7 Complications of giant cell arteritis BO-ERIC
MALMVALL
Polymyalgia rheumatica is a clinical manifestation of giant cell arteritis (GCA) (Bengtsson and Malmvall, 1982). This inflammatory disease involves large and medium-sized arteries. The complications of the disease are mainly caused by arteritic lesions resulting in ischaemia of different organs. Vascular complications are threats to the lives of GCA patients as the disease can involve vital arteries such as the coronaries, the aorta and the cerebral vessels. Fortunately such complications seldom occur in patients who have had a proper diagnosis and corticosteroid treatment. However, series of patients reported before 1950, when corticosteroid treatment became available, include a high frequency of ocular and neurovascular complications. It is now well-established that ischaemic complications of GCA can be prevented by adequate corticosteroid treatment. This chapter will deal mainly with the vascular complications of the disease but it will also discuss the complications in joints. The complications of the disease in the eye and ocular nerve are discussed in Chapter 6. The liver involven~ent of GCA is discussed in Chapter 8, and complications of treatment are discussed in Chapter 9.
MORTALITY GCA is a disease of elderly people. All studies on mortality risks must therefore be based on comparisons with life expectancy of the general population in the same age range. There are several studies concluding that the expected survival time for patients with GCA is not reduced compared with the general population. Other studies have found an increased risk of death after the onset of GCA. In a retrospective study performed at the Mayo Clinic, Hauser et al (1971) found that survival determinations by life-table methods revealed no evidence of reduced survival in individuals who had temporal arteritis. All the patients in this study were treated with corticosteroids. Huston et al (1978) came to the same conclusion in their study of 42 cases of temporal arteritis in Olmsted County, Minnesota. A Swedish prospective study of 90 patients, all treated with corticosteroids and followed for 3-10 years, reported that 13 patients died during the Bailli~re's Clinical Rheumatology-Vol. 5, No. 3, December 1991 ISBN 0-7020-1537-7
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follow-up period. The expected mortality according to age and sex was calculated to be 25. Thus, in this study the mortality rate in GCA patients was reduced as compared with the general Swedish population (Bengtsson and Malmvall, 1981). The same series of patients was followed up at a median time of 11.3 years after diagnosis. The number of GCA patients still alive after 5 years was higher than expected. After 10 and 15 years the number of patients surviving equalled the expected number (Andersson et al, 1986). In a Scottish study of 136 cases of histologically proven temporal arteritis there was no reduction in survival time as compared with expected numbers of deaths (Jonasson et al, 1979). Contrary to the findings in these studies, Graham et al (1981) reported significantly increased mortality among women but not among men in a study of 90 patients. High maintenance dose of corticosteroids and visual loss were significantly associated with a shortened life span. The patients in this retrospective study were all attending departments of ophthalmology or neurology and were therefore highly selected cases with a high frequency of visual and neurological complications. The different survival rate in this report can be explained by the selection of the patients. In a recent study from Gothenburg, Sweden, death rates and causes of death were studied in 284 consecutive patients with GCA confirmed by biopsy (Nordborg and Bengtsson, 1989). All patients who had had a temporal artery biopsy performed were included. During the first year after diagnosis the number of deaths from vascular disorders was 21, as compared with the expected number seven: a highly significant difference. Seventeen of these 21 subjects died within 4 months of diagnosis. All 17 were treated with corticosteroids but in 13 the treatment was insufficient to suppress symptoms and signs of the disease. The authors conclude that patients with GCA run an increased risk of dying from vascular disorders in the initial phase of the disease. Four months after the start of corticosteroid treatment, the risk equalled that of the general population. The risk of death for patients who are not treated with corticosteroids is not known. The increased mortality rate in vascular disorders during the first months and the well-established occurrence of vascular complications in untreated patients may be reasons for assuming that untreated GCA is a lifethreatening vascular disease. However, it can be concluded that the survival rate in patients with GCA on maintenance corticosteroid therapy, in doses sufficient to control the symptoms and inflammatory blood parameters, is equal to the general population with respect to age and sex. The doctor treating an elderly woman with GCA can, after the first months, assure the patient that her disease is not reducing her life expectancy. VASCULAR COMPLICATIONS The most common severe complications of GCA are caused by arteritic lesions in the aortic wall, the coronary arteries and arteries supplying the brain with blood.
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Aortitis and aortic stenosis
In one of the earliest reports on temporal arteritis, Jennings (1938) reported that the blood pressure in the arms differed in one patient. Gilmour (1941) described autopsy findings of arteritis in the aorta and its branches in four cases of GCA. Heptinstall et al (1954) reported another two cases of widespread aortitis. The histological changes in the aorta were similar to those found in the temporal arteries of 11 patients. In his extensive work on GCA, Hamrin (1972) made very careful clinical observations. By using the name polymyalgia arteritica he stressed the close relationship between the rheumatic complex of symptoms and the underlying arteritic disease. In his series from Vfixj6, Sweden, he described aortic arch syndrome in 14 out of 93 patients. Arteriography showed severe stenotic changes, often in the axillary artery. In the USA Hunder et al (1967) described a woman with stenotic changes in the aorta and large arteries close to the aorta visualized by angiography. The diagnosis was established by a temporal artery biopsy, and improvement of the peripheral pulses followed treatment with prednisone. In a large series of 248 patients with GCA seen at the Mayo Clinic, 34 patients showed evidence that the disease affected the aorta or its major branches (Klein et al, 1975) and recent reports on patients with GCA include cases of aortic and large vessel involvement (Kyle et al, 1987; Ninet et al, 1990). The involvement of the aorta is usually restricted to its thoracic portion. Most cases have no symptoms of their aortitis. The lesions are segmentally distributed and segments of the vessel severely affected by stenosis can be found, with normal portions between (Ostberg, 1972). The clinical manifestation may only be a difference in arterial blood pressure between the arms, while other patients suffer from pulseless disease with absence of radial pulses. Murmurs Over the aorta and the large arteries are common in series of GCA. Hamrin (1972) found arterial murmurs in 47% of his 93 patients when examined after 18 months of disease, as compared with 10% in controls. In another Swedish study on 73 patients, 8% had a difference in systolic blood pressure of more than 25 mmHg between the arms (Bengtsson and Malmvall, 1982). Dissecting aortic aneurysm
The arteritic lesions caused by GCA in the aorta can result in a dissecting aneurysm. In her morphological description of 16 autopsy cases with GCA engaging the aorta and its branches, Ostberg (1972) reported aortic dissecting aneurysm in two patients. In the large Mayo Clinic series of 248 patients, three patients died with aortic rupture (Klein et al, 1975). GCA as a cause of death was illustrated by a report on nine cases with fatal arteritic lesions (Sfive-S6derbergh et al, 1986). Two of these patients died with dissecting aortic aneurysms. Both were old women. One had suffered from fatigue and fever for months until she died; autopsy revealed the diagnosis. The second patient had had a diagnosis of GCA by temporal artery biopsy. When the corticosteroids were reduced the disease flared up, resulting in the fatal rupture of the aorta.
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A recent paper from Japan describes two elderly women who both died suddenly as a result of aortic dissection. Histologically, marked inflammation with giant cells was observed in the wall of aorta as well as in other arteries, including the cranial arteries (Murai et al, 1989).
Coronary arteritis A few cases of G C A in the coronary arteries have been described. Martin et al (1980) drew attention to this uncommon complication to G C A by reporting one elderly woman who died from G C A of the coronary arteries. In one of the arteries a thrombus was found superimposed on active arteritic changes. The same year, Paulley (1980) wrote in a letter to the Lancet that numerous cases of ischaemic heart disease and claudication due to G C A continued to come his way and that these benefited dramatically from corticosteroids. This letter was written as a complement to the paper of Strachan et al (1980), who described four cases of G C A with some of its lesser known presentations, which the authors described as 'masked giantcell arteritis'. In a polemic article in the American Heart Journal, How et al (1980) appointed G C A a cardiological blind spot. He argued that G C A involvement of the coronaries is frequently missed by cardiologists due to the dominance of atherosclerosis in the league of diseases in western countries. In more recent literature, little is written about G C A as a cause of myocardial infarction. S~ive-S6derbergh et al (1986) described two cases of fatal G C A in the coronary arteries. One of these women had a recent diagnosis of G C A , while the second had suffered from polymyalgia rheumatica for 3 years and died when she sustained a flare-up of the disease. Autopsy gave the histological diagnosis: G C A in the coronary arteries. Thus, coronary G C A is a well-described, sometimes fatal complication of GCA. The frequency is not known. The increased number of deaths from vascular disorders during the first 4 months after the diagnosis of G C A , as observed by Nordborg and Bengtsson (1989), is interesting. Myocardial infarction and cardiac failure were the causes of death in six of 17 subjects dying during the first period of onset of GCA. The appointment of G C A as the cardiological blind spot made by How (1980) also seems to be appropriate in the 1990s. For a patient with general symptoms of fever and fatigue, and laboratory parameters indicating inflammation, a differential diagnosis in the case of chest pains can be G C A in the coronaries. Most but not all patients with myocardial infarction suffer from arteriosclerosis; some may have an inflammatory coronary disease which can be treated successfully with corticosteroids.
Pericarditis Pericarditis is a well-known p h e n o m e n o n in different types of vasculitis. In G C A it seems to be a rare complication as very few cases of pericarditis in patients with G C A have been described. There are no systematic studies searching for pericarditis in G C A patients. In our series of 95 cases of newly
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diagnosed GCA we found two cases with chest pain during the acute phase of GCA, in whom pericardiac effusion was visualized by ultrasonography (Bengtsson and Malmvall, 1982). In addition to our cases, just a few others have been reported in the literature. All the reported cases of GCA pericarditis have promptly improved on corticosteroids (Clementz et al, 1989; Sonnenblick et al, 1989). Arteritis in vessels to the brain
The connection between an inflammatory disease of the temporal artery and loss of sight was described in the tenth century in the Tadkivat ofAli Ibn Isa (Wood, 1936). In modern medicine this old observation was rediscovered and reported by Jennings (1938). It became well known during the 1940s that ischaemic damage to the optic nerve was a frequent complication of temporal arteritis. Other cerebrovascular complications were described as rare cases, although the pathological basis of neurological complications, namely arteritis in the cerebral arteries, was reported as early as 1941 by Gilmour. In an extensive review, Hollenhorst et al (1960) summarized the clinical findings in 175 patients with GCA diagnosed at the Mayo Clinic during the years 1931-1959. Neurological complications of temporal arteritis, other than those related to the vision were noted, but at an incidence rate that was described as exceedingly low. As many as 102 (58%) patients had some form of ocular involvement, 73 (42%) permanently lost part or all of their vision and 21 (12%) were completely blind in both eyes at the time of discharge. Two patients had cerebral haemorrhage, one had a stroke several weeks after the onset of the disease and one suffered acute toss of hearing. In October 1949, adrenocorticosteroids became available and all patients with temporal arteritis were treated as emergencies with cortisone or other adrenocorticosteroids. Only one patient lost vision after this therapy was started. Some years later, Meadows (1966) described 80 personal cases of temporal arteritis with neuro-ophthalmic complications. Blindness and ophthalmoplegia were the dominating findings. One of his cases died of coronary occlusion and autopsy revealed GCA in the vertebral artery with parenchymatous changes in the brain stem, cerebellum and vermis. Another case with clinical evidence of brain-stem infarction was also reported. He concluded, based on his own experience and a literature review, that there were adequate pathological, angiographic and clinical evidence for the view that affection of the vertebral, internal carotid and cerebral arteries is as much a part of the spectrum of GCA as is involvement of the temporal artery and ophthalmic vessels. Four cases who died during the active phase of GCA were described in detail by Wilkinson and Russell (1972). They had also found another eight cases in the literature between the years 1940 and 1971 where autopsy findings after adequate post-mortem examinations were reported. The superficial temporal, vertebral, ophthalmic and posterior ciliary arteries were those most frequently and severely involved in the disease. The vertebral artery was severely involved throughout its length, with a sharply
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defined upper border just above the point of dural perforation in their four cases. They also noticed that the intracranial portion of the arteries was not involved in the inflammatory process, apart from the first 5 mm of the vertebral arteries inside the dura. They related the inflammatory reaction to the structures in the arteries rich in elastin. According to these authors, the relatively low amount of elastic tissue in intracranial arteries was the explanation for the absence of inflammatory changes inside the skull. Others, however, have reported intracranial distribution of the arteritis in G C A (Kjeldsen and Reske-Nielsen, 1968). In an article on G C A as a cause of death, S/ive-S6derbergh et al (1986) made a careful analysis of autopsy findings of arteritis. Five of the nine fatal cases described died from cerebral stroke. The arteritis was found in the carotid arteries and the vertebral arteries supplying the brain, but also in the intracranial arteries, particularly the basal cerebral arteries. The regular finding was arteritis of the vertebral artery resulting in infarctions in the occipital part of the brain, the brain stem, pons and cerebellum. The finding of arteritis in intracranial segments of the arteries in six patients is contradictory to the theory of Wilkinson and Russel. In one case, however, the severe arteritic changes were seen in the vertebral artery only outside the dura and just at the point of passage to the skull. In seven out of these nine cases the first symptoms and signs of cerebral ischaemia started before or during the first weeks of corticosteroid treatment. The other two cases had corticosteroid treatment in insufficient doses, as indicated by symptoms of G C A and elevated ESR. In a systematic study on 166 biopsy-proven cases of G C A seen at the Mayo Clinic, Caselli et al (1988a) carefully registered neurological symptoms in the period of clinically active GCA. Cerebrovascular events as transient ischaemic attacks or brain infarctions were registered in 12 patients (7%). Compared with cerebral infarctions due to all causes, vertebrobasilar distribution of the damage was more c o m m o n among the GCArelated ischaemic events. A recent case report stresses that G C A can present with symptoms due to vertebral arteritis without any other clinical manifestation of the disease (Collado et al, 1989). By using modern neuroimaging techniques as computerized tomography and magnetic resonance imaging, a diagnosis of multi-infarct dementia was established in three cases of GCA. The multiple infarctions were found mainly in the posterior part of the brain and cerebellum. All three patients developed their dementia during periods of corticosteroid reduction. Increased dose of corticosteroids is recommended to suppress the arteritis (Caselli, 1990). Cerebrovascular disease can be considered as one of the leading causes of death not only in untreated G C A but also during early or insufficient treatment. The frequency of cerebrovascular disease caused by G C A is of course difficult to assess as G C A is a disease of elderly people. The aetiological relationship between G C A cerebrovascular disease in only presumptive in cases that have not been examined by an autopsy. However, the frequency with which this complication occurs is estimated to be 1-3% of all
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GCA patients. The risk of fatal cerebrovascular disease caused by GCA is reduced when the disease activity has been controlled by corticosteroid treatment for a couple of months. For newly diagnosed cases of GCA with symptoms indicating cerebrovascular involvement, high dose corticosteroid (prednisolone 60 mg/day) treatment is recommended. Hypopituitarism, probably due to pituitary infarction, was described by Hamrin (1972) as another extremely rare intracranial manifestation of GCA. Inappropriate secretion of antidiuretic hormone in four cases of temporal arteritis indicates the arteritis can result in ischaemia of the pituitary gland or the hypothalamic region (Gentric et al, 1988).
Neuro-otological impairment The literature on GCA includes a few reports of impaired hearing and severe vertigo (Soelberg-S6rensson and Lorenzen, 1977; Jonasson et al, 1979; Caselli et al, 1988a). In the study by Caselli et al (1988a) on 166 consecutive biopsy-proven GCA cases seen at the Mayo Clinic, 11 (7%) had neuro-otological syndromes: eight had isolated vertigo, one vertigo and unilateral hearing loss, and two unilateral tinnitus. In our prospective study on 95 patients seen in Gothenburg (1972-1979), we asked about reduced hearing capacity during the active phase of GCA (Bengtsson and Malmvall, 1982). Six patients reported hearing impairment; one of them became completely deaf in her right ear. Before deafness, this patient had suffered from severe rotating vertigo and nystagmus. The vertigo disappeared after about i week but her deafness became permanent. Audiograms in all six patients revealed hearing reduction of neurogenic type. Repeated audiograms during corticosteroid treatment failed to show any improvement. In a case report, Kramer et al (1988) describe an 82-yearold man with sensorineural hearing loss as a presenting symptom of GCA. In this case the corticosteroid treatment was followed by a considerable improvement of hearing ability in one but not the other ear. The most likely explanation of the hearing loss and vertigo in GCA patients is deprivation of blood supply to the terminal cochleovestibular vessels (Sofferman, 1980). Another explanation could be arteritis more proximally, in the basilar artery or the posterior auricular artery, causing ischaemia in the hearing apparatus (Kramer et al, 1988).
Peripheral neuropathicsyndromes Peripheral neuropathies have not been given much attention in the literature on GCA. Mononeuropathies in the nerves of the arms and legs have been described but the pathogenetic relationship to GCA has been difficult to establish (Feigal et al, 1985). Caselli et al (1988b) have reported that 23 out of 166 patients with biopsy-proven GCA seen at the Mayo Clinic had clinically-diagnosed peripheral neuropathic syndromes. Electrophysiological studies in 16 patients confirmed the diagnosis. Of the 23 patients, 11 had a generalized peripheral
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neuropathy, nine had multiple mononeuropathies and three had a mononeuropathy. The nerves most commonly affected were the median, ulnar, peroneal and tibial nerves. Most patients' neuropathies improved after treatment with corticosteroids. Angiography of the lower limb arteries in two of the patients with severe neuropathies showed multiple high grade stenosis. One patient underwent amputation above the knee. Widespread chronic vasculitis of the medium and large arteries and ischaemic necrosis of nerve fascicles were found. The authors argue that the neuropathy resulted from nerve ischaemia due to vascular occlusion. A case report by Bridges et al (1989) describes a patient with biopsyproven GCA, leg ulcers and neuropathy. The ischaemic nature of the neuropathy is stressed and in this case the abnormalities improved after retreatment with prednisolone.
Lingual and skin necrosis The external carotid arteries are probably the most common site of arteritis in GCA. The disease affects this part of the circulation in most cases. Classical symptoms of GCA, such as temporal headache, scalp tenderness and jaw claudication, result from impaired circulation and rapidly disappear after corticosteroid administration. Severe impairment of the circulation in the external carotid vascular area can rarely result in tissue necrosis. Missen (1961) examined lingual arteries at autopsy in nine cases of cranial arteritis and found that nine of ten specimens demonstrated arteritis. In a clinical report on three cases, Sofferman (1980) points out that the lingual gangrene is preceded by lingual claudication. Pain in the tongue and paroxysmal blanching are important warnings of glossal ischaemia and impending lingual infarction. Tongue symptoms seem to be rather common among GCA patients, while established tongue gangrene is rare. The arteritic pathogenesis of the tongue infarction was proved in one of the cases by histological findings of arteritis in the lingual arteries. Skin necrosis of the head has been described in rare cases (Fleischel and Oldham, 1960; Abdullah et al, 1989). The necrosis may be localized to one or both sides and it may extend to a large area, with much of the scalp involved. After corticosteroid administration the skin defect healed in most of the reported cases.
Thyroid involvement The connection between temporal arteritis and goitre was observed by Lucien et al (1939) during the first years after temporal arteritis was regarded as a clinical entity. Arteritis was found in a small thyroid artery and was in fact the first histological evidence that the disease engages arteries other than the temporal vessels. In our series of 68 prospectively diagnosed cases of GCA, we observed subacute thyroiditis in two patients who had active arteritis (Malmvall and Bengtsson, 1978). The similarities between subacute thyroiditis and GCA with regard to histopathological findings and
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response to steroids are striking. The association between these two diseases have, however, not been discussed by other authors. Both hyperthyroidism and hypothyroidism are reported preceding or appearing simultaneously with active GCA (Sonnenblick et al, 1989; Wiseman et al, 1989). The published cases of thyroid disease and GCA probably just reflects the coincidence of two not uncommon diseases.
Renal involvement Unlike findings in other arteritic diseases, the kidney is not a target for pathology in GCA. Renal manifestations are most unusual in GCA and, when present, the most common findings are microscopic haematuria and red blood cell casts. Large series of patients with GCA do not include cases with impaired renal function due to GCA. In the few cases of decreased kidney function reported in the literature on GCA, other causes of renal failure have not been ruled out. In some other cases the arteritis described seems to be of a type other than GCA and affects small arteries and arterioles (Elling and Kristensen, 1980). Although the aorta is a main site of GCA, and arteritis is commonly found in the arteries close to the aorta, the renal arteries seem to be something of an exception. Severe renal artery stenosis has not been described in clinical and angiographic studies on GCA. Series of patients examined at post mortem include only a few cases of slight to moderate renal artery involvement (Ostberg, 1972).
Miscellaneous arteritic complications Abdominal symptoms of impaired mesenteric circulation have been reported in clinical series of GCA patients (Hamilton et al, 1971). Postmortem examinations of patients who have died with GCA have shown arteritis of mesenteric vessels (Hamrin et al, 1968; Ostberg, 1972). Rare cases of arteritis in the mesenteric arteries have been described as resulting in intestinal gangrene and perforation. Stenwig (1976) reported a case of GCA involving branches of the superior mesenteric artery as well as the temporal artery. The intestinal wall was necrotic and arteritis in mediumsized and small arteries was found in several sections of the mesentery. A similar case was reported from Canada by Srigley and Gardiner (1980). A patient with small intestinal perforation secondary to localized GCA in the mesenteric vessels but with no evidence of arteritis at other sites is also reported (Smith et al, 1988). In three recently described cases of temporal arteritis intestinal perforation occurred after the resolution of cranial manifestations when the patients were on corticosteroids (Patsner et al, 1989). The female genital tract has been reported to harbour GCA in a few rare cases. Arteritis has been found in myometrial arteries (Kyle et al, 1987) and in myometrium, as well as parametrium and ovarian arteries (Birch and Buchanan, 1989).
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SYNOVITIS In the literature on GCA, and particularly the clinical syndrome of polymyalgia rheumatica (PMR), there are different opinions about the importance of joint involvement. Dixon (1983) stated that true synovitis does not occur in patients with PMR. Traditionally, PMR and GCA have been viewed as a vascular disease, with muscle symptoms most probably caused by impaired circulation. Pain in the neck, the shoulders, in the lumbar region and around the hips are the characteristic symptoms of PMR. These symptoms are believed to be caused by the arteritis in the vessels to the muscles. Arteritis in, for example, the gluteal arteries has been demonstrated by Hamrin (1972). In several large Scandinavian series of patients with GCA, synovitis is reported in a small number of cases (Fauchald et al, 1972; Hamrin, 1972; Soelberg-S6rensen and Lorenzen, 1977; Malmvall and Bengtsson, 1978). The objective signs of synovitis as joint swellings were rare and often mild and transient. Synovial biopsies from large joints have revealed mild and non-specific synovitis in patients suffering from PMR in a few studies (Bruk, 1967; Henderson et al, 1975). By using joint scintigrams one research group has demonstrated abnormal uptake mainly in the shoulders of patients with PMR (O'Duffy et al, 1976, 1980). These findings were interpreted as evidence of chronic axial synovitis. The results have been debated as there was a poor correlation between clinical and scan abnormalities. The isotope scan results in these studies may have been overinterpreted because of degenerative diseases in this group of elderly patients (Kyle et al, 1990). In a recent American survey of 520 patients with biopsy-proven GCA, 19 were found to have persistent symmetric polyarthritis indistinguishable from rheumatoid arthritis (Ginsburg et al, 1985). However, none had nodules or extra-articular features. In three patients the polyarthritis and GCA had a simultaneous onset, while seven developed polyarthritis within 3 years of the onset of GCA. In one patient who underwent total knee arthroplasty the pathological examination revealed mononuclear cell infiltration and giant cells in the synovium. The authors are cautious in their interpretation: patients seen at a referral centre such as the Mayo Clinic are not representative, and the number of patients with two diseases may be higher than expected. However, they stress that seronegative polyarthritis, although uncommon, may be a clinical manifestation of GCA. The rarity of synovitis in PMR is illustrated by a study by Kyle et al (1990). By using X-rays, isotope scans, thermography and clinical examination in a prospective study, three patients out of 56 were found to have joint pains and swelling coincidentally with PMR. Wrist synovitis was present in one patient; the sternoclavicular and acromioclavicular joints were affected in the other two. The conclusion of this paper is that peripheral and axial synovitis is uncommon in PMR patients. In the rare patient where synovitis occurs, it is transient, non-erosive and non-deforming. The frequency of rheumatoid factors in the serum of patients with GCA does not differ from that of controls in the same age range (Malmvall et al, 1981; Ginsburg et al, 1985).
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In conclusion, synovitis is not a common clinical feature of GCA. The pains cannot usually be explained by joint involvement. Coincidence of synovitis and other symptoms of GCA occur in a minority of patients. The manifestations of joint involvement of GCA are usually mild and transient when corticosteroids are given. REFERENCES Abdullah AN, Keczkes K & Wyatt E H (1989) Skin necrosis in giant cell (temporal) arteritis; report of three cases. British Journal of Dermatology 120: 843-846. Andersson R, Malmvall BE & Bengtsson BA, (1986) Long-term survival in giant cell arteritis including temporal arteritis and polymyalgia rheumatica. Acta Medica Scandinavica 220: 361-364. Bengtsson B ~ & Malmvall BE (1981) Prognosis of giant cell arteritis including temporal arteritis and polymyalgia rheumatica, a follow-up study on 90 patients treated with corticosteroids. Acta Medica Scandinavica 209: 337-345. Bengtsson BA & Malmvall BE (1982) Giant cell arteritis. Acta Medica Scandinavica, Supplement 658: 1-102. Birch PJ & Buchanan R (1989) A gynaecological complication of polymyalgia rheumatica/giant cell arteritis. British Journal of Obstetrics and Gynaecology 96: 1356-1358. Bridges A J, Porter J & England D (1989) Lower extremity peripheral neuropathy and ischemic ulcers associated with giant cell arteritis. Journal of Rheumatology 16: 1366-1369. Bruk MI (1967) Articular and vascular manifestations of polymyalgia rheumatica. Annals of the Rheumatic Diseases 26: 103-113. Caselli RJ (1990) Giant cell (temporal) arteritis: a treatable cause of multi-infarct dementia. Neurology 40: 753-755. Caselli RJ, Hunder G G & Whisnant JP (1988a) Neurologic disease in biopsy-proven giant cell (temporal) arteritis. Neurology 38: 352-359. Caselli RJ, Daube JR, Hunder G G & Whisnant JP (1988b) Peripheral neuropathic syndromes in giant cell (temporal) arteritis. Neurology 38: 685-689. Clementz GL, Gold F, Khaiser N, Zolin WD & Jalovec L (1989) Giant cell arteritis associated with pericarditis and pancreatic insufficiency in a patient with psoriatic arthritis. Journal of Rheumatology 16: 128-129. Collado A, Santamaria J, Ribalta T et al (1989) Giant-cell arteritis presenting with ipsilateral hemiplegia and lateral medullary syndrome. European Neurology 29: 266-268. Dixon A St J (1983) Polymyalgia rheumatica. In Hawkins C & Currey HLF (eds) Reports on Rheumatic Diseases, No. 86. London: Arthritis and Rheumatism Council. Elling H & Kristensen IB (1980) Fatal renal failure in polymyalgia rheumatica caused by disseminated giant cell arteritis. Scandinavian Journal of Rheumatology 9: 206-208. Fauchald P, Rygvold O & Oystese B (1972) Temporal arteritis and polymyalgia rheumatica. Annals of Internal Medicine 77: 845-852. Feigal DW, Robbins DL & Leek JC (1985) Giant cell arteritis associated with mononeuritis multiplex and complement-activating 19S IgM rheumatoid factor. American Journal of Medicine 79: 495-500. Fleischl P & Oldham BE (1960) Temporal (giant-cell) arteritis associated with gangrene of scalp. British Medical Journal 1: 439-440. Gentric A~ Baccino E, Mottier D, Islam S &Cledes J (1988) Temporal arteritis revealed by a syndrome of inappropriate secretion of antidiuretic hormone. American Journal of Medicine 85: 559-560. Gilmour JR (1941) Giant-cell chronic arteritis. Journal of Pathology 53: 263-277. Ginsburg WW, Cohen MD, Hall SB, Vollertsen RS & Hunder GG (1985) Seronegative polyarthritis in giant cell arteritis. Arthritis and Rheumatism 28: 1362-1366. Graham E, Holland A, Avery A & Russel RWR (1981) Prognosis in giant-cell arteritis. British Medical Journal 282: 269-271. Hamilton CR, Shelley WM & Tumulty PA (1971) Giant cell arteritis: Including temporal arteritis and polymyalgia rheumatica. Medicine 50: 1-27.
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Hamrin B (1972) Polymyalgia arteritica. Acta Medica Scandinavica, Supplement 533: 1-164. Hamrin B, Jonsson N & Hellsten S (1968) Polymyalgia arteritica. Further clinical and histopathological studies with a report of six autopsy cases. Annals of the Rheumatic Diseases 27: 397-405. Hauser WA, Ferguson RH, Holley KE & Kurtland LT (1971) Temporal arteritis in Rochester, Minnesota, 1951 to 1967. Mayo Clinic Proceedings 46: 597-602. Henderson DRF, Tribe CR & Dixon ASTJ (1975) Synovitis in polymyalgia rheumatica. Rheumatology and Rehabilitation 14: 244-250. Heptinstall RH, Porter KA & Barkley H (1954) Giant cell (temporal) arteritis. Journal of" Pathology and Bacteriology 67: 507-519. Hollenhorst RW, Brown JR, Wagener HP & Schick RM (1960) Neurologic aspects of temporal arteritis. Neurology 10: 490-498. How J, Strachan RW & Bewsher PD (1980) Giant cell arteritis--a cardio-logical blind spot? American Heart Journal 100: 405-407. Hunder GG, Ward EL & Burbank MK (1967) Giant cell arteritis producing an aortic arch syndrome. Annals" of Internal Medicine 66: 578-582. Huston KA, Hunder GG, Lie JT, Kennedy RH & Elveback LR (1978) Temporal arteritis. A 25-year epidemiological, clinical and pathologic study. Annals of Internal Medicine 88: 162-167. Jennings GH (1938) Arteritis of the temporal vessels. Lancet i: 424-428. Jonasson F, Cullen JF & Elton R A (1979) Temporal arteritis. A 14 year epidemiological, clinical and prognostic study. Scottish Medical Journal 24: III. Kjeldsen MH & Reske-Nielsen E (1968) Pathological changes of the central nervous system in giant-cell arteritis. Acta Ophthalmologica 46: 49-56. Klein RG, Hunder GG, Stanson AW & Sheps SG (1975) Large artery involvement in giant cell (temporal) arteritis. Annals oflnternal Medicine 83: 806-812. Kramer MR, Nesher G & Sonnenblick M (1988) Steroid-responsive hearing loss in temporal arteritis. Journal of Laryngology and Otology 102: 524-525. Kyle V, Hamilton Dutoit S, Elias-Jones J & Hazleman B (1987) Giant cell arteritis of myometrial and axillary arteries and polymyalgia rheumatica. Annals of the Rheumatic Diseases 46: 256-258. Kyle V, Tudor J, Wraight EP, Gresham GA & Hazleman BL (1990) Rarity of synov!tis in polymyalgia rheumatica. Annals of the Rheumatic Diseases 49: 155-157. Lucien M, Mathieu L & Verain M (1939) Art6rite nodulaire de la t6te et du cou. Archives des Maladies du Coeur et des Vaisseaux 32: 603-605. Malmvall BE & Bengtsson BA (1978) Giant cell arteritis. Clinical features and involvement of different organs. Scandinavian Journal of Rheumatology 7: 154-158. Malmvall BE, Bengtsson BA., Nilsson LA, & Bjursten LM (1981) Immune complexes, rheumatoid factors, and cellular immunological parameters in patients with giant cell arteritis. Annals of the Rheumatic Diseases 40: 276-280. Martin JF, Kittas C & Triger D R (1980) Giant cell arteritis of coronary arteries causing myocardial infarction. British Heart Journal 43: 487-489. Meadows SP (1966) Temporal or giant cell arteritis. Proceedings of the Royal Society of Medicine 59: 329-333. Missen GAK (1961) Gangrene of the tongue. British Medical Journal 1: 1393-1394. Murai T, Saito K, Kuroda N e t al (1989) Acute aortic dissection due to giant cell arteritis. Report of two autopsy cases. Acta Pathologica Japonica 39: 821-826. Ninet JP, Bachet P, Dumontet CM et al (1990) Subclavian and axillary involvement in temporal arteritis and polymyalgia rheumatica. American Journal of Medicine 88:13-20. Nordborg E & Bengtsson B ~ (1989) Death rates and causes of death in 284 consecutive patients with giant cell arteritis confirmed by biopsy. British Medical Journal 299: 549-550. O'Duffy JD, Wahner HW & Hunder GG (1976) Joint imaging in polymyalgia rheumatica. Mayo Clinic Proceedings 51: 519-524. O'Duffy JD, Hunder G G & Wahner HW (1980) A follow-up study of polymyalgia rheumatica: evidence of chronic axial synovitis. Journal of Rheumatology 7: 685-693. C)stberg G (1972) Morphological changes in the large arteries in polymyalgia arteritica. Acta Medica Scandinavica, Supplement 533: 135. Patsner B, Pitzele S, Mann WJ & Chalas E (1989) Temporal arteritis and intestinal perforation. New York State Journal of Medicine 89: 476-477.
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Paulley JW (1980) Ischaemic heart disease in giant cell arteritis. Lancet i: 421. Sfive-S6derbergh J, Malmvall BE, Andersson R & Bengtsson BA (1986) Giant cell arteritis as a cause of death. Journal of the American Medical Association 255: 493-496. Smith JAE, O'Sullivan M, Gough J & Williams BD (1988) Small-intestinal perforation secondary to localized giant-cell arteritis of the mesenteric vessels. British Journal o f Rheumatology 27" 236-238. Soelberg-SOrensen P & Lorenzen I (1977) Giant-ceU arteritis, temporal arteritis and polymyalgia rheumatica. Acta Medica Scandinavica 201: 20%213. Sofferman RA (1980) Lingual infarction in cranial arteritis. Journal of the American Medical Association 243: 2422-2423. Sonnenblick M, Nesher G & Rosin A (1989) Nonclassical organ involvement in temporal arteritis. Seminars in Arthritis and Rheumatism 19: 183-190. Srigley JR & Gardiner GW (1980) Giant cell arteritis with small bowel infarction. American Journal of Gastroenterology 73: 157-161. Stenwig JT (1976) Intestinal gangrene due to giant cell arteritis. Report of a case. Journal of Oslo City Hospital 26: 49-55. Strachan RW, How J & Bewsher PD (1980) Masked giant-cell arteritis. Lancet i: 194-196. Wilkinson IMS & Russel RWR (1972) Arteries of the head and neck in giant cell arteritis. A pathological study to show the pattern of arterial involvement. Archives o f Neurology 27: 378-391. Wiseman P, Stewart K & Rai GS (1989) Hypothyroidism in polymyalgia rheumatica and giant cell arteritis. British Medical Journal 298: 64%648. Wood CA (1936) A Memorandum Book of a Tenth Century Oculist, a translation of the Tadkivat o f Ali Ibn Isa. Chicago: Northwestern University Press.
MALMVALL
Polymyalgia rheumatica is a clinical manifestation of giant cell arteritis (GCA) (Bengtsson and Malmvall, 1982). This inflammatory disease involves large and medium-sized arteries. The complications of the disease are mainly caused by arteritic lesions resulting in ischaemia of different organs. Vascular complications are threats to the lives of GCA patients as the disease can involve vital arteries such as the coronaries, the aorta and the cerebral vessels. Fortunately such complications seldom occur in patients who have had a proper diagnosis and corticosteroid treatment. However, series of patients reported before 1950, when corticosteroid treatment became available, include a high frequency of ocular and neurovascular complications. It is now well-established that ischaemic complications of GCA can be prevented by adequate corticosteroid treatment. This chapter will deal mainly with the vascular complications of the disease but it will also discuss the complications in joints. The complications of the disease in the eye and ocular nerve are discussed in Chapter 6. The liver involven~ent of GCA is discussed in Chapter 8, and complications of treatment are discussed in Chapter 9.
MORTALITY GCA is a disease of elderly people. All studies on mortality risks must therefore be based on comparisons with life expectancy of the general population in the same age range. There are several studies concluding that the expected survival time for patients with GCA is not reduced compared with the general population. Other studies have found an increased risk of death after the onset of GCA. In a retrospective study performed at the Mayo Clinic, Hauser et al (1971) found that survival determinations by life-table methods revealed no evidence of reduced survival in individuals who had temporal arteritis. All the patients in this study were treated with corticosteroids. Huston et al (1978) came to the same conclusion in their study of 42 cases of temporal arteritis in Olmsted County, Minnesota. A Swedish prospective study of 90 patients, all treated with corticosteroids and followed for 3-10 years, reported that 13 patients died during the Bailli~re's Clinical Rheumatology-Vol. 5, No. 3, December 1991 ISBN 0-7020-1537-7
461 Copyright 9 1991, by Bailli6re Tindall All rights of reproduction in any form reserved
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follow-up period. The expected mortality according to age and sex was calculated to be 25. Thus, in this study the mortality rate in GCA patients was reduced as compared with the general Swedish population (Bengtsson and Malmvall, 1981). The same series of patients was followed up at a median time of 11.3 years after diagnosis. The number of GCA patients still alive after 5 years was higher than expected. After 10 and 15 years the number of patients surviving equalled the expected number (Andersson et al, 1986). In a Scottish study of 136 cases of histologically proven temporal arteritis there was no reduction in survival time as compared with expected numbers of deaths (Jonasson et al, 1979). Contrary to the findings in these studies, Graham et al (1981) reported significantly increased mortality among women but not among men in a study of 90 patients. High maintenance dose of corticosteroids and visual loss were significantly associated with a shortened life span. The patients in this retrospective study were all attending departments of ophthalmology or neurology and were therefore highly selected cases with a high frequency of visual and neurological complications. The different survival rate in this report can be explained by the selection of the patients. In a recent study from Gothenburg, Sweden, death rates and causes of death were studied in 284 consecutive patients with GCA confirmed by biopsy (Nordborg and Bengtsson, 1989). All patients who had had a temporal artery biopsy performed were included. During the first year after diagnosis the number of deaths from vascular disorders was 21, as compared with the expected number seven: a highly significant difference. Seventeen of these 21 subjects died within 4 months of diagnosis. All 17 were treated with corticosteroids but in 13 the treatment was insufficient to suppress symptoms and signs of the disease. The authors conclude that patients with GCA run an increased risk of dying from vascular disorders in the initial phase of the disease. Four months after the start of corticosteroid treatment, the risk equalled that of the general population. The risk of death for patients who are not treated with corticosteroids is not known. The increased mortality rate in vascular disorders during the first months and the well-established occurrence of vascular complications in untreated patients may be reasons for assuming that untreated GCA is a lifethreatening vascular disease. However, it can be concluded that the survival rate in patients with GCA on maintenance corticosteroid therapy, in doses sufficient to control the symptoms and inflammatory blood parameters, is equal to the general population with respect to age and sex. The doctor treating an elderly woman with GCA can, after the first months, assure the patient that her disease is not reducing her life expectancy. VASCULAR COMPLICATIONS The most common severe complications of GCA are caused by arteritic lesions in the aortic wall, the coronary arteries and arteries supplying the brain with blood.
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Aortitis and aortic stenosis
In one of the earliest reports on temporal arteritis, Jennings (1938) reported that the blood pressure in the arms differed in one patient. Gilmour (1941) described autopsy findings of arteritis in the aorta and its branches in four cases of GCA. Heptinstall et al (1954) reported another two cases of widespread aortitis. The histological changes in the aorta were similar to those found in the temporal arteries of 11 patients. In his extensive work on GCA, Hamrin (1972) made very careful clinical observations. By using the name polymyalgia arteritica he stressed the close relationship between the rheumatic complex of symptoms and the underlying arteritic disease. In his series from Vfixj6, Sweden, he described aortic arch syndrome in 14 out of 93 patients. Arteriography showed severe stenotic changes, often in the axillary artery. In the USA Hunder et al (1967) described a woman with stenotic changes in the aorta and large arteries close to the aorta visualized by angiography. The diagnosis was established by a temporal artery biopsy, and improvement of the peripheral pulses followed treatment with prednisone. In a large series of 248 patients with GCA seen at the Mayo Clinic, 34 patients showed evidence that the disease affected the aorta or its major branches (Klein et al, 1975) and recent reports on patients with GCA include cases of aortic and large vessel involvement (Kyle et al, 1987; Ninet et al, 1990). The involvement of the aorta is usually restricted to its thoracic portion. Most cases have no symptoms of their aortitis. The lesions are segmentally distributed and segments of the vessel severely affected by stenosis can be found, with normal portions between (Ostberg, 1972). The clinical manifestation may only be a difference in arterial blood pressure between the arms, while other patients suffer from pulseless disease with absence of radial pulses. Murmurs Over the aorta and the large arteries are common in series of GCA. Hamrin (1972) found arterial murmurs in 47% of his 93 patients when examined after 18 months of disease, as compared with 10% in controls. In another Swedish study on 73 patients, 8% had a difference in systolic blood pressure of more than 25 mmHg between the arms (Bengtsson and Malmvall, 1982). Dissecting aortic aneurysm
The arteritic lesions caused by GCA in the aorta can result in a dissecting aneurysm. In her morphological description of 16 autopsy cases with GCA engaging the aorta and its branches, Ostberg (1972) reported aortic dissecting aneurysm in two patients. In the large Mayo Clinic series of 248 patients, three patients died with aortic rupture (Klein et al, 1975). GCA as a cause of death was illustrated by a report on nine cases with fatal arteritic lesions (Sfive-S6derbergh et al, 1986). Two of these patients died with dissecting aortic aneurysms. Both were old women. One had suffered from fatigue and fever for months until she died; autopsy revealed the diagnosis. The second patient had had a diagnosis of GCA by temporal artery biopsy. When the corticosteroids were reduced the disease flared up, resulting in the fatal rupture of the aorta.
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A recent paper from Japan describes two elderly women who both died suddenly as a result of aortic dissection. Histologically, marked inflammation with giant cells was observed in the wall of aorta as well as in other arteries, including the cranial arteries (Murai et al, 1989).
Coronary arteritis A few cases of G C A in the coronary arteries have been described. Martin et al (1980) drew attention to this uncommon complication to G C A by reporting one elderly woman who died from G C A of the coronary arteries. In one of the arteries a thrombus was found superimposed on active arteritic changes. The same year, Paulley (1980) wrote in a letter to the Lancet that numerous cases of ischaemic heart disease and claudication due to G C A continued to come his way and that these benefited dramatically from corticosteroids. This letter was written as a complement to the paper of Strachan et al (1980), who described four cases of G C A with some of its lesser known presentations, which the authors described as 'masked giantcell arteritis'. In a polemic article in the American Heart Journal, How et al (1980) appointed G C A a cardiological blind spot. He argued that G C A involvement of the coronaries is frequently missed by cardiologists due to the dominance of atherosclerosis in the league of diseases in western countries. In more recent literature, little is written about G C A as a cause of myocardial infarction. S~ive-S6derbergh et al (1986) described two cases of fatal G C A in the coronary arteries. One of these women had a recent diagnosis of G C A , while the second had suffered from polymyalgia rheumatica for 3 years and died when she sustained a flare-up of the disease. Autopsy gave the histological diagnosis: G C A in the coronary arteries. Thus, coronary G C A is a well-described, sometimes fatal complication of GCA. The frequency is not known. The increased number of deaths from vascular disorders during the first 4 months after the diagnosis of G C A , as observed by Nordborg and Bengtsson (1989), is interesting. Myocardial infarction and cardiac failure were the causes of death in six of 17 subjects dying during the first period of onset of GCA. The appointment of G C A as the cardiological blind spot made by How (1980) also seems to be appropriate in the 1990s. For a patient with general symptoms of fever and fatigue, and laboratory parameters indicating inflammation, a differential diagnosis in the case of chest pains can be G C A in the coronaries. Most but not all patients with myocardial infarction suffer from arteriosclerosis; some may have an inflammatory coronary disease which can be treated successfully with corticosteroids.
Pericarditis Pericarditis is a well-known p h e n o m e n o n in different types of vasculitis. In G C A it seems to be a rare complication as very few cases of pericarditis in patients with G C A have been described. There are no systematic studies searching for pericarditis in G C A patients. In our series of 95 cases of newly
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diagnosed GCA we found two cases with chest pain during the acute phase of GCA, in whom pericardiac effusion was visualized by ultrasonography (Bengtsson and Malmvall, 1982). In addition to our cases, just a few others have been reported in the literature. All the reported cases of GCA pericarditis have promptly improved on corticosteroids (Clementz et al, 1989; Sonnenblick et al, 1989). Arteritis in vessels to the brain
The connection between an inflammatory disease of the temporal artery and loss of sight was described in the tenth century in the Tadkivat ofAli Ibn Isa (Wood, 1936). In modern medicine this old observation was rediscovered and reported by Jennings (1938). It became well known during the 1940s that ischaemic damage to the optic nerve was a frequent complication of temporal arteritis. Other cerebrovascular complications were described as rare cases, although the pathological basis of neurological complications, namely arteritis in the cerebral arteries, was reported as early as 1941 by Gilmour. In an extensive review, Hollenhorst et al (1960) summarized the clinical findings in 175 patients with GCA diagnosed at the Mayo Clinic during the years 1931-1959. Neurological complications of temporal arteritis, other than those related to the vision were noted, but at an incidence rate that was described as exceedingly low. As many as 102 (58%) patients had some form of ocular involvement, 73 (42%) permanently lost part or all of their vision and 21 (12%) were completely blind in both eyes at the time of discharge. Two patients had cerebral haemorrhage, one had a stroke several weeks after the onset of the disease and one suffered acute toss of hearing. In October 1949, adrenocorticosteroids became available and all patients with temporal arteritis were treated as emergencies with cortisone or other adrenocorticosteroids. Only one patient lost vision after this therapy was started. Some years later, Meadows (1966) described 80 personal cases of temporal arteritis with neuro-ophthalmic complications. Blindness and ophthalmoplegia were the dominating findings. One of his cases died of coronary occlusion and autopsy revealed GCA in the vertebral artery with parenchymatous changes in the brain stem, cerebellum and vermis. Another case with clinical evidence of brain-stem infarction was also reported. He concluded, based on his own experience and a literature review, that there were adequate pathological, angiographic and clinical evidence for the view that affection of the vertebral, internal carotid and cerebral arteries is as much a part of the spectrum of GCA as is involvement of the temporal artery and ophthalmic vessels. Four cases who died during the active phase of GCA were described in detail by Wilkinson and Russell (1972). They had also found another eight cases in the literature between the years 1940 and 1971 where autopsy findings after adequate post-mortem examinations were reported. The superficial temporal, vertebral, ophthalmic and posterior ciliary arteries were those most frequently and severely involved in the disease. The vertebral artery was severely involved throughout its length, with a sharply
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defined upper border just above the point of dural perforation in their four cases. They also noticed that the intracranial portion of the arteries was not involved in the inflammatory process, apart from the first 5 mm of the vertebral arteries inside the dura. They related the inflammatory reaction to the structures in the arteries rich in elastin. According to these authors, the relatively low amount of elastic tissue in intracranial arteries was the explanation for the absence of inflammatory changes inside the skull. Others, however, have reported intracranial distribution of the arteritis in G C A (Kjeldsen and Reske-Nielsen, 1968). In an article on G C A as a cause of death, S/ive-S6derbergh et al (1986) made a careful analysis of autopsy findings of arteritis. Five of the nine fatal cases described died from cerebral stroke. The arteritis was found in the carotid arteries and the vertebral arteries supplying the brain, but also in the intracranial arteries, particularly the basal cerebral arteries. The regular finding was arteritis of the vertebral artery resulting in infarctions in the occipital part of the brain, the brain stem, pons and cerebellum. The finding of arteritis in intracranial segments of the arteries in six patients is contradictory to the theory of Wilkinson and Russel. In one case, however, the severe arteritic changes were seen in the vertebral artery only outside the dura and just at the point of passage to the skull. In seven out of these nine cases the first symptoms and signs of cerebral ischaemia started before or during the first weeks of corticosteroid treatment. The other two cases had corticosteroid treatment in insufficient doses, as indicated by symptoms of G C A and elevated ESR. In a systematic study on 166 biopsy-proven cases of G C A seen at the Mayo Clinic, Caselli et al (1988a) carefully registered neurological symptoms in the period of clinically active GCA. Cerebrovascular events as transient ischaemic attacks or brain infarctions were registered in 12 patients (7%). Compared with cerebral infarctions due to all causes, vertebrobasilar distribution of the damage was more c o m m o n among the GCArelated ischaemic events. A recent case report stresses that G C A can present with symptoms due to vertebral arteritis without any other clinical manifestation of the disease (Collado et al, 1989). By using modern neuroimaging techniques as computerized tomography and magnetic resonance imaging, a diagnosis of multi-infarct dementia was established in three cases of GCA. The multiple infarctions were found mainly in the posterior part of the brain and cerebellum. All three patients developed their dementia during periods of corticosteroid reduction. Increased dose of corticosteroids is recommended to suppress the arteritis (Caselli, 1990). Cerebrovascular disease can be considered as one of the leading causes of death not only in untreated G C A but also during early or insufficient treatment. The frequency of cerebrovascular disease caused by G C A is of course difficult to assess as G C A is a disease of elderly people. The aetiological relationship between G C A cerebrovascular disease in only presumptive in cases that have not been examined by an autopsy. However, the frequency with which this complication occurs is estimated to be 1-3% of all
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GCA patients. The risk of fatal cerebrovascular disease caused by GCA is reduced when the disease activity has been controlled by corticosteroid treatment for a couple of months. For newly diagnosed cases of GCA with symptoms indicating cerebrovascular involvement, high dose corticosteroid (prednisolone 60 mg/day) treatment is recommended. Hypopituitarism, probably due to pituitary infarction, was described by Hamrin (1972) as another extremely rare intracranial manifestation of GCA. Inappropriate secretion of antidiuretic hormone in four cases of temporal arteritis indicates the arteritis can result in ischaemia of the pituitary gland or the hypothalamic region (Gentric et al, 1988).
Neuro-otological impairment The literature on GCA includes a few reports of impaired hearing and severe vertigo (Soelberg-S6rensson and Lorenzen, 1977; Jonasson et al, 1979; Caselli et al, 1988a). In the study by Caselli et al (1988a) on 166 consecutive biopsy-proven GCA cases seen at the Mayo Clinic, 11 (7%) had neuro-otological syndromes: eight had isolated vertigo, one vertigo and unilateral hearing loss, and two unilateral tinnitus. In our prospective study on 95 patients seen in Gothenburg (1972-1979), we asked about reduced hearing capacity during the active phase of GCA (Bengtsson and Malmvall, 1982). Six patients reported hearing impairment; one of them became completely deaf in her right ear. Before deafness, this patient had suffered from severe rotating vertigo and nystagmus. The vertigo disappeared after about i week but her deafness became permanent. Audiograms in all six patients revealed hearing reduction of neurogenic type. Repeated audiograms during corticosteroid treatment failed to show any improvement. In a case report, Kramer et al (1988) describe an 82-yearold man with sensorineural hearing loss as a presenting symptom of GCA. In this case the corticosteroid treatment was followed by a considerable improvement of hearing ability in one but not the other ear. The most likely explanation of the hearing loss and vertigo in GCA patients is deprivation of blood supply to the terminal cochleovestibular vessels (Sofferman, 1980). Another explanation could be arteritis more proximally, in the basilar artery or the posterior auricular artery, causing ischaemia in the hearing apparatus (Kramer et al, 1988).
Peripheral neuropathicsyndromes Peripheral neuropathies have not been given much attention in the literature on GCA. Mononeuropathies in the nerves of the arms and legs have been described but the pathogenetic relationship to GCA has been difficult to establish (Feigal et al, 1985). Caselli et al (1988b) have reported that 23 out of 166 patients with biopsy-proven GCA seen at the Mayo Clinic had clinically-diagnosed peripheral neuropathic syndromes. Electrophysiological studies in 16 patients confirmed the diagnosis. Of the 23 patients, 11 had a generalized peripheral
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neuropathy, nine had multiple mononeuropathies and three had a mononeuropathy. The nerves most commonly affected were the median, ulnar, peroneal and tibial nerves. Most patients' neuropathies improved after treatment with corticosteroids. Angiography of the lower limb arteries in two of the patients with severe neuropathies showed multiple high grade stenosis. One patient underwent amputation above the knee. Widespread chronic vasculitis of the medium and large arteries and ischaemic necrosis of nerve fascicles were found. The authors argue that the neuropathy resulted from nerve ischaemia due to vascular occlusion. A case report by Bridges et al (1989) describes a patient with biopsyproven GCA, leg ulcers and neuropathy. The ischaemic nature of the neuropathy is stressed and in this case the abnormalities improved after retreatment with prednisolone.
Lingual and skin necrosis The external carotid arteries are probably the most common site of arteritis in GCA. The disease affects this part of the circulation in most cases. Classical symptoms of GCA, such as temporal headache, scalp tenderness and jaw claudication, result from impaired circulation and rapidly disappear after corticosteroid administration. Severe impairment of the circulation in the external carotid vascular area can rarely result in tissue necrosis. Missen (1961) examined lingual arteries at autopsy in nine cases of cranial arteritis and found that nine of ten specimens demonstrated arteritis. In a clinical report on three cases, Sofferman (1980) points out that the lingual gangrene is preceded by lingual claudication. Pain in the tongue and paroxysmal blanching are important warnings of glossal ischaemia and impending lingual infarction. Tongue symptoms seem to be rather common among GCA patients, while established tongue gangrene is rare. The arteritic pathogenesis of the tongue infarction was proved in one of the cases by histological findings of arteritis in the lingual arteries. Skin necrosis of the head has been described in rare cases (Fleischel and Oldham, 1960; Abdullah et al, 1989). The necrosis may be localized to one or both sides and it may extend to a large area, with much of the scalp involved. After corticosteroid administration the skin defect healed in most of the reported cases.
Thyroid involvement The connection between temporal arteritis and goitre was observed by Lucien et al (1939) during the first years after temporal arteritis was regarded as a clinical entity. Arteritis was found in a small thyroid artery and was in fact the first histological evidence that the disease engages arteries other than the temporal vessels. In our series of 68 prospectively diagnosed cases of GCA, we observed subacute thyroiditis in two patients who had active arteritis (Malmvall and Bengtsson, 1978). The similarities between subacute thyroiditis and GCA with regard to histopathological findings and
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response to steroids are striking. The association between these two diseases have, however, not been discussed by other authors. Both hyperthyroidism and hypothyroidism are reported preceding or appearing simultaneously with active GCA (Sonnenblick et al, 1989; Wiseman et al, 1989). The published cases of thyroid disease and GCA probably just reflects the coincidence of two not uncommon diseases.
Renal involvement Unlike findings in other arteritic diseases, the kidney is not a target for pathology in GCA. Renal manifestations are most unusual in GCA and, when present, the most common findings are microscopic haematuria and red blood cell casts. Large series of patients with GCA do not include cases with impaired renal function due to GCA. In the few cases of decreased kidney function reported in the literature on GCA, other causes of renal failure have not been ruled out. In some other cases the arteritis described seems to be of a type other than GCA and affects small arteries and arterioles (Elling and Kristensen, 1980). Although the aorta is a main site of GCA, and arteritis is commonly found in the arteries close to the aorta, the renal arteries seem to be something of an exception. Severe renal artery stenosis has not been described in clinical and angiographic studies on GCA. Series of patients examined at post mortem include only a few cases of slight to moderate renal artery involvement (Ostberg, 1972).
Miscellaneous arteritic complications Abdominal symptoms of impaired mesenteric circulation have been reported in clinical series of GCA patients (Hamilton et al, 1971). Postmortem examinations of patients who have died with GCA have shown arteritis of mesenteric vessels (Hamrin et al, 1968; Ostberg, 1972). Rare cases of arteritis in the mesenteric arteries have been described as resulting in intestinal gangrene and perforation. Stenwig (1976) reported a case of GCA involving branches of the superior mesenteric artery as well as the temporal artery. The intestinal wall was necrotic and arteritis in mediumsized and small arteries was found in several sections of the mesentery. A similar case was reported from Canada by Srigley and Gardiner (1980). A patient with small intestinal perforation secondary to localized GCA in the mesenteric vessels but with no evidence of arteritis at other sites is also reported (Smith et al, 1988). In three recently described cases of temporal arteritis intestinal perforation occurred after the resolution of cranial manifestations when the patients were on corticosteroids (Patsner et al, 1989). The female genital tract has been reported to harbour GCA in a few rare cases. Arteritis has been found in myometrial arteries (Kyle et al, 1987) and in myometrium, as well as parametrium and ovarian arteries (Birch and Buchanan, 1989).
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SYNOVITIS In the literature on GCA, and particularly the clinical syndrome of polymyalgia rheumatica (PMR), there are different opinions about the importance of joint involvement. Dixon (1983) stated that true synovitis does not occur in patients with PMR. Traditionally, PMR and GCA have been viewed as a vascular disease, with muscle symptoms most probably caused by impaired circulation. Pain in the neck, the shoulders, in the lumbar region and around the hips are the characteristic symptoms of PMR. These symptoms are believed to be caused by the arteritis in the vessels to the muscles. Arteritis in, for example, the gluteal arteries has been demonstrated by Hamrin (1972). In several large Scandinavian series of patients with GCA, synovitis is reported in a small number of cases (Fauchald et al, 1972; Hamrin, 1972; Soelberg-S6rensen and Lorenzen, 1977; Malmvall and Bengtsson, 1978). The objective signs of synovitis as joint swellings were rare and often mild and transient. Synovial biopsies from large joints have revealed mild and non-specific synovitis in patients suffering from PMR in a few studies (Bruk, 1967; Henderson et al, 1975). By using joint scintigrams one research group has demonstrated abnormal uptake mainly in the shoulders of patients with PMR (O'Duffy et al, 1976, 1980). These findings were interpreted as evidence of chronic axial synovitis. The results have been debated as there was a poor correlation between clinical and scan abnormalities. The isotope scan results in these studies may have been overinterpreted because of degenerative diseases in this group of elderly patients (Kyle et al, 1990). In a recent American survey of 520 patients with biopsy-proven GCA, 19 were found to have persistent symmetric polyarthritis indistinguishable from rheumatoid arthritis (Ginsburg et al, 1985). However, none had nodules or extra-articular features. In three patients the polyarthritis and GCA had a simultaneous onset, while seven developed polyarthritis within 3 years of the onset of GCA. In one patient who underwent total knee arthroplasty the pathological examination revealed mononuclear cell infiltration and giant cells in the synovium. The authors are cautious in their interpretation: patients seen at a referral centre such as the Mayo Clinic are not representative, and the number of patients with two diseases may be higher than expected. However, they stress that seronegative polyarthritis, although uncommon, may be a clinical manifestation of GCA. The rarity of synovitis in PMR is illustrated by a study by Kyle et al (1990). By using X-rays, isotope scans, thermography and clinical examination in a prospective study, three patients out of 56 were found to have joint pains and swelling coincidentally with PMR. Wrist synovitis was present in one patient; the sternoclavicular and acromioclavicular joints were affected in the other two. The conclusion of this paper is that peripheral and axial synovitis is uncommon in PMR patients. In the rare patient where synovitis occurs, it is transient, non-erosive and non-deforming. The frequency of rheumatoid factors in the serum of patients with GCA does not differ from that of controls in the same age range (Malmvall et al, 1981; Ginsburg et al, 1985).
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In conclusion, synovitis is not a common clinical feature of GCA. The pains cannot usually be explained by joint involvement. Coincidence of synovitis and other symptoms of GCA occur in a minority of patients. The manifestations of joint involvement of GCA are usually mild and transient when corticosteroids are given. REFERENCES Abdullah AN, Keczkes K & Wyatt E H (1989) Skin necrosis in giant cell (temporal) arteritis; report of three cases. British Journal of Dermatology 120: 843-846. Andersson R, Malmvall BE & Bengtsson BA, (1986) Long-term survival in giant cell arteritis including temporal arteritis and polymyalgia rheumatica. Acta Medica Scandinavica 220: 361-364. Bengtsson B ~ & Malmvall BE (1981) Prognosis of giant cell arteritis including temporal arteritis and polymyalgia rheumatica, a follow-up study on 90 patients treated with corticosteroids. Acta Medica Scandinavica 209: 337-345. Bengtsson BA & Malmvall BE (1982) Giant cell arteritis. Acta Medica Scandinavica, Supplement 658: 1-102. Birch PJ & Buchanan R (1989) A gynaecological complication of polymyalgia rheumatica/giant cell arteritis. British Journal of Obstetrics and Gynaecology 96: 1356-1358. Bridges A J, Porter J & England D (1989) Lower extremity peripheral neuropathy and ischemic ulcers associated with giant cell arteritis. Journal of Rheumatology 16: 1366-1369. Bruk MI (1967) Articular and vascular manifestations of polymyalgia rheumatica. Annals of the Rheumatic Diseases 26: 103-113. Caselli RJ (1990) Giant cell (temporal) arteritis: a treatable cause of multi-infarct dementia. Neurology 40: 753-755. Caselli RJ, Hunder G G & Whisnant JP (1988a) Neurologic disease in biopsy-proven giant cell (temporal) arteritis. Neurology 38: 352-359. Caselli RJ, Daube JR, Hunder G G & Whisnant JP (1988b) Peripheral neuropathic syndromes in giant cell (temporal) arteritis. Neurology 38: 685-689. Clementz GL, Gold F, Khaiser N, Zolin WD & Jalovec L (1989) Giant cell arteritis associated with pericarditis and pancreatic insufficiency in a patient with psoriatic arthritis. Journal of Rheumatology 16: 128-129. Collado A, Santamaria J, Ribalta T et al (1989) Giant-cell arteritis presenting with ipsilateral hemiplegia and lateral medullary syndrome. European Neurology 29: 266-268. Dixon A St J (1983) Polymyalgia rheumatica. In Hawkins C & Currey HLF (eds) Reports on Rheumatic Diseases, No. 86. London: Arthritis and Rheumatism Council. Elling H & Kristensen IB (1980) Fatal renal failure in polymyalgia rheumatica caused by disseminated giant cell arteritis. Scandinavian Journal of Rheumatology 9: 206-208. Fauchald P, Rygvold O & Oystese B (1972) Temporal arteritis and polymyalgia rheumatica. Annals of Internal Medicine 77: 845-852. Feigal DW, Robbins DL & Leek JC (1985) Giant cell arteritis associated with mononeuritis multiplex and complement-activating 19S IgM rheumatoid factor. American Journal of Medicine 79: 495-500. Fleischl P & Oldham BE (1960) Temporal (giant-cell) arteritis associated with gangrene of scalp. British Medical Journal 1: 439-440. Gentric A~ Baccino E, Mottier D, Islam S &Cledes J (1988) Temporal arteritis revealed by a syndrome of inappropriate secretion of antidiuretic hormone. American Journal of Medicine 85: 559-560. Gilmour JR (1941) Giant-cell chronic arteritis. Journal of Pathology 53: 263-277. Ginsburg WW, Cohen MD, Hall SB, Vollertsen RS & Hunder GG (1985) Seronegative polyarthritis in giant cell arteritis. Arthritis and Rheumatism 28: 1362-1366. Graham E, Holland A, Avery A & Russel RWR (1981) Prognosis in giant-cell arteritis. British Medical Journal 282: 269-271. Hamilton CR, Shelley WM & Tumulty PA (1971) Giant cell arteritis: Including temporal arteritis and polymyalgia rheumatica. Medicine 50: 1-27.
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