vasculitis), lymphadenopathy, Ocular: keratoconjunctivitis, episcleritis, sicca syndrome

Investigations:
1) Antinuclear antibodies: Anti-ds-DNA antibodies by ELISA + radioimmunoassays
2) Antiphospholipid antibodies

Management:
1) NSAIDS (renal disease?) - this is to manage artcular symptoms
2) Antimalarials: skin lesions
3) Corticosteroids: life threatening manisfestations - take them off as soon as remission occurs
4) Immunosuppressives: reserved for those with glomerulonephritis or steroid doses are high as to cause side effects

MIXED CONNECTIVE TISSUE DISEASE (Davidsons 18th pp 857)
This is when there is mixed signs of SLE, systemic sclerosis and polymyositis. Clinically they might have: Raynaud's phenomenon, dermatomyositis, scleroderma, polyarthritis, oesophageal motility problems. 

SYSTEMIC SCLEROSIS AND SCLERODERMA SYNDROMES (Davidsons 18th pp 858)
Epidemiology: 4:1 = F:M
Aetiology/Pathogenesis: Genetics (HLA-DR1-3/5), and Environmental (silica dusts, vinyl chloride). There is excessive production and cross linking of Type I collagen --> progressive intimal thickening. This causes release of powerful vasconstrictors such as: endothelin (see how this leads to the presentation of the patient below).

Clinical Features:
1) Raynaud's phenomenon (read above --> Pathogenesis): This is often the presenting complaint --> digital ischaemia, pulp infarcts, gangrene. This may precede systemic features by months or years.
Other manisfestations:
1) Skin changes: shiny, taut, diffuse oedema, nail capillaries are dilated and tortutous, calcinosis
2) Musculoskeletal: myositis, arthralgia/arthritis, "leathery crepitus"
3) GIT: dysphagia, reflux oesophagitis 2nd to hiatus hernia
4) Lung: pulmonary fibrosis (patient has antibodies to Scl-70)
5) Other: pulmonary HTN, pericarditis, cardiomyopathy, renal hypertension

Investigations:
1) Anti-nuclear antibodies: +ve in 50% of pts
2) Anti - Scl-70 antibodies: Pulmonary involvement
3) Nail-fold capillaroscopy: Dilated tortutous capillary loops --> pathognomic of systemic sclerosis

Management (no drug can arrest the progressive sclerosis):
This is directed towards the symptoms. 
1) Skin changes: Ca2+ antagonists --> Raynaud's phenomenon
2) Articular changes: corticosteroids
3) Renal: ACE inhibitor to treat renal hypertension
4) Chest infections: treat accordingly

Prognosis is worse in pts with late onset and widespread systemic involvement. CREST syndrome is "Limited cutaneous systemic sclerosis" - and only involves distal areas to the elbow and knee.