Giant cell arteritis M31.6

Hutchinson 1890; Horton 1934

Chronic, segmental, granulomatous, obliterating "large vessel" vasculitis, which usually manifests itself on the carotid artery and its outlets. Preferential infestation of the temporalis, ophthalmic, facial, occipital, lingual and maxillary arteries with corresponding symptoms. There are no large vessels on the skin; however, the disease can affect vessels supplying the skin areas.

Remark: 50% of the patients also suffer from polymyalgia rheumatica!

Incidence: 9/1,00,000 inhabitants, in < 50-year-olds: <5/100,000; 6.dec.: 40/100,000; 7.dec.: 40/100,000 inhabitants.

The annual incidence in Northern Europe is >17/100,000 for people > 50 years.

In Southern Europe the incidence is < 12/100,000.

Unknown! A T-cell-dependent (auto)immune event with genetic predisposition, possibly triggered by infection, is discussed.

Age > 50 years

Associations with viral infections (HBV, VZV, Parvovirus B19, SARS-CoV-2 - Mursi AM et al.2022) or Borrelia, Mycoplasma and Chlamydia (Chlamydia pneumoniae) are not certain.

Pathogenetically, it is a granulomatous giant cell arteritis in the media and adventitia of the affected arterial segments with consecutive sclerotic vessel wall senescence.

Age group > 50 years; preferred by women (75%), mostly Caucasians.

Sudden onset of disease!

General symptoms: initially: throbbing, temporal headache, fever, feeling sick, arthralgias, myalgias, morning stiffness and weight loss. 50% of patients have concomitant polymyalgia rheumatica. Furthermore: orthostatic dizziness (40%); seizures and hemiparesis (<10%); nonspecific skin involvement: erythema nodosum or urticaria (15%).

Arteriitis cranialis with variable often simultaneous pattern of involvement (Note: A. temporalis affected in most cases):

• Temporal artery: often severe unilateral or bilateral throbbing headache, especially temporal and frontal (50%), not infrequently pain when chewing (jaw claudication; masseteric claudication), redness in the area of the cord-like thickened temporal artery: not infrequently small or large necroses of the skin (and galea) in the catchment area of the temporal artery may occur.
• Ophthalmic artery (30% of cases): Visual disturbances, amaurosis fugax, risk of blindness; possibly double vision (diplopia).
• Lingual artery: painful redness, blisters, necrosis on the tongue.
• Brachial artery: claudication of the arms (50%); blood pressure differences of more than 30 mm Hg in both arms (64%); absent pulses (50%).
• A. femoralis: claudication of the lower extremities (10%);
• Aorta: aortic aneurysm or insufficiency (10%) - aortic arch syndrome -.

Apparative diagnostics:

• Evaluation of the temporal artery in comparison to the sides (hardened, tortuous arteries, palpable, laterally differentiated pulsations).
• Doppler sonographic examination of the head arteries (including exclusion of high-grade internal carotid stenoses).
• Colour duplex of the temporal arteries (wall thickening, pulsations).

Severe increase in ESR (often > 80 mm/hour; normal in 5% of patients)

C-reactive protein (increase in > 90%, more meaningful as a progression parameter than ESR)

Eosinophilia, leukocytosis

Increase in the alpha-2-globulin fraction in the blood (norm: ~ 7.1 - 11.8% from 14 years; reference value central laboratory Heidelberg University Hospital), e.g. haptoglobin in the blood (norm: 0.3-2.0 g/dL), and possibly VLDL, alpha-2-macroglobulin and/or coeruloplasmin

Increase in fibrinogen i.P. (norm: 200-450 mg/dL)

Infectious anemia (hemoglobin < 13 mg/dL in men, < 12 mg/dL in non-pregnant women);

Absence of a positive rheumatoid factor or ANA and ANCA detection.

Clinical diagnosis according to criteria of the American College of Rheumatology (ACR) for the diagnosis of the temporalis (Hunder et al. 1990):

1. Age: > 50 years
2. secondary headache
3. Abnormal temporal arteries (pressure bulge, weakened pulsation).
4. BSG > 50 mm in the first hour.
5. Histological changes in biopsy of the temporal artery (important: segmental vasculitis "skip lesions"; possibly several biopsies necessary! Before that, arterial Doppler to exclude flow sounds!)

If 3 of 5 criteria are met, a sensitivity of 75-95%, a specificity of 90-93%, a positive predictive value of only 29% and a negative predictive value of 99% are achieved.

Furthermore, rheumatoid factor or antibodies against CCP (cyclic citrullinated peptide), CRP are to be determined.

If necessary, biopsy of the temporal artery (possibly on both sides, approx. 3 cm long segment due to segmental infestation). Note: Before biopsy, Doppler sonographic clarification of the arterial flow conditions.

Arteriosclerosis; thrombangitis obliterans; syphilis; in case of necrosis of the scalp, necrotizing zoster, erosive pustular dermatitis and bullous autoimmune diseases have to be considered; furthermore: ergotism (migraine therapeutics!);

The therapeutic goal is to reduce the inflammation of the vascular wall. Indicators are the humoral symptoms of inflammation. Of crucial importance is the ocular symptomatology. Flow in the central retinal artery should be measured and can be included as a therapeutic control symptom.

• Glucocorticoids: Prednisone equivalents in an initial dosage of 1.0-1.5 mg/kg bw for 7-14 days, then reduction by 10 mg/day up to a dosage of 25-40 mg/day for 4 weeks; further reduction by 5 mg/week up to a maintenance dose of < 10 mg/day p.o. for 1 year. Subsequent therapy depending on the clinic (acute phase reaction as indicator of inflammatory symptoms).
• Already in case of unilateral ocular symptoms (visual disturbances up to blindness), higher prednisone equivalents (1.5-2.0 mg/kg bw/day) should be started. If this therapy regime is not sufficient (recurrences during treatment), an additive therapy with cyclophosphamide (2 mg/kg bw/day) according to the standard scheme of Fauci is necessary. This can still benefit about 4% (!) of glucocorticoid-resistant patients. Methotrexate can be administered as an alternative to cylophosphamide.
• Non-steroidal anti-inflammatory drugs: Complementary to the therapy with glucocorticoids NSAIDs in medium dosage.
• In 2017, the IL-6 receptor inhibitor tocilizumab (e.g. Actemra®) was approved as a biologic that demonstrated efficacy in RZA and showed superiority to glucocorticosteroids. The drug has already been approved for rheumatoid arthritis (RA) since 2009. Approved.

The arteriitis temporalis is synonymous with the term giant cell arteriitis and is compared to the Takayasu arteriitis. This is incorrect, since the histological substrate of both entities is the "giant cell arteritis" and thus no difference is expressed.

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