DEFINITION
Horton disease or Giant-cell arteritis is an inflammatory disease of blood vessels.
Horton disease typically causes inflammation of the network of small vessels (vasa vasorum) that supplies the larger arteries. GCA affects arteries of the head and neck, including the three arteries that branch out from the arch of the ascending aorta, and their branches—the thoracic aorta, the axillary arteries, the vertebral arteries, and further on in the head in the ophthalmic and external carotid arteries (the temporal and occipital arteries).
It can cause occlusion of the arteries and ischema (tissue death).
The name (giant cell arteritis) reflects the type of inflammatory cell involved.
The arteries of the face and scalp.
(Giant-cell arteritis)
EPIDEMIOLOGY
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 those residing at higher latitudes. The mean age of onset is >55 years, and it is rare in those less than 55 years of age.
For affected people it represent a major cause of headache.
(Giant cell arteritis and polymyalgia rheumatica: an update, 2015)
Inheritance
Familial aggregation has been observed.
Usually sibs have been affected, but mother-daughter or father-daughter pairs have been reported.
Familial aggregation in this condition is probably of the same order and same basis as that of many autoimmune disorders such as Hashimoto struma, Schmidt syndrome, autoimmune hemolytic anemia, lupus erythematosus, alopecia areata, pernicious anemia, etc.
(Temporal Arteritis, 1981)
SYMPTOMS
Patients present with fever, headache and tenderness and sensivity on the scalp.
Oral symptoms like jaw claudication (pain in jaw when chewing), tongue claudication (pain in tongue when chewing) and necrosis are also frequent.
The inflammation may also affect blood supply to the eye and blurred vision, sudden blindness or diplopia (double vision) may occur. In 76% of cases involving the eye, the ophthalmic artery is involved causing arteritic anterior ischemic optic neuropathy.
Loss of vision in both eyes may occur very abruptly (>20% of cases) and this disease is therefore a medical emergency.
Patients present also atypical symptoms like cough without radiological signs and arthritis affecting large joints and responding to nonsteroidal antiinflammatories.
(Acute bilateral tongue necrosis--a case report, 2008)
(Suspected giant cell arteritis: a study of referrals for temporal artery biopsy, 2008)
Associated conditions:
The disorder may coexist (in a 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.
Other diseases related with temporal arteritis are systemic lupus erythematosus, rheumatoid arthritis, and severe infections.
Giant-cell arteritis can involve branches of the aorta as well leading to aortic aneurysm or dissection. For this reason, patients should be followed with serial chest X-rays.
Ocular complications:
Permanent visual loss (PVL) is the most dreaded complication of giant cell arteritis (GCA).
It results from anterior ischemic optic neuropathy or, less commonly, retinal artery occlusion.
This complication still occurs in 14 to 20% of patients and is typically devastating and permanent, although it is highly preventable by an early diagnosis of giant cell arteritis and appropriate glucocorticoid treatment.
Transient ischemic symptoms such as amaurosis fugax, episodes of blurred vision or diplopia may occur, either heralding visual loss or remaining isolated.
(Ocular complications of giant cell arteritis, 2013)
(Retinal vessel oxygen saturation in giant cell arteritis patients without ocular symptoms, 2013)
DIAGNOSIS
The diagnosis of this disease is often difficult because in many cases there is prevalence of systemic symptoms; there is another difficulty in the diagnosis: the elderly often suffer from other diseases that simulates Horton disease's symptoms.
Physical exam:
In physical exam it is possible to indentify symptoms like tenderness of the temporal area or the presence of prominent temporal arteries with or without pulsation.
Decreased pulses may be found throughout the body.
The examination of fundal may reveal evidence of ischemia due to the affected oxygen metabolism.
Laboratory tests:
- LFTs, liver function tests, are abnormal particularly raised ALP- alkaline phosphatase.
- Erythrocyte sedimentation rate, an inflammatory marker, >60 mm/hour (normal 1–40 mm/hour).
- C-reactive protein, another inflammatory marker, is also commonly elevated.
- Platelets may also be elevated.
Imaging studies:
Imaging is becoming a relevant tool for the assessment of patients with systemic vasculitis.
Temporal artery examination by color duplex ultrasonography (CDUS) is a valuable approach to the diagnosis of giant-cell arteritis.
Evaluation of additional arteries may increase its diagnostic performance.
However, CDUS-specific findings may not be detected in arteries with early inflammation and CDUS-guidance of temporal artery biopsy does not seem to significantly increase its diagnostic yield.
Contrast enhanced brain MRI and CT is generally negative in this disorder. Recent studies have shown that MRI using super high resolution imaging and contrast injection can non-invasively diagnose this disorder with high specificity and sensitivity.
Data generated by existing and emerging imaging techniques are expected to have a major impact in the diagnosis, appraisal of disease extent, evaluation of disease activity and response to treatment in patients with systemic vasculitis.
(Imaging in systemic vasculitis, 2015)
(Diagnostic Value of High-Resolution MR Imaging in Giant Cell Arteritis, 2007)
Biopsy:
The gold standard for diagnosing temporal arteritis is biopsy, which involves removing a small part of the vessel and examining it microscopically for giant cells infiltrating the tissue.
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). This validates the minimum recommended biopsy length and displays the importance of achieving this standard.
So, a negative result does not definitely rule out the diagnosis. Thus, currently biopsy is only considered confirmatory for the clinical diagnosis, or one of diagnostic criteria.
Histopathology of giant cell vasculitis in a cerebral artery.
(Temporal artery biopsies: do they make the cut?, 2014)
PATHOGENESIS
Although its cause is unknown, the condition is characterized by segmental and patchy granulomatous inflammation of the blood vessels.
Giant cell arteritis (GCA) is considered to be a T cell-dependent disease. Autoantibodies have not consistently been found in GCA.
This inflammation leads to arterial stenosis. There is also irregular fibrosis of the blood vessels due to chronic vasculitis, leading to sometimes massive intimal fibrosis (fibrosis of the inner section of the blood vessels).
The genetic contribution to the pathogenesis of GCA is supported by the genetic association with HLA class II complex.
To address the question of whether gene products of the HLA class II complex might contribute to GCA, Weyand et al. analyzed the functionally most important locus, HLA-DRB1, in a cohort of patients with biopsy-proven disease.
Among the patients, 3 allelic variants of the HLA-DRB1*04 family were found to be overrepresented. Interestingly, GCA was linked to the same allelic variant as rheumatoid arthritis . However, a consecutive case series study demonstrated that GCA and RA rarely co-occurred, supporting the interpretation that distinct functional domains of the HLA-DR molecule are implicated in the pathomechanisms of these 2 autoimmune diseases.
(The HLA-DRB1 locus as a genetic component in giant cell arteritis, 1992)
(Temporal arteritis)
TREATMENT
Corticosteroids, typically high-dose prednisone (1 mg/kg/day), must 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.
Chemical structure of prednisone
The dose of prednisone is lowered after 2–4 weeks, and slowly tapered over 9–12 months. Tapering may require two or more years. Oral steroids are at least as effective as intravenous steroids, except in the treatment of acute visual loss where intravenous steroids appear to offer significant benefit over oral steroids.
It is unclear if adding a small amount of aspirin is beneficial or not as it has not been studied.
Unlike methotrexate and tumor necrosis factor-α antagonists (also used in Horton' therapy), anti-interleukin-6 receptor therapy appears to be useful in patients with GCA who are refractory to corticosteroids.
Figure 1: High-resolution MRI of the frontal branch of the right temporal artery
Figure 2: High-resolution MRI of the same patient after 8 weeks of corticosteroids at nearly the same region and identical scan parameters as in Figure 1
(Histological parameters helpful in recognising steroid‐treated temporal arteritis: an analysis of 35 cases, 2007)
(Steroid management in giant cell arteritis, 2001)
(Giant cell arteritis and polymyalgia rheumatica: an update, 2015)
(Images)
