Background. Thromboangitis obliterans (TAO or Buerger's Disease) is most commonly associated with tobacco exposure. A similar cannabis induced form of thromboangitis obliterans has been suggested in the literature. Unfortunately, most patients reported in the literature with radiologic evidence of thromboangitis obliterans and cannabis exposure are noted to have concomitant exposure to tobacco. This confounds the results and questions the validity of true thromboangitis obliterans secondary to cannabis. Case Report. In this case we report a young female with clinical and radiologic evidence of thromboangitis obliterans. Notably, the patient had no history of tobacco exposure confirmed by laboratory studies. The patient did have extensive exposure to cannabis. Cessation of cannabis use led to resolution of her symptoms. Conclusion. This case suggests that thromboangitis obliterans or a similar arterial pathology can develop with the use of cannabis and without concomitant exposure to tobacco.
VASCULAR DISEASE MANAGEMENT 2011;8:E124–E126
Buerger’s disease (thromboangitis obliterans or TAO) is a non-atherosclerotic inflammatory disease of the arteries and veins of unknown etiology. The disease is almost exclusively associated with tobacco use. Although rare, cannabis use has similarly been implicated as a causative agent in the inflammatory response resulting in lesions consistent with Buerger’s disease.1,3 Unfortunately, the great majority of cannabis users who develop Buerger’s type lesions are concomitant users of tobacco.1,2,3 This has made it difficult to determine whether a true “cannabis arteritis” (CA) exists. Some authors have gone as far as to recommend striking the term “cannabis arteritis” from the literature.2
We present a case of digital ischemia in a young female with a long history of daily cannabis use. Of importance, the patient had not utilized tobacco in over a decade. This case would suggest that cannabis may be an independent risk factor for Buerger’s disease or a similar arteritis process.
A 36-year-old female presented to our clinic with acute onset of pain, numbness, and coolness in her right index finger. The symptoms initially developed 2 weeks prior to presentation. She did not recall an inciting event or trauma to the finger but noted the symptoms in her right hand upon awakening one morning. The symptoms were most prominent in her right index finger although she did relay similar but less distressing symptoms in her right thumb and middle digit. She did not note any exacerbating or remitting factors. She had decreased function of her right hand due to decreased sensation and pain. She denied any previous episodes of similar symptoms. She stated she did not recall any repetitive use activity of her right upper extremity. She had not had any recent cold exposure and denied any previous history suggestive of Raynaud’s syndrome.
She had smoked a few cigarettes in college over 10 years ago but none in the last decade. She did, however, indicate that she smoked cannabis on a nightly basis prior to going to bed. This use had been consistent for the last 7 years.
Her previous workup prior to presentation included an EMG, cervical spine MRI and MRA right upper extremity. Inflammatory, rheumatologic, hypercoagulable, autoimmune markers were all negative on serum evaluation, with the exception of heterozygote status for factor V Leyden mutation. In addition, the patient demonstrated no evidence of tobacco exposure based upon serum cotinine levels. Her EMG was normal with sensory and motor nerve conduction studies. She demonstrated tenderness along the first 3 digits of the right hand. Furthermore, a temperature difference of approximately 5 degrees centigrade between the second digit and the fourth digit with the second digit being the cooler finger was discovered. MRA suggested abnormal digital arterial perfusion. Noninvasive vascular laboratory studies demonstrated severely blunted waveforms in the index finger on the right. Waveforms in the middle finger and thumb were also abnormal. All other digital waveforms appeared normal and triphasic.
The patient subsequently underwent thoracic aortogram with right arm runoff including magnified views of her right hand. Her aortogram and brachiocephalic, subclavian, axillary, brachial, radial and ulnar arteries did not demonstrate any disease or stenosis. No evidence of compression with provocative maneuvers was appreciated. Segmental occlusions in the digital arteries were noted most prominently in the index finger but with evidence of disease in her other symptomatic digits including thumb and middle finger (Figure 1).
Following angiography the patient stopped use of cannabis. The patient’s discomfort in the index finger quickly resolved, as did discoloration in the digit.
TAO is a progressive nonatherosclerotic vascular disease characterized by minimal presence of atheromas with segmental occlusion of small- and medium-sized arteries and veins of the upper and lower extremities. Angiographically there is segmental occlusive thrombosis of small- to medium-sized arteries and veins with the hallmark finding of small-vessel "corkscrew collaterals" bridging the occlusions. During the initial phase the affected vessels are associated with highly cellular PMN and multinucleated giant cell infiltrates and microabscesses. Secondary spread from the affected small- and medium-sized arteries to contiguous veins and nerves is often observed during this phase. With disease progression, thrombi begin to mature and organization occurs with an associated loss of cellular infiltrates; often there is recanalization of the affected vessel lumen. End-stage of the disease is marked by mature thrombus with scarring and fibrosis of the involved vessels.
The underlying cause of TAO disease is not fully understood. Use and exposure to tobacco, however, is often considered essential for both diagnosis and progression of the disease. Epidemiological reports have shown the disease to be more common in countries with heavy tobacco use.4 Although TAO disease is most common with the smoked form of tobacco, a few cases have been reported in nonsmokers using chewing tobacco. Nicotine patches and secondhand tobacco smoke have also been attributed to progression of disease in patients with already established pathology.5 Cannabis has been reported in a number of cases as a cause of TAO as well but its factor as causative agent has often been confounded by concomitant tobacco use.
TAO is more common in men (77% of cases) compared with women (23%).6 When associated with tobacco, the disease also appears to more commonly afflict the lower extremities than the upper extremities although it is certainly common to see both involved.6,7 There have been around 60 cases describing CA and unfortunately the majority of the described patients used tobacco concurrently with the majority of described reports involving men.2 Much like tobacco-associated TAO, most cases of cannabis arteritis are described in the lower extremities rather than the upper extremity in women (75%) and in men (93%). In contrast to TAO, however, CA is felt to develop sooner and with lesser amounts of cannabis than with tobacco.4 Additionally it is felt by many authors that the collateral vessels in CA are less developed than in TAO.2 Unlike our case, the majority of cases reporting CA implicate larger arteries than in classic tobacco-associated TAO (in our case the disease was limited to the digital arteries).
The mechanism of TAO is largely unknown; in parallel the mechanism of CA remains largely a mystery. The psychoactive constituent of cannabis, Δ9-tetrahydrocannabinol, is itself a vasoconstrictor, which may in part explain the CA pathogenesis.3 Several other theories have been postulated, ranging from frostbite-induced,2 other sympathomimetic drug use (cocaine, methamphetamine)8 or a common constituent found within the smoke of combusted material aside from the source (tobacco, cannabis or otherwise) as the offending or inciting agent. One of the more compelling theories involves arsenic as a potential inciting substance. Blackfoot disease is an endemic form of TAO and is associated with high levels of arsenic in drinking water in Taiwan.1,9
A number of authors have attempted to identify a predisposing genetic component that would help to explain the appearance of TAO in certain smoking populations while remaining absent in others. To date, several studies looking for haplotypes associated with TAO have not identified any distinctive pattern.10 Researchers have had more success associating abnormalities in coagulation in patients with TAO. Several studies have suggested greater prevalence of factors associated with hypercoagulability in patients with TAO including (and notable for our case) Factor V Leyden.11
Our case represents a number of unusual aspects of either Buerger’s disease or a similar entity associated with the use of cannabis. The patient’s clinical presentation and radiologic findings are consistent with those found in TAO despite only a remote (and extremely limited) exposure to tobacco. It is also interesting that this was discovered in a female patient with symptoms exclusively in the upper extremity, as these are not hallmarks of classic TAO. It is also curious that our patient was found to be heterozygote for Factor V Leyden, which raises the possible interplay between this genetic state and exposure to the chemical constituents in cannabis leading to an exaggerated inflammatory response in the small vessels.
We believe that our case and similar cases presented in the literature suggest that use of cannabis can lead to a pathologic syndrome that is either identical to or mimics TAO. While the current etiology of either TAO or CA is poorly understood, these independent factors may help lead to better understanding of the pathophysiology and mechanisms behind TAO. It should also be stressed that detailed history should be elicited from the young patient with evidence of digital ischemia even in the absence of tobacco use.
- Combemale P, Consort T, Denis-Thelis L, et al. Cannabis arteritis. Br J Dermatol 2005 Jan;152(1):166–169.
- Grotenherman F. Cannabis-associated arteritis. Vasa 2010 Feb;39(1):43–53.
- Peyrot I, Garsaud AM, Saint-Cyr I, et al. Cannabis arteritis: A new case report and a review of literature. J Eur Acad Dermatol Venereol 2007 Mar;21(3):388–391.
- Ducasse E, Chevalier J, Dasnoy D, et al. Popliteal Artery Entrapment Associated with Cannabis Arteritis. Eur J Vasc Endovasc Surg 2004;27:327–332.
- Lazarides MK, Georgiadis GS, Papas TT, et al. Diagnostic Criteria and Treatment of Beurger's Disease: A review. Int J Low Extem Wounds 2006;5(2):89–95.
- Olin JW, Young JR, Graor RA, et al. The changing spectrum of thromboangitis obliterans (Buerger’s disease). Circulation 1990;825(suppl):IV3–IV8.
- Sasaki S, Sakuma M, Kunihara T, Yasuda K. Distribution of arterial involvement in thromboangitis obliterans (Buerger’s disease): Results of a study conducted by the Intractable Vasculitis Syndromes Research Group in Japan. Surg Today 2000;30:600–605.
- Leithauser B, Langheinrich AC, Rau WS, et al. A 22-year-old woman with lower limb arteriopathy. Buerger's disease, or methamphetamine- or cannabis-induced arteritis? Heart Vessels 2005;20:39–43.
- Noel B, Ruf I, Panizzon RG. Cannabis arteritis. J Am Acad Dermatol 2008;58(Suppl 1):S65–67.
- Mills JL, Taylor LM Jr, Porter JM. Buerger’s disease in the modern era. Am J Surg 1987;154:123–129.
- Brodman M, Renner W, Stark G, et al. Prothrombotic risk factors in patients with thromboangitis obliterans. Throm Res 2000;99:483–486.
- Schneider HJ, Jha S, Burnand KG. Progressive Arteritis Associated with Cannabis Use. Eur J Vasc Endovasc Surg 1999;18;366–337.
- Adar R, Papa MZ, Halpern Z, et al. Cellular sensitivity to collagen in thromboangitis obliterans. N Engl J Med 1983 May;308(19):1113–1116.
- Eichhorn J, Sima D, Lindschau C, et al. Antiendothelial cell antibodies in thromboangitis obliterans. Am J Med Sci 1998 Jan;315(1):17–23.
- Karila L, Danel T, Coscas D, et al. Progressive cannabis-induced arteritis: A clinical thromboangitis obliterans sub-group? Presse Med 2004 Oct;33(Suppl 18):21–23.
From the 1Minneapolis Heart Institute, Minneapolis, Minnesota, 2Hennepin County Medical Center, Minneapolis, Minnesota.
The authors report no financial relationships or conflicts of interest regarding the content herein.
Manuscript submitted March 29, 2011, provisional acceptance given April 28, 2011, final version accepted April 28, 2011.
Address for correspondence: Jason Q. Alexander, MD, Minneapolis Heart Institute, 920 East 28th Street, Suite 300, Minneapolis, MN 55407. Email: firstname.lastname@example.org