Takayasu’s arteritis associated with Crohn’s disease: a case report and literature review

Abstract

Takayasu’s arteritis and inflammatory bowel disease are rarely found together, although the number of cases reported in the literature is increasing. Takayasu’s arteritis has been studied in 31 patients from the Arab world but in none of them was it associated with Crohn’s disease. We report the case of a Saudi woman previously diagnosed with Crohn’s disease who subsequently developed Takayasu’s arteritis, which may represent one of many extra-intestinal manifestations of inflammatory bowel disease. The possible aetiological factors, diagnostic methods, differential diagnoses and common pathophysiological mechanisms of the two diseases are discussed. This is the first case report of these two diseases in an Arab patient.

BACKGROUND

Takayasu’s arteritis and Crohn’s disease are chronic granulomatous inflammatory processes involving different target organs, namely the large elastic arteries and the gastrointestinal tract, respectively. The coexistence of both diseases is described in the literature in 29 case reports, in 88% of which Crohn’s disease preceded Takayasu’s arteritis, raising the possibility that it could be regarded as an extra-intestinal manifestation of Crohn’s disease.¹ Thirty one cases of Takayasu’s arteritis have been previously reported from the Arab world, but our case the first combining both diseases.

CASE REPORT

A 30-year-old Saudi woman was seen first at a surgery clinic with symptoms of abdominal pain, diarrhoea mixed with mucus and blood, and anal pain. Examination revealed a chronic anal fissure which was treated with lateral internal closed sphincterotomy. The patient was referred to a gastroenterology clinic where she was investigated for possible inflammatory bowel disease. Colonoscopy showed multiple aphthous ulcers mainly in the left sided colon and rectum. Biopsies revealed mild active chronic non-specific colitis. Barium small bowel follow-through showed the terminal ileum with multiple cobblestone filling defects suggestive of mucosal oedema.

As the findings were mostly consistent with Crohn’s disease, the patient was started on budesonide 9 mg once a day, azathioprine 50 mg once a day and mesalazine 1 g three times a day. She responded rapidly to the treatment with the disappearance of all her symptoms. When treatment stopped after 1 year, she had recurrence of her symptoms with the additional finding of a perianal fistula.

A second colonoscopy showed a severely inflamed (fig 1) ileo-cecal valve. There was ulceration and narrowing of the terminal ileum, although the remainder of the colon was normal. Biopsies showed acute inflammation of the terminal ileum with granulation tissue (fig 2); colon biopsies were normal. Follow-up small bowel follow-through revealed a persistent area of narrowing of about 5 cm proximal to ileo-cecal valve and possibly post-inflammatory. Computed tomography scan of the abdomen showed terminal ileal thickening and perirectal inflammation. The Mantoux test was negative and a chest x ray was normal. The patient was started on induction treatment with infliximab 5 mg/kg at 0, 2 and 6 weeks. Follow-up during this period revealed resolution of disease activity and healing of the perianal fistula. However, following the fourth dose of infliximab, the patient had an anaphylactic reaction with dyspnoea, pain in the right arm and generalised erythema which ceased when the drug was stopped and hydrocortisone was injected. It was decided to re-evaluate the patient at a later date to see if she could resume taking infliximab. Three months after the infliximab anaphylaxis she was admitted to hospital and found to have a perianal abscess, fever, weight loss, night sweats, right arm intermittent claudication and wrist pain which was severe at times. Her clinical examination showed a weight loss of 3 kg, a perianal abscess, absent right radial pulse and absent right brachial pulse with un-recordable blood pressure in the right arm. There were no features of arthritis or uveitis. Her blood investigations showed white cell count 8.4×10⁹/l, haemoglobin 11.4 g/dl, platelet count 393×10⁹/l, ESR 92 mm/h and C-reactive protein 50 mg/l. Liver function tests, renal function tests, thyroid function tests and lipid profile were normal. A 24-h urine collection showed creatinine of 7.3 mmol/day, creatinine clearance of 70 ml/min and albumin of 6 mg/day. Autoimmune screening showed anti-nuclear antibody (ANA) titre of 1/320 speckled pattern and anti-DNA 15.4 U/ml, while p-ANCA and c-ANCA were negative. Magnetic resonance angiography showed complete occlusion of the right subclavian artery and partial occlusion of the left subclavian artery suggestive of Takayasu’s arteritis (fig 3). Subsequently, angiography showed an occluded right subclavian artery after the origin of the right vertebral and internal mammary artery (fig 4). Multiple collaterals from the cervico-thoracic trunk had grown to fill the distal portion of the axillary artery which was faintly opacified. Carotid angiogram demonstrated no significant stenosis although there were small plaques at the origin of the internal carotid arteries. Intra-cranial circulation on both sides including posterior circulation through the right vertebral artery showed no abnormality. Both vertebral arteries were patent with normal origin.

Figure 1.

Colonoscopy showing severe Crohn’s ileitis with the ileo-cecal valve severely inflamed with ulcers and narrowing of the terminal ileum.

Figure 2.

Terminal ileal biopsies showed acute inflammation of the terminal ileum with granulation tissue.

Figure 3.

Magnetic resonance angiography showing complete occlusion of the right subclavian artery and partial occlusion of the left subclavian artery suggestive of Takayasu’s arteritis.

Figure 4.

Angiography showing an occluded right subclavian artery after the origin of the right vertebral and internal mammary artery.

Abdominal aortogram also showed normal origins of both renal arteries. Echocardiography showed normal left and right ventricle function with ejection fraction of 60% and no valvular lesion. Based on magnetic resonance angiogram findings of Takayasu’s arteritis, the patient was started on prednisolone 60 mg/day and methotrexate 10 mg/week. She showed an impressive clinical response with general clinical and biochemical well-being. She was discharged on a tapering dose of oral prednisolone over 6 weeks and methotrexate 10 mg/week. She was advised to continue anticoagulant and antiplatelet medications.

DISCUSSION

Takayasu’s arteritis is a granulomatous panarteritis of the aorta and its major branches.² It is extremely rare in North America and is found most commonly in young Asian women under 40 years of age.³ It has a worldwide distribution with the greatest prevalence in Asian populations.^4,5 It has been estimated that 150 new cases occur each year in Japan.⁶ The cases of 31 patients from the Arab world with Takayasu’s arteritis have been reported and to the best of our knowledge ours is the first reported case of Takayasu’s arteritis and Crohn’s disease in a Saudi woman.

Although Takayasu’s arteritis classically presents with an absent radial pulse because of subclavian arteritis, early symptoms include fever, night sweats, arthralgia and myalgia,² which may be described as stage 1 (constitutional symptoms are common in stage 1 of the disease). In an NIH (National Institute of Health) series including 60 patients observed over 20 years, only 33% of patients had constitutional symptoms and the mortality rate was 3%. Stage 2 is a vascular inflammatory stage in which stenosis, aneurysm and vascular pain tend to occur.

Symptoms vary depending upon the involvement of specific arteries. The disease mainly involves the large and medium sized arteries, especially the aorta and its branches. The vascular stage is characterised by arm claudication, blurred vision, amaurosis fugax, strokes, transient ischaemic attacks and seizures. The third stage is the burned out stage when fibrosis sets in. Anti-endothelial cell antibodies are frequently present in Takayasu’s arteritis and perhaps play a role in its pathogenesis.⁷ Various HLA haplotypes are seen in patients with both diseases, although a direct genetic linkage has not been found. In Asians Takayasu’s arteritis was associated with HLA-A31, B52, B39, B5 and DR2, in Arabs with HLA-A2, A9, B35, and DR7, in North Americans with HLA-DR4 and in Mexicans with HLA-B5, B52 and DR6.⁸ Aortography revealing the abnormal dilatation and stenosis of the aorta and its major branches, is diagnostic,² although the useful contribution of duplex Doppler is highlighted in a study by Todini et al.⁹ Arterial revascularisation by vascular surgery or angioplasty with stenting may be required depending upon the amount of stenosis, but the mainstay of treatment is a tapering dose of steroids with cytotoxic agents.

The association of Takayasu’s arteritis and Crohn’s disease has been reported in the literature in 29 cases, in 88% of which Crohn’s disease preceded Takayasu’s arteritis. The expected chance prevalence of Crohn’s disease in patients with Takayasu’s arteritis is approximately 0.05%–0.2%. The distribution of vascular lesions in both diseases appears to be the same.¹⁰ Wakefield et al examined the resected intestines of patients with Crohn’s disease and found evidence of granulomatous vasculitis in 15 of 24 patients.¹¹

This case highlights some important findings, and a failure to recognise them could lead to misdiagnosis. The presenting features of abdominal pain, chronic diarrhoea and intermittent per rectal bleeding could be common to both Crohn’s disease and Takayasu’s arteritis. A history of chronic anal fissure and the development of a perianal fistula favours Crohn’s disease. Computed tomography scan and barium follow-through is usually normal in arteritis or may show non-specific changes such as bowel wall oedema, but our patient had narrowing of the terminal ileum with a cobblestone appearance which also suggests Crohn’s disease. The colon biopsies taken at the first and second colonoscopies showed chronic active inflammation of the colon and acute inflammation of the terminal ileum with granulation tissue, respectively. The absence of ischaemia, microthrombi or aneurysmal dilatation of the capillaries makes arteritis less likely as a cause of intestinal problems. Takayasu’s arteritis most often affects the aorta and its branches; the splanchnic vessels are rarely involved. The fact that the colon ulcers seen on the first colonoscopy were not found in the subsequent colonoscopy is attributed to the treatment for Crohn’s disease and in particular azathioprine.

The interval between the diagnoses of Crohn’s disease and Takayasu’s arteritis in our patient was 1 year. During this time the patient was given infliximab for Crohn’s disease (which had a severity index score of more than 300) and also because of the perianal fistula. When she developed anaphylaxis following the fourth dose of infliximab she was followed up closely in the outpatient department and it was discovered that she had persistent right shoulder and right wrist joint pain. This was thought to be arthralgia related to Crohn’s disease or possibly underlying lupus erythematosus related to infliximab induced antinuclear antibody. However, it was unclear how the joint pains were related to infliximab, and indeed a pilot study of relapsing Takayasu’s arteritis demonstrated that the addition of anti-TNF therapy resulted in improvement in 14 of 15 patients and sustained remission in 10 of 15 patients.¹² Following elective admission to hospital, investigation revealed that the patient’s joint pains could be due to claudication, especially as the patient had no blood pressure recordings at the right arm and an absent right radial pulse. The results of these investigations led to the diagnosis of Takayasu’s arteritis. It is important to recognise arthritis as an extra-intestinal manifestation of inflammatory bowel disease and claudication as secondary to vascular stenosis for early identification of the disease: the history of right wrist and arm pain in his patient might have been overlooked if it had been attributed to the usual arthritis associated with Crohn’s disease. Although infliximab has revolutionised the treatment of Crohn’s disease, its use can be complicated by adverse reactions. However, in several placebo controlled randomised clinical trials, acute and long term infusion reactions showed the development of autoantibodies in less than 10% of patients and drug induced lupus was seen in less than 1%. In our patient, the development of antinuclear antibody, anti-DNA, high ESR and mildly increased CRP initially suggested infliximab induced lupus but a simple clinical examination revealed the absent pulse which lead to radiological investigations.

LEARNING POINTS

• Takayasu’s arteritis and Crohn’s disease may coexist in the same patient.

• The natural history of Takayasu’s arteritis may present as an extra-intestinal manifestation of inflammatory bowel disease.

• Early diagnosis of vascular lesions in patients with Crohn’s disease is encouraged to rule out Takayasu’s arteritis.

• High clinical suspicion with complete physical examination, proper imaging and consideration of the differential diagnosis are important for the correct diagnosis and management of patients with both Takayasu’s arteritis and Crohn’s disease.