Giant cell arteritis

from Wikipedia, the free encyclopedia
Histopathology with evidence of numerous multinucleated giant cells in the vessel wall of an affected cerebral artery. Elastic coloring.
1 Temporal artery
2 Frontal branch
3 Parietal branch
Classification according to ICD-10
M31.5 Giant cell arteritis in polymyalgia rheumatica
M31.6 Other giant cell arteritis
ICD-10 online (WHO version 2019)

The giant (RZA) (formerly arteritis cranial , temporal arteritis , Horton's disease , Horton Magath-Brown syndrome ) is a systemic vasculitis ( vasculitis ), which (especially in the elderly, the temporal arteries temporal arteries attacks). If left untreated, there is a 20 percent risk of going blind , as the inflammation of the arteries leads to insufficient blood flow to the optic nerve papilla. With appropriate diagnostics and a rapid start of therapy with cortisone preparations , the course of the disease is usually benign, albeit protracted.

The giant cell arteritis is counted together with the Takayasu arteritis to the group of large vessel vasculitis.

frequency

The RZA affects over 75% older women. The incidence (new cases per year) in people under 60 is less than 5: 100,000. By the age of 70 it rises to over 10, in the 8th decade to 40 and then to 50: 100,000. Women are affected 2 to 6 times more often than men.

Pathogenesis

RZA is a T-cell- dependent autoimmune disease with a genetic predisposition . Infections can trigger an outbreak of disease; viruses ( e.g. HBV , influenza viruses and VZV ) and bacteria such as Borrelia and Klebsiella are discussed in particular .

Granulomatous vasculitis usually develops, which predominantly affects the large and medium-sized arteries . The most common cranial involvement pattern is the superficial temporal artery , often at the same time as the other superficial cranial arteries (e.g. occipital branch). Involvement of the ophthalmic artery in 30% of cases is feared and can lead to blindness. Infection of the deep temporal artery with an accompanying inflammatory reaction of the temporal muscle can also occur and may cause the chewing pain often complained of by patients. In the extra-cranial pattern of involvement, the aorta and aortic branches are primarily affected. Intracranial vessels, coronary arteries, and other organs are rarely affected (less than one percent). There is a relationship to polymyalgia rheumatica , but both diseases can occur independently of each other.

The inflammation, which can also occur segmentally, leads to edema within the vessel wall. The edematous thickening of the vascular wall leads to a narrowing of the vascular lumen, which can result in reduced blood flow to the areas supplied by the affected artery. If the central retinal artery is affected, this can lead to irreversible damage to the retina within an hour .

Symptoms

More than 70 percent of patients report a severe, piercing headache as the first symptom, which is often exacerbated by chewing ( claudication masticatoria ). A one-sided, sudden onset of severe visual impairment up to blindness is also typical, which occurs in around 30% of patients and requires immediate therapy. In addition, thickened, hard, increasingly tortuous, pulseless and pressure-sensitive temporal arteries are found on both sides of the temples. Drooping of an eyelid ( ptosis ) or other eye muscle paralysis as well as common symptoms such as fever, weight loss, fatigue, tiredness and muscle pain occur in 12–15% of cases . In some of the patients with RZA, however, these head-related symptoms do not occur, which is why a distinction has been made between a classic cranial infestation pattern and an extra-cranial infestation pattern. In patients with an extra-cranial infestation pattern, the symptoms are much less specific. They include e.g. B. tiredness, fatigue, fever, an unspecific systemic inflammatory reaction without a clear focus. The diagnosis usually reveals an aortitis, i. H. detect an inflammation of the main artery. While the classic cranial infestation pattern occurs more frequently in older patients (> 80 years of age), a larger proportion with extra-cranial infestation is found in patients under 70 years of age.

Diagnosis

ACR criteria (see text)
criteria sensitivity Specificity
Age of onset> 50 years 98.6% 63.9%
Novel or emerging
localized headache 		64.5% 81.9%
Abnormal temporal artery (tenderness,
decreased pulsation) 		57.3% 96.8%
ESR > 50 mm in the first hour 86.5% 47.7%
Histological changes on temporal artery
biopsy		 92.9% 73.1%

Diagnostic ACR criteria

The American College of Rheumatology (ACR) published criteria for diagnosing RZA in 1990, which have found their way into various guidelines (for example, the German Society for Neurology from 2003) as “diagnostic ACR criteria” . Table 1 shows these criteria and their sensitivity and specificity based on a comparison of 214 patients with cranial arteritis with 593 people with other vasculitis. If three of the five criteria are met, the diagnosis of RZA can be made with a sensitivity of 75% and a specificity of 92%. The ACR criteria are based on the classic cranial infestation pattern of the RZA and have only a limited sensitivity for the diagnosis of a GCC with an extra-cranial infestation pattern.

Sonography

The sonographic examination of the temporal artery and its side branches typically reveals a hypoechoic concentric wall thickening ( halo ) of the affected sections in the RZA . This so-called halo sign has the highest sensitivity for the diagnosis of a cranial RZA. Other features of duplex sonography are stenoses and occlusions of the temporal arteries as well as a lack of compressibility. According to the recommendations of the European League against Rheumatism (EULAR), duplex sonography of the temporal arteries may include the Aa. axillares the method of first choice in the diagnosis of a RZA with a cranial infestation pattern.

Magnetic resonance imaging

Using magnetic resonance imaging (MRI) of the cranial arteries, the diagnosis of cranial RZA can be made with an even higher sensitivity of 93% than with sonography with 78%, while the specificity with sonography is 91% higher than with MRI with 81%. The European Rheumatism League therefore recommends the use of MRI as an alternative to sonography.

Temporal artery biopsy

The diagnosis of cranial RZA is still often confirmed by a minor surgical procedure with a biopsy of the temporal artery. The biopsy of the temporal artery has long been considered the gold standard for detecting GCA. According to the more recent EULAR recommendations, non-invasive imaging is initially preferable to biopsy. If the clinical picture is clear and the imaging results are positive, a biopsy is no longer required for diagnosis. If the imaging is not clear, the biopsy can help with further clarification. The procedure can be performed under local anesthesia - also on an outpatient basis. The biopsy is usually done on one side. A piece of artery about 2.5 cm long should be removed. Since only individual segments of the vessels can be affected, a negative finding does not reliably rule out the disease. Histologically, there is panarteritis with granulomatous inflammation of the tunica media , with predominantly mononuclear infiltrate of the tunica adventitia . The eponymous giant cells are usually located between the intima and media. In addition, calcifications can be observed in the intima.

Ophthalmological examination

The typical symptom is a one-sided, sudden deterioration in visual acuity or field of vision. The cause of this is typically an occlusion of the vessels supplying the retina or the optic nerves: In ophthalmoscopy , the optic nerve papilla is pale and edematous (inflammatory anterior ischemic optic neuropathy). This delimits their edge in an unsharp manner. However, complete or incomplete occlusions of the arteries or veins of the retina can also occur. The retinal arteries are then thread-thin and show irregular reflexes due to the wall thickening in the context of the inflammation.

laboratory

In the laboratory tests, signs of inflammation such as a greatly increased rate of blood sedimentation (ESR), which can be referred to as a fall, increased C-reactive protein (CRP), leukocytosis with eosinophilia, α 2 -globulin proliferation and possibly iron deficiency anemia can be determined.

Differential diagnosis

therapy

The RZA is an emergency. Even if there is an urgent suspicion of the disease, high doses of glucocorticoids (cortisone preparations) are administered systemically , not least because the inflammation can spread to the cerebral vessels and then lead to a life-threatening stroke . The informative value of a biopsy is not affected by the administration of cortisone in the first few days. In 2003, the guidelines of the German Society for Neurology recommended a dose of 60–100 mg per day in the absence of eye involvement, 200–500 mg per day for recent unilateral blindness and 500–1000 mg per day for impending blindness. Maintenance therapy with a reduced dose is then necessary for years; around half of the patients can stop therapy after two years.

Methotrexate

In order to reduce or avoid the side effects of cortisone, the cytostatic methotrexate (MTX) , which is effective in inflammatory rheumatic diseases, can be used as a basic therapy (DMARD) . The amount of methotrexate used is much lower than in cancer therapy.

Tocilizumab

So far, there has been no specific therapy, and long-term glucocorticoid treatment could lead to significant complications. In May 2017, tocilizumab was approved as the first specific drug for the treatment of giant cell arteritis as a break-through therapy in a fast-track process with a shortened review by the American approval authority FDA , two months before the official publication of the phase III study . The humanized monoclonal antibody against the interleukin-6 (IL-6) receptor thus inhibits one of the central inflammation mediators. In the randomized placebo -controlled , double-blind - study were 251 patients at least 50 years old (75% female, 97% white) treated, of which a week, received 100 50 biweekly tocilizumab subcutaneously, while the prednisolone was reduced over 26 weeks. In the first placebo group with 50 patients, prednisolone was also reduced over 26 weeks, in the second placebo group (51 patients) over 52 weeks. After 52 weeks, 56% and 53% in the tocilizumab groups and 14% and 18% in the placebo groups were in sustained remission . The cumulative amount of predisolone averaged 1862 mg in the two therapy groups and 3296 mg and 3818 mg in the placebo groups.

Significant side effects were observed in 15% and 14% of the therapy groups and 22% and 25% in the placebo groups. An optic -Neuropathie it once came in the second treatment group. Nonetheless, further studies and follow-up observations are required, since tocilizumab may only block the manifestation of giant cell arteritis in the form of IL-6-triggered systemic inflammation, but not the actual arteritis. In addition to its proinflammatory effect, IL-6 could also promote angiogenesis and reduce the risk of blindness . The risk of opportunistic infections has also not been clarified.

forecast

The GCC usually responds well to cortisone therapy , followed by a complete remission within a period of 6–24 months. Even with appropriate therapy, there is a risk of permanent blindness in the affected eye. Recurrences can rarely occur, and chronic courses of up to 14 years are also possible.

literature

Individual evidence

  1. ↑ Gerd Herold : Internal Medicine . Cologne 2007, p. 611 .
  2. ^ Klaus Poeck , Werner Hacke : Neurology. 12th, updated and expanded edition. Springer, Heidelberg 2006, ISBN 3-540-29997-1 , pp. 412-413.
  3. ↑ Don Gilden et al .: Prevalence and distribution of VZV in temporal arteries of patients with giant cell arteritis. In: Neurology. May 12, 2015, accessed April 20, 2016 .
  4. ↑ Thorsten Klink, Julia Geiger, Marcus Both, Thomas Ness, Sonja Heinzelmann: Giant Cell Arteritis: Diagnostic Accuracy of MR Imaging of Superficial Cranial Arteries in Initial Diagnosis — Results from a Multicenter Trial . In: Radiology . tape 273 , no. 3 , August 6, 2014, ISSN  0033-8419 , p. 844–852 , doi : 10.1148 / radiol.14140056 ( rsna.org [accessed May 31, 2019]).
  5. ↑ Simon Veldhoen, Thorsten Klink, Julia Geiger, Peter Vaith, Cornelia Glaser: MRI displays involvement of the temporalis muscle and the deep temporal artery in patients with giant cell arteritis . In: European Radiology . tape 24 , no. 11 , November 1, 2014, ISSN  1432-1084 , p. 2971-2979 , doi : 10.1007 / s00330-014-3255-1 .
  6. ↑ Hubert de Boysson, Eric Liozon, Olivier Espitia, Aurélie Daumas, Mathieu Vautier: Different patterns and specific outcomes of large-vessel involvements in giant cell arteritis . In: Journal of Autoimmunity . May 24, 2019, ISSN  0896-8411 , doi : 10.1016 / j.jaut.2019.05.011 ( sciencedirect.com [accessed May 31, 2019]).
  7. ↑ a b Hubert de Boysson, Aurélie Daumas, Mathieu Vautier, Jean-Jacques Parienti, Eric Liozon: Large-vessel involvement and aortic dilation in giant cell arteritis-. A multicenter study of 549 patients . In: Autoimmunity Reviews . tape 17 , no. 4 , April 2018, p. 391–398 , doi : 10.1016 / j.autrev.2017.11.029 ( elsevier.com [accessed May 26, 2019]).
  8. ^ Wolfgang Andreas Schmidt: Duplex sonography in the diagnosis of temporal arteritis and other vasculitides. Habilitation thesis . Humboldt University, Charité Medical Faculty, Berlin 2002.
  9. ↑ Thomas Daikeler, Christof Rottenburger, Daniel Staub, Markus Aschwanden, Gregor Sommer: The clinical benefit of imaging in the diagnosis and treatment of giant cell arteritis . In: Swiss Medical Weekly . tape 148 , no. 3334 , August 22, 2018, doi : 10.4414 / smw.2018.14661 ( smw.ch [accessed on May 31, 2019]).
  10. ↑ a b c Christian Dejaco, Sofia Ramiro, Christina Duftner, Florent L Besson, Thorsten A Bley, Daniel Blockmans, Elisabeth Brouwer, Marco A Cimmino, Eric Clark, Bhaskar Dasgupta, Andreas P Diamantopoulos, Haner Direskeneli, Annamaria Iagnocco, Thorsten Klink, Lorna Neill, Cristina Ponte, Carlo Salvarani, Riemer HJA Slart, Madeline Whitlock, Wolfgang A Schmidt: EULAR recommendations for the use of imaging in large vessel vasculitis in clinical practice . Ed .: Annals of Rheumatic Diseases. tape 77 , 2018, p. 636–643 , doi : 10.1136 / annrheumdis-2017-212649 .
  11. ↑ T. Ness, T. Bley, W. Schmidt, P. Lamprecht: Diagnosis and therapy of giant cell arteritis. In: Deutsches Ärzteblatt. 2013, 21, p. 381.
  12. ↑ M. Brody, I. Böhm, R. Bauer: Mechanism of action of methotrexate: experimental evidence that methotrexate blocks the binding of interleukin 1 beta to the interleukin 1 receptor on target cells. In: European journal of clinical chemistry and clinical biochemistry: journal of the Forum of European Clinical Chemistry Societies. Volume 31, Number 10, October 1993, pp. 667-674, PMID 8292668 .
  13. ↑ IB Boehm, GA Boehm, R. Bauer: Management of cutaneous lupus erythematosus with low-dose methotrexate: indication for modulation of inflammatory mechanisms. In: Rheumatology international. Volume 18, Number 2, 1998, pp. 59-62, PMID 9782534 .
  14. ↑ FDA: FDA News Release - FDA approves first drug to specifically treat giant cell arteritis , May 22, 2017, [1]
  15. ↑ John H. Stone, Katie Tuckwell, Sophie Dimonaco, Micki Klearman, Martin Aringer, Daniel Blockmans, Elisabeth Brouwer, Maria C. Cid, Bhaskar Dasgupta, Juergen Rech, Carlo Salvarani, Georg Schett, Hendrik Schulze-Koops, Robert Spiera, Sebastian H. Unizony, Neil Collinson: Trial of Tocilizumab in Giant-Cell Arteritis . New England Journal of Medicine 2017, Volume 377, Issue 4, July 27, 2017, pages 317-328, [DOI: 10.1056 / NEJMoa1613849]
  16. ↑ David B. Hellmann: Giant-Cell Arteritis - More Ecstasy, Less Agony New England Journal of Medicine 2017, Volume 377, Issue 4 of July 27, 2017, pages 385-386, [DOI: 10.1056 / NEJMe1706439]