CASE REPORT
DOI 10.1111/J.1365-2133.2005.06340.X
Cannabis arteritis
P. Combemale, T. Consort, L. Denis-Thelis, J-L. Estival, M. Dupin and J. Kanitakis*
Department of Dermatology, Desgenettes Hospital, 108 Bd Pinel, 69003 Lyon, France
*Department of Dermatology, Ed. Herriot Hospital, 5 Place d’Arsonval, 69003 Lyon, France
Summary
Correspondence
Patrick Combemale.
E-mail: [email protected]
Accepted for publication
5 August 2004
Key words:
Buerger’s disease, cannabis, drug abuse, juvenile
arteritis
Conflict of interest:
None declared.
The main causes of arteriopathy in young patients include drugs, metabolic diseases, pseudoxanthoma elasticum and Buerger’s disease. Arteritis due to Cannabis
indica was first reported in 1960, and the role of this drug as a risk factor for
arteritis was confirmed in several subsequent publications. A 38-year-old smoker
with no previous contributory medical history except for long-standing cannabis
abuse developed a dry necrotic lesion of the left big toe. Imaging examinations
revealed proximal arteriopathy of the lower limbs that predominated on the left
side. He had no atherogenic or thrombogenic risk factors, and no signs of pseudoxanthoma elasticum were found. Remarkably, the development of arteritis paralleled cannabis abuse. The course was slowly favourable after weaning from the
drug, vasodilator treatment and hyperbaric oxygen therapy. Despite some subtle
clinical differences (more proximal than distal involvement), cannabis arteritis
may be considered as a particular form of Buerger’s disease, where cannabis,
along with tobacco, seems to cause arterial lesions. Along with the noxious
effects of cannabis on vessels, a role for contaminating arsenic is also possible.
Cannabis arteritis is not widely known, but may prove not to be so rare if one
considers consumption of cannabis besides that of tobacco.
Juvenile arteritis (Buerger’s disease)1 is a well-known entity
affecting young patients, and is caused by smoking. In 1960
the first cases of young cannabis abusers with arteritis were
reported.2 These observations remained forgotten until 1999,
when new similar cases were reported, and the triggering role
of cannabis was reconsidered.3 We report a further case and
review the relevant literature.
Case report
A 38-year-old man consulted for a painful necrosis of the left
big toe of some weeks’ duration. His past medical history was
unremarkable: he did not have Raynaud’s syndrome or arterial
hypertension, and had had no medical treatment. Notably, he
had been smoking 20 cigarettes daily and three to five cannabis-containing cigarettes daily for over 20 years. He denied
other drug intake (such as cocaine), as confirmed by toxicological analysis. Between June and November 2002 he had
developed painful nodules of both legs that regressed within
weeks but recurred regularly; a presumptive diagnosis of
superficial migratory phlebitis was made. While incarcerated
from November 2002 to May 2003 the patient continued
tobacco (but not cannabis) smoking, and the development of
nodules ceased. A fortnight before release from prison, he sustained traumatic injury on the left big toe; this seemed mild
166
and was neglected. After release the patient resumed cannabis
abuse. Two weeks later his left big toe suddenly became bluish and extremely painful, and within days a necrotic lesion
developed at the site of the wound. Because of the analgesic
effect of cannabis he increased consumption up to eight cigarettes daily, but consulted because the necrotic lesion became
extensive and the pain worsened, spreading to the whole foot.
Examination revealed a dry necrotic lesion of the left big
toe (Fig. 1). The left pedal and tibial pulses were not felt, and
the right ones were very weak. Auscultation revealed a right
femoral thrill. Peripheral pulses were felt on the upper limbs,
but Allen’s manoeuvre was clearly positive with a delay of
refilling of palmar arcades. No signs of local infection (cellulitis, purulent discharge or lymphadenopathy) were present.
Examination was otherwise unremarkable: in particular, there
were no signs of pseudoxanthoma elasticum (PXE). Doppler
ultrasound examination showed arteriopathy predominating
on the left leg, with disappearance of peroneal arteries; the left
posterior tibial artery was atheromatous, partly calcified, narrowed and lacked pulsed flow. Lower limb arteriography
showed proximal narrowing of the right iliac artery by 30%
and the popliteal artery by 50%, occlusion of the left tibial–
peroneal trunks, and 70% narrowing of the left anterior tibial
artery at the level of the ankle. Neither corkscrew-like nor
trapped popliteal arteries were observed (Fig. 2). Doppler
2005 British Association of Dermatologists • British Journal of Dermatology 2005 152, pp166–169
Cannabis arteritis, P. Combemale et al. 167
Fig 1. Necrosis of the toe.
Fig 3. Involvement of digital arteries.
Fig 2. Narrowing of the left tibial–peroneal artery.
Fig 4. Time-course of cutaneous lesions according to cannabis and
tobacco intoxication.
ultrasound examination of the supra-aortic trunk was normal,
but a computed tomographic scan showed bilateral distal
involvement of the hand arteries with a greatly tapered
appearance, namely at the level of the intermetacarpal branches leading to the collateral digital arteries (Fig. 3). Laboratory tests for thrombophilic factors (including proteins S and
C, antithrombin III, factor II mutation, resistance to activated
C protein, circulating anticoagulant antibody, anticardiolipid,
b2 glycoprotein-1, factor VIII, hyperhomocysteinaemia), cryoglobulins, polycythaemia and monoclonal gammopathy
proved negative. Blood glucose, calcium and lipids were normal. Signs of emboligenic cardiopathy were not found. Ophthalmological examination did not show angioid streaks, and
the possibility of infraclinical PXE was further ruled out by
skin biopsy.
Considering these clinical features, namely the patient’s
young age, heavy smoking and the probable previous
superficial migrating phlebitis, the diagnosis of Buerger’s disease (thrombangiitis obliterans, TAO) was considered. However, the improvement of this condition during incarceration
was puzzling, as tobacco smoking was not discontinued. Conversely, the clinical symptoms clearly paralleled cannabis
consumption (Fig. 4).
Surgical revascularization was not envisaged. The patient
discontinued cannabis but not tobacco smoking. Despite treatment with anticoagulants and prostaglandin (Ilomedin,
Schering) the lesion worsened. Treatment with chemical sympatholytics and hyperbaric oxygen therapy was tried, resulting
in pain relief and regression of the necrosis starting from the
border of the ulcer. Oral buflomedil and platelet aggregation
inhibitors were given on day 28, resulting in almost complete
healing 1 month after release. The patient was seen 3 months
later for a new post-traumatic painful necrotic lesion of the
left little toe and a relapse of the ulceration of the big toe. He
2005 British Association of Dermatologists • British Journal of Dermatology 2005 152, pp166–169
168 Cannabis arteritis, P. Combemale et al.
admitted having resumed cannabis abuse. With psychiatric
assistance he achieved tobacco and cannabis weaning, leading
to progressive healing of skin lesions.
Discussion
In our patient the rare causes of arteritis in young patients
were ruled out, including PXE and drugs (ergotamine alkaloids, beta-blockers, cytostatics, calcium inhibitors).4 According to the criteria of Langeron5 and Mozes et al.,6 the
diagnosis of juvenile arteritis appeared likely considering the
patient’s young age, probable recurring superficial phlebitis
and popliteal arterial lesions in the absence of risk factors
other than tobacco smoking; however, the proximal femoral
involvement and the absence of segmental stenoses and corkscrew-like vessels were unusual for TAO.1 Smoking was the
only atherogenic factor present; furthermore, the patient was a
heavy cannabis abuser, and his cutaneous signs closely paralleled drug abuse, strongly suggesting the diagnosis of cannabis
arteritis (CA). Other causes of arteriopathy [e.g. chronic vasospasm to cocaine, a synthetic amphetamine containing 1-phenylethylamine, or ergotamine-containing lysergic acid (LSD)7]
were excluded by history and laboratory tests.
Cannabis is a mild drug extracted from the plant Cannabis
sativa;7 it is added to tobacco (‘joint’ in cigarettes, ‘kif’ in
pipes) or more rarely chewed in various preparations (‘mahjoun’). It causes strong intoxication and occasionally aggressive
behaviour [‘assassin’ (murderer) probably derives from the
word ‘hashishin’], followed by a euphoric state responsible
for addiction.2 Its main biological effects are due to cannabinoid-rich substances such as d-9-tetrahydrocannabinol
(D9THC). It is available in preparations of various concentrations, including (in increasing order of strength) the dried
plant (‘marijuana’), resin (‘hashish’ or ‘shit’), distillation
product (‘oil’) and a high-concentration variety (‘nederweit’
or ‘skunk’) found in the Netherlands.
The first cases of CA were reported in 1960,2 but remained
poorly known and were not mentioned in a review of the
effects of cannabis.8 From 1999 the role of cannabis in juvenile arteritis was reconsidered.7 Our literature review revealed
48 cases of CA.2,7,9–12 Clinically, CA is very similar to TAO.
Most (46 of 48) patients were young men presenting with
extremely painful paroxystic subacute episodes of distal ischaemia, affecting mainly the lower limbs. The upper limbs
were also affected in three cases,10,12 and exclusively affected
in one.11 Trophic problems (digital or pulpar necrosis)11 or
gangrene occur frequently and early, and may be associated
with Raynaud’s phenomenon or venous thromboses.3 Arteriography reveals distal, often bilateral, segmental stenoses below
the knees or elbows; in contrast with TAO, the compensatory
networks are less developed, and proximal atheromatous
lesions are occasionally seen.3,9,10,12
Pathological data are sparse. One case showed thrombosis
and endarteritis with a neutrophilic and mononuclear cell
infiltrate invading the media and damaging the inner elastic
lamina;7 another case showed noninflammatory arteritis with
lipid deposits and thrombosis.2 These differences are probably
due to a different age of the lesions. Some observations were
made on amputation specimens2 that probably contained scarring lesions.7 These findings differ from TAO, showing initially a hypercellular thrombus with microabscesses and giant
cells, followed in the subacute phase by thrombus organization sparing the arterial wall.1
Smoking may be heavy (up to 15 pipes daily2) or lighter
(one to five cigarettes daily or weekly during an average of
8Æ5 years3,12). This discrepancy is probably due, at least partly,
to the highly variable concentration of cannabis in the selfprepared products. None of the patients reported significant
abuse of other drugs (cocaine, heroin, LSD, amphetamines),
but tobacco smoking was always associated; although moderate (20 cigarettes daily), it was repeatedly noted that disease
flares were linked to cannabis intake and not to tobacco smoking (which was continuous,2,12 as in our patient). This parallelism strongly suggests the (co)responsibility of cannabis in
the development of arteriopathy.
There is no specific biological marker for CA. Serum cholesterol levels are occasionally low due to inhibition of 3-hydroxy-3-methylglutaryl coenzyme A reductase by cannabis.7
The diagnosis should be considered after excluding other causes of arteriopathy including PXE, hyperviscosity, thrombophilia or thromboembolic disease, systemic vasculitis or
vascular trap.7
The spontaneous course of CA may be severe and can lead
to amputation (40% of patients in two series). Weaning usually leads to improvement, but the symptoms recur if abuse is
resumed. Apart from mandatory tobacco and cannabis weaning, the treatment is mainly medical as the distal involvement
limits considerably the possibility of surgical correction. It
comprises vasodilator drugs (buflomedil, prostaglandins) and
anticoagulants during the acute phase, followed by platelet
aggregation inhibitors. Severe forms can be treated with
sympatholytics, hyperbaric oxygen therapy, thrombolysis, or a
distal rescue bypass.
Concerning the pathogenesis, a vasoconstrictor effect of
D9THC seems probable. Animal studies have shown that
D9THC exerts peripheral vasoconstriction via a tyramine-like
effect on adrenergic nerve endings;13 however, tobacco smoking is always associated, raising a nosological problem regarding Buerger’s disease and atheromatosis. The signs and
symptoms are similar, although the proximal involvement is
distinctive. Pathological data are too sparse and controversial to
be used diagnostically. Currently, insufficient evidence exists to
consider CA as a separate entity; instead, this should be regarded as a particular aetiological form of TAO. Because of
tobacco cointoxication, a synergistic noxious effect of tobacco
and cannabis seems likely, along with that of a probable common contaminant. An attractive hypothesis concerns arsenic,14
which is able to induce in rats a disease similar to TAO. Arsenic
would impair angiogenesis through inhibition of vascular
endothelial growth factor and induction of endothelial cell
apoptosis. Endemic forms of TAO exist in Taiwan, correlated
with arsenic concentration in water. Arsenic concentration is
2005 British Association of Dermatologists • British Journal of Dermatology 2005 152, pp166–169
Cannabis arteritis, P. Combemale et al. 169
high in some self-made cigarettes in Asia, whereas in Europe
this concentration has been controlled since 1957, probably
explaining the decreasing incidence of TAO in Europe (6%) in
comparison with 60% in India, Korea and Japan. However, in
Western countries drugs such as heroin, cocaine and cannabis
may contain considerable amounts of arsenic.14
In conclusion, cannabis seems to be an aetiological factor of
arteritis and should be searched for, all the more so now that
the increasingly authorized use of this drug, the recent introduction of highly concentrated varieties and the uncontrolled
arsenic content in self-made preparations will probably lead to
an increased incidence of CA.
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