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Keywords:

  • Giant cell arteritis;
  • Temporal arteritis;
  • Polymyalgia rheumatica;
  • Prevalence;
  • Epidemiology

Abstract

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. SUBJECTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. Acknowledgements
  8. REFERENCES
  9. Supporting Information

Objective

To elucidate epidemiologic and clinical manifestations of Japanese patients with giant cell arteritis (GCA), the first nationwide survey for GCA was conducted in 1998 in Japan.

Methods

The first questionnaire on GCA for patients treated in 1997 was sent to 10,717 medical departments in Japan. A total of 177 patients were reported. Among the 177 patients, 66 GCA patients with detailed clinical and epidemiologic features on second survey were analyzed.

Results

Prevalence in patients 50 years of age and older in 1997 was 1.47 per 100,000 population in Japan. The average age at onset was 71.5 years old. The male:female ratio was 1:1.7. The association with permanent and complete visual loss (6.5%), jaw claudication (15.2%), and polymyalgia rheumatica (PMR) (30.3%) were low in frequency compared with those reported from other countries. All patients were treated with corticosteroids. Only 3 (4.5%) patients were reported as deceased due to other causes.

Conclusion

The prevalence of GCA in Japan was revealed to be extremely low compared with other countries. Clinical findings of permanent and complete visual loss, jaw claudication, and PMR were infrequent among Japanese patients with GCA.


INTRODUCTION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. SUBJECTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. Acknowledgements
  8. REFERENCES
  9. Supporting Information

Giant cell (temporal) arteritis (GCA) is a form of vasculitis of unknown etiology usually involving medium and large vessels with predisposition to 1 or more branches of the carotid artery, especially the temporal artery, in the elderly. The incidence and prevalence of this arteritis vary widely in different geographic regions (1–3). A high incidence has been reported in northern Europe and parts of the northern United States compared with a lower incidence in southern Europe and Japan (4, 5). Among the vasculitides that affect medium and large arteries, Takayasu's arteritis occurs commonly among young Japanese females and Kawasaki's disease occurs commonly in Japanese infants and children under 5 years of age as compared with GCA, which occurs exclusively in individuals older than 50 years of age. So far, only 71 documented patients have been previously reported in the Japanese literature (6). Moreover, the clinical and epidemiologic features among Japanese patients with this arteritis are obscure. To elucidate this question, the Research Committee on Intractable Vasculitides and the Research Committee on Epidemiology of Intractable Diseases, both belonging to the Ministry of Health and Welfare of Japan, conducted the first nationwide epidemiologic and clinical survey on GCA in Japan in 1998. We report the epidemiologic and clinical manifestations of patients with GCA in Japan.

SUBJECTS AND METHODS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. SUBJECTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. Acknowledgements
  8. REFERENCES
  9. Supporting Information

This survey was designed in the form of 2 investigations. The first survey was for the epidemiologic study, which investigated only the number of patients with GCA who were treated at the hospital during 1997, and the second survey was for the clinical study in which a questionnaire of clinical manifestations was sent to only the departments that had treated GCA patients during 1997.

According to the Nationwide Epidemiological Survey Manual issued by the Research Committee on Epidemiology of Intractable Disease (7, 8), the hospitals were selected with the stratification classified by the number of beds in the hospital; the greater the number of beds the hospital has, the higher the probability to be selected. The selection rate was 100% for university hospitals and hospitals with ≥500 beds, whereas only 5% of the hospitals with <100 beds were randomly selected. Next, the following departments were selected: rheumatology, cardiology, neurology, internal medicine, nephrology, respiratory disease, neurosurgery, orthopedics, cardiosurgery, gynecology, ophthalmology, dermatology, pediatrics, and otorhinolaryngology. From these selections, 10,717 (24.2%) of 44,324 departments were selected. Then, the first questionnaire was sent with the diagnostic guideline: the classification criteria of American College of Rheumatology (ACR) for GCA in 1990 (9) asking for only the number of patients with GCA treated in 1997 (Appendix A available at the Arthritis Care & Research web site at http://www.mrw.interscience.wiley.com/suppmat/0004-3591:1/suppmat/art.11195.html). A total 6,835 (63.8%) of 10,717 departments responded to the first questionnaire and 177 patients with GCA were reported.

Next, the second survey questionnaire asking for detailed clinical features of each patient was sent to the only departments where the patients with GCA were treated during 1997 (Appendix B available at the Arthritis Care & Research website at http://www.mrw.interscience.wiley.com/suppmat/0004-3591:1/suppmat/art.11195.html). The reports of 71 (40.1%) of 177 patients from the second questionnaire were returned. Of the 71 reports, 5 reports were incomplete, therefore, 66 patients were enrolled and extensively examined in this study. A biopsy of the temporal artery was performed in 42 (63.6%) of 66 patients; 30 (71.4%) patients were positive and 12 patients were negative for the characteristic histologic findings of GCA. In some of the questionnaires, the answers were not attained in full from all of the patients, therefore, the actual total number of patients was less than 66.

Laboratory data were recorded at the time of diagnosis. The values of serum C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), white blood cell count, and platelet count requested in the questionnaire were reported from only a small number of patients; therefore, these values were omitted from analyses of this study. Corticosteroid treatment was assessed in terms of milligrams prednisolone/day or equivalent dosage. The efficacy of treatment was judged by each physician according to the improvement of constitutional symptoms, symptoms specific for GCA, and ESR or CRP.

Statistical significance was analyzed by the nonparametric Mann-Whitney U test and the 2-tailed Fisher's exact test.

RESULTS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. SUBJECTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. Acknowledgements
  8. REFERENCES
  9. Supporting Information

Prevalence.

The annual number of patients treated for GCA in 1997 in Japan was estimated to be 690 patients (95% confidence interval [95% CI] 400–980). From these data, an annual prevalence of GCA in the population of 50 years of age and older was 1.47 per 100,000 population. Department of internal medicine (43.9%), ophthalmology (27.3%), and neurology (15.2%) were the major departments in which patients were treated.

Characteristics of patients.

Sixty-six patients (24 men and 42 women) with a male:female ratio 1:1.75 were examined. The average age ± SD at the onset of disease was 72.5 ± 10.3 years (n = 61). The age of onset ranged from 52 to 87 years in the male patients and from 49 to 92 years in the female patients. The male patients had a peak at the age of 60 years and female patients had 2 peaks at the ages of late 60s and late 70s. The average period from onset to diagnosis was 6.2 ± 14.2 months (n = 62). The mean age at which the diagnosis was made was 72.8 ±10.8 years (n = 58).

One case was reported to be associated with rheumatoid arthritis (RA). There were no other patients with association to other vasculitides. One case whose mother had RA was reported. Familial studies did not reveal any other patients with vasculitis in their relatives.

Biopsy and angiography.

Biopsy of the temporal artery was performed in 42 of 63 patients. Characteristic histologic findings were revealed in 30 (71.4%) of 42 patients, and giant cells were revealed in 5 of 30 patients. Although angiographic findings were not included in the ACR criteria, arch aortogram was performed in 15 (22.7%) of 66 patients. Stenosis or obstruction of the carotid subclavian and axillary arteries were observed by angiography in 7 patients. Aneurysm or dilatation was not reported. Angiography of the complete aorta was not reported.

Clinical manifestations at the onset of illness.

Manifestations at the onset of illness are listed in Table 1. Constitutional symptoms such as fever and weight loss were reported in 43.9% (29/66) of the patients. Headache at the temporal area and pain of the temporal artery were reported in 57.6% and 58.5% of the patients, respectively. Ocular manifestation as the initial symptom was reported in 36.4% (24/66) of the patients. Two patients (3.2%; 2/62) who already had unilateral, permanent, complete loss of vision were reported.

Table 1. Clinical manifestations at the onset and during the illness
Clinical manifestationAt the onsetDuring the illness
Cases*%Cases*%
  • *

    Denominator indicates the number of patients recorded.

General symptom29/6643.936/6555.4
 Fever15/6124.620/6132.8
 Weight loss13/5523.614/5525.5
 Systolic hypertension (>160 mm Hg)8/6013.315/6025.0
 Diastolic hypertension (>95 mm Hg)5/608.39/6015.0
 Lymphoadenopathy0/540.01/541.9
 Edema1/571.85/578.8
Neuropsychiatric manifestation51/6677.361/6692.4
 Headache at temporal region38/6657.653/6680.3
 Tenderness of scalp24/6040.038/6063.3
 Pain in temporal artery region38/6558.551/6578.5
 Decreased pulsation of temporal artery16/5529.122/5540.0
 Pulsating headache at temporal artery region21/5736.830/5752.6
 Cranial nerve symptom2/663.06/669.1
 Cerebral infarction1/661.58/6612.1
 Mononeuritis multiplex with motor disturbance1/631.61/631.6
 Mononeuritis multiplex without motor disturbance0/620.01/621.6
 Scalp nodules7/6410.910/6415.6
 Jaw claudication4/666.110/6615.2
 Claudication on mastication, deglutition2/653.110/6515.4
 Dysphagia1/661.54/666.0
 Loss of consciousness0/660.02/663.0
 Convulsion0/660.00/660.0
 Cerebral hemorrhage0/660.01/661.5
 Psychiatric symptom1/661.55/667.6
 Aseptic meningitis0/660.00/660.0
Skin manifestation34.28/5813.8
 Erythema1/561.83/565.4
 Livedo0/540.00/540.0
 Gangrene0/580.00/580.0
Skeletal and muscle manifestation13/6619.729/6445.3
 Polymyalgia rheumatica18/6527.720/6630.3
 Muscle atrophy1/571.85/578.8
 Decreased muscle power3/565.410/5617.9
 Other musculoskeletal pains12/6119.718/6129.5
Ocular manifestation24/6636.434/6651.5
 Ophthalmalgia7/6610.614/6621.2
 Impaired vision21/6631.829/6643.9
 Diplopia4/656.25/657.7
 Amaurosis fugax1/651.52/653.1
 Ischemic optic neuritis11/6616.714/6621.2
 Optic nerve atropy5/667.612/6618.2
 Permanent complete visual loss2/623.24/626.5
 Ophthalmoptosis0/551.51/661.5
Cardiac manifestation0/551.46/5710.5
 Endocarditis1/550.00/550.0
 Pericarditis0/570.00/550.0
 Condunction disturbance0/571.84/557.3
 Myocardial infarction00.02/573.5
 Angina pectoris00.03/575.3
Respiratory manifestation0/590.06/6010.0
 Bronchial asthma0/570.02/593.4
 Pleuritis0/570.00/570.0
 Pulmonary infarction00.01/571.8
 Pulmonary hypertension0/600.00/550.0
Digestive system symptom0/600.04/606.7
 Melena0/580.02/603.3

Clinical manifestations during the illness.

Clinical manifestations during the illness are shown in Table 1. The average period of observation from onset to the final visit to the clinic was reported to be 39.9 ± 54.6 months. Ocular manifestations were reported in 51.5% of 66 patients, and permanent complete loss of vision was recorded in 4 (6.5% of 62 patients; 2 patients for right eyes, 1 for left, and 1 for both eyes). Jaw claudication was recorded in 15.2% of 66 patients. The association of polymyalgia rheumatica (PMR) was reported in 20 (30.3%) patients (4 men and 16 women).

Laboratory findings.

Elevated ESR and CRP were recorded in 84.8% and 76.9%, respectively, during the illness. Positivity for rheumatoid factor and antinuclear antibody was recorded in 28.3% and 30.2%, respectively, in 53 patients during the illness (data not shown).

Treatment and efficacy.

All patients were treated with corticosteroids, and 51.5% of the patients were treated with <40 mg/day of prednisolone and 25.8% with <60 mg/day of prednisolone (Table 2). Twelve patients were treated with methylprednisolone pulse therapy. Cytotoxic drugs were used in 6 patients; 2 patients were treated with cyclophosphamide, 3 patients with azatioprine, and 1 patient with methotrexate. Efficacy of prednisolone was 82.9% with <40 mg/day and 88.2% with <60 mg/day, whereas the efficacy of prednisolone >60 mg/day was 64.3%.

Table 2. Treatment and efficacy
TreatmentPatients treatedPatients reported efficacy
n*%n*%
  • *

    Denominator indicates the number of patients recorded.

  • Methylpredisolone was used at 250–1,000 mg/day for 3 days.

Corticosteroid66/66*10060/64*93.8
 Prednisolone   
  <40 mg/day34/6651.534/4182.9
  <60 mg/day17/6625.811/1788.2
  >60 mg/day15/6622.79/1464.3
 Methylpredisolone pulse12/6518.511/1478.6
Cyclophosphamide (≤100 mg/day)2/523.81/250.0
Azatioprine3/535.72/2100
Methotrexate1/531.91/1100
Cyclophosporine0/5301/1100

Complications.

Nine (15.3%) patients were reported to have complications of infectious diseases, 4 (7.0%) patients had gastrointestinal ulcer, 4 (6.8%) patients had cerebral infarction, and 3 (5.2%) patients had malignant tumors (data not shown).

Prognosis and cause of death.

The majority of the patients (81.8%) improved during the period this survey was conducted. Only 1 patient (1.5%) deteriorated. Three female patients (4.5%) were reported as deceased. The cause of death was malignant disorder, infection, and decrepitude, which were comorbid conditions unrelated to GCA. The frequency of relapse was not investigated in this study.

DISCUSSION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. SUBJECTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. Acknowledgements
  8. REFERENCES
  9. Supporting Information

GCA is recognized worldwide; however, the incidence of this arteritis varies widely in different geographic regions and ethnic backgrounds (1–3, 10). Incidence or prevalence of GCA has not been investigated in Asian countries, including Japan (11, 12). As expected, the prevalence of GCA in Japan in 1997 (revealed to be 1.47 per 100,000 population older than 50 years of age according to the 1997 Japan census data) (13) is extremely low compared with the prevalence in the United States (reported as approximately 200 per 100,000 population older than 50 years of age) (10). A prevalence of 60 per 100,000 population aged 50 and older in the northern region of Spain in 1991 has been reported (14). Only 690 (95% CI 400–980) Japanese were estimated to have GCA in 1997 as compared with 110,000 Americans based on the 1990 US census data (10). Because the present study was not designed to determine the annual incidence of GCA, we have a new survey underway to identify the annual incidence of GCA in Japan.

HLA class II antigen DR4 has been identified in association with GCA and PMR (15, 16). The paucity of GCA among blacks has been linked to the low frequency of HLA–DR4 observed in this population (17). The majority of the patients (60%) expressed the HLA–DRB1*0401 or DRB1*0404 (18, 19). However, both HLA–DRB1*0401 and DRB1*0404 are less frequent, 2.9% and 0.7%, respectively, as determined in 493 randomly selected Japanese individuals compared with 15.9% and 3.2%, respectively, for 63 US individuals (20). The positivity rate of HLA–DRB1*0401 among the Japanese population is statistically less frequent than that in the US (P < 0.001). These data indicate 1 of the explanations for the low prevalence of GCA in Japan.

The clinical manifestations among Japanese patients with GCA revealed in our survey appear to be similar to those reported from other countries. However, PMR was reported in 30.3%, jaw claudication in 15.2%, and complete visual loss in 4 patients (6.5%), which were less frequent compared with those reported as 40–60%, 8–50%, 8–22%, respectively, in Western countries (1, 3, 4, 21–25). The incidence of musculoskeletal pains as revealed in our results were similar to those reported in other countries (1, 14, 26). Our data were supported by the report of Yamaguchi and Ohta (6), which reviewed 71 documented Japanese patients in literature and reported that 26.8% of the patients had PMR, 14.0% had jaw claudication, and 12.7% had visual loss.

Almost 50% of the patients were treated with <40 mg/day of prednisolone, which coincides with a previous Japanese review that described that 56.5% (26/46) of patients were treated with <40 mg/day of prednisolone (6). Because the Japanese, especially elderly individuals, have smaller physiques compared with individuals of the Western countries, a smaller dose of prednisolone has been speculated to be effective in these patients (about 50% of Japanese GCA patients).

In conclusion, the first clinical epidemiologic report of GCA from Asian countries revealed extremely low prevalence of GCA in Japan. The overall clinical manifestations of GCA in Japan were similar to those reported in Western countries, even though complete visual loss, jaw claudication, and PMR were infrequent in Japanese patients with GCA. We assumed that the low prevalence of GCA in Japan is due to the genetic background, such as HLA–DRB1*0401 and HLA–DRB1*0404 (19, 27).

Acknowledgements

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. SUBJECTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. Acknowledgements
  8. REFERENCES
  9. Supporting Information

We would like to express our sincere gratitude to all doctors who kindly cooperated in this survey.

REFERENCES

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. SUBJECTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. Acknowledgements
  8. REFERENCES
  9. Supporting Information
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Supporting Information

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. SUBJECTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. Acknowledgements
  8. REFERENCES
  9. Supporting Information
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