Carotidynia as the First Manifestation of Takayasu Arteritis: Report of Two Cases and a Brief Review of Literature

Abstract

Carotidynia is a neck pain syndrome characterized by tenderness at the carotid bifurcation secondary to various aetiologies. We describe two young females who presented with carotidynia and on evaluation were diagnosed with Takayasu arteritis. Carotidynia in a young female should alert the clinician to evaluate for Takayasu arteritis.

Introduction

Carotidynia is a rare idiopathic syndrome characterized by neck pain with tenderness at the carotid bifurcation. The causes of carotidynia are broad ranging from infection, malignancy, dissection, arteriosclerosis and large vessel vasculitis and patients may initially present to primary care physicians or otorhinolaryngologists [1]. Takayasu arteritis is a large vessel vasculitis which typically affects young females of Asian ethnicity and involves the aorta with its large branches like the subclavian artery. Occasionally the vasculitic process can involve the carotid arteries leading to inflammation and subsequent tenderness on palpation [2]. Carotidynia as the first manifestation of Takayasu arteritis is rare. We aim to describe two young females who presented with carotidynia which was treated elsewhere as bacterial pharyngitis. On further evaluation, both patients were diagnosed with Takayasu arteritis. We have also done a brief literature review on carotidynia as the presenting feature of Takayasu arteritis.

Case 1

A 36-year-old female presented with anterior neck pain, fatigue and low-grade fever for 1 month duration. In view of the neck discomfort, neutrophilic leucocytosis and elevated C- reactive protein (CRP) during initial evaluation, she was treated with oral amoxicillin/clavulanic acid combination as a case of bacterial pharyngitis elsewhere. However, her symptoms persisted and over the next three weeks, she received multiple courses of oral antibiotics and underwent an ultrasound study of neck with doppler which showed wall thickening of bilateral carotid arteries with adjacent inflammatory changes. At this point, she was referred to our centre to evaluate for large vessel vasculitis. Clinical examination revealed tenderness at bilateral carotid artery bifurcation. All peripheral pulses were palpable and there was no vascular bruit. Laboratory investigations revealed normocytic normochromic anaemia, neutrophilic leucocytosis and thrombocytosis with elevated ESR and CRP (Table 1). In view of bilateral carotidynia in a young female, with evidence of systemic inflammation, a diagnosis of pre pulseless phase of Takayasu arteritis was considered. CT aortogram showed diffuse wall thickening involving bilateral common carotid and brachiocephalic trunk confirming diagnosis of Takayasu arteritis Type IIA (Fig. 1A). She was started on 1 mg/kg oral prednisolone and oral methotrexate 15 mg/week. She showed a good clinical response with normalization of ESR and CRP and is currently on tapering doses of oral prednisolone and 25 mg/week oral methotrexate as steroid sparing agent.

Table 1.

Laboratory characteristics of the patients on admission

Parameter	Case 1	Case 2	Normal reference range
Hemoglobin	9.8	9.4	13.5–17.5 g/dl
Total leukocyte count	13,600	14,400	4000–11,000 cells/mcl
Differential leukocyte count	P82 L16 E1 M1	P80 L18 M2	P 40–60% L 20–40% M 2–8% E 1–4%
Platelet count	6.12	5.94	1.5–5.5 lakh
Blood urea	16	18	7–20 mg /dL
Serum creatinine	0.7	0.6	0.4–1.4 mg/dl
Total bilirubin	0.8	0.7	< 1 mg/dl
Direct bilirubin	0.2	0.2	< 0.4 mg/dl
Total protein	7.6	7	6–8 g/dl
Serum albumin	3.4	3.8	3.5–5.5 g/dl
AST/ALT	10/12	19/20	(8-45U/L)/ (7-56U/L)
Serum alkaline phosphatase	128	98	44–147 IU/L
Serum sodium	138	140	135–145 mEq/L
Serum potassium	4.2	3.8	3.5–5.5 mEq/L
ESR	78	96	0–22 mm/hr
CRP	64	50	0–6 mg/L
Peripheral blood smear	Normocytic normochromic anemia, neutrophilic leukocytosis, thrombocytosis	Normocytic normochromic anemia, neutrophilic leukocytosis, thrombocytosis

g/dl-gram per decilitre, mcl-microlitre, AST-Aspartate amino transferase, ALT-Alanine amino transferase, IU/L-international units per litre, U/L-Units per litre, mEq/L-milli equivalents per litre, mm/h-millimeter per hour, mg/L-milli gram per litre, ESR- erythrocyte sedimentation rate, CRP- C-reactive protein, P-Polymorph, L-Lymphocyte, E-eosinophil, M- monocyte

Abnormal values are indicated in bold

Fig. 1.

CT aortogram images of the patients

(A): Axial images of CT aortogram showing diffuse wall thickening of bilateral common carotid arteries denoted by blue arrows in case 1

(B): Axial images of CT aortogram in case 2 showing diffuse wall thickening of bilateral common carotid arteries denoted by yellow arrows

Case 2

A 30-year-old lady presented with anterior neck pain which aggravated with swallowing, weight loss and low-grade fever for 8 months duration. She had received multiple courses of oral antibiotics elsewhere with a diagnosis of bacterial pharyngitis/pharyngotonsillitis. Three months before admission at our centre, she developed claudication pain in left upper limb. She was referred to us a case of pyrexia of unknown origin. On review of her past records there were multiple reports of neutrophilic leucocytosis, thrombocytosis and elevated acute phase reactants which persisted despite numerous courses of antibiotics. Upon examination she had tenderness at the bifurcation of bilateral carotids. The left radial artery and bilateral subclavian artery pulse was not palpable. There was unequal blood pressure in bilateral upper limbs. Laboratory investigations showed evidence of active vasculitis in the form of neutrophilic leucocytosis, thrombocytosis, elevated ESR and CRP (Table 1). CT aortogram showed diffuse wall thickening of bilateral common carotid arteries and long segment narrowing and thickening of left subclavian artery (Fig. 1B). Hence a diagnosis of Takayasu arteritis type IIA was made and she was initiated on 0.5 mg/kg oral prednisolone and mycophenolate mofetil. She showed good clinical response and is currently on 5 mg oral prednisolone and 2 g/ day of oral mycophenolate mofetil.

Discussion

Takayasu arteritis is a large vessel vasculitis with two phases- pre pulseless phase and pulse less phase. The pre pulse less phase is characterized by non-specific symptoms like fatigue, fever, weight loss, and myalgia, often associated with elevated acute phase reactants. The pulseless phase is due to the chronic vascular inflammation leading to stenosis/occlusion of vessel characterized by symptoms like claudication pain in limbs, unequal pulse and blood pressure, vascular bruit, renovascular hypertension, abdominal angina, ischemic retinopathy and stroke [3].

Carotidynia is a neck pain syndrome with tenderness at the bifurcation of carotid and the pain is usually felt unilaterally as a dull aching or throbbing pain which may be aggravated by coughing, swallowing or head movements. The differential diagnosis for carotidynia includes infections of oral cavity and oropharynx, head and neck neoplasms, trigeminal neuralgia, carotid dissection and large vessel vasculitis [4]. Though carotidynia is seen in around one third of patients with Takayasu arteritis, carotidynia as the presenting manifestation is extremely rare [5]. Maita et al. [6] reported a 51-year-old lady with anterior neck pain of 1 month duration followed by development of fever of unknown origin, liver dysfunction and anemia. The patient had received acetaminophen and levofloxacin from elsewhere without improvement. FDG PET showed abnormal uptake in bilateral common carotid artery and other large branches of aorta leading to a diagnosis of Type 5 Takayasu arteritis. Patient showed clinical improvement with oral prednisolone 30 mg. Zeina et al. [7] described a 41-year-old lady with recurrent anterior neck pain for a year which did not improve with non-steroidal anti-inflammatory drugs and antibiotics. She had tenderness over carotid bifurcations, raised inflammatory markers and magnetic resonance angiography (MRA) showed significant tubular stenosis of both common carotid arteries and proximal segment of left subclavian artery consistent with a diagnosis of Takayasu arteritis. She was initiated on glucocorticoids which led to clinical improveent. Maruyama et al. [8] reported a 15-year-old girl with left neck pain, fever and raised CRP and ESR. MRA showed thickening of left carotid artery and FDG PET showed uptake in left carotid artery, ascending aorta, arch of aorta, descending and abdominal aorta establishing a diagnosis of Takayasu arteritis in pre-pulseless phase. The patient was initiated on prednisolone which led to improvement of clinical and laboratory parameters. Yadava et al. [9] described a 31-year-old female with left sided neck pain and headache for a month and on evaluation MRI neck with contrast revealed hyperintensity and postcontrast enhancement surrounding the distal left common carotid, at the left carotid bifurcation, and proximal left internal carotid leading to a diagnosis of Takayasu arteritis. She was started on oral prednisolone 60 mg which led to resolution of clinical symptoms and later azathioprine 100 mg was added as a steroid sparing agent.

Similar to previous case reports [6–9], our patient was treated with multiple courses of antibiotics for neck pain by primary care physicians with a presumptive diagnosis of bacterial pharyngitis. Though neutrophilic leucocytosis may be seen in both acute bacterial pharyngitis and active Takayasu arteritis, the presence of normocytic normochromic anemia, thrombocytosis, persistently elevated CRP, ESR and neutrophilic leucocytosis point more towards active Takayasu arteritis. A novel association of carotidynia with prior recurrent pharyngitis was described by Quinn et al. [10] implicating an infectious trigger leading to direct seeding of carotid arteries. Though idiopathic carotidynia is a self-limiting condition, carotidynia in Takayasu arteritis can persist or have a relapsing course leading to vessel wall damage [10, 11]. Hence it is imperative to make an early diagnosis of Takayasu arteritis in a case of carotidynia to prevent long term vascular inflammation which can lead to organ ischemia and complications.

Conclusion

Takayasu arteritis is an underdiagnosed cause of carotidynia and a high index of suspicion is required to make an early diagnosis. The presence of persistently elevated inflammatory markers in a young female with carotidynia should make one consider the possibility of Takayasu arteritis.

Authors contributions

HG contributed to the conception and design of the work. All authors contributed to the acquisition of data for the work. All authors contributed to drafting of the work. All authors contributed in final approval of the version to be published. All authors agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Ethical Statement

We obtained informed consent from the patients including consent for publication.