疾患詳細

疾患詳細





187360
Temporal arteritis
(Giant cell arthritis; GCA)
(Cranial arthritis)
(Polymyalgia rheumatica)

側頭動脈炎
(巨細胞性動脈炎)
(頭蓋動脈炎)
(リウマチ性多発性筋痛)
指定難病41 巨細胞性動脈炎

遺伝子座:不明
遺伝形式:常染色体優性

(症状)
(GARD)
<80%-99%>
 Anorexia (食思不振) [HP:0002039] [01401]
 Cerebral ischemia (大脳虚血) [HP:0002637] [1126]
 Fatigue (疲労) [HP:0012378] [01410]
 Fever (発熱) [HP:0001945] [01413]
 Headache (頭痛) [HP:0002315] [01414]
 Impaired mastication (咀嚼障害) [HP:0005216] [08001]
 Joint stiffness (関節硬直) [HP:0001387] [15100]
 Vasculitis (血管炎)  [HP:0002633] [1125]
 Weight loss (体重喪失) [HP:0001824] [01411]
<30%-79%>
 Alopecia (禿頭) [HP:0001596] [17100]
 Arthritis (関節炎) [HP:0001369] [15115]
 Depressivity (うつ) [HP:0000716] [0206]
 Elevated erythrocyte sedimentation rate (赤沈亢進) [HP:0003565]
 Ophthalmoparesis (眼球運動不全麻痺) [HP:0000597] [0698]
<5%-29%>
 Abdominal aortic aneurysm (腹部大動脈瘤) [HP:0005112] [1120]
 Abdominal pain (腹痛) [HP:0002027] [01420]
 Abnormal thrombocyte morphology (血小板形態異常) [HP:0001872]
 Abnormality of the pleura (胸膜異常) [HP:0002103] [-]
 Amaurosis fugax (一過性黒内障) [HP:0100576] [06522]
 Aortic dissection (大動脈解離] [HP:0002647] [1120]
 Arterial thrombosis (動脈血栓) [HP:0004420] [2225]
 Arthralgia (関節痛) [HP:0002829] [15115]
 Ataxia (運動失調) [HP:0001251] [028]
 Conductive hearing impairment (伝音難聴) [HP:0000405] [0911]
 Cough (咳嗽) [HP:0012735]
 Diabetes insipidus (尿崩症) [HP:0000873] [2164]
 Diplopia (複視) [HP:0000651] [06004]
 Double outlet right ventricle with subpulmonary ventricular septal defect without pulmonary stenosis (両大血管右室起始-肺動脈弁下心室中隔欠損-肺動脈弁狭窄なし) [HP:0011658] [1120]
 Epistaxis (鼻出血) [HP:0000421] [2207]
 Gangrene (壊疽) [HP:0100758] [18035]
 Gastrointestinal infarctions (胃腸梗塞] [HP:0005244] [-]
 Glossitis (舌炎) [HP:0000206] [08105]
 Hematuria (血尿)  [HP:0000790] [0196]
 Hepatic failure (肝不全) [HP:0001399] [01811]
 Hyperhidrosis (多汗) [HP:0000975] [18016]
 Mediastinal lymphadenopathy (縦隔リンパ節腫大) [HP:0100721] [2228]
 Meningitis (髄膜炎) [HP:0001287] [01423]
 Muscle weakness (筋力低下) [HP:0001324] [0270]
 Myalgia (筋痛) [HP:0003326] [01420]
 Nystagmus (眼振) [HP:0000639] [06609]
 Optic atrophy (視神経萎縮) [HP:0000648] [06522]
 Paresthesia (異常感覚) [HP:0003401] [02510]
 Pericarditis (心外膜炎) [HP:0001701] [1122]
 Ptosis (眼瞼下垂) [HP:0000508] [06807]
 Recurrent pharyngitis (反復性咽頭炎) [HP:0100776] [01423]
 Renal insufficiency (腎不全) [HP:0000083] [0196]
 Skin ulcer (皮膚潰瘍) [HP:0200042] [18035]
 Sudden cardiac death (突然死) [HP:0001645] [0115]
 Vertigo (眩暈] [HP:0002321] [01427]
 Visual field defect (視野障害) [HP:0001123] [06010]
 Visual loss (視力喪失) [HP:0000572] [06011]

 Autosomal dominant inheritance (常染色体優性遺伝) [HP:0000006]
 Blindness (盲) [HP:0000618] [06011]
 Retinal vasculitis (網膜血管炎) [HP:0025188] [0652]

(UR-DBMS)
【血管】側頭動脈炎
 巨細胞性動脈炎
 リウマチ性多筋痛 (PMR)
Persistent, severe head pain, usually in your temple area
Scalp tenderness
Jaw pain when chew or open mouth wide
Fever
Fatigue
Unintended weight loss
【眼】網膜動脈炎
 盲
double vision
【検査】血沈亢進
【その他】ステロイドに反応

<指定難病41 巨細胞性動脈炎>
1.概要
 大型・中型の動脈に巨細胞を伴う肉芽腫を形成する動脈炎である。大動脈とその主要分枝, 特に外頸動脈を高い頻度で傷害する。しばしば側頭動脈を傷害する。このため, 以前は「側頭動脈炎」と呼ばれていたが, 現在は「巨細胞性動脈炎」とその名称が変更された。50歳以上の高齢者に発症し, 若年者に発症する高安動脈炎と対照的である。男女比はほぼ1:2~3である。
 しばしばリウマチ性多発筋痛症を伴い, 後述するように両者は極めて近似した疾患と考えられている。地理的な偏り及び遺伝素因が認められ, 欧米白人に多く, 日本を含めアジア人には少ない。
 
2.原因
  原因は不明だが, ウイルスなど微生物感染などの環境因子の存在が疑われ, 遺伝要因としてHLA-DR*04遺伝子との相関が報告されている。
 
3.症状
 約3分の2の症例で側頭部の頭痛を認める。下顎跛行は約半数の症例で認める特徴的な自覚症状である。血管炎による血流低下・消失による虚血性視神経症のため, 発症初期に視力・視野異常を呈し, 約20%が視力の完全又は部分性の消失を来す。患者の40%にリウマチ性多発性筋痛症を認め, リウマチ性多発性筋痛症の約15%は巨細胞性動脈炎を合併する。全身症状として発熱(多くの場合は微熱, ときに弛張熱), 倦怠感を約40%の患者で認める。咳嗽, 咽頭痛, 嗄声などの呼吸器・耳鼻科領域の症状, 末梢神経障害を認める。一過性虚血発作, 脳梗塞などの神経症状は約15%に出現する。まれに舌梗塞や聴力・前庭障害など耳鼻咽喉科領域の症状も認められる。
 大動脈とその分枝部の病変は20%に認められる。大動脈瘤は胸部・腹部に起こる。発症初期に15%認めるが, ゆっくりと増大し, 3~5年以上経てから発見される。巨細胞性動脈炎における胸部及び腹部動脈瘤は健常者のそれぞれ17倍, 2.5倍多いと報告されている。
 画像診断上, 約42%の患者に鎖骨下動脈や腋窩動脈の狭窄を認めるが, 多くは無症状である。また, 下肢では, 約37%に浅大腿動脈, 腸骨動脈, 膝窩動脈に病変を認める。多く両側性であり, 女性に多く(84%), 側頭動脈炎の症状は42%と少ない。また, 側頭部症状を有する症例と比べより平均6歳若い。巨細胞性動脈炎を疑う場合には, 四肢・頸動脈の拍動を触診すること, 血管雑音を聴取することが重要である。
 
4.治療法
 プレドニゾロン治療を開始する。失明の恐れがある場合には, ステロイドパルス療法を含むステロイド大量療法を行う。経口ステロイドは4週間の初期治療の後に漸減する。副腎皮質ステロイド維持量を必要とする症例が多く, 漸減は更に慎重に行う。ステロイド抵抗性の症例, ステロイドの漸減に伴い再燃する症例においては, メトトレキサート(MTX)を中心とした免疫抑制薬の併用を検討する。失明や脳梗塞を予防するために低用量アスピリンによる抗凝固療法を併用する必要がある。
 
5.予後
 最も留意すべき点は失明に対する配慮であるが, 早期からのステロイド治療により防止が可能である。巨細胞性動脈炎患者では胸部大動脈瘤の頻度が高く, 平均7年後に認められる。定期的画像診断(単純X線, CT angiography, MRA, 超音波, FDG-PET CT scanなど)によって, 大動脈径の変化を追跡する。

<指定難病診断基準>
巨細胞性動脈炎の分類基準(1990 年,アメリカリウマチ学会による)
1.発症年齢が 50 歳以上
臨床症状や検査所見の発現が 50 歳以上
2.新たに起こった頭痛
新たに出現した。または,新たな様相の頭部に限局した頭痛
3.側頭動脈の異常
側頭動脈の拍動性圧痛,または,動脈硬化に起因しない頸動脈の拍動の低下
4.赤沈の亢進
赤沈が 50 ㎜/時間以上(Westergren 法による=1.6cc採血の通常の方法)
5.動脈生検組織の異常
単核球細胞の浸潤または肉芽腫を伴う炎症があり、多核巨細胞を伴う。
分類目的には,5 項目中少なくても 3 項目を満たす必要がある。(感度 93%,特異度 91%)

(Note)
Clinical Features
Temporal arteritis is the local (and most frequent) manifestation (in temporal artery) of giant cell arteritis (GCA). Polymyalgia rheumatica (PMR), although separately described initially, is known to be the same fundamental process. Involvement of the retinal artery with blindness is a dreaded complication. Elevated erythrocyte sedimentation rate (ESR) is a regular laboratory feature. Adrenal glucocorticoids are effective therapy. Temporal arteritis was first described by Jonathan Hutchinson (1890) in 'an old man named Rumbold, the father of a well-remembered beadle at the London Hospital College....He was...quite bald....he had had red 'streaks on his head' which were painful and prevented his wearing his hat. The 'red streaks' proved on examination to be his temporal arteries, which on both sides were found to be inflamed and swollen. The streaks extended from the temporal region almost to the middle of the scalp, and several branches of each artery could be distinctly traced. The condition was nearly symmetrical. During the first week that he was under observation pulsation could be feebly detected in the affected vessels, but it finally subsided, and the vessels were left impervious cords.'

Foroozan et al. (2002) compared platelet counts, complete blood counts, and Westergren sedimentation rates (WESR) of biopsy-positive GCA patients with biopsy-negative patients. They found that elevated WESR was more sensitive (79%), while elevated platelet count was more specific (91%) than elevated WESR or the combination of elevated WESR and elevated platelet count. The authors concluded that in patients suspected of having GCA, an elevated platelet count greater than 400,000/mcl is a useful marker of positive temporal artery biopsy.

Pache et al. (2002) tested the hypothesis that plasma endothelin-1 (131240) would be increased in 4 patients with biopsy-proven giant cell arteritis. All patients showed significantly increased plasma levels of endothelin-1, although the clinical relevance of the increase required further evaluation.

Salvarani et al. (2002) reviewed polymyalgia rheumatica and giant cell arteritis in detail.

Hall et al. (2003) examined the role of unilateral temporal artery biopsy in suspected giant cell arteritis. In their series of 181 patients, unilateral temporal artery biopsy was associated with an extremely low frequency (1%) of subsequent positive contralateral biopsy and was not associated with adverse visual or neurologic outcomes for any subject. The authors concluded that in the hands of experienced physicians, a unilateral temporal artery biopsy is sufficient to exclude a diagnosis of GCA in populations for which clinical suspicion is low. Jaw claudication, pale optic disc edema (particularly 'chalky white' disc edema), fever, or any systemic symptom other than headache should raise suspicion of a diagnosis of GCA.

Among patients with giant cell arteritis who experienced visual deterioration, Hayreh and Zimmerman (2003) reported that further visual loss occurred in a few patients despite treatment with corticosteroids: 13% of patients treated with intravenous steroids versus 3% of patients who received oral steroids developed further visual deterioration. However, the difference between the 2 groups was not statistically significant.

Inheritance
Familial aggregation has been observed. Usually sibs have been affected, but mother-daughter or father-daughter pairs have been reported. Granato et al. (1981) reviewed familial occurrences of giant cell arteritis and PMR and reported father and daughter with giant cell arteritis. How et al. (1981)reported PMR developing in 2 sisters at ages 74 and 72 years, respectively. Familial aggregation in this condition is probably of the same order and same basis as that of many autoimmune disorders (109100) such as Hashimoto struma (140300), Schmidt syndrome (269200), autoimmune hemolytic anemia (205700), lupus erythematosus (152700), alopecia areata (104000), pernicious anemia (170900), etc.

Zauber et al. (1997) described temporal arteritis in a man and his daughter who presented with symptoms at ages 78 and 59 years, respectively. The father's brother had also had a clinical diagnosis of temporal arteritis.

Population Genetics
Liu et al. (2001) reviewed 121 consecutive patients who underwent temporal artery biopsy for possible GCA. The mean age of the patients with biopsy-proven GCA was higher than that in the biopsy-negative group (75 years vs 69 years). The authors found no statistical correlation between biopsy-positive and biopsy-negative groups with respect to gender or ESR. However, when they controlled for race, the ESR was higher among white patients. Positive biopsies were found in 29% of white patients, 11% of Asian patients, and none of 40 Hispanic and 6 African American patients. The authors concluded that further studies were needed to determine the genetic factors protecting Hispanic patients against GCA.

Lam et al. (2007) performed a prospective survey of 134 of 257 patients at their institution who underwent temporal artery biopsy over a 6-year period. They found the prevalence and clinical course of GCA to be similar in the 65 Hispanic and 69 non-Hispanic patients.

From a retrospective review, Pereira et al. (2011) found that biopsy-proven giant cell arteritis was 20 times less frequently seen in Asian than in Caucasian persons in their patient population. The population served by their facility was 42% Caucasian, 28% Asian, and 30% other. The difference in the proportion of GCA in Asians and Caucasians was statistically significant (odds ratio = 0.049; CI, 0.0065-0.374; p = 0.036).

Molecular Genetics
To address the question of whether gene products of the HLA class II complex might contribute to GCA, Weyand et al. (1992) analyzed the functionally most important locus, HLA-DRB1 (see 142860), in a cohort of patients with biopsy-proven disease. Among the patients, 3 allelic variants of the HLA-DRB1*04 family were found to be overrepresented. Interestingly, GCA was linked to the same allelic variant as rheumatoid arthritis (RA;180300). However, a consecutive case series study demonstrated that GCA and RA rarely co-occurred, supporting the interpretation that distinct functional domains of the HLA-DR molecule are implicated in the pathomechanisms of these 2 autoimmune diseases. Such was supported further by the finding of a sequence motif spanning the amino acid positions 28-31 that was shared by all GCA patients and different from that found in RA patients. This sequence stretch translated into a polymorphic site in the antigen-binding groove of the HLA-DR molecule, suggesting a crucial role in the selection and presentation of antigen to T lymphocytes.

(文献)
(1) Hutchinson J: Diseases of arteries. Arch. Surg. 1: 323 only, 1890
(2) Liang GC et al. Familial aggregation of polymyalgia rheumatica and giant-cell arteritis. Arthritis Rheum. 17: 1-10, 1974
(3) Granato JE et al. Familial association of giant cell arteritis: a case report and brief review. Arch. Intern. Med. 141: 115-117, 1981
(4) How J et al. Familial polymyalgia rheumatica. Scot. Med. J. 26: 59-61, 1981
(5) Weyand CM et al. The HLA-DRB1 locus as a genetic component in giant cell arteritis: mapping of a disease-linked sequence motif to the antigen binding site of the HLA-DR molecule. J. Clin. Invest. 90: 2355-2361, 1992
(6) Zauber P et al. Familial occurrence of temporal arteritis. (Letter) J. Rheumat. 24: 611-612, 1997
(7) Liu NH et al. The epidemiology of giant cell arteritis: a 12-year retrospective study. Ophthalmology 108: 1145-1149, 2001
(8) Foroozan, R.; Danesh-Meyer, H.; Savino, P. J.; Gamble, G.; Mekari-Sabbagh, O. N.; Sergott, R. C. : Thrombocytosis in patients with biopsy-proven giant cell arteritis. Ophthalmology 109: 1267-1271, 2002
(9) Pache M et al. Increased endothelin-1 plasma levels in giant cell arteritis: a report on four patients. Am. J. Ophthal. 133: 160-162, 2002
(10) Salvarani C et al. Polymyalgia rheumatica and giant-cell arteritis. New Eng. J. Med. 347: 261-271, 2002
(11) Hall, J. K.; Volpe, N. J.; Galetta, S. L.; Liu, G. T.; Syed, N. A.; Balcer, L. J. : The role of unilateral temporal artery biopsy. Am. Acad. Ophthal. 110: 543-548, 2003
(12) Hayreh, S. S.; Zimmerman, B. : Visual deterioration in giant cell arteritis patients while on high doses of corticosteroid therapy. Ophthalmology 110: 1204-1215, 2003
(13) Lam, B. L.; Wirthlin, R. S.; Gonzalez, A.; Dubovy, S. R.; Feuer, W. J. : Giant cell arteritis among Hispanic Americans. Am. J. Ophthal. 143: 161-163, 2007
(14) Pereira, L. S., Yoon, M. K., Hwang, T. N., Hong, J. E., Ray, K., Porco, T., McCulley, T. J. Giant cell arteritis in Asians: a comparative study. Brit. J. Ophthal. 95: 214-216, 2011

2007/03/31
2011/12/17