Giant cell arteritis

Common symptoms of giant cell arteritis include:

• bruits
• fever
• headache{{cite journal | vauthors = Moutray TN, Williams MA, Best JL | title = Suspected giant cell arteritis: a study of referrals for temporal artery biopsy | journal = Canadian Journal of Ophthalmology | volume = 43 | issue = 4 | pages = 445–448 | date = August 2008 | pmid = 18711459 | doi = 10.3129/i08-070 }}
• tenderness and sensitivity on the scalp
• jaw claudication (pain in jaw when chewing)
• tongue claudication (pain in tongue when chewing) and necrosis{{cite journal | vauthors = Sainuddin S, Saeed NR | title = Acute bilateral tongue necrosis--a case report | journal = The British Journal of Oral & Maxillofacial Surgery | volume = 46 | issue = 8 | pages = 671–672 | date = December 2008 | pmid = 18499311 | doi = 10.1016/j.bjoms.2008.03.027 }}{{cite journal | vauthors = Zadik Y, Findler M, Maly A, Rushinek H, Czerninski R | title = A 78-year-old woman with bilateral tongue necrosis | journal = Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics | volume = 111 | issue = 1 | pages = 15–19 | date = January 2011 | pmid = 21176820 | doi = 10.1016/j.tripleo.2010.09.001 | doi-access = free }}
• reduced visual acuity (blurred vision)
• acute visual loss (sudden blindness)
• diplopia (double vision)
• limb claudication{{cite journal | vauthors = Walz-Leblanc BA, Ameli FM, Keystone EC | title = Giant cell arteritis presenting as limb claudication. Report and review of the literature | journal = The Journal of Rheumatology | volume = 18 | issue = 3 | pages = 470–472 | date = March 1991 | pmid = 1856819 | url = https://pubmed.ncbi.nlm.nih.gov/1856819 }}
• polymyalgia rheumatica (in 50%){{cite web| vauthors = Hunder GG |title=Polymyalgia rheumatica and giant cell (temporal) arteritis|url=http://www.uptodate.com/contents/polymyalgia-rheumatica-and-giant-cell-temporal-arteritis-beyond-the-basics?view=print|website=uptodate.com|publisher=Wolters Kluwer|access-date=23 September 2015|url-status=live|archive-url=https://web.archive.org/web/20150925110253/http://www.uptodate.com/contents/polymyalgia-rheumatica-and-giant-cell-temporal-arteritis-beyond-the-basics?view=print|archive-date=25 September 2015}}

The inflammation may affect blood supply to the eye; blurred vision or sudden blindness may occur. In 76% of cases involving the eye, the ophthalmic artery is involved, causing arteritic anterior ischemic optic neuropathy.{{cite web |author=Hayreh |title=Ocular Manifestations of GCA |url=http://webeye.ophth.uiowa.edu/dept/GCA/04-ocular.htm |date=April 3, 2003 |publisher=University of Iowa Health Care |access-date=2007-10-15 |url-status=dead |archive-url=https://web.archive.org/web/20071025074136/http://webeye.ophth.uiowa.edu/dept/GCA/04-ocular.htm |archive-date=2007-10-25 }}

Giant cell arteritis may present with atypical or overlapping features.{{cite journal | vauthors = Rana AQ, Saeed U, Khan OA, Qureshi AR, Paul D | title = Giant cell arteritis or tension-type headache?: A differential diagnostic dilemma | journal = Journal of Neurosciences in Rural Practice | volume = 5 | issue = 4 | pages = 409–411 | date = October 2014 | pmid = 25288850 | pmc = 4173245 | doi = 10.4103/0976-3147.140005 | doi-access = free }} Early and accurate diagnosis is important to prevent ischemic vision loss. Therefore, this condition is considered a medical emergency.

While studies vary as to the exact relapse rate of giant cell arteritis, relapse of this condition can occur. It most often happens at low doses of prednisone (<20 mg/day), during the first year of treatment, and the most common signs of relapse are headache and polymyalgia rheumatica.{{Cite web|url=https://www.uptodate.com/contents/treatment-of-giant-cell-arteritis?source=history_widget#references|title=UpToDate|website=www.uptodate.com|access-date=2019-11-25}}

The varicella-zoster virus (VZV) antigen was found in 74% of temporal artery biopsies that were GCA-positive, suggesting that the VZV infection may trigger the inflammatory cascade.{{cite journal | vauthors = Gilden D, White T, Khmeleva N, Heintzman A, Choe A, Boyer PJ, Grose C, Carpenter JE, Rempel A, Bos N, Kandasamy B, Lear-Kaul K, Holmes DB, Bennett JL, Cohrs RJ, Mahalingam R, Mandava N, Eberhart CG, Bockelman B, Poppiti RJ, Tamhankar MA, Fogt F, Amato M, Wood E, Durairaj V, Rasmussen S, Petursdottir V, Pollak L, Mendlovic S, Chatelain D, Keyvani K, Brueck W, Nagel MA | title = Prevalence and distribution of VZV in temporal arteries of patients with giant cell arteritis | journal = Neurology | volume = 84 | issue = 19 | pages = 1948–1955 | date = May 2015 | pmid = 25695965 | pmc = 4433460 | doi = 10.1212/WNL.0000000000001409 }}

The disorder may co-exist (in about half of cases) with polymyalgia rheumatica (PMR), which is characterized by sudden onset of pain and stiffness in muscles (pelvis, shoulder) of the body and is seen in the elderly. GCA and PMR are so closely linked that they are often considered to be different manifestations of the same disease process. PMR usually lacks the cranial symptoms, including headache, pain in the jaw while chewing, and vision symptoms, that are present in GCA.{{Cite web|url=https://bestpractice.bmj.com/topics/en-gb/177/differentials|title=Giant cell arteritis|website=BMJ Best Practice|access-date=2019-11-25}}

Giant cell arteritis can affect the aorta and lead to aortic aneurysm and aortic dissection. Up to 67% of people with GCA having evidence of an inflamed aorta, which can increase the risk of aortic aneurysm and dissection.{{cite journal | vauthors = Chen JJ, Warrington KJ, Garrity JA, Prasad S | title = Is Routine Imaging of the Aorta Warranted in Patients With Giant Cell Arteritis? | journal = Journal of Neuro-Ophthalmology | volume = 37 | issue = 3 | pages = 314–319 | date = September 2017 | pmid = 28614098 | doi = 10.1097/WNO.0000000000000538 | s2cid = 3747982 }} There are arguments for the routine screening of each person with GCA for this possible life-threatening complication by imaging the aorta. Screening should be done on a case-by-case basis based on the signs and symptoms of people with GCA.

The pathological mechanism is the result of an inflammatory cascade that is triggered by an as of yet undetermined cause resulting in dendritic cells in the vessel wall recruiting T cells and macrophages to form granulomatous infiltrates. These infiltrates erode the middle and inner layers of the arterial tunica media leading to conditions such as aneurysm and dissection. Activation of T helper 17 (Th17) cells involved with interleukin (IL) 6, IL-17, IL-21 and IL-23 play a critical part; specifically, Th17 activation leads to further activation of Th17 through IL-6 in a continuous, cyclic fashion. This pathway is suppressed with glucocorticoids,{{cite journal | vauthors = Weyand CM, Goronzy JJ | title = Clinical practice. Giant-cell arteritis and polymyalgia rheumatica | journal = The New England Journal of Medicine | volume = 371 | issue = 1 | pages = 50–57 | date = July 2014 | pmid = 24988557 | pmc = 4277693 | doi = 10.1056/NEJMcp1214825 | veditors = Solomon CG }} and more recently it has been found that IL-6 inhibitors also play a suppressive role.

• Palpation of the head reveals prominent temporal arteries with or without pulsation.{{cite web |url=https://www.lecturio.com/concepts/giant-cell-arteritis/| title=Giant Cell Arteritis

|website=The Lecturio Medical Concept Library | date=26 November 2020

|access-date= 23 July 2021}}

• The temporal area may be tender.
• Decreased pulses may be found throughout the body
• Evidence of ischemia may be noted on fundal exam.
• Bruits may be heard over the subclavian and axillary arteries

File:Giant cell arteritis -- intermed mag.jpg showing giant cell arteritis in a temporal artery biopsy. The arterial lumen is seen on the left. A giant cell is seen on the right at the interface between the thickened intima and media.  H&E stain]]

• Erythrocyte sedimentation rate, an inflammatory marker, >60 mm/hour (normal 1–40 mm/hour)
• C-reactive protein, another inflammatory marker, may be elevated
• LFTs, liver function tests, are abnormal particularly raised ALP- alkaline phosphatase
• Platelets may also be elevated

File:Cerebral Giant-Cell Vasculitis.jpg

The gold standard for diagnosing temporal arteritis is biopsy, which involves removing a small part of the vessel under local anesthesia and examining it microscopically for giant cells infiltrating the tissue.{{cite journal | vauthors = Cahais J, Houdart R, Lupinacci RM, Valverde A | title = Operative technique: Superficial temporal artery biopsy | journal = Journal of Visceral Surgery | volume = 154 | issue = 3 | pages = 203–207 | date = June 2017 | pmid = 28601496 | doi = 10.1016/j.jviscsurg.2017.05.001 | doi-access = }} However, a negative result does not definitively rule out the diagnosis; since the blood vessels are involved in a patchy pattern, there may be unaffected areas on the vessel and the biopsy might have been taken from these parts. Unilateral biopsy of a 1.5–3 cm length is 85-90% sensitive (1 cm is the minimum).{{cite journal | vauthors = Ypsilantis E, Courtney ED, Chopra N, Karthikesalingam A, Eltayab M, Katsoulas N, Tang TY, Ball RY | title = Importance of specimen length during temporal artery biopsy | journal = The British Journal of Surgery | volume = 98 | issue = 11 | pages = 1556–1560 | date = November 2011 | pmid = 21706476 | doi = 10.1002/bjs.7595 | s2cid = 20149393 }} Characterised as intimal hyperplasia and medial granulomatous inflammation with elastic lamina fragmentation with a CD4+ predominant T cell infiltrate, currently biopsy is only considered confirmatory for the clinical diagnosis, or one of the diagnostic criteria.

Radiological examination of the temporal artery with ultrasound yields a halo sign. Contrast-enhanced brain MRI and CT are generally negative in this disorder. Recent studies have shown that 3T MRI using super high resolution imaging and contrast injection can non-invasively diagnose this disorder with high specificity and sensitivity.{{cite journal | vauthors = Bley TA, Uhl M, Carew J, Markl M, Schmidt D, Peter HH, Langer M, Wieben O | title = Diagnostic value of high-resolution MR imaging in giant cell arteritis | journal = AJNR. American Journal of Neuroradiology | volume = 28 | issue = 9 | pages = 1722–1727 | date = October 2007 | pmid = 17885247 | pmc = 8134183 | doi = 10.3174/ajnr.A0638 | doi-access = free }} Temporal artery thickening on imaging has been demonstrated to have highest positive likelihood ratios for GCA when compared with other non invasive diagnostic tests.{{cite journal | vauthors = van der Geest KS, Sandovici M, Brouwer E, Mackie SL | title = Diagnostic Accuracy of Symptoms, Physical Signs, and Laboratory Tests for Giant Cell Arteritis: A Systematic Review and Meta-analysis | journal = JAMA Internal Medicine | volume = 180 | issue = 10 | pages = 1295–1304 | date = October 2020 | pmid = 32804186 | pmc = 7432275 | doi = 10.1001/jamainternmed.2020.3050 }}

Women and men approximately 45 years old and who suffer from several complaints (at least 5 of the 16 symptoms){{Cite web |title=Symptomatix Home |url=https://www.symptomatrix-eng.eu/index.htm |access-date=2023-05-07 |website=www.symptomatrix-eng.eu}} listed below could have giant cell arteritis.

• Fatigue and apathy
• Stiffness in joints and/or muscles
• Painful jaws when chewing
• Sensitive scalp
• Physical malaise and/or weakness
• Bloated arteries of the temples
• Headaches, migraine
• Tongue problems
• Bleakness, depression
• Changed eyesight
• Poor or lack of appetite
• Reduced eyesight, blindness
• Unusual loss of weight
• A temperature
• Unusual perspiration
• Night sweats

GCA is considered a medical emergency due to the potential of irreversible vision loss. Corticosteroids, typically high-dose prednisone (1 mg/kg/day), should be started as soon as the diagnosis is suspected (even before the diagnosis is confirmed by biopsy) to prevent irreversible blindness secondary to ophthalmic artery occlusion. Steroids do not prevent the diagnosis from later being confirmed by biopsy, although certain changes in the histology may be observed towards the end of the first week of treatment and are more difficult to identify after a couple of months.{{cite journal | vauthors = Font RL, Prabhakaran VC | title = Histological parameters helpful in recognising steroid-treated temporal arteritis: an analysis of 35 cases | journal = The British Journal of Ophthalmology | volume = 91 | issue = 2 | pages = 204–209 | date = February 2007 | pmid = 16987903 | pmc = 1857614 | doi = 10.1136/bjo.2006.101725 }} The dose of corticosteroids is generally slowly tapered over 12–18 months.{{cite journal | vauthors = Mackie SL, Dejaco C, Appenzeller S, Camellino D, Duftner C, Gonzalez-Chiappe S, Mahr A, Mukhtyar C, Reynolds G, de Souza AW, Brouwer E, Bukhari M, Buttgereit F, Byrne D, Cid MC, Cimmino M, Direskeneli H, Gilbert K, Kermani TA, Khan A, Lanyon P, Luqmani R, Mallen C, Mason JC, Matteson EL, Merkel PA, Mollan S, Neill L, Sullivan EO, Sandovici M, Schmidt WA, Watts R, Whitlock M, Yacyshyn E, Ytterberg S, Dasgupta B | title = British Society for Rheumatology guideline on diagnosis and treatment of giant cell arteritis | journal = Rheumatology | volume = 59 | issue = 3 | pages = e1–e23 | date = March 2020 | pmid = 31970405 | doi = 10.1093/rheumatology/kez672 | hdl-access = free | doi-access = free | hdl = 10044/1/76450 }} Oral steroids are at least as effective as intravenous steroids,{{cite web |url=http://www.bestbets.org/bets/bet.php?id=708 |title=BestBets: Steroids and Temporal Arteritis |url-status=live |archive-url=https://web.archive.org/web/20090227170010/http://www.bestbets.org/bets/bet.php?id=708 |archive-date=2009-02-27 }} except in the treatment of acute visual loss where intravenous steroids appear to offer significant benefit over oral steroids.{{cite journal | vauthors = Chan CC, Paine M, O'Day J | title = Steroid management in giant cell arteritis | journal = The British Journal of Ophthalmology | volume = 85 | issue = 9 | pages = 1061–1064 | date = September 2001 | pmid = 11520757 | pmc = 1724128 | doi = 10.1136/bjo.85.9.1061 }} Short-term side effects of prednisone are uncommon but can include mood changes, avascular necrosis, and an increased risk of infection.{{cite journal | vauthors = Richards RN | title = Side effects of short-term oral corticosteroids | journal = Journal of Cutaneous Medicine and Surgery | volume = 12 | issue = 2 | pages = 77–81 | date = March 2008 | pmid = 18346404 | doi = 10.2310/7750.2008.07029 | s2cid = 30995207 }} Some of the side effects associated with long-term use include weight gain, diabetes mellitus, osteoporosis, avascular necrosis, glaucoma, cataracts, cardiovascular disease, and an increased risk of infection.{{cite journal | vauthors = Youssef J, Novosad SA, Winthrop KL | title = Infection Risk and Safety of Corticosteroid Use | journal = Rheumatic Disease Clinics of North America | volume = 42 | issue = 1 | pages = 157–176 | date = February 2016 | pmid = 26611557 | pmc = 4751577 | doi = 10.1016/j.rdc.2015.08.004 }}{{cite journal | vauthors = Oray M, Abu Samra K, Ebrahimiadib N, Meese H, Foster CS | title = Long-term side effects of glucocorticoids | journal = Expert Opinion on Drug Safety | volume = 15 | issue = 4 | pages = 457–465 | date = 2016-04-02 | pmid = 26789102 | doi = 10.1517/14740338.2016.1140743 | s2cid = 39396172 }} It is unclear whether adding a small amount of aspirin is beneficial or not as it has not been studied.{{cite journal | vauthors = Mollan SP, Sharrack N, Burdon MA, Denniston AK | title = Aspirin as adjunctive treatment for giant cell arteritis | journal = The Cochrane Database of Systematic Reviews | volume = 2014 | issue = 8 | pages = CD010453 | date = August 2014 | pmid = 25087045 | pmc = 10589060 | doi = 10.1002/14651858.CD010453.pub2 }} Injections of tocilizumab may also be used.{{cite web|title=Press Announcements - FDA approves first drug to specifically treat giant cell arteritis|url=https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm559791.htm|archive-url=https://web.archive.org/web/20170602023517/https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm559791.htm|url-status=dead|archive-date=June 2, 2017|website=www.fda.gov|access-date=10 February 2018}} Tocilizumab is a humanized antibody that targets the interleukin-6 receptor, which is a key cytokine involved in the progression of GCA.{{cite journal | vauthors = Mariano VJ, Frishman WH | title = Tocilizumab in Giant Cell Arteritis | journal = Cardiology in Review | volume = 26 | issue = 6 | pages = 321–330 | date = 2018 | pmid = 29570475 | doi = 10.1097/CRD.0000000000000204 | s2cid = 4227514 }} Tocilizumab has been found to be effective at minimizing both recurrence, and flares of GCA when used both on its own and with corticosteroids. Long term use of tocilizumab requires further investigation. Tocilizumab may increase the risk of gastrointestinal perforation and infections, however it does not appear that there are more risks than using corticosteroids.{{cite journal | vauthors = Rinden T, Miller E, Nasr R | title = Giant cell arteritis: An updated review of an old disease | journal = Cleveland Clinic Journal of Medicine | volume = 86 | issue = 7 | pages = 465–472 | date = July 2019 | pmid = 31291180 | doi = 10.3949/ccjm.86a.18103 | doi-access = free }}

Giant cell arteritis typically only occurs in those over the age of 50; particularly those in their 70s. It affects about 1 in 15,000 people over the age of 50 per year. It is more common in women than in men, by a ratio of 2:1, and more common in those of Northern European descent, as well as in those residing further from the Equator. Roughly 1 in 5 people with polymyalgia rheumatica also have giant cell arteritis.{{Cite journal |last1=Buttgereit |first1=Frank |last2=Dejaco |first2=Christian |last3=Matteson |first3=Eric L. |last4=Dasgupta |first4=Bhaskar |date=2016-06-14 |title=Polymyalgia Rheumatica and Giant Cell Arteritis: A Systematic Review |url=http://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2016.5444 |journal=JAMA |language=en |volume=315 |issue=22 |pages=2442–2458 |doi=10.1001/jama.2016.5444 |pmid=27299619 |issn=0098-7484|url-access=subscription }}

Giant cell arteritis and its treatment impact on people's lives because of symptoms, adverse effects of GCs and disruption to normal life.{{cite journal | vauthors = Liddle J, Bartlam R, Mallen CD, Mackie SL, Prior JA, Helliwell T, Richardson JC | title = What is the impact of giant cell arteritis on patients' lives? A UK qualitative study | journal = BMJ Open | volume = 7 | issue = 8 | pages = e017073 | date = August 2017 | pmid = 28838902 | pmc = 5724062 | doi = 10.1136/bmjopen-2017-017073 }} People with GCA have previously ranked ‘losing sight in both eyes permanently’, ‘having intense or severe pain’ and ‘feeling weak, tired or exhausted’ as important quality of life domains.{{cite journal | vauthors = Hellmann DB, Uhlfelder ML, Stone JH, Jenckes MW, Cid MC, Guillevin L, Moreland L, Dellaripa PF, Hoffman GS, Merkel PA, Spiera R, Brown L, Hernández-Rodríguez J, Rubin HR | title = Domains of health-related quality of life important to patients with giant cell arteritis | journal = Arthritis and Rheumatism | volume = 49 | issue = 6 | pages = 819–825 | date = December 2003 | pmid = 14673969 | doi = 10.1002/art.11464 }}

The terms "giant cell arteritis" and "temporal arteritis" are sometimes used interchangeably, because of the frequent involvement of the temporal artery. However, other large vessels such as the aorta can be involved.{{cite journal | vauthors = Walter MA, Melzer RA, Graf M, Tyndall A, Müller-Brand J, Nitzsche EU | title = [18F]FDG-PET of giant-cell aortitis | journal = Rheumatology | volume = 44 | issue = 5 | pages = 690–691 | date = May 2005 | pmid = 15728420 | doi = 10.1093/rheumatology/keh551 | doi-access = free }} Giant-cell arteritis is also known as "cranial arteritis" and "Horton's disease".{{cite book | vauthors = James WD, Elston DM, Berger TG, Andrews GC |title=Andrews' Diseases of the Skin: clinical Dermatology |publisher=Saunders Elsevier |year=2006 |page=840 |isbn=978-0-7216-2921-6 |oclc= 663444979 }} The name (giant cell arteritis) reflects the type of inflammatory cell involved.{{DorlandsDict|one/000008441|giant cell arteritis}}

{{Reflist}}

• {{cite journal | vauthors = Mackie SL, Dejaco C, Appenzeller S, Camellino D, Duftner C, Gonzalez-Chiappe S, Mahr A, Mukhtyar C, Reynolds G, de Souza AW, Brouwer E, Bukhari M, Buttgereit F, Byrne D, Cid MC, Cimmino M, Direskeneli H, Gilbert K, Kermani TA, Khan A, Lanyon P, Luqmani R, Mallen C, Mason JC, Matteson EL, Merkel PA, Mollan S, Neill L, Sullivan EO, Sandovici M, Schmidt WA, Watts R, Whitlock M, Yacyshyn E, Ytterberg S, Dasgupta B | title = British Society for Rheumatology guideline on diagnosis and treatment of giant cell arteritis | journal = Rheumatology | volume = 59 | issue = 3 | pages = e1–e23 | date = March 2020 | pmid = 31970405 | doi = 10.1093/rheumatology/kez672 | hdl-access = free | doi-access = free | hdl = 10044/1/76450 }}

{{Medical resources

| DiseasesDB = 12938

| ICD11 = {{ICD11|4A44.2}}

| ICD10 = {{ICD10|M|31|5|m|30}}-{{ICD10|M|31|6|m|30}}

| ICD9 = {{ICD9|446.5}}

| ICDO =

| OMIM = 187360

| MedlinePlus = 000448

| eMedicineSubj = neuro

| eMedicineTopic = 592

| MeshID = D013700

| SNOMED CT = 414341000

| Orphanet = 397

}}

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Category:Medical emergencies

Category:Neurological disorders

Category:Rheumatology

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Category:Steroid-responsive inflammatory conditions

Category:Vascular-related cutaneous conditions