Autoimmunity Associated with Cardiac, Respiratory, and Renal Disease
Cardiac disease 1: myocarditis and cardiomyopathy
Myocarditis
This is associated with connective tissue diseases, especially SLE, and vasculitis, particularly Churg-Strauss syndrome.
May present with congestive heart failure, arrhythmias, and chest pain.
There appears to be an association with anti-ribonucleoprotein (anti-RNP) antibodies.
There is usually good response to steroids.
Cardiomyopathy
Anti-cardiac antibodies are associated with dilated cardiomyopathy, which may also have features of myocarditis on biopsy.
Anti-cardiac antibodies are also found in 20% of cases of type II autoimmune polyglandular syndrome, but in this syndrome they are not associated with cardiomyopathy but with an increase in blood pressure.
Antibodies are directed against cardiac atrial cells producing atrial natriuretic peptide.
Dilated cardiomyopathy is associated with M7 anti-mitochondrial antibodies recognizing mitochondrial flavoproteins, including riboflavin.
Cardiac disease 2: eosinophilic syndromes
Rare eosinophilic syndromes may affect the myocardium, eventually leading to endomyocardial fibrosis.
Churg-Strauss syndrome frequently involves the myocardium—check ANCA and IgE.
Idiopathic eosinophilic syndromes may affect heart.
Echocardiography is required.
Cardiac disease 3: recurrent pericarditis and Dressler’s syndrome
Recurrent pericarditis
May occur as a disease in its own right, although it is a common feature of connective tissue diseases including:
autoinflammatory diseases, e.g. familial Mediterranean fever (see Chapter 14, p.342).
The pericardium is thickened, with an infiltrate of inflammatory cells.
No specific immunological tests.
NSAIDs are the first line of treatment. Steroids may be required, and colchicine has been suggested as a useful agent.
Pericardectomy may be required.
Dressler’s syndrome
This is (myo-)pericarditis occurring 2-3 weeks after a myocardial infarction and presenting with typical pericarditic pain.
It is very rare since thrombolytic therapy has been introduced.
Antibodies to cardiac muscle are often present.
Post-pericardotomy syndrome is similar but follows cardiac surgery.
NSAIDs and steroids may be required but the syndromes settle spontaneously.
Cardiac disease 4: rheumatic fever
Clinical features
Incidence is now increasing.
Mainly affects children but can be seen in adults.
Immunopathology
Appears to be due to an aberrant immunological response to the streptococcal M-proteins (M-proteins 5, 14, 24), some of which generate antibodies that are cross-reactive with human sarcolemmal proteins and myosin.
Other streptococcal M-proteins cause cross-reactive antibodies reacting with the vimentin of glomerular mesangial cells, and therefore are associated with glomerulonephritis.
M-protein types 1, 5, and 18 cross-react with cartilage epitopes, thus potentially leading to arthritis.
In addition, the M-proteins may act as bacterial superantigens, enhancing the autodestructive immune response.
Treatment
Antibiotics to eliminate the organism.
NSAIDs for arthralgia.
Corticosteroids for carditis.
Long-term penicillin prophylaxis is required as the syndrome will recur on subsequent group A streptococcal infection.
Respiratory disease 1: idiopathic pulmonary fibrosis (cryptogenic fibrosing alveolitis)
Clinical features
Patients present with severe progressive breathlessness. A fulminant presentation, often with fever and cough, is referred to as the Hamman-Rich syndrome.
Inflammatory lung fibrosis may occur in association with connective tissue diseases (SLE, Sjögren’s syndrome, antisynthetase syndrome) and as a consequence of drug exposure, especially nitrofurantoin.
Many cases have no obvious trigger or association.
Immunopathogenesis
Biopsies show activated macrophages and a neutrophil infiltrate.
In the early stages there is a lymphoid infiltrate (before fibrosis develops), and excess local cytokine production can be demonstrated (TNFα, IL-2, γ-IFN, TGF-β, IL-8).
Investigations
Lung function shows a reduced forced vital capacity (FVC) and diffusion capacity, with desaturation on exercise.
BAL may be helpful as part of the diagnostic work-up (see Part 2), particularly where there is a lymphocytosis.
Biopsy (transbronchial or trans-thoracic) may be required.
Most patients show an acute-phase response with a polyclonal hypergammaglobulinaemia.
Treatment
Treatment is with steroids, with either azathioprine or cyclophosphamide, but the response is often poor and the disease is progressive.
Respiratory disease 2: pulmonary alveolar proteinosis (PAP)
Clinical features
May be congenital or acquired (silicosis, immunodefieincy, malignancy).
Gradual onset of exertional dyspnoea, fever, fatigue and weight loss.
Immunopathogenesis
Congenital PAP is an autosomal recessive disease caused by mutations in the surfactant protein B (SP-B) gene.
Investigations
Associated with polyclonal hypergammaglobulinaemia (unless secondary to immune deficiency).
Respiratory disease 3: lymphoid interstitial pneumonitis and sarcoidosis
Lymphoid interstitial pneumonitis
Clinical features
Patients present with chronic cough, shortness of breath, and chest pain.
May occur alone, but is more usually found in autoimmune diseases, such as Sjögren’s syndrome, SLE, dermatomyositis, and polymyositis, and in association with drugs.
Investigations
Treatment
Corticosteroids and immunosuppressive drugs (cyclophosphamide and azathioprine) may be used.
Treatment of underlying infection, where present.
Sarcoidosis
See Chapter 14.
Although not normally considered an autoimmune disease, some patients with histologically proven sarcoidosis have anti-nuclear and dsDNA antibodies.
Respiratory disease 4: eosinophilic lung syndromes
The lung is affected by a variety of hypereosinophilic syndromes:
Löeffler’s syndrome (a hypersensivity reaction to drugs or parasites, or idiopathic)
chronic eosinophilic pneumonia
tropical pulmonary eosinophilia (due to filariasis)
Churg-Strauss syndrome (eosinophilic vasculitis—often associated with neuropathy) (see Chapter 13)
eosinophilia-myalgia syndrome (contaminated l-tryptophan)
bronchopulmonary aspergillosis
eosinophilic granuloma (Langerhans cell histiocytosis).
Investigations
Investigations which may help distinguish the cause, other than standard respiratory investigations (CXR, RFTs, CT), include:
BAL, with lymphocyte subpopulation analysis—if Langerhans cell histiocytosis is suspected, then antibodies to the S-100 antigen should be included in the panel
biopsy
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