Simultaneous Presentation of Takayasu Arteritis and Crohn’s Disease in a Middle-Aged Patient: Are they two sides of the same coin?

Abstract

Autoimmune disorders have a wide spectrum of symptoms, often with multiorgan involvement. Multiple autoimmune disorders also often occur concurrently in the same patient. These two possibilities must be distinguished in patients with multiorgan involvement to ensure early diagnosis and treatment. Here, we report a case of a previously healthy man who presented with simultaneous Takayasu arteritis and Crohn’s disease. He presented with heart failure with reduced ejection fraction and severe aortic regurgitation. An echocardiogram demonstrated a greatly dilated aorta, and a diagnosis of Takayasu arteritis was made, confirmed with CT aortogram. Inpatient treatment was begun, but the patient subsequently developed bloody diarrhoea a few days after admission. Colonoscopy done to locate the source of bleeding showed colonic ulcers; a biopsy confirmed a diagnosis of Crohn’s disease. The patient was successfully managed with medical management of heart failure, steroids, mesalamine and azathioprine, and has been in remission for the last 2 years.

Background

Crohn’s disease (CD) is an inflammatory bowel disease (IBD), which can present at any age; its prevalence and incidence are increasing worldwide, particularly in developed countries.^1–4 Diarrhoea and abdominal pain are the most common presenting symptoms, although the patient can also present with non-specific signs of systemic inflammation such as fever, weight loss, fatigue and anorexia.^{1 4} Although it primarily affects the colon and terminal ileum, up to 40% of patients⁵ with CD have been reported to experience extraintestinal manifestations of the disease; this can include dermatological, musculoskeletal, hepatopancreatobiliary and renal involvement.2 3 6 7 Though several types of vasculitis have been noted as an uncommon complication of pre-existing IBD on treatment,⁸ it is much rarer for Takayasu arteritis and CD to present simultaneously, as it did in our patient.

Takayasu arteritis is a large vessel idiopathic granulomatous vasculitis that affects women more than men⁹ and largely involves the aorta and its major branches.^{10 11} It causes arterial inflammation, with thickening of the wall and lymphocytic infiltration of the arterial media, and can lead to intimal thickening, fibrosis, stenosis and thrombus formation.^{12 13} It can also present with extravascular involvement causing oral ulcers, arthritis and sacroilitis.¹⁴

Case presentation

A man in his late 30s presented to our general medicine out-patient department with complaints of progressive cough and breathlessness for the last 10 days. He had no associated of fever or chest pain. He had no previously diagnosed comorbidities. There was no significant medical history in his immediate family. On examination, he was conscious, cooperative and well oriented to time, place and person. His pulse was 78 beats per minute, blood pressure 190/90 mm Hg in the right brachial artery and 176/80 mm Hg in the left brachial artery, the respiratory rate was 22 cycles per minute, SpO2 was 99% and was afebrile. Head to toe examination revealed no pallor, icterus, cyanosis, clubbing or pedal oedema. No vascular bruit was auscultated. Respiratory, abdominal and neurological examinations were within normal limits. Cardiovascular examination revealed a high-volume collapsing pulse in the right radial artery, symmetric pulses, cardiac apex palpable in the left sixth intercostal space in the midclavicular line and parasternal heave. Suprasternal pulsations and P2 were also palpable. On auscultation, a grade 3 ejection systolic murmur and an early diastolic murmur were audible in the aortic area. The patient was admitted for symptomatic treatment and further evaluation.

Initial lab investigations on admission (table 1) were significant for elevated white cell count of 14.1x10⁹ cells/L and an elevated erythrocyte sedimentation rate (ESR) and C reactive protein (CRP). In view of the patient’s symptoms, along with the cardiovascular findings, an echocardiogram was performed. The echocardiogram showed a globally hypokinetic left ventricle, with severe left ventricular systolic dysfunction and an ejection fraction of 34%, suggestive of heart failure with reduced ejection fraction. The aortic root, arch, descending aorta, thoracic aorta and abdominal aorta showed significant dilatation with no dissection flap, and severe aortic regurgitation was present. Syphilis and systemic lupus erythematosus were ruled out as a cause by negative Treponema pallidum haemagglutinin test and negative antinuclear antibodies, respectively. Echocardiogram findings, coupled with an elevated ESR narrowed down the provisional diagnosis to Takayasu arteritis. CT aortogram (CTA) (figure 1) was done to confirm the diagnosis—this study confirmed the echocardiogram findings, and measured the maximum calibre of the aorta to be 4.9 cm at the ascending aorta. In addition, mild cardiomegaly was noted, and circumferential mild irregular wall thickening along the entire length of the aorta with underlying intimal wall calcifications, which are features likely suggestive of changes secondary to aortoarteritis/early onset atherosclerosis. Ophthalmology consult was sought to rule out uveitis as a complication of Takayasu arteritis. The patient was given intravenous diuretics, hydralazine, isosorbide dinitrate, digoxin and ivabradine for symptomatic management of his heart failure.

Table 1.

Baseline investigations on admission

Test	Result	Reference range
Haemoglobin	10.7	13.0–17.0 g/dL
WCC	14.1	4-10x109/L
Platelets	373	150-400x109/L
ESR	39	0–20 mm/hour
CRP	56.75	0–5 mg/L
Urea	35	10–40 mg/dL
Creatinine	1.57	0.7–1.2 mg/dL
Sodium	135	136–145 mol/L
Potassium	4.9	3.5–5.1 mol/L

CRP, C reactive protein; ESR, Erythrocyte Sedimentation Rate; WCC, white cell count.

Figure 1.

CT aortogram showing significant dilation of the aortic root, arch, descending aorta, thoracic aorta and abdominal aorta, circumferential mild-irregular wall thickening along the entire length of the aorta and underlying intimal wall calcifications.

While the treatment was ongoing, the patient had new-onset painful bleeding per-rectum. Repeat blood investigations (table 2) at this time showed a drop in his haemoglobin from 10.7 g/dL on admission to 6.4 g/dL during this period. In view of this, the patient was transfused with 2 pints of cross-matched packed red blood cells, post which his haemoglobin rose to 8.5 g/dL. Local causes for rectal bleeding such as anal fissure, anal polyps were ruled out, and thus the decision was made to perform a colonoscopy to further evaluate for the source of the bleeding. The colonoscopy showed the presence of discrete punched out ulcers scattered through the rectum and entire colon, measuring 4–5 mm and covered with whitish slough, with a few of the ulcers appearing linear with hyperaemic edges. The terminal ileum showed a few discrete ulcers, while the proximal ileum appeared normal. Biopsies were taken from the terminal ileum and colonic ulcers for histopathological examination and to rule out tuberculous aetiology. Negative reverse transcription PCR (RT-PCR) for Mycobacterium tuberculosis ruled out tuberculosis. Histopathology (figure 2) showed foci of ulcerated mucosa with crypt disarray, focal mucin depletion, cryptitis, crypt abscesses and occasional small aggregates of epithelioid histiocytes with no dysplasia, confirming a diagnosis of CD. The patient was treated for the same with mesalamine and azathioprine. The patient was also started on prednisolone 1 mg/kg/day to treat his aortitis.

Table 2.

Investigations on day 6 of admission

Test	Result	Reference range
Haemoglobin	6.4	13.0–17.0 g/dL
WCC	18.3	4-10x109/L
Platelets	305	150-400x109/L
Urea	42	10–40 mg/dL
Creatinine	1.5	0.7–1.2 mg/dL
Sodium	131	136–145 mol/L
Potassium	3.6	3.5–5.1 mol/L

WCC, white cell count.

Figure 2.

Biopsy of terminal ileum and colonic ulcers—histopathology (H&E, ×400). (A) Microgranulomas composed of aggregates of epitheloid cells. (B) Focus of ulceration with dense mixed inflammatory infiltrate. (C) Cryptitis and dense mixed inflammatory cells in the lamina propria (arrow)

The patient experienced a satisfactory remission of his cardiovascular and gastrointestinal symptoms and was discharged on oral medications and monthly follow-up to monitor for recurrence of symptoms and early detection of multiorgan involvement. Blood investigations on discharge are listed in table 3.

Table 3.

Investigations on discharge

Test	Result	Reference range
Haemoglobin	9.0	13.0–17.0 g/dL
WCC	14.6	4-10x109/L
Platelets	351	150-400x109/L
Urea	31	10–40 mg/dL
Creatinine	1.0	0.7–1.2 mg/dL
Sodium	133	136–145 mol/L
Potassium	3.6	3.5–5.1 mol/L

WCC, white cell count.

Differential diagnosis

Tuberculosis was considered as a potential aetiology that could explain both the patient’s aortitis and colonic ulceration, especially in the setting of a tuberculosis-endemic region. It was ruled out by means of a negative RT-PCR for M. tuberculosis in a biopsy sample from the patient’s colonic ulcers.

Tertiary syphilis was considered as a cause of his aortitis—it was effectively ruled out by negative T. palladum haemagglutinin test.

Systemic lupus erythematosus was also considered as a cause of the aortic dilation and signs of systemic inflammation (elevated C-Reactive Protein and Erythrocyte Sedimentation Rate)—it was ruled out through negative antinuclear antibody tests.

Behcet’s disease was ruled out due absence of recurrent oral and genital ulcers which are typical of the disease. Our patient also had no evidence of uveitis, which is a common complication of this disease.

Treatment

The patient’s aortitis was treated with oral prednisolone 1 mg/kg/day, and the patient was monitored for any adverse reactions. Prior to initiating steroids, Mantoux test was performed to rule out latent tuberculosis and prevent reactivation of the same. The patients CD was treated with mesalamine and azathioprine.

Post-treatment, the patient was symptomatically better and was discharged on oral digoxin, hydralazine, isosorbide dinitrate, Fruselac (furosemide+spirinolactone), atorvastatin, mesalamine, azathioprine and prednisolone 50 mg.

Outcome and follow-up

The patient symptomatically improved with the given medication and was discharged from the hospital. His symptoms have been well controlled with the prescribed medication, and he is currently on monthly outpatient follow-up to monitor for symptom recurrence and multiorgan involvement. He has been compliant with his medication and has had no exacerbations of CD or Takayasu arteritis since discharge. CT angiogram was repeated 2 years after diagnosis during routine follow-up—it showed no significant disease progression (the diameter of the ascending aorta appeared to be within normal limits, while the descending aorta was mildly dilated at 4.7 cm). CRP measured at this time was normal at 1.52 mg/L.

Discussion

Takayasu arteritis is a large vessel vasculitis which causes granulomatous inflammation of the aorta and its branches. It has a worldwide incidence of 1–2 per million and is much more common in females (9:1).⁹ Characteristic features of Takayasu arteritis (TA) include diminished/absent pulses, vascular bruits, hypertension, Takayasu retinopathy, aortic regurgitation as a consequence of dilation of ascending aorta, congestive cardiac failure and other symptoms such as dyspnoea and headaches.¹² Common extravascular manifestations include arthritis, sacroilitis and oral ulcers.¹⁴ The gold standard for diagnosis of TA was angiography; currently CTA Angiography is being used as a non-invasive method of initial staging.^{9 12} Histological diagnosis is generally impractical, given the vessels involved.¹²

CD causes a similar granulomatous inflammation of the colon and terminal ileum. It usually presents with abdominal pain and diarrhoea, along with signs of systemic inflammation (fever, fatigue, weight loss).^{1 4} Extraintestinal manifestations occur in up to 40% of patients, involving dermatological, musculoskeletal, hepatopancreatobiliary and renal systems. Pericarditis is the most common cardiovascular symptom, though myocarditis, thromboembolism, arteriovenous block, endocarditis and Takayasu arteritis can also occur.¹⁵ Ileocolonoscopy is the first procedure to establish a diagnosis; biopsies can be taken during the procedure to histologically confirm the diagnosis.¹⁶

While CD is a relatively common disorder, Takayasu arteritis is uncommon, and it is very rare to see both diseases presenting simultaneously in the same patient. A review of the literature revealed few reported cases of the coexistence of both disease in patients, with the earliest reported case dating back to the 1970s.¹⁷ In most of these reported cases, the diagnosis of CD preceded that of TA by several months to years,^18–25 and the IBD was in remission at time of vasculitis onset.⁸ Most of the reported patients also presented with non-specific signs of inflammation, fever, weight loss and anorexia. Very few cases have been reported where a diagnosis of TA preceded that of Crohn’s disease,^{26 27} or where both have presented simultaneously.^27–30 Our case is rare in that the initial presenting symptom was vascular, with onset of gastrointestinal symptoms within a week of admission. Most literature reports cases in female patients, with less reported occurrence in male patients^{26 30}—an expected finding due to the higher association of both diseases with the female gender.²⁸

Many of the authors of previously reported cases of concurrent CD and Takayasu arteritis have suggested that both diseases could share a common aetiology. HLA-B*52:01 and IL12B have been suggested to be common in TA and IBD by several studies.²⁸ Both diseases are granulomatous in nature and have a cell mediated autoimmune component in their pathogenesis.^{5 12} An infectious cause due to M. tuberculosis has also been considered, though there is no direct evidence supporting this theory.^{31 32}

The possibility of a common genetic pathway of pathogenesis suggests that similar treatments may be effective.²⁸ There are overlaps in pharmacological treatment guidelines for CD and Takayasu arteritis—steroids, disease-modifying antirheumatic drugs and biological medications including tumour necrosis factor inhibitors.²⁹ Surgical intervention may be required for patients with significant vascular disease. There are reported incidents of similar patients requiring vascular interventions—angioplasty of the left renal artery for stenosis, axillary artery bypass, saccular aneurysm of descending aorta requiring repair and a haemodynamically significant aortic valve insufficiency necessitating valve replacement.2 10 28 30 However, most patients improve with medical management as our patient did, and surgical intervention is usually unnecessary.²⁸

Learning points.

• Symptoms of autoimmune disorders can often overlap, and multiorgan involvement of one autoimmune disorder must be differentiated from the concurrent presence of a second disorder.

• Though most patients with Crohn’s disease and Takayasu arteritis concurrently or individually are young females, these disorders can also occur in atypical patient populations. Our patient was a male in his 30s—while this is a typical patient demographic for Takayasu arteritis, it is not for Crohn’s disease. Thus, a high degree of suspicion should be maintained to enable early diagnosis to prevent complications and morbidity.

• CT aortogram should be performed early when the index of suspicion for Takayasu arteritis is high to allow for early diagnosis and treatment initiation.

• Tuberculosis should be ruled out as an infectious cause, especially in tuberculosis-endemic regions of the world.

• Prompt initiation of treatment can cause complete resolution of symptoms, and medication adherence can induce prolonged remission, as seen in our patient.

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