Takayasu's arteritis and Crohn's disease: an unusual association

Abstracts

A arterite de Takayasu e a doença de Crohn são doenças inflamatórias com etiologia desconhecida. Raramente ocorrem de modo concomitante em um mesmo indivíduo, havendo menos de 30 casos relatados na literatura. Este trabalho descreve essa associação em uma paciente de 36 anos de idade portadora de doença de Crohn, que apresentou redução dos pulsos no membro superior esquerdo e pressão arterial de 60/40 mmHg. A angiotomografia evidenciou estenose segmentar de artéria subclávia esquerda e espessamento parietal circunferencial da aorta na transição toracoabdominal entre T10 e L1, estabelecendo o diagnóstico de arterite de Takayasu. Ambas as patologias são mediadas imunologicamente e apresentam granulomas e vasculite granulomatosa, o que contribui para reforçar a hipótese de uma origem imunológica comum no seu desenvolvimento. Acreditamos que este seja o primeiro caso relatado na literatura brasileira da presença concomitante destas duas enfermidades.

Doença de Crohn; doença de Takayasu; arterite de Takayasu; doença inflamatória intestinal

CASE REPORT

Takayasu's arteritis and Crohn's disease: an unusual association

Clóvis Konopka^I; Stela Karine Braun^II; Gabriela Machado^III

^IProfessor assistente, Cirurgia Vascular, Serviço de Cirurgia Vascular, Hospital Universitário de Santa Maria (HUSM), Santa Maria, RS

^IIAcadêmica de Medicina (6º ano), Universidade Federal de Santa Maria (UFSM), Santa Maria, RS. Monitora, Serviço de Cirurgia Vascular, HUSM, Santa Maria, RS

^IIIAcadêmica de Medicina (6º ano), UFSM, Santa Maria, RS

Correspondence

Abstract

Takayasu's arteritis and Crohn's disease are chronic inflammatory diseases with unknown etiology. They rarely occur together in the same individual, with less than 30 cases reported in the literature. This case report describes this association in a 36-year-old woman with Crohn’s disease and weak pulses in her left arm with blood pressure of 60/40 mmHg. Angiotomography showed segmental stenosis in the left subclavian artery and circumferential thickening of the aortic wall between T10 and L1, establishing the diagnosis of Takayasu's arteritis. Both are organ-specific and immune-mediated diseases and exhibit granulomas and granulomatous vasculitis, which contribute to reinforce the hypothesis of a common immunologic origin. We believe that this is the first case of concomitant presence of these two diseases reported in the Brazilian literature.

Keywords: Crohn's disease, Takayasu's disease, Takayasu's arteritis, inflammatory bowel disease.

Introduction

Takayasu's arteritis (TA) is a chronic inflammatory disease of medium and large diameter arteries, such as the aorta and its main arteries, especially near the aortic arch. It is found mostly in Asian women below the age of 40.¹ On occasion, TA has been reported as associated with inflammatory bowel disease (IBD).^1-15 The literature suggests a shared etiopathogenic mechanism, since the development of granulomas and granulomatous vasculitis in both Crohn's disease (CD) and TA could explain both conditions.² In this study, we report the case of a female patient, 36 years of age, who suffered from CD and developed TA. We believe this is the first case report in Brazilian literature of TA associated with CD.

Case report

The patient was female, 36 years old, white, with a history of chronic diarrhea, abdominal pain, and long-running fever. She was submitted to explorative laparotomy following an acute abdominal episode, with resection of a segment of the terminal ileum, cecum, and ascending colon. Histopathological analysis revealed fistulizing segmental enteritis suggestive of CD. After the surgery, the patient suffered occasional episodes of fever and had reduced pulse, with 60/40 mmHg blood pressure in the upper left limb, as well as systolic bruit in the epigastrium and left subclavian artery. All other peripheral pulses were normal. Angiographic tomography of the thoracoabdominal aorta and supra-aortic trunks showed segmental stenosis in the left subclavian artery and circumferential thickening of the aortic wall between T10 and L1 (emergence of celiac trunk), determining the narrowing of the aortic lumen to 0.9 cm (Figures 1 and 2). These data established the diagnosis of type III Takayasu's arteritis (Herrera classification.³ The patient had a sister, also diagnosed with CD.

Discussion

Also known as "pulseless disease", Martorell Syndrome, and occlusive thromboartopathy,⁴ TA is a rare form of vasculitis involving the thoracoabdominal aorta,¹ pulmonary arteries and coronary arteries,² either alone or in association. It can affect a localized arterial segment or a whole vessel.⁵ According to Herrera et al., TA can be categorized as:

- Type I - involvement limited to aortic arch and its branches;

- Type II - involvement of descending thoracic and abdominal aorta, without involvement of the aortic arch;

- Type III - simultaneous compromise of type I and type II structures (or mixed form);

- Type IV - involvement of any structural site of types I, II or III associated with compromise of the pulmonary artery.³

Like IBD, it is a chronic inflammatory disease of unknown origin.⁶ The first reported case was described by Yamamoto in 1830.⁷ TA has an incidence of 2.6 cases per million inhabitants per year in North America, predominantly women (> 80%) ages 3 to 35. Most patients are Asians, especially Japanese, though there may be universal distribution.²

The course of TA can be divided in two stages: at first, there are unspecific symptoms, such as night sweats,⁸ fever, arthralgia, myalgia, and anorexia;² next, there are arterial lesions such as stenoses, thromboses, and aneurisms, usually with absent or decreased pulse and other symptoms, depending on which arteries are involved. Segmental stenoses are often found in imaging examinations. Secondary hypertension is a frequent symptom, often secondary to coarctation of the aorta or stenosis of renal arteries (renovascular hypertension).² Systemic manifestations depend on the arteries involved and may include visual conditions, strokes, myocardial infarctions, dissection and aneurism of the aorta, renal infarctions, mesenteric ischemia, and peripheral vascular disease, especially of the upper limbs.⁸ Diagnosis of TA is based on clinical history, associated with imaging techniques or compatible histological findings in materials collected during surgery.⁹ The presence of bruits and lower peripheral pulses are the most frequent diagnostic characteristics.² When TA is suspected, computed angiographic tomography (CTA) is recommended for early diagnosis instead of angiography or magnetic angiographic resonance (MAR). CTA easily provides typical images of segmental narrowing of the arterial lumen and of circumferential thickening (stenoses).¹⁰ However, both CTA and MAR are useful for following up on this group of patients.⁸

CD is a chronic pathology and a cause of transmural inflammatory disease, primarily affecting the gastrointestinal mucosa. CD has an incidence of approximately two cases per 100,000 inhabitants, and prevalence of 50 cases per 100,000 with geographic and ethnic variation, most often found among Caucasian populations. The disease is more common among women, peaking at the age of 20 and later between the ages of 50 and 70.⁷

TA and IBD are rarely found together in the same patient. The first case reported in the literature was of a white female, 35 years of age, suffering from ulcerative rectocolitis (URC), admitted with fever, night sweats, arthralgia, and pleuritic chest pain. Aortography and biopsy revealed TA.^2,8 Since then, only 37 case reports from Japanese patients have described concomitant URC and TA.¹¹ Despite the description of various HLA haplotypes in patients suffering from both diseases, no clear genetic link has been found as of yet. In turn, the literature features only circa 29 cases of patients suffering from both TA and CD, with CD preceding TA in 88 percent of cases,⁷ increasing the likelihood that the latter is an extraintestinal manifestation of the former.^2,7

Unlike findings from cases involving URC, no shared HLA haplotypes were found for TA and DC.^2,8

Kerr et al. conducted a follow-up study of 60 TA patients, 97 percent of whom were women, with an average age of 25 for disease onset. Of the 60 patients, 7 percent had CD or URC.¹³ Reny et al. studied 44 TA patients, 4 of whom (9%) also had IBD (2 CD, 2 URC).¹² Both studies showed that IBD was found more often in TA patients than in the general population. In the study by Reny et al., TA diagnosis was made at the same time or following the diagnosis of CD in 87 percent of cases,¹² like in the patient in this study.

The onset of granulomas and granulomatous vasculitis in TA and CD is probably the consequence of an etiopathogenic mechanism shared by both diseases.² Focal granulomatous vasculitis has been reported in intestinal segments of CD patients. In TA patients, the primary histopathological findings are mononuclear cells and granulomatous infiltration of the vasa vasorum of the aortic wall.⁸

Maksimowicz-Mckinnon & Hoffman¹⁴ have pointed to the many similarities between TA and CD, despite the differences in presentation between the two. Both are common in young women, occurring most often during the third decade of life. The pathogenesis of both predominantly includes granulomatous inflammation, Th1 lymphocytes, proinflammatory cytokines like tumor necrosis factor (TNF) alpha and interleukins (IL).^7,14 Biopsies of CD ulcers show granulomas and well-defined vasculitis, suggesting that vasculitis may be an important pathogenic mechanism for CD.

Given the inflammatory nature of CD as well as TA, the therapy for both should be similar. Treatment for TA consists of using high doses of corticosteroids, with approximately 60 percent of patients responding favorably to this course. In resistant TA cases, one can use immunosuppressants, the most common of which is cyclophosphamide. However, 23 percent of patients do not respond to either kind of drug treatment.² In the last few years, tumor necrosis factor inhibitors (TNF-I) have been used, the most common of which is Infliximab.² Recently, a study assessed the effect of a combination of azathioprine and prednisolone on TA, showing that the combination effectively controls systemic symptoms and disease activities.¹⁵ Therefore, the drugs used in treating TA and CD are usually the same. Thus far, there has been no randomized study of therapies for the association of both diseases; therefore, there is no consensus treatment for TA concurrent with CD.¹⁶

Revascularization, either vascular or through percutaneous transluminal angioplasty, is recommended in cases of ischemia unresponsive to initial drug treatments.^2,8 However, performing the intervention in periods of disease remission is crucial for minimizing the risk of restenosis.²

In conclusion, both TA and DC are chronic inflammatory diseases and apparently share a single etiopathogenic mechanism. According to the literature, association of TA and CD is highly unusual; this is the first report of an association of the two diseases to appear in Brazilian literature.

References

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Publication Dates

• Publication in this collection
  11 Sept 2009
• Date of issue
  Dec 2009

History

• Received
  11 May 2009
• Accepted
  15 June 2009