Rheumatology - Connective tissue diseases Flashcards
What is SLE? In which patients is it most common?
SLE is the commonest, autoimmune systemic connective tissue disease. It is associated with pathogenic autoantibodies resulting in immune complex formation and complement mediated tissue damage.
The disease course is relapsing and remitting and it has a variable course and prognosis - 95% 5 year survival.
The peak incidence for SLE in women is in late middle age and is slightly later for men. In all age groups except neonates, lupus is more common in females than males.
What are the clinical features of lupus?
The general features of lupus are relatively non specific and include fatigue, fever, lymphadenopathy, and weight loss. It should be noted that lymphoma is the most common malignancy that occurs in the early stages of lupus, so patients presenting with lymphadenopathy should have a biopsy to rule out malignancy. Myositis is rare, but patients do report myalgia.
SLE can mimic RA or bacterial endocarditis and may cause nephrotic syndrome.
Which system is most commonly involved in SLE?
The musculoskeletal system is most commonly involved in SLE in over 90% of cases. Patients experience:
- myalgia
- arthralgia (but not inflammatory synovitis as seen in RA)
- migratory polyarthralgia with early morning stiffness
- Jaccoud’s deformity: non deforming, reducible arthropathy caused by tendonitis rather than synovitis affecting the fingers, wrists, elbow, shoulders, knees and ankle
- avascular necrosis (hip) due to prolonged steroid therapy
What rashes are common in lupus?
Mucocutaneous involvement is common in lupus and occurs in about 80% of cases (this includes skin and mucuous membranes). The classic rash of lupus is the malar “butterfly” rash which bridges the nose and cheeks but spares the area between the nose and lips. This helps distinguish it from the rash of acne rosacea which is also common in older women.
Photosensitivity is also common and causes most of the rashes in lupus. These patients can only be briefly exposed, but the rash persists for a long time.
The discoid or scarring rash also appears in a photosensitive distribution and me be the only manifestation of lupus - subacute cutaneous lupus. If these patients have a positive ANA they are more likely to develop systemic disease.
Vasculitis rashes may also occur.
Other than rashes, what are the other mucocutaneous features of SLE?
- Raynauds phenomenon (25-50% of cases)
- non-specific erythema
- alopecia
- oral and mucosal ulceration
- nail fold infarcts
- livedo reticularis (“fish net stockings”) predominantly on the legs
What are Sicca symptoms?
Many patients with lupus and other rheumatological conditions can have dry eyes and mouth which is more typically associated with Sjogren’s disease. When they appear in SLE or other diseases they are referred to as secondary Sjogrens.
What are the significant pulmonary features of lupus?
Lung involvement in present in 40-50% of cases.
Pleurisy is most common, which can occasionally occur with an effusion. It is also important to investigate patients presenting with pleuritic chest pain for a PE and infection.
Patchy consolidation and areas of collapse or diffuse reticular shadowing on X-ray is also common.
Less common are:
- “shrinking lung syndrome”
- lupus pneumonitis, which may cause fibrosis or be haemorrhagic (rare but often fatal)
- PE in patients with antiphospholipid syndrome
- pulmonary hypertension
What are the cardiac manifestations of lupus?
- mild pericarditis (may be the first presenting complaint)
- myocarditis is less common (presents as heart failure or arrhythmias)
- non-infective thrombotic endocarditis (Libman-Sacks)
- hypertension is usually associated with renal involvement
- coronary artery disease
How does lupus affect the kidneys?
SLE is associated with a range of glomerulonephritides. Almost all patients will have histological abnormalities on biopsy and 50% will have clinical renal involvement.
Clinical presentation includes:
- hypertension
- haematuria
- proteinuria
- nephrotic syndrome
- AKI
- end stage renal disease
Most renal disease is asymptomatic and serum creatinine will only increase when eGFR is reduced below 50%.
What are the indications for renal biopsy in lupus patients?
Proteinuria of > 0.5g/24 hour collection is the main indication for biopsy. Especially if red or white cells are present in the urine in the absence of infection or menstrual loss.
If there are red cell casts and proteinuria it is highly likely that there will be a proliferative nephropathy on biopsy. If there is proteinuria but not casts it is likely the patient will have nephrotic syndrome and a membranous nephropathy.
What are the neurological features of lupus?
Neurological involvement of lupus usually arises in the context of active systemic disease. These can include:
- headache
- stroke (vasculitis or atherosclerosis)
- polyneuropathy (glove and stocking)
- mononeuropathy (single due to vasculitis affecting vasa nervorum; or multiplex)
- seizure
- tremor
- psychosis
CNS manifestations are associated with a poorer prognosis.
What are the reproductive complications of lupus?
Patients who have the antiphospholipid syndrome are predisposed to recurrent miscarriages and foetal growth restriction.
Transmission of anti-Ro and anti-La antibodies (ENAs) across the placental can lead to neonatal lupus syndrome, where babies are born with a photosensitive lupus rash, or congenital heart block.
What is anti-phospholipid syndrome?
Although first described as part of SLE, most patients with antiphospholipid syndrome do not meet the criteria for SLE.
APS is an autoimmune disorder characterised by:
- venous (DVT/ PE) or arterial thromboses (TIA/ CVA or MI)
- obstetric morbidity (recurrent spontaneous miscarriages usually in the second or third trimester)
- thrombocytopenia and abnormalities of the CNS, skin and heart valves
What are the haematological findings in SLE?
1) Anaemia
- most patients with lupus will have a normochromic normocytic anaemia of chronic disease
- sometimes it has an iron deficiency pattern and is due to blood loss that can be precipitated by drugs (e.g. steroids, NSAIDs)
- less common but more characteristic is a haemolytic anaemia (Coombs positive, high reticulocytes, raised haptolgobins)
2) Leucopaenia
- lymphopaenia (common) - >1/7
- neutropaenia
3) Thrombocytopaenia
- moderately reduced due to anti-phospholipid antibodies
- severe reduction may be due to other antibodies causing bleeding disorders
4) Raised ESR but LOW CRP (SLE has a poor acute phase response)
What auto-antibodies are used to diagnose lupus?
Antibodies to nuclear antigens (ANA) are sensitive but not specific for SLE, and ANA positive antibodies are found in all patients with active disease.
Antibodies to double stranded DNA (dsDNA) are specific for lupus or lupus overlap disorders. They are useful for identifying patients at risk of renal disease (lupus nephritis) and monitoring disease activity. Other antibodies do not fluctuate with disease activity as much as dsDNA.
Antibodies to extractable nuclear antigens (ENA) are common - e.g. anti-Sm, Ro, La, RNP