What is Giant Cell Arteritis?
Giant cell arteritis (Horton’s syndrome, temporal, or cranial, arteritis) is a kind of inflammatory lesion of medium and large arteries in the elderly.
Pathogenesis during Giant Cell Arteritis
There are specific indications of the presence of cellular and humoral immune responses in relation to the elastic tissue of the arteries. Some authors have found in the active phase of the disease a moderate increase in serum immunoglobulins and immune complexes, an increased number of circulating lymphoblasts, and sometimes the deposition of immunoglobulins and complement in the arterial wall. These data, however, have not yet led to the creation of a sound concept regarding the regular changes in the immune status of the disease in question. Giant cell arteritis develops predominantly in the white race, which suggests some role for genetic factors. This also corresponds to several reports of the occurrence of the disease among members of one family, including monozygous twins. At the same time, associations with any histocompatibility antigens are not observed.
The localization of vascular changes and their histological picture somewhat resemble Takayasu’s syndrome, although these diseases differ sharply in the age composition of patients. In principle, with giant cell arteritis, almost any large or medium artery can be involved in the process. Changes in arterioles and capillaries does not happen. In patients who died in the active phase of the disease, lesions of the temporal, vertebral, ocular and posterior ciliary arteries are most often found. Also characteristic changes in the carotid arteries, central retinal arteries, aorta (with the possible development of its aneurysms and ruptures), subclavian, iliac, and mesenteric arteries are quite common. There are reports of inflammation of the coronary arteries with the corresponding ischemic manifestations.
The nature of the lesion of the arteries is almost always focal or segmental; for a considerable length of time, the vessels are not involved in the process. In the early stages, lymphocytic infiltration of the inner and outer elastic membranes, intimal thickening are noted. Later in the arteries of medium caliber in the intima and media find clusters of cells in the form of granulomas consisting of lymphocytes, plasma and epithelioid cells, histiocytes and giant multinucleated cells. The latter, although they gave the name to the entire nosological unit, are not defined in some patients in the biopsy material and therefore cannot be considered a mandatory histological basis for the diagnosis. There may also be eosinophils in the granulomas; neutrophils are uncharacteristic. In the aorta and large vessels, the inflammatory process is especially pronounced in the media, and fragmentation of elastic fibers is also observed. Accordingly, foci of inflammation may occur thrombosis. Fibrinoid necrosis, so typical of necrotizing arteritis, is not characteristic of Horton syndrome.
Giant cell arteritis is a disease of old and old age – the average age of its onset is about 70 years (with fluctuations from 50 to 90 years and older). The onset of the disease before the age of 50 is a very rare exception and always raises doubts in the diagnosis. Men and women get sick with approximately the same frequency, some authors point to the predominance of women. It draws attention that even those who are sick at old age are almost always physically and mentally well-preserved people, which may indirectly indicate the need for a sufficiently high level of immunity for the development of this disease.
Symptoms of Giant Cell Arteritis
The onset of the disease can be both acute and gradual. Specific clinical signs associated with the defeat of certain arteries are often preceded by such common symptoms as an increase in body temperature (from subfebrile to 39-40 ° C), weakness, loss of appetite, sweating, and noticeable weight loss. Unidentified fever, genesis in elderly people, combined with high ESR, is often a manifestation of giant cell arteritis. Among the symptoms that directly reflect the involvement of the arteries in the process, the most frequent is headache, which occurs in 60-70% of patients. Sometimes it turns out to be the first sign of a disease. Her character is different both in intensity, and in localization and duration. In some cases, the pain corresponds to the location of the superficial arteries of the head (temporal, occipital), but is often perceived as diffuse. The same applies to palpation pain of the skin of the head – it is especially pronounced when pressing on these arteries, but can be spilled. In some patients, the individual superficial arteries of the head (often the temporal) are not only painful, but also unevenly compacted and tortuous, the skin over them is sometimes weakly erythematous. An infrequent, but practically pathognomical symptom of giant cell arteritis is periods of severe pain in the masticatory muscles and tongue during chewing and speaking, which causes Temporarily to stop the corresponding movements (syndrome of “intermittent claudication” of the masticatory muscles and tongue caused by insufficient blood supply to their muscles).
Each patient with giant cell arteritis causes a special vigilance regarding possible damage to the organ of vision. Relatively often observed ocular pathology includes diplopia, ptosis, partial or complete loss of vision, which can be both temporary and permanent. It is believed that blindness is more often caused by ischemia of the optic nerve due to inflammation of the branches of the ophthalmic or posterior ciliary artery, than by thrombosis of the affected retinal arteries. Rarely, blindness may be the first sign of illness, but usually develops weeks and months after the onset of other symptoms (including ocular symptoms), and therefore promptly prescribed treatment can prevent this pathology. At the slightest suspicion of giant cell arteritis, a careful re-examination of the fundus is necessary.
Clinical symptoms of involvement in the process of large arteries are observed in 10-15% of patients. These include the reduction or absence of a pulse in the arteries of the neck or arms, noise above the carotid, subclavian and axillary arteries, periods of pain and weakness in the muscles of the limbs. During angiography, alternation of arterial stenosis with smooth internal contours (sometimes also complete vascular obstruction) and sections of arteries of normal or increased diameter are of the greatest diagnostic value. Also characteristic localization of lesions is taken into account. Among the specific manifestations of vascular pathology, angina, myocardial infarction and circulatory failure, strokes with hemiparesis, psychosis, depression, stupefaction, acute hearing loss, peripheral neuropathy, aortic ruptures, mesenterial thrombosis were observed. In cases of severe narrowing of the arteries, rare cases of gangrene of the limbs, scalp, and even the tongue are described.
A peculiar manifestation of giant cell arteritis can be rheumatic polymyalgia syndrome. Its main clinical features are severe pain and a feeling of stiffness in the muscles of the shoulder and pelvic girdle and proximal arms and legs, which severely limits movement. We are talking about muscle pain, although they are often incorrectly interpreted as joint pain. Actually arthralgia with the considered syndrome is rare, and true synovitis, sometimes described, is an obvious exception. The development of the symptom complex of rheumatic polymyalgia must necessarily give rise to the idea of the possibility of giant cell arteritis, although more often rheumatic polymyalgia appears to be an independently existing syndrome (also in the elderly and old) without objective clinical and morphological signs of vasculitis.
The most important laboratory feature of giant cell arteritis (as well as isolated rheumatic polymyalgia) is an increase in ESR, usually up to 50-70 mm / h. Other laboratory parameters include mild normochromic anemia, normal white blood cell count, elevated a2-globulin and platelet levels. There are indications of the possibility of a slight increase in serum alkaline phosphatase activity and aminotransferase.
Diagnosis of Giant Cell Arteritis
The diagnosis of giant cell arteritis usually presents great difficulties for doctors and very rarely is established at the onset of the disease. The main obstacle to its proper recognition is a low awareness of the disease, and therefore even rheumatologists do not have appropriate assumptions. Giant cell arteritis should be suspected in the elderly with an inexplicable sharp increase in ESR combined with moderate anemia, and sometimes with high fever (permanent or episodic) even in cases where no other symptoms are detected. The purposeful study of the temporal, occipital, carotid and distally located arteries is extremely important, which allows us to establish in some patients their sensitivity, thickening of the walls (sometimes clearly defined), weakening of the pulsation, the appearance of noise over large arterial trunks. It is clear that in the syndrome of rheumatic polymyalgia the need for such a study is most obvious. Symptoms such as severe headache, sharp recurrent pain and spasm of the masticatory muscles, direct consequences of impaired blood circulation (heart attack, stroke, etc.) reinforce the diagnosis in many patients. For proper recognition of the disease, eye symptoms are also very important (blurred vision, double vision, etc.), which at the same time are an indication of the real threat of blindness. With the help of ophthalmoscopy most often reveal the development of ischemic neuritis of the optic nerve. The presence of a normal or only slightly increased ESR, as well as the young age of the patients, practically excludes the diagnosis of giant cell arteritis. Informative vivid therapeutic effect of adequate doses of prednisone, in particular, the rapid normalization of temperature.
In case of doubt, arteriography and especially a biopsy of the temporal artery should be resorted to. If the latter is clearly changed, then for the biopsy a limited segment is taken from the affected part of the vessel. In the absence of clinical changes in the artery, histological confirmation of the diagnosis sometimes required a section of the vessel 4–6 cm long.
Treatment of Giant Cell Arteritis
The main and essentially the only effective method of treating patients with giant cell arteritis and at the same time reliable secondary prevention of its catastrophic complications is the administration of sufficiently high doses of corticosteroids. Treatment with these drugs should begin immediately after diagnosis. As a rule, therapy begins with 50-60 mg of prednisolone per day, administered after a meal in 3 divided doses. This dose is recommended to remain unchanged for 4 weeks, after which they begin its slow and gradual decrease in such a way that hormone therapy is canceled in 10-12 months. Very rarely, therapy has to be carried out for more than a year – while the patient usually takes maintenance doses for a long time — about 10 mg of prednisone. Treatment with prednisone in the indicated initial doses (50-60 mg) in at least 90% of patients gives a vivid effect, manifested in the rapid elimination of fever, general weakness, headache, rheumatic polymyalgia syndrome (this syndrome usually disappears or decreases sharply during the first days ) and a steady decline in ESR. As a rule, clinical symptoms subside within a few days, and ESR and hemoglobin levels normalize within 2 weeks. After 1-2 months, an objective improvement can be recorded on arteriograms.
The first dose reduction of prednisolone can be carried out only after the clinical symptoms are completely eliminated and the ESR is normalized, and subsequently the doses should be reduced under mandatory clinical and laboratory control. Even a mild return of clinical symptoms and an increase in ESR indicate that the next dose reduction was premature. In approximately 10% of patients, an initial daily dose of prednisone equal to 60 mg is ineffective and should be increased to 80 mg. In such cases, it seems reasonable to start treatment with a three-day pulse therapy with methylprednisolone (1000 mg per day intravenously), and then switch to taking the drugs by mouth. This method is especially indicated for those patients who have threatening signs of ocular pathology. There is a message about the rapid recovery of vision in a patient with giant cell arteritis after intravenous administration of 500 mg of methylprednisolone (immediately after the development of blindness). This fact is of particular importance, since the appointment of prednisolone inside after the loss of vision can not lead to success.
It should be emphasized that in some patients the complete suppression of the symptoms of giant cell arteritis is achieved by lower doses of hormonal drugs. So, we observed patients with a true remission of the disease as a result of prednisone administration in the initial daily dose of 40 mg (including in suppositories) and even 15 mg. Naturally, these individuals did not have ocular symptoms, which made it possible to begin treatment with lower doses.
Tolerance to prednisolone in patients with giant cell arteritis is relatively good, although one constantly has to bear in mind that we are talking about patients of old and old age, in whom steroid complications, in particular, osteoporosis, occur relatively often. Attempts to concomitantly use long-acting drugs (azathioprine, D-penicillamine, plaquenil, dapsone, and especially cyclophosphamide) for the “basic” suppression of the pathological process and a possible reduction in the dose of prednisolone have not yet led to convincing results. Therefore, long-term administration of corticosteroids (primarily prednisolone) is still considered the only reliable and almost “specific” method for treating giant cell arteritis. It should be borne in mind that the dose of the drug should be evenly distributed throughout the day (usually it is prescribed in 3 doses). Taking the entire daily dose in the morning and especially the alternating dose (i.e. the use of prednisone every other day) is much less effective and not recommended.
Hormone therapy can be considered justified even if only serious suspicions of giant cell arteritis occur. In such cases, a quick and bright positive effect of treatment becomes an important additional criterion for diagnosis. If a patient with an inaccurate, but supposed diagnosis of giant cell arteritis develops any ocular symptoms, then the immediate prescription of prednisone is necessary.