CHAPTER 1

INTRODUCTION

Buerger's disease is also called thromboangiitis obliterans is a rare disease of the

small to medium sized arteries and veins in the arms and legs. Buerger's disease,
is a nonatherosclerotic, segmental, inflammatory disease which is characterized by
highly cellular and inflammatory occlusive thrombus with relative sparing of the
blood vessel wall. Since oxygenated blood cannot get to the tissues, this will
eventually damages or destroys skin tissues and may lead to infection, peripheral
skin ulcers and gangrene along with intractable pain.1
Buerger's disease was first reported by Felix von Winiwarter in 1879 in Austria.
Leo Buerger working at Mount Sinai Hospital in New York, reported the results of
pathologic examination of 11 amputated limbs from young men in whom
progressive veno-occlusive disease resulted in amputations. Buerger termed the
entity Thromboangiitis Obliterans.1,2
Buerger's disease with the incidence of 1/8000 people, which is much more
common in men with the typical age of onset younger than 40 years than in
women, and is closely associated with heavy cigarette and/or cannabis smoking,
or with tobacco chewing. Buerger's disease appears to be more common in Asians
and in the Middle East example Japan, India and Manipur, and is rare among
African-Americans, and is very rare in children.1
In North America, the prevalence of this disease has declined in the past 30 years
due to a decline in smoking. In other parts of the world, the prevalence of this
disease among patients with arterial occlusive disease varies widely, ranging from
0.5 to 5.6 percent in Western Europe to as high as 45 to 63 percent in India. Of
patients diagnosed with Buergers disease, 70 to 91 percent are male and 11 to 30
percent are female. However, there are reports of increasing prevalence of disease
in women, possibly due to the increasing use of cigarettes among women.1,2

CHAPTER 2
CONTENT

2.1 Etiopathogenesis
The etiology of thromboangiitis obliterans (Buergers disease) is not known
although there is a definite relationship to cigarette smoking / tobacco use in
patients with the disease. This implies that tobacco plays a role in the
pathogenesis of the disease or that tobacco is a highly contributive factor at the
very least. Moreover, all types of tobacco have been implicated to the disease. The
specific substance however hasnt been yet defined.3,4
The role of cannabis (marijuana) was recently reconsidered, resulting in a specific
type of arteritis (cannabis arteritis) which is very similar in term of clinical
features and pathological lesions to Buergers disease despite of some
unconvincing differences. This makes the role of cannabis remains controversial.
Attempts to investigate the possibility of autoimmune mechanism have also been
carried out. Hypersensitivity to type I and III collagen associated with the
presence of anti-collagen or anti-elastin antibodies has been shown but these
conditions isnt specific and havent been confirmed. It is also possible that such
conditions occur secondarily to inflammatory modification rather than being the
cause.3
In the initial stages, polymorphonuclear leukocytes infiltrate the walls of small
and medium sized arteries and veins. The internal elastic lamina is preserved and
thrombus may develop in the vessel lumen. As the disease progresses,
mononuclear cells, fibroblast, and giant cells replace the neutrophils. At the later
stages, perivascular fibrosis and recanalization take place. These conditions lead
to the blockage of blood flow to parts of the body (primarily upper and lower
limb) supplied by the affected blood vessel resulting in ischemia. In severe
ischemia, painful ulcerations and gangrene may develop.4

2.2 Clinical Manifestation

Buergers disease generally begins in young male smokers with hand or foot
ischaemia due to distal small arteries and veins involvement of the limbs. 3 The
other clinical manifestation are :
a. Ischaemia of the lower and upper limb
The commonest presenting symptoms are ischaemic manifestations of the
lower limbs. Claudication in the arch of the foot is an early sign and is
suggestive of, or even specific to Buergers Disease. This condition is a
manifestation of infrapopliteal vessel occlusive disease. Rest pain
generally occurs on the forefoot, causing continuous pain and obliging
patients to sleep with their legs dangling downwards. The intensity of this
pain often contrasts with the apparently limited, almost benign appearance
of the ischaemic trophic lesions. Superinfection often occurs and the
lesions progress towards necrosis and distal gangrene. And also there will
be involvement of ischaemia of the upper limb in 40-50% patients. The
hands and feet of patients with the disease are usually cool and mildly
edematous.3,5

Figure 1. Healed ischaemic lesions of the forefoot in a young patient with Buergers
disease1

b. Superficial thrombophlebitis
Superficial thrombophlebitis is observed in 4060% of cases. This
superficial thrombophlebitis is migratory and recurrent and affects the
arms and legs. Migrating phlebitis (phlebitis saltans) in young patients is
therefore highly suggestive of Buergers Disease.3,5
3

c. Paresthesias lower and upper limb

Paresthesias (numbness, tingling, burning, hypoesthesia) of the feet and
hands and impaired distal pulses in the presence of normal proximal pulses
are usually found in patients with the disease.5
d. Systemic sign and symptom
Systemic signs and symptoms are very rare in patients with Buergers
Disease. Buergers Disease may begin with joint manifestations. Patients
present recurrent episodes of arthritis of the large joints, with transient,
migratory single-joint

episodes

accompanied

by local

signs

of

inflammation. The wrists and knees are the most frequently involved
joints. The duration of signs and symptoms ranges from 2 to 14 days. The
arthritis is nonerosive. Arthritis disappears definitively with the appearance
of ischaemic signs.3
2.3 Diagnosis
Since the specificity of Buerger's disease is characterized by peripheral ischemia
of inflammatory nature with a selflimiting course, diagnostic criteria should be
discussed from clinical point of view. Several different criteria have been
proposed for the diagnosis of thromboangiitis obliterans. 6
a. Diagnostic criteria of Shionoya (1998)
smoking history;
onset before the age of 50 years;
infrapopliteal arterial occlusions;
either arm involvement or phlebitis migrans;
absence of atherosclerotic risk factors other than smoking.
b. Diagnostic criteria of Olin (2000)
age under 45 years;
current or recent history of tobacco use;
the presence of distal-extremity ischemia indicated by claudication,
pain at rest, ischemic ulcers or gangrenes and documented by non

invasive vascular testing;

exclusion of autoimmune diseases, hypercoagulable states and

diabetes mellitus;
exclusion of a proximal source of emboli by echocardiography or
arteriography;

consistent arteriographic findings in the clinically involved and non-

involved limbs.
c. Diagnostic methods
No specific laboratory test for diagnosing Buerger's disease is available.
Unlike other types of vasculitis, in patients with Buerger's disease the
acute-phase reactions (such as the erythrocyte sedimentation rate and Creactive protein level) are normal. Recommended tests to rule out other
causes of vasculitis include a complete blood cell count; liver function
tests; determination of serum creatinine concentrations, fasting blood sugar
levels and sedimentation rate; tests for antinuclear antibody, rheumatoid
factor, serologic markers for CREST (calcinosis cutis, Raynaud
phenomenon, sclerodactyly and telangiectasia) syndrome and scleroderma,
and screening for hypercoagulability. Screening for hypercoagulopathy
including antiphosolipid antibodies and homocystein in patients with
Buerger's disease, is recommended. If a proximal source of embolization is
suspected, transthoracic or transesophageal echocardiography and
arteriography should be performed. Angiographic findings include severe
distal segmental occlusive lesions. The more proximal arteries are normal.
The role of modern imaging methods, such as computerised tomography
(CT) and magnetic resonance imaging (MRI) in diagnosis and differential
diagnosis of Buerger's disease still remains unsettled. In patients with leg
ulceration suspected of having Buergers Disease, the Allen test should be
performed to assess the circulation in the hands and fingers. 6

d. Allens Test
In the Allen test, the patient is instructed to make a fist, which will empty
the blood from the hand and fingers (Panel A). The examiners thumbs are
then pressed down across the thenar and hypothenar eminences to the wrist
to occlude the radial and ulnar arteries. The patient then opens the hand,
making sure not to overextend the fingers, since this can cause a false
positive result. The pressure on the ulnar artery is then released while the
5

radial artery is still compressed (Panel B). The hand does not fill with
blood. Note the paleness of the hand on the right compared with the hand
on the left, indicating occlusion of the ulnar artery distal to the wrist
(positive test result). If there is prompt return of color to the hand
(indicating a negative test result), the pressure on the radial artery is
released while the ulnar artery remains compressed.7 An abnormal Allen
test result indicating distal arterial disease and establishing involvement of
the upper extremities in addition to the lower extremities helps
differentiate thromboangiitis obliterans from atherosclerotic disease.5

e. Histopathology
While the clinical criteria of Buergers Disease are relatively well defined,
there is no consensus on the histopathological findings. It is particularly
difficult

to

distinguish

morphologically

Buergers

Disease

from

ateriosclerosis obliterans (ASO). Histopatological findings are also known

to vary according to the duration of the disease. The findings are most
likely to be diagnostic in the acute phase of the disease, most commonly at
biopsy of a segment of a vessel with superficial thrombophlebitis. Other
histopathological phases, such as intermediate (subacute) and endstate
(chronic) phases, have been described. The acute-phase lesions include an
occlusive, highly cellular, inflammatory thrombus with less inflammation
6

in the walls of the blood vessels. Polymorphonuclear leukocytes,

microabscesses and multinucleated giant cells may exist. When Buergers
Disease occurs in unusual locations, the diagnosis should be made only
when histopathological examination identifies the acute-phase lesion. In
the intermediate phase of disease there is progressive organization of the
thrombus in the arteries and veins. When only organized thrombus and
fibrosis are found in the blood vessels, the phase is considered to be endstage.6

Figure 2. Typical Acute Histologic Lesion of Buergers Disease in a Vein with

Intens Thromboangiitis, Showing a Microabscess in the Thrombus and Two

Multinucleated Giant Cells (Arrows) (Hematoxylin and Eosin, x400).7

Figure 3. Biopsy of a subcutaneous nodule of superficial thrombophlebitis:

moderate non-specific inflammatory infiltrate mostly located in the thrombus.3

f. Imaging
Arterial duplex, CT angiography, magnetic resonance angiography, and
digital subtraction angiography are all useful radiological imaging
techniques that show medium and small vessel occlusion, often with
'corkscrew'-shaped collateral vessels (Martorell's sign). An angiogram,
helps to see the condition of arteries. A special dye is injected into an
artery, after which undergo X-rays or other imaging tests. The dye helps to
delineate any artery blockages that show up on the images. Buerger's
disease almost always affects more than one limb, and this test may detect
early signs of vessel damage.3
Characteristic angiographic findings include extensive arterial occlusive
disease accompanied by the development of corkscrew collateral vessels.
More than one limb is usually affected with predominantly the lower
limbs. The small and medium-sized arteries are affected in a segmental and
often bilateral manner. In the legs, infrapopliteal lesions predominate,
affecting one or several vascular beds, but particularly the anterior and
posterior tibial arteries. In the arms, the lesions primarily concern the
radial and cubital arteries, together with the palmar arcades and the digital
arteries.3
Ultrasound is also used as one of the diagnosis of Buergers disease. It is
used to identify the site of arterial occlusions.3
2.4 Differential diagnosis
A clinical diagnosis of Buergers disease requires exclusion of disorders that may
mimic the disease. The most important disorder to exclude is atherosclerotic
vascular disease, thromboembolic disease, and autoimmune disease such as
scleroderma or CREST (calcinosis, Raynaud phenomenon, esophagal dysmotility,
sclerodactyly, telanglectasia) syndrome. In most cases the combination of

serological testing, echocardiography and arteriography can exclude these

disorders and help establish the diagnosis of Buergers disease.8
A scleroderma or CREST syndrome diagnosis is typically suggested by clinical
presentation, including skin findings. Nailfold capillaroscopy may be performed
and is usually quite distinctive in patients with these disorders. However,
characteristics findings of capillary loop dropout in scleroderma and CREST
syndrome may be observed in some patients with Buergers disease. Detection of
serological markers such as anti-ACL-70 or anticentromere antibodies provides
further evidence for scleroderma or CREST syndrome.8
Clinicians should evaluate patients for features of other autoimmune diseases such
as systemic lupus erythematosus, rheumatoid arthritis, and other vasculitides.
Serological markers are often helpful in excluding such disorders. Patients with
antiphospholipid antibody syndrome pose a particular diagnostic challenge
because they may be present in both arterial and venous thrombotic events.
Antiphospholipid antibody syndrome is suggested by detection of lupus type
anticoagulants or presence of elevated titres of anticardiolipin antibodies. Of note,
lupus anticoagulant and anticardiolipin antibodies can be detected in some
patients with Buergers disease, but may also indicate an unrelated thrombophilia.
Pathological examination can clearly differentiate between the two disorders
because antiphospholipid antibody syndrome is characterized by the presence of
bland thrombosis, whereas Buergers disease results in an inflammatory
thrombus.8
Thromboangitis obliterans (Buergers disease) is differentiated from other
vasculitides in that it results in distal extremity ischemia, whereas patients with
Takayasus arthritis or GCA present with more proximal arterial involment.
Arteriographic features of Buergers disease are also quite distinctive from that
observed in Takayasus arteritis or giant cell arteritis. In addition, vasculitides
such as Takayasus arteritis and GCA are typically associated with elevations in
inflammatory markers including erythrocyte sedimentation rate and C-reactive
protein.8

Clinicians evaluating patients with suspected Buergers disease should inquire

about possible ergotamine or cocaine abuse, in addition to disorders of repetitive
mechanical trauma such as vibration induced vascular injury and hypothenar
hammer syndrome. Serum ergotamine levels can be obtained to exclude vascular
injury caused by this drug. Because it can mimic Buergers disease, all patients
should be questioned about cocaine abuse. A complete toxicology screen is
recommended in patients who present with a history and physical compatible with
Buergers disease, especially if they deny tobacco use8.
2.5 Management
a. Pharmacology
The first and foremost treatment for Buergers disease is smoke cessation
and behavioural therapy where complete discontinuation of smoking
cigarette and tobacco is advised. As for pharmacological management,
there are certain treatment options.
In acute complaints, vasodilation caused by medicines and medical
procedures appear to have reduced the painful sensation. Prostaglandins
for example Limaprost5 are vasodilators that relieves pain but helps little in
improving the diseases course.
In chronic cases, treatment with intravenous Iloprost, which is a
prostaglandin analogue, is used. Iloprost dilates systemic and pulmonary
arterial vascular beds, aiding in vasodilation.9 It has been proved to be
effective in improving the symptoms and accelerating the resolutions of
the distal extremity trophic changes, and thus, reducing the rate of
amputations. Intravenous Iloprost also helps to slow down progressive
tissue loss, in this case, reducing amputation caused by gangrene. The
duration of the treatment is typically 3 days. This is usually repeated every
8 to 12 weeks. Lumbar sympathectomy helps by reducing vasoconstriction
and increases blood flow to limbs and also aids in healing and giving relief
from pain of ischemic ulcers.10 Bypass can sometimes be helpful in treating
limbs with poor perfusion secondary to this disease. Thrombolytic therapy
has shown positive results in treating but is still in the research stage.
10

The usage of antibiotics, non-steroidal, steroidal, narcotic analgesics,

Calcium channel blockers, anti-inflammatory agents like corticosteroids,
anti-platelet drugs and anti-coagulants to treat ulceration, infection and
inflammation have been proven to be ineffective and in some cases,
dangerous.11However, a few cases have been proven to respond to these
drugs as a pain relief therapy, but only when used in low dosage
intermittent form.
b. Non-pharmacology
The most effective treatment for Buergers disease is smoking cessation. It
is therefore essential that patients diagnosed with Buergers disease stop
smoking immediately and completely to prevent progression of the disease
and avoid amputation. Smoking as few as 1 or 2 cigarettes daily, using
chewing tobacco or even using nicotine replacements may keep the disease
active.6,5
Given the diffuse segmental nature of Buergers disease and the fact that
the disease primarily affects small- and medium-sized arteries, surgical
revascularization for Buergers disease is usually not feasible and is
extremely rare.7,5 However supportive care should be directed towards
maximizing blood supply including avoiding vasoconstriction from
exposure to cold or drugs.6 Several strategies are important in prevention
of complications from Buergers disease, including the use of well-fitting
protective footwear to prevent foot trauma and thermal or chemical injury
and early aggressive treatment of extremity injuries to protect against
infections.5
The role of bypass to the distal arteries for patients with Buergers disease
remains controversial because of the high incidence of graft failure.
However, if the patient has severe ischemia and there is a distal target
vessel, bypass surgery with the use of an autologous vein should be
considered. Sympathectomy decreases arterial spasm, which is the reason
for assessing this procedure in patients with Buergers disease.

11

Laparoscopic method for sympathectomy has also been used. However,

sympathectomy only seems to provide short-term pain relief and promotes
ulcer healing in some patients with Buergers disease, but carries no longterm benefit. Spinal cord stimulator and vascular endothelial growth factor
gene therapy have been used experimentally in patients with Buergers
disease with promising results.6 Ultimate surgical therapy for refractory
Buerger disease (in patients who continue smoking) is distal limb
amputation for non-healing ulcers, gangrene, or intractable pain. Avoid
amputation when possible, but, if it is necessary, perform the operation in a
way that preserves as much of the limb as possible.5
2.6 Complications
Buerger's disease typically affects the extremities leading to claudication,
ischemic ulcers, and digital infarction. If Buerger's disease worsens, blood flow to
your arms and legs decreases. This is due to blockages that make it hard for blood
to reach the tips of your fingers and toes. Tissues that don't receive blood don't get
the oxygen and nutrients they need to survive. This can cause the skin and tissue
on the ends of your fingers and toes to die (gangrene). Signs and symptoms of
gangrene include black or blue skin, a loss of feeling in the affected finger or toe,
and a foul smell from the affected area. Gangrene is serious condition that usually
requires amputation of the affected finger or toe. Buergers disease also can
develop any infection and ulceration due to necrosis of the tissue.12,13,14

2.7 Prognosis
The disease is progressive in patients who do not stop smoking. Among patients
with who quit smoking, 94% avoid amputation; among patients who quit smoking
before gangrene develops, the amputation rate is near 0%. If the condition is
diagnosed early, a fair outcome including partial healing of the affected area and
some restoration of blood flow can sometimes be achieved if the individual quit
from smoking. This is contrast to patients who continue smoking, for whom there

12

is a 43% chance that an amputation will be required sometime during a 7- to 8year period. It is not uncommon for patients with Buerger disease who continue to
smoke to require multiple amputations, and reports have even been made of
patients who have required bilateral above-knee and above-elbow amputations.
While smoking cessation generally removes the need for limb amputation,
patients may continue to have claudication or Raynaud phenomenon even after
complete discontinuation of tobacco use.5,14

CHAPTER 3
CONCLUSION

Buerger's disease, is a nonatherosclerotic, segmental, inflammatory disease which

is characterized by highly cellular and inflammatory occlusive thrombus with

13

relative sparing of the blood vessel wall. Since oxygenated blood cannot get to the
tissues, this will eventually damages or destroys skin tissues and may lead to
infection, peripheral skin ulcers and gangrene along with intractable pain. The
etiology of thromboangiitis obliterans (Buergers disease) is not known although
there is a definite relationship to cigarette smoking / tobacco use in patients with
the disease. Clinical manifestations include hand or foot ischaemia due to distal
small arteries and veins involvement of the limbs, ischaemia of the lower and
upper limb, superficial thrombophlebitis, parasthesias lower and upper limb, and
systemic sign and symptom. The diagnosis of Buergers disease is can be done by
history taking and physical examination to see the clinical manifestation but it is
difficult caused by the lack of specific clinical, radiological and biological
features, the rarity of histopathological evidence of inflammatory vascular lesions
and the lack of diagnostic criteria validated or accepted internationally. The
diagnosis criteria that can be used such as Shionoyas and Olins criteria.
Therefore, the diagnosis is made at the end of investigations aiming to eliminate
differential diagnoses and to search for other signs of the disease. The most
important

treatment

for

Buergers disease

is

smoking

cessation,

but

pharmacological treatment such as prostaglandins analogue as vasodilator and

thrombolytic drugs can be used. Surgical therapy also can be done as a supporting
therapy. The complication of Buergers disease includes ulceration, gangrenes,
infections, and amputation. The risk of amputation is higher in patients who
continue smoking and significantly lower after the patients stop smoking.

14