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NAL NIFEDIPINE OROS STUDY: INTERVENTION AS A GOAL IN HYPERTENSION TREATMENT. PLEASE REVIEW FULL PRODUCT INFORMATION BEFORE PRESCRIBING. References: 1. Brown MJ et al. Lancet372. 2. British Cardiac Society, British Hyperlipidaemia Association, British Hypertension Society. Heart 1998; 80 (suppl. 2): S1-S29. Use: Calcium channel blocker. Mild to moderate hypertension; chronic stableaxis) Contraindications: Cardiogenic shock; <8 days post MI; Kock pouch; concomitant rifampicin; pregnancy, lactation, hypersensitivity to dihydropyridines. Precautions: CHF; severe hypotension; lab tests;
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N HIGH RISK PATIENTS WITH HYPERTENSION. RISK REDUCTION CALCULATED BY THE BRITISH HYPERTENSION SOCIETY RISK ASSESSOR PROGRAMME,2
BASED ON FRAMINGHAM DATA.
S reduces cardiovascular events by approximately 50%.2*
an autoimmune disease, particularly SLE. An ANA is a sensitive test for screening for connective tissue
diseases. Several patterns are distinguished which generally correlate with particular autoimmune dis-
orders (figure 1, page 4, and table 3, above). In this case, the ANA pattern was homogenous with a
titre of 1:2560.
Question 2: What is the titre’s signifi-
cance?
The titre for this kind of test is the high-
est dilution of serum at which the
immunofluorescent pattern indicating a
positive test result is still visible under
the microscope. The higher the titre, the
more likely a connective tissue disease
will be present (figure 4, page 5).
Question 3: What further tests should be performed?
In this case, SLE is suspected on the basis of the positive ANA. The ANA test is used for screening
because it has a sensitivity of greater than 99% for SLE diagnosis. However, because it is positive in
other autoimmune disorders, its specificity is only about 60%. Therefore, more specific tests should be
performed to help confirm this diagnosis. Tests for antibodies to dsDNA and ENAs may be helpful.
Antibodies to dsDNA are specific for SLE but are only found in 50-70% of patients, so this test is not
very sensitive. ENAs are ribonucleic acid complexes extracted from the nucleus of mammalian cells.
Some patients’ sera contain specific antibodies to these antigens. The presence of these antibodies
allows further classification of connective tissue diseases (table 4).
In view of the relatively low sensitivities of anti-dsDNA and ENA antibodies for autoimmune diseases,their absence does not invalidate a diagnosis of an autoimmune disease on clinical grounds. On the
other hand, detection of the antibodies confirms diagnosis and may assist with decisions about treat-
ment and prognosis.
Other investigations that should be performed to assess disease activity and organ involvement include
a full blood count, electrolytes and renal function tests, ESR, C-reactive protein, serum complement
levels, and urinalysis for protein, red cells and casts.
Question 4: Are auto-antibody tests useful for monitoring autoimmune disease?
There is no role for serial ANA measurements to monitor the activity of autoimmune disease because
the titre does not correlate with the disease’s activity or its response to treatment.
Table 3: Common ANA patterns and disease associations
ENA testing at initial presentation is usually sufficient because, once developed, patients tend to
maintain the same auto-antibody profile over the course of their illness. None of the antibodies to
ENA is useful for evaluating disease changes or progression.
However, the levels of anti-DNA antibodies may be helpful in following serial progress of patients
and their response to treatment.
Case 2A 50-year-old male presents with a one-month history of right knee pain and recurrent low-grade
fever. In the past week he has experienced profound difficulty in walking due to pain. Examination
reveals a hot, swollen knee with a markedly limited range of movement. A recent test for ANA —
performed by another doctor — was positive, with a speckled pattern and titre of 1:640. The ESR
was 110 and he had normocytic, normochromic anaemia and mild leukocytosis.
Question: What is the most likely diagnosis?
The clinical presentation suggests an inflammatory joint disease. Because a single joint is involved,
an infective arthritis must be excluded by aspirating the joint. Examination of the joint fluid will
also help to exclude other causes of
monoarthritis, such as gout or other
crystal-induced arthritis. Despite the
positive test for ANA, an autoimmune
disease is unlikely. ANA may be pres-
ent in inflammatory conditions other
than autoimmune disorders, including
infections and other causes of inflammation (table 5). In these cases, the ANA is usually transient
and resolves after the underlying inflammatory process has been treated.
Case 3A 50-year-old female presents with a two-year history
of Raynaud’s phenomenon. She also complains of indi-
gestion and nocturnal cough and has noticed skin
changes. Examination shows mild skin thickening over
her fingers. An ANA test is positive at a titre of
1:2560, with the pattern as demonstrated in figure 5.
Question 1: What is the most likely diagnosis?
The clinical history is consistent with a diagnosis of systemic sclerosis. The auto-antibody detecteddisplays an anti-centromere pattern that supports the diagnosis of CREST syndrome, also called
limited variant systemic sclerosis.
This is one of the few situations where the ANA is diagnostic. The importance of the distinction
between systemic sclerosis — characterised by Scl-70 antibodies — and CREST is that the latter has
a more favourable prognosis. A centromere pattern can also be present in primary biliary cirrhosis
and in generalised systemic sclerosis.
Case 4A 70-year-old woman presents with a six-month history of weight gain, hair loss and cold intoler-
Question 1: Apart from thyroid function tests, what auto-antibody tests may be useful?Anti-thyroid peroxidase antibodies — formerly anti-thyroid microsomal antibodies — are useful to
establish an underlying autoimmune basis for thyroid disease. They are not useful for subclassification
of thyroid disease because, although they are found in 80–99% of people with hypothyroid autoim-
mune thyroiditis, they may also be found in up to 80% of cases of hyperthyroidism secondary to
Graves’ disease. Anti-thyroglobulin antibodies are less useful than anti-thyroid peroxidase antibodies
because the latter may be the sole antibody present in up to 65% of cases.
In addition to these thyroid auto-antibodies, measurement of antibodies against gastric parietal cells is
indicated. Detection of these antibodies is more commonly found in people with autoimmune thyroid
disorders and is often associated with vitamin B12 deficiency, secondary to autoimmune gastritis.
Question 2: What is the significance of the detection of anti-thyroid peroxidase antibodies in the
absence of overt hypothyroidism?Subclinical hypothyroidism — raised TSH, normal T4 — may be present in up to 5–10% of women,
whereas biochemical hypothyroidism is present in only 1%. The detection of antithyroid peroxidase
antibodies is associated with the development of hypothyroidism, although this progression is slow
and may take up to 20 years to occur.3 This progression is generally more rapid the higher the anti-
body titre and the higher the initial TSH. In these circumstances, patients should be screened yearly
for thyroid function.
Case 5A 60-year-old man presents with dizziness. On examination, he is found to have pigmentation of his
buccal mucosa and postural hypotension.
Question 1: What auto-antibody tests may help in establishing the diagnosis?The clinical presentation raises the possibility of Addison’s disease. Anti-adrenal antibodies are detect-
ed by indirect immunofluorescence using human or mammalian adrenal gland. These are present in
50-90% of patients with Addison’s disease. However, these antibodies may also be detected in up to
5% of healthy people, although long-term follow-up suggests the majority of such patients will
develop adrenal insufficiency in time. This is true for several organ-specific autoimmune disorders —
such as diabetes — in which autoimmune reactivity precedes the overt clinical manifestations of the
condition. This is because the symptoms of disease appear only when most of the endocrine organ has
been destroyed by the autoimmune process.
Question 2: What other autoimmune diseases may be present?
There is considerable overlap between the presence of auto-antibodies to the adrenal and antibodies to
other steroid-producing organs, such as the ovary. Therefore, patients with anti-adrenal antibodies are
at increased risk of developing gonadal failure.
References and reading list available on request.
Practice pointsnNot all auto-antibodies are associated with autoimmune disease
nThe detection of auto-antibodies does not on its own support a diagnosis of autoimmune disease
nTesting for auto-antibodies should be done selectively and only when the suspicion of disease is high
nDiagnosis of systemic connective tissue disease is best accomplished by using a sequential testing approach —
screening with the most sensitive test first and, if positive, confirm with more specific tests
nOrgan-specific autoimmune diseases often occur in clusters