Elsevier

Autoimmunity Reviews

Volume 14, Issue 4, April 2015, Pages 352-357
Autoimmunity Reviews

Review
Giant cell arteritis restricted to the limb arteries: An overlooked clinical entity

https://doi.org/10.1016/j.autrev.2014.12.005Get rights and content

Abstract

Objective

Giant cell arteritis (GCA) is a systemic vasculitis typically affecting temporal arteries. In at least 15% of cases, GCA also features inflammation of the aorta and its primary branches. Large-vessel inflammation restricted to proximal limb arteries in the absence of temporal and aortic involvement (Limb Restricted, LR) is rare and not well described in literature. Hence, we aim to characterize this neglected clinical entity.

Methods

We describe a series of three cases of LR-GCA. All patients were older than 50 years, had increased erythrocyte sedimentation rate (ESR), normal cholesterol and triglycerides serum levels, negative temporal artery biopsy, suggestive F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) findings, and responded to immunosuppressive therapy. We also reviewed all published cases of LR-GCA (76 cases), for a total of 79 patients.

Results

Limb claudication was reported in 87% of the patients, and cranial symptoms and polymyalgia rheumatica in 20%. Constitutional symptoms were never reported. Median ESR levels were 66.5 mm/1 h. Upper and lower limb arteries were involved in 86% and 9% of the patients respectively, and the remaining 5% had simultaneous upper and lower limb vessel involvement. Conventional angiography was performed in 63% of the cases, color-doppler ultrasound in 20%, FDG-PET in 14%, and computed tomography angiography in 3%.

Conclusion

If temporal biopsy and aortic imaging are negative for GCA in patients older than 50 years with bilateral limb claudication, elevated ESR, and suggestive vascular radiological findings, LR-GCA should be suspected. Upper limb arteries are more frequently involved. Since constitutional symptoms are typically absent in LR-GCA, differential diagnosis with atherosclerotic plaques may be challenging.

Introduction

Giant-cell arteritis (GCA) is a systemic large-vessel vasculitis of unknown etiology. GCA owes its name to the typical inflammatory infiltrate found in vessel walls [1]. Disease incidence is 200 cases per 100,000 people over 50 years in Western countries, and females are more commonly affected (2:1) [2]. Susceptibility to GCA has been suggested to be associated with several genetic factors that may interact with the environment and regulate the threshold of autoreactivity, but evidence is still not conclusive [2], [3], [4]. Although the role of some soluble mediators such as interleukin (IL)-6, IL-1 and interferon gamma has been shown to be implicated in the disease, the pathophysiology of GCA is still poorly understood [1], [5].

GCA typically affects the temporal arteries and other branches of the external carotid arteries, thus leading to clinical manifestations in the cranial area. Common complaints include new-onset headache, jaw claudication, tenderness of the temporal area, and scalp sensitivity, as well as constitutional symptoms, such as fever, malaise, fatigue and weight loss. Acute visual loss represents an infrequent, yet dramatic disease manifestation [2], [4]. Polymyalgia rheumatica (PMR), which is characterized by pain and stiffness in the shoulder or pelvic girdle, may coexist in up to 40% of the GCA cases [6].

In a relevant fraction of cases, GCA may also affect non-cranial vessels, specifically the ascending aorta and its main tributaries brachiocephalic, left common carotid, and left proximal subclavian arteries. Occasionally, GCA may involve more distal vessels, such as distal subclavian, brachial, axillary, iliac or femoral arteries, leading to intermittent limb claudication and other vascular symptoms [4], [5]. Clinically apparent extra-cranial involvement develops in approximately 15–27% of patients with a positive temporal artery biopsy (TAB) [7], although silent aortic involvement likely occurs in a more sizeable proportion of patients [8]. Inflammation of extra-cranial vessels, with or without temporal involvement, is usually referred to as ‘large-vessel GCA’ [6], [7]. Rarely, GCA may be restricted to the limb arteries, without typical temporal artery and aorta involvement [6]. Given its rarity and the protean, still undefined clinical presentation, the diagnosis of this neglected condition, onwards referred to as limb-restricted GCA (LR-GCA), is challenging also for the experienced immunologist. LR-GCA has been rarely reported in literature, and probably has been overlooked.

The aim of our investigation is to describe three cases of TAB negative LR-GCA and provide a critical appraisal of the published literature, in order to better define its clinical presentation and its preferential sites of involvement. Moreover, we review the diagnostic role of different imaging techniques, namely F-18 fluorodeoxyglucose positron emission tomography (FDG-PET), conventional angiography, computed tomographic angiography (CTA), color-doppler ultrasound (US) and magnetic resonance angiography (MRA), in the evaluation of LR-GCA [9], [10], [11], [12], [13], [14], [15].

Section snippets

Case 1

A previously healthy 78-year-old man was referred to our Institution for a 6-month-history of bilateral, progressive numbness and hypoesthesia of the hands, associated with claudication of the upper limbs. He denied systemic and craniocervical symptoms.

Physical examination revealed a systolic aortic murmur. Radial pulses were present and symmetric. The temporal arteries were non-tender and displayed normal pulsation. Blood tests revealed increased erythrocyte sedimentation rate (ESR, 52 mm/1 h,

Review of the literature and inclusion criteria

In order to better characterize LR-GCA, we searched the English-language medical literature indexed in PubMed using the keywords ‘peripheral GCA’, ‘extracranial GCA’, ‘brachial GCA’, and ‘large-vessel GCA’. We excluded all cases in which a temporal biopsy was positive for GCA, and cases in which either the aorta or its primary branches (brachiocephalic trunk, common carotid, and proximal left subclavian) were involved. We also excluded patients younger than 50 years, in order to rule out cases

Results

A total of 79 patients, three patients with LR-GCA diagnosed in our Department and 76 previously published cases, met our inclusion criteria [6], [16], [17], [18], [19], [20]. In all 79 patients, we were able to evaluate the sites of vasculitis involvement and the radiologic investigations used for diagnosis. Conversely, in order to better characterize the clinical presentation of LR-GCA, we only considered patients with clinical and laboratory features clearly reported, for a total of 15 out

Discussion

LR-GCA is a rare clinical entity characterized by inflammation of proximal limb arteries, in the absence of typical temporal and aortic involvement of GCA [6], [16], [17], [18], [19], [20]. The indolent clinical course of LR-GCA and the poor specificity of clinical and laboratory signs account for the difficulties in the assessment of the correct diagnosis.

In order to better characterize clinical manifestations, sites of vasculitis involvement, and radiologic investigations used for diagnosis

Conflicts of interest and authors' contribution

All the authors have neither funding sources nor conflicts of interest relevant to the present work. All authors had access to the data, had an active role in the study, approved the present version of the manuscript, and agreed with its submission.

In particular:

  • Study concept and design: Dagna L., Berti A.

  • Acquisition of data: Berti A., Pepe G., Dagna L.

  • Analysis and interpretation of data: Berti A., Dagna L., Pepe G.

  • Drafting of the manuscript: Berti A., Dagna L.

  • Literature review: Berti A.,

Take-home messages

  • Limb restricted-giant cell arteritis (LR-GCA) is an overlooked clinical entity of GCA characterized by limb artery involvement without classical temporal and aortic involvement.

  • Bilateral upper limb claudication, elevated ESR, suggestive vascular radiological findings and good corticosteroid response support the diagnosis in patients older than 50 years, when temporal biopsy and aortic imaging are negative for GCA.

  • Constitutional symptoms, frequently present in temporal and classical large-vessel

References (30)

  • D.M. Nuenninghoff et al.

    Incidence and predictors of large-artery complication (aortic aneurysm, aortic dissection, and/or large-artery stenosis) in patients with giant cell arteritis: a population-based study over 50 years

    Arthritis Rheum

    (Dec. 2003)
  • S. Prieto-González et al.

    Large vessel involvement in biopsy-proven giant cell arteritis: prospective study in 40 newly diagnosed patients using CT angiography

    Ann Rheum Dis

    (Jul. 2012)
  • J. Narváez et al.

    Giant cell arteritis and polymyalgia rheumatica: usefulness of vascular magnetic resonance imaging studies in the diagnosis of aortitis

    Rheumatology (Oxford)

    (Apr. 2005)
  • J. Meller et al.

    Early diagnosis and follow-up of aortitis with [(18)F]FDG PET and MRI

    Eur J Nucl Med Mol Imaging

    (May 2003)
  • C. Mukhtyar et al.

    EULAR recommendations for the management of large vessel vasculitis

    Ann Rheum Dis

    (Mar. 2009)
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