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The Raynaud's patient:
how to evaluate, how to treat
ROBERT P JACOBS, MD
are absent, Raynaud's disease. tients with connective tissue
In the first group (see "Ana- diseases. 3 4 It is a characteristomic abnormalities associat- tic feature of progressive sysed with Raynaud's", p 35), an temic sclerosis (scleroderma),
anatomic abnormality or some the CREST syndrome (Calcinoother extrinsic factor can be sis, Raynaud's phenomenon,
identified that might result in Esophageal dysfunction, Sclervasospasm in one anatomic re- odactyly, Telangiectasia), and
gion. Depending on the site of many of the connective tissue
the lesion, these disorders are overlap disorders. Up to 36% of
most likely to result in a Ray- patients with primary Sjonaud's phenomenon that is gren's syndrome5 and 40% of
asymmetric or primarily in- patients with systemic lupus
volves the lower extremities, erythematosus 6 show sympdepending on the site of the toms of Raynaud's phenomenon, and it is a common manianatomic lesion.
4
The second group is com- festation of the arteritides. To
posed of systemic disorders in a lesser degree, it is also assowhich Raynaud's phenomenon ciated with rheumatoid arthriis but one clinical manifesta- tis and polymyositis, as well as
tion (see "Systemic diseases primary pulmonary hypertenassociated with Raynaud's", p sion.
After ruling out the known
37). These include diseases
characterised by intravascular causes of Raynaud's phenomeabnormalities such as sludg- non, we are left with a third
ing or hyperviscosity, adverse group of patients who appear
reactions to drugs or toxins to have no anatomic abnormalthat promote vasospasm or ity or underlying systemic disRaynaud's phenomenon
vascular occlusion, and con- ease to explain their vasospasor Raynaud's disease?
tic symptoms. In these
nective tissue diseases.
Raynaud's phenomenon is patients, who are typically
The disorders associated with
commonly
encountered in pa- young, healthy women, a diag1
3
Raynaud's phenomenon " can
nosis of Raynaud's disease can
be c a t e g o r i s e d into three
be made only after several
groups: conditions character- Dr Jacobs is professor of medicine and diyears of careful observation.7 It
ised by regional anatomic ab- rector, division of rheumatology, George
Washington University Medical Centre,
is possible that these patients
normalities; systemic dis- Washington, DC, USA, and wrote this artihave a forme fruste of one of the
orders; and, if other ailments cle specially for Modern Medicine.
Raynaud's phenomenon is a
peripheral vascular disorder
characterised by paroxysmal
vasospasm in the digits or
other acral parts and manifested by pallor and/or cyanosis,
followed by reactive hyperaemia. In addition, patients often
complain of pain, dysaesthesia, and paraesthesia. The episodes usually are precipitated
by exposure to cold or emotional stress, suggesting several
different pathogenic mechanisms.
While many patients with
Raynaud's phenomenon will
manifest the entire spectrum of
symptoms enumerated above,
the presence of episodic coldor emotional-stress-induced
vasospasm manifested by pallor or cyanosis, and followed
by reactive hyperaemia, is sufficient to establish the presence of the phenomenon.
MODERN MEDICINE OF SOUTH AFRICA/30 MARCH 1984
3 3
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CA o r TPArts
/HHun
After the known causes of
Raynaud's phenomenon haveb e e n
m | e d
o u t
R a y n a u d
.
s
disease can be diagnosed
only after years of
observation.
Anatomic abnormalities
associated with Raynaud's
connective tissue diseases, but
this will be resolved only after
diagnostic techniques become
more specific and sensitive.
Dx: rule out
underlying disease
Given the many causes of
Raynaud's phenomenon, it is
important to identify any clinical or laboratory clues that
might indicate an underlying
systemic disease 8 (see "Clues
that suggest underlying disease", p 39). For example, the
presence of a systemic disease
is suggested when Raynaud's
phenomenon is the sole or presenting problem in a man or an
older woman, and symptoms
are intense, are of rapid onset,
or involve the lower extremities. Careful examination of
the skin of these patients might
reveal subtle ischaemic or trophic changes, including digital tip atrophy, pitted scars,
sclerodactyly, and nondigital
cutaneous lesions.
The periungual region and
mucosal surface of patients
with Raynaud's phenomenon
should be examined carefully
for telangiectases, because of
the association of these lesions
with connective tissue disease.
Another indication of possible
connective tissue disease is involvement of other organ systems; thus a complete medical
Neurogenic
lesions
Occlusive arterial
diseases
Occupational
disorders
Thoracic outlet
syndrome
Thromboangiitis
obliterans
"Pneumatic hammer"
disease
Carpal tunnel
syndrome
Atherosclerosis
Disorders caused by
typing and piano
playing
Post-traumatic
vasospasm
Arterial emboli
Cold injury
evaluation is required.
Laboratory findings that
should alert the clinician to the
presence of underlying systemic disease include haematological abnormalities, elevated
sedimentation rate, abnormal
urinalysis, elevated creatine
kinase, positive rheumatoid
factor, and positive antinuclear antibody. The anticentromere antibody assay can help
to identify the patients with
CREST syndrome.9
Additional data often useful
in the evaluation of Raynaud's
phenomenon are serum protein electrophoresis, cryoglo-
bulins, cold agglutinins, Sjogren's antibodies (anti-SSA
and anti-SSB), 5 immunological abnormalities associated
with systemic lupus erythematosus, 1 0 and hepatitis B surface antigen. 11 Noninvasive
vascular studies can help rule
out proximal anatomic lesions
in patients with unilateral or
atypical Raynaud's phenomenon.
Rx: reassurance
and vasodilators
Treatment of Raynaud's phenomenon must be adjusted to
MODERN MEDICINEOF SOUTH AFRCA/30 MARCH 1984
3 5
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Suspect systemic disease when
FAST TRACK
Raynaud's is the sole or
presenting symptom in a man or
older woman, and the symptoms are
intense, of rapid onset, or
involve lower extremities.
Systemic diseases associated with Raynaud's
Intravascular
abnormalities
Ergot*
Progressive systemic
sclerosis (scleroderma)
Methysergide*
CREST syndrome
Cryoglobulinemia
Methylamphetamine*
Overlap syndromes
(mixed connective
tissue disease)
Cold agglutinin disease
Beta-adrenergic
blockers
Sjogren's syndrome
Polyvinyl chloride
Systemic lupus
erythematosus
Bleomycin
Arteritides
Birth control pills
Rheumatoid arthritis
Paraproteinaemia (eg,
macroglobulinaemia)
Polymyositis
Primary pulmonary
hypertension
'Vasospastic agents.
MODERN MEDICINEOF SOUTH AFRICA/30 MARCH 1984
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The patient must understand,
FAST TRACK
and thus avoid, the effects
of cold, stress, and smoking
on his vascular disorder.
-
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Clues that suggest underlying disease
»
the needs of the patient. The
intensity and frequency of
symptoms, presence of ischaemic lesions, anticipated seas o n a l or environmental
changes, patient compliance,
and the risk-benefit ratio of potential therapeutic measures
should all be considered in the
treatment protocol. Patients
with a correctable anatomic
abnormality or a manageable
systemic disease must be identified and appropriately treated. It is extremely important to
recognise those individuals
with Raynaud's disease and reassure them of a good longterm prognosis.
All patients must understand — and thus aviod — the
effects of cold, stress, and
smoking on their vascular disorder. In some, psychotherapy
or behavioural therapy might
prove beneficial, and these options should be explored. Success has been reported with
such diverse measures as behaviour-modification techniques, temperature biofeedback, and hypnosis. 1 2 , 1 3
Vasodilators are the mainstay of medical therapy for
Raynaud's phenomenon 14 (see
"A guide to drug therapy for
Raynaud's phenomenon", p
41). These agents can be divided into several classes according to their mechanism of action. Sympatholytics, includ-
Clinical findings
Laboratory findings
Lower-extremity symptoms
Haematological abnormalities
Intense symptoms
Abnormal urinalysis
Symptoms of rapid onset
Elevated sedimentation rate
Male or older female
Elevated creatine kinase
Digital ischaemia
Positive rheumatoid factor
Cutaneous lesions
(pitted scars, scierodactyly,
telangiectasis, nondigital
infarcts)
Positive antinuclear antibody
Abnormal protein electrophoresis
Other organ involvement
Presence of cryoglobulins
Presence of cold agglutinins
Presence of Sjogren's antibodies
Other immunological abnormalities
associated with systemic lupus
erythematosus
Presence of hepatitis B surface antigen
MODERN MEDICINE OF SOUTH AFRICA/30 MARCH 1984
3 9
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Vasodilators are the
mainstay of medical therapy .
for Raynaud's phenomenon,
with sympatholytics appearing
to be most effective.
FAST TRACK
A guide to drug therapy for Raynaud's phenomenon
Class
Sympatholytics*
Calcium channel
blockerst (listed in
order of decreasing
vasodilating effect)
Agent
Dosage
Remarks
Reserpine
0,25 to 0,5 mg per day
Personal preference in patients with mild
symptoms
Guanethidine
10 to 50 mg per day
For patients with moderate to severe
symptoms
Methyldopa
250 to 500 mg bid to qid
For patients with mild to moderate
symptoms
Tolazoline HCI
10 to 50 mg prn
Parenteral administration
Phenoxybenzamine
10 to 50 mg per day
For patients with severe symptoms
Prazosin HCI
1 to 5 mg bid to qid
Personal preference for patients with
moderate to severe symptoms
Nifedipine
10 to 40 mg qid
Verapamil
80 to 160 mg tidtoqid
Calcium blockers are useful in patients
with Raynaud's phenomenon associated
with migraine headaches and/or variant
angina
Diltiazem HCI
30 to 60 mg tid to qid
" Sympatholytics must be administered and monitored carefully because of adverse effects,
t Hole in treatment of Raynaud's phenomenon is still experimental.
Source: Robert P Jacobs, MD.
40
MODERN MEDICINE OF SOUTH AFRICA/30 MARCH 1984
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In a world of conflict
and tension...
•'q
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FAST TRACK
Calcium channel blockers,
specifically nifedipine,
have been reported to be
effective in Raynaud's
phenomenon.
Tracing the aetiology of Raynaud's phenomenon
To develop a rational treatment approach to Raynaud's phenomenon, we must understand its aetiology. In 1862, Maurice Raynaud described the problem
as an automatic neurosis,17 suggesting that the abnormality lay in the sympathetic nervous system. Even
today, many investigators agree with this hypothesis.
Because Raynaud's phenomenon can appear following intense emotional stress, some researchers
feel it may have a psychogenic component.
Other scientists suggest that Raynaud's phenomenon is due to a local fault in the vessel wall. Some
attribute it to an increased vascular sensitivity to alpha-adrenergic stimuli, although there does not appear to be a circulating neurohumeral defect in these
patients. Still others speculate that individuals with
ing agents that inhibit alphaadrenergic stimulation of
peripheral blood vessels, appear to be the most effective. I
prefer reserpine (Serpasil, et
al) for patients with relatively
mild disease, and prazosin
HCI (Minipress) or guanethidene sulphate (Ismelin Sulphate) for those with more intense vasospastic symptoms.
Direct-acting vasodilators and
beta-adrenergic agonists appear to be of limited efficacy.
There are several new classes of vasodilators whose role in
the treatment of Raynaud's
phenomenon remains experimental. Calcium channel
blockers, specifically nifedipine (Adalat), have been reported to be effective, 15 al42
Raynaud's phenomenon have a structural abnormality that is characterised by luminal narrowing18 -—
which may be congenital, as in those with Raynaud's
disease, or acquired, as in patients with a connective
tissue disease. Supporting this argument is evidence
that uncomplicated vasoconstriction in an otherwise
normal vessel cannot be maintained long enough to
result in ischaemia and tissue necrosis.19
Haematological abnormalities are associated with
Raynaud's phenomenon, although there is disagreement as to whether they contribute to its appearance
in all patients with a systemic disease. Studies of
plasmapheresis will help answer this question as well
as define its role in the treatment of this interesting
phenomenon.
though comparative studies
with the sympatholytics have
not yet been conducted. Several prostaglandins exhibit vasodilatory action when administered parenterally, 16 although
their use in the treatment of
Raynaud's phenomenon is also
experimental.
The role of surgical sympathectomy appears limited in
patients with Raynaud's phenomenon associated with one
of the systemic diseases. While
it does produce an immediate
clinical response, this often is
COMING
MODERN MEDICNE OF SOUTH AFRICA/30 MARCH 1984
self-limiting and does not alter
the long-term course of the disease. In patients with intense,
acute-onset digital vasospasm
that is accompanied by impending or actual ischaemic
change, sympathetic blockade
seems to be a reasonable emergency measure. I personally
prefer a cervical sympathetic or
digital block over a surgical
procedure, depending on the
location and extent of the disease.!
References for this article are obtainable
from the Editor• Box 375, Claremont 7735.
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