Collagen disease

Japanese: 膠原病

(1) Collagen disease
Connective tissue diseases are systemic inflammatory diseases that occur when immune tolerance to self-constituents breaks down, with connective tissues in all parts of the body being a common site of inflammation. Central or peripheral neuropathy is common, and sometimes only neurological symptoms may be evident. Possible mechanisms of symptom manifestation include direct inflammation mediated by autoantibodies in nervous tissue, ischemic lesions mediated by vasculitis, or secondary effects associated with visceral damage. In recent years, the introduction of new immunosuppressants and biological agents as anti-cytokine therapy has significantly changed the treatment of connective tissue diseases.
a. Systemic lupus erythematosus (SLE)
Neurological disorders are thought to occur in 25-75% of patients with systemic lupus erythematosus, and are one of the three major causes of death from systemic lupus erythematosus. Traditionally, central nervous system symptoms associated with SLE were called CNS lupus, but recently, peripheral neuropathy has been referred to as neuropsychiatric SLE (NPSLE). Central nervous system disorders are broadly divided into neurological syndromes and psychiatric/neuropsychological syndromes. The former consist of aseptic meningitis, cerebrovascular disorders, demyelinating lesions, headaches including those caused by benign intracranial hypertension, involuntary movements (mainly chorea), and convulsions. The involvement of antiphospholipid syndrome is important in the development of cerebrovascular disorders, and in such cases, attention should be paid to the complication of venous sinus thrombosis. The latter are characterized by acute confusion, anxiety, mood, and cognitive disorders. Recently, the presence of antibodies against N-methyl-d-aspartate receptors (NMDAR), a type of glutamine receptor, has been attracting attention as a factor in the development of psychiatric and cognitive dysfunction. On the other hand, if the above symptoms appear during treatment with corticosteroids, it is important to differentiate it from steroid psychosis. Spinal cord lesions include transverse myelitis, and peripheral neuropathy includes polyneuritis and mononeuritis multiplex. Cerebrospinal fluid often shows increased cell count, total protein concentration, IL-6, IL-8, IFN-α, etc. Electroencephalograms frequently show abnormalities such as diffuse slow waves and spikes, and head CT scans show thickening of the dura and calcification mainly in the basal ganglia, especially in chronic cases. MRI also shows various edematous and demyelinating lesions corresponding to the symptoms. Serum anti-DNA antibodies and complement are not related to the severity of NPSLE, but anti-Sm antibodies are elevated in patients with organic psychiatric disorders. The presence of anti-ribosomal P antibodies in serum is also considered useful in diagnosing this condition. Treatment involves methylprednisolone 1 g/day for 3 days in pulse therapy or oral prednisolone 1.0 mg/kg/day. In refractory cases, cyclophosphamide pulse therapy and other immunosuppressants are used in combination. [⇨10-4]
b. Antiphospholipid antibody syndrome (APS)
Antiphospholipid syndrome is the most common cause of cerebrovascular disease in young people, and 10% of deep vein thrombosis cases in people under 50 years of age are positive for antiphospholipid antibodies (aPL). APL is also frequently detected in patients with habitual miscarriage of unknown cause (primary antiphospholipid syndrome). When it occurs in association with an autoimmune disease, it is called secondary antiphospholipid syndrome, and most of the underlying diseases are systemic lupus erythematosus. It is said that 10-20% of patients with systemic lupus erythematosus show antiphospholipid syndrome. In antiphospholipid syndrome, recurrent thrombosis occurs in various sites, and thrombus formation is observed without the involvement of vasculitis. Cerebrovascular disease accounts for more than 90% of cases, and thrombus formation is often in the middle cerebral artery, but venous sinus thrombosis also occurs concomitantly. Epilepsy, intractable headache, cognitive decline, chorea, and transverse spinal cord disorder due to microvascular disease are also seen, and this condition is also involved in idiopathic intracranial hypertension.
The antigen of aPL associated with thrombosis is β2 _- GPI bound to phospholipids, and it is thought that the coagulation inhibitory function of β2 _- GPI is blocked by aPL, enhancing the coagulation system and resulting in thrombus formation. Treatment includes corticosteroids and immunosuppressants, as well as anticoagulant therapy with warfarin for thrombosis and antiplatelet therapy. [⇨10-10]
c. Sjögren's syndrome In Sjögren's syndrome, exocrine gland tissues such as the lacrimal gland and salivary gland are damaged by infiltrating lymphocytes, resulting in a dry skin syndrome. Lesions also occur widely in the nervous system, including the central nervous system, peripheral nerves, and muscles. Peripheral neuropathy is frequently present, with trigeminal neuropathy in the cranial nerves and sensory ataxic neuropathy and painful neuropathy in the limbs. The responsible lesion for sensory ataxic neuropathy is thought to be the dorsal root ganglion. Muscle lesions are considered to be an overlap between this syndrome and dermatomyositis/polymyositis. Central nervous system complications include myelitis and aseptic meningitis. Of these, optic neuritis and encephalomyelitis are noteworthy, with a frequency of 5-30%. Symptoms include cranial nerve symptoms such as visual impairment, diplopia, and facial paralysis, cerebellar symptoms such as ataxia and dysarthria, and transverse spinal cord disorders such as paralysis and sensory disturbances in the lower limbs. These symptoms appear subacutely to chronically and show a relapsing-remitting or chronic progressive course, making it difficult to differentiate from multiple sclerosis. Anti-aquaporin-4 antibodies are frequently detected in the serum of Sjögren's syndrome patients with this condition, and there is discussion about whether this condition is different from neuromyelitis optica (NMO), a demyelinating disease limited to the central nervous system.
Treatment involves the administration of corticosteroids (prednisolone 30-60 mg/day), but steroid pulse therapy has been attempted for central nervous system disorders, and high-dose intravenous immunoglobulin therapy (IVIg) has been attempted for refractory cases of peripheral neuropathy. [⇨10-3]
d. Rheumatoid arthritis (RA)
In this disease, inflammation causes deformed joint lesions, resulting in entrapment nerve disorders such as carpal tunnel syndrome and peroneal nerve damage. In addition, serious complications such as spinal cord injury due to subluxation of the atlantoaxial joint in the cervical spine and rheumatic meningitis require careful attention. The former requires surgical joint fixation at an early stage of onset. The latter develops without much relation to the severity of joint lesions in the limbs, and it is thought that vasculitis in the pia mater forms the pathology. Furthermore, severe cases in which rheumatoid arthritis is accompanied by systemic necrotizing vasculitis are called malignant rheumatoid arthritis. The most prominent symptom is quadriplegia due to mononeuritis multiplex, and test findings include high serum rheumatoid factor (RF), low complement value, positive immune complexes, and high CRP. Treatment requires the administration of sufficient antirheumatic drugs as well as aggressive administration of corticosteroids and immunosuppressants. [⇨10-2-1), 10-2-2]
e. Polymyalgia rheumatica (PMR)
It is a rheumatic disease of unknown cause that often develops after the age of 50. It causes marked muscle pain and stiffness in the posterior neck muscles, shoulder girdle muscles, and lumbar muscles that last for more than a month. For this reason, it can be mistaken for meningitis. There is no muscle atrophy or weakness. It is accompanied by fever, fatigue, loss of appetite, and weight loss. Approximately 30% of patients are complicated by temporal arteritis. Elevated CRP levels, elevated erythrocyte sedimentation rate of 100 mm/hour or more, marked increase in IL-6, and elevated fibrinogen levels are observed, but there is no increase in myogenic enzymes such as CK and aldolase, and electromyograms and muscle biopsy are normal.
For treatment, if temporal arteritis is not present, muscle pain will improve dramatically within a few days with low-dose prednisolone at around 10 to 20 mg/day. However, there are many cases of relapse when the drug is reduced or discontinued, making it necessary to administer small amounts of steroids over a long period of time. Furthermore, if temporal arteritis is present, high-dose steroid therapy, including steroid pulse therapy, is administered from the early stages to prevent loss of vision due to inflammation of the ophthalmic artery. [⇨10-2-4)]
f. Systemic sclerosis (SSc)
Neuromuscular complications are relatively rare, but peripheral neuropathy occurs in around 20% of cases. Peripheral neuropathy is most often due to entrapment injury, but it is also possible that it is due to ischemic factors. Muscle symptoms are a frequent complication, and in most cases are not accompanied by muscle weakness or elevated CK levels, and although muscle biopsy reveals perimysial fibrosis, there is little evidence of muscle cell necrosis or inflammatory cell infiltration. There are also cases with prominent muscle weakness that suggests an overlap syndrome with polymyositis. Treatment involves the use of vasodilators, d-penicillamine, or low doses of steroids. [⇨10-5]
g. mixed connective tissue disease (MCTD)
Mixed connective tissue disease is a disease in which symptoms of systemic lupus erythematosus, systemic sclerosis, and polymyositis/dermatomyositis appear simultaneously or over time in the same patient, and anti-U1 snRNP antibodies are detected in the serum. Raynaud's phenomenon is often the initial symptom, and localized skin sclerosis limited to the fingers and edematously swollen sausage-like digits are seen throughout the course of the disease. Arthritis is often mild and does not involve joint destruction. Other symptoms include systemic lupus erythematosus-like skin rash, fever, hepatosplenomegaly, muscle pain/weakness, lymphadenopathy, serositis, leukopenia, anemia, poor esophageal peristalsis, aseptic meningitis, and trigeminal neuralgia. Anti-U1 snRNP antibodies, especially those that react with the 70 kDa first stem-loop, are specific markers for diagnosing MCTD. Other laboratory data include hypergammaglobulinemia, presence of immune complexes in the blood, decreased complement levels, lymphopenia, and positive RF.
Treatment should be selected according to symptoms, but peripheral circulation improvers, platelet aggregation inhibitors, nonsteroidal anti-inflammatory drugs, and corticosteroids are used for acute inflammatory symptoms such as arthritis and myositis. [⇨10-7] [Ikeda Shuichi]
■ References <br /> Neuromuscular disorders associated with collagen diseases. Journal of the Japanese Society of Internal Medicine, 99(8), 2010.
Collagen diseases and neurological disorders: from basic to clinical applications. Clinical Neuroscience, 28(2), 2010.

Collagen disease (liver damage associated with other diseases)

(3) Collagen vascular disease Most liver damage associated with collagen vascular disease is mild. Damage may be caused by the collagen vascular disease itself, fatty liver caused by steroids, drug-induced liver damage caused by immunosuppressants or anti-inflammatory drugs, damage caused by a collagen vascular disease-like disease, or damage caused by conditions secondary to collagen vascular disease such as amyloidosis.
a. Systemic lupus erythematosus (SLE) In SLE, serum transaminases and biliary enzymes are elevated in 30-60% of cases, and hepatomegaly is seen in 20-50%. Liver damage is often caused by SLE itself or by medications such as steroids. In SLE, fatty liver and nonspecific reactive hepatitis (NSRH) account for approximately 40% of cases, while active hepatitis and cirrhosis are rare. In rare cases, vasculitis and nodular regenerative hyperplasia (NRH) are seen. Autoimmune hepatitis (AIH) with positive LE cell phenomenon is a disease that must be differentiated from SLE with liver damage. AIH has higher gamma globulin levels than SLE, and many cases have positive anti-smooth muscle antibodies and negative anti-ds-DNA antibodies. In AIH, chronic active hepatitis accompanied by plasma cell infiltration and hepatocellular necrosis is observed, whereas liver lesions in SLE are mild and show nonspecific reactive hepatitis accompanied by nonspecific lymphocytic infiltration in the portal tract.
b. Rheumatoid arthritis (RA)
Liver damage is observed in 20% to 50% of patients with rheumatoid arthritis. Examination of liver tissue reveals nonspecific reactive hepatitis in 40% and fatty liver in 20%, and hepatic amyloidosis may also be present. Autoimmune hepatitis and primary biliary cirrhosis (PBC) are rarely associated with rheumatoid arthritis, but the incidence of rheumatoid arthritis in AIH and PBC is thought to be approximately 10% and 5%, respectively. Felty syndrome, the three main symptoms of which are rheumatoid arthritis, splenomegaly, and leukopenia, is associated with a high rate of liver damage, with 40% to 60% of patients showing elevated AST, ALT, and ALP levels, and 70% showing hepatomegaly. Portal hypertension is also relatively common, and in many cases histological findings show nodular regenerative hyperplasia accompanied by portal tract fibrosis. Liver damage is also seen at a high rate in adult-onset Still's disease, the three main symptoms of which are fever, skin rash, and arthralgia, with 50% of patients showing hepatomegaly, 65% showing splenomegaly, and 85% showing liver damage.
c. Sjögren syndrome (SjS)
Liver damage is seen in 10-30% of cases of Sjögren's syndrome, and splenomegaly is present in approximately one-quarter of cases. The incidence of primary biliary cirrhosis and autoimmune hepatitis in Sjögren's syndrome is low, but the incidence of primary biliary cirrhosis and autoimmune hepatitis associated with Sjögren's syndrome is relatively high, reportedly at 20% and 10%, respectively.
d. Systemic scleroderma
Systemic sclerosis is classified into generalized type, in which skin sclerosis spreads throughout the body, and localized type, in which skin sclerosis is limited to the fingers. Gastrointestinal lesions are frequently observed, but liver damage is rare. In localized CREST syndrome, overlap with PBC has been noted, and in overlapping cases, the positivity rate of anticentromere antibodies is extremely high, at over 90%.
e. Polyarteritis nodosa (PN)
Autopsy reveals lesions in the hepatic artery in approximately half of the cases of PN, but clinical liver damage is rare. However, vasculitis can cause aneurysms, which can rupture or cause hepatic infarction, resulting in serious complications. [Shuhei Nishiguchi]

Source : Internal Medicine, 10th Edition About Internal Medicine, 10th Edition Information

Japanese:

（1）膠原病（collagen disease）
　膠原病は自己の構成成分に対する免疫寛容が破綻して生じる全身性炎症疾患であり，身体のあらゆる部位にある結合組織を共通の炎症の場とする．中枢または末梢神経障害を呈する頻度が高く，ときに神経症状のみが前景に出る場合もある．神経組織における自己抗体を介した直接の炎症，血管炎を介した虚血性病変，または内臓障害に伴う二次的影響などが症状発現の機序として考えられる．近年，新規免疫抑制薬や抗サイトカイン療法としての生物学的製剤の導入により，膠原病に対する治療法が大きく変化している．
a．全身性エリテマトーデス（systemic lupus erythematosus：SLE）
　全身性エリテマトーデスの25～75％に神経障害を合併するとされ，神経障害は全身性エリテマトーデスの3大死因の1つである．従来はSLE関連の中枢神経症状をCNS lupusとよんでいたが，最近は末梢神経障害を含めてneuropsychiatric SLE（NPSLE）とよぶ傾向にある．中枢神経障害は神経症候群と精神・神経心理学的症候群に大別される．前者は無菌性髄膜炎，脳血管障害，脱髄病変，良性頭蓋内圧亢進症を含む頭痛，不随意運動（おもに舞踏病），痙攣からなる．脳血管障害の発現には抗リン脂質抗体症候群の関与が重要であり，その際には静脈洞血栓症の合併に注意する．後者では急性錯乱状態，不安・気分・認知障害が出現する．最近，精神・認知機能障害の発現にはグルタミン受容体の一種であるN-methyl-d-aspartate受容体（NMDAR）に対する抗体の存在が注目されている．一方，副腎皮質ステロイド薬で治療中に上記症状が出現する場合はステロイド精神病（steroid psychosis）との鑑別が重要である．脊髄病変としては横断性脊髄炎を，末梢神経障害では多発神経炎や多発単神経炎を合併する．髄液では細胞数，総蛋白濃度，IL-6，IL-8，IFN-αなどの増加がみられることが多い．脳波ではびまん性徐波・棘波などの異常が高頻度に出現し，頭部CTでは慢性例を中心に硬膜の肥厚，基底核部を中心とする石灰化がみられる．またMRIでは症状に対応して種々な浮腫性，脱髄性病変が検出される．血清中の抗DNA抗体や補体はNPSLEの重症度とは関連しないが，抗Sm抗体は器質性精神障害の患者で高値を示す．また血清中の抗リボソームP抗体の存在は本病態の診断に有用とされている．治療はメチルプレドニゾロン1 g/日，3日間のパルス療法や，経口プレドニゾロン1.0 mg/kg/日の投与を行う．難治例ではシクロホスファミドのパルス療法その他の免疫抑制薬を併用する．【⇨10-4】
b．抗リン脂質抗体症候群（antiphospholipid antibody syndrome：APS）
　抗リン脂質抗体症候群は若年者の脳血管障害の原因としては最も多く，50歳以下の深部静脈血栓症の10％に抗リン脂質抗体（antiphospholipid antibody ：aPL）が陽性とされる．また原因不明の習慣性流産患者にも高率にaPLが検出される（原発性抗リン脂質抗体症候群）．自己免疫疾患に合併する場合は二次性抗リン脂質抗体症候群といわれ，その基礎疾患のほとんどが全身性エリテマトーデスである．全身性エリテマトーデスで抗リン脂質抗体症候群を示すものは10～20％とされる．抗リン脂質抗体症候群では種々な部位に再発性血栓症を生じ，血管炎の関与なしに血栓形成がみられる．脳血管障害が90％以上を占め，中大脳動脈での血栓形成が多いが，静脈洞血栓症も併発する．微小血管障害によるてんかん，難治性頭痛，認知機能低下，舞踏病，横断性脊髄障害などもみられ，特発性頭蓋内圧亢進症にも本病態が関与している．
　血栓症に関連するaPLの抗原はリン脂質に結合したβ₂-GPIであり，β₂-GPIの凝固抑制機能がaPLでブロックされて凝固系が亢進し，血栓形成を生じると考えられる．治療は副腎皮質ステロイド，免疫抑制薬に加え，血栓症に対してワルファリンによる抗凝固療法，抗血小板療法が行われる．【⇨10-10】
c．Sjögren症候群
　Sjögren症候群は涙腺・唾液腺などの外分泌腺組織が浸潤リンパ球で傷害され，乾燥症候群を生じる．神経系においても，中枢神経，末梢神経，筋に広く病変を生じる．末梢神経障害の合併頻度が高く，脳神経では三叉神経障害を，四肢では感覚失調性ニューロパチー，有痛性ニューロパチーの像を呈する．感覚失調性ニューロパチーの責任病巣は後根神経節と考えられている．筋病変は本症候群と皮膚筋炎/多発筋炎の重複と位置付けられる．中枢神経系合併症としては脊髄炎，無菌性髄膜炎がある．この中で注目すべきは視神経炎・脳脊髄炎の合併であり，その頻度は5～30％とされている．症状は視力障害，複視，顔面神経麻痺などの脳神経症状，失調や構音障害などの小脳症状，下肢の麻痺と感覚障害などの横断性脊髄障害であり，これらの症状が亜急性から慢性に出現して，再発寛解や慢性進行性の経過を示すことから，多発性硬化症との鑑別が常に問題となる．本病態を伴うSjögren症候群患者では血清中に抗アクアポリン-4抗体が高率に検出されており，中枢神経系に限局した脱髄疾患である視神経脊髄炎（neuromyelitis optica：NMO）との異同が論議されている．
　治療は副腎皮質ステロイド（プレドニゾロン30～60 mg/日）投与を行うが，中枢神経障害にはステロイドパルス療法を，末梢神経障害の難治例には免疫グロブリンの大量静注療法（IVIg）が試みられている．【⇨10-3】
d．関節リウマチ（rheumatoid arthritis：RA）
　本疾患では炎症で変形した関節病変により手根管症候群，腓骨神経障害などの絞扼性神経障害を生じる．また重篤な合併症として，頸椎の環軸関節の亜脱臼による頸髄損傷，リウマチ性髄膜炎があり注意を要する．前者は発症早期に外科的な関節固定を必要とする．また後者は四肢の関節病変の重篤度とはあまり関連がなく発症し，脳軟膜における血管炎が病態を形成すると考えられている．さらに関節リウマチに全身性の壊死性血管炎を伴う重篤な場合は，悪性関節リウマチといわれる．多発単神経炎による四肢麻痺が目立ち，検査所見では血清中のリウマトイド因子（RF）高値，低補体価，免疫複合体陽性，CRP高値などがみられる．治療は十分な抗リウマチ薬の投与に加えて副腎皮質ステロイド・免疫抑制薬の積極的投与が必要である．【⇨10-2-1），10-2-2）】
e．リウマチ性多発筋痛症（polymyalgia rheumatica：PMR）
　50歳以降に発症することの多い原因不明のリウマチ性疾患であり，後頸部筋，肩甲帯筋，腰帯筋群に著明な筋痛とこわばりが1カ月以上続く．このため髄膜炎と誤認されうる．筋萎縮・筋力低下はみられない．発熱，疲労感，食欲低下，体重減少などを伴う．30％程度に側頭動脈炎を合併する．CRPの高値，100 mm/時以上の赤沈亢進，IL-6著増，フィブリノゲン高値などがみられるが，CK，アルドラーゼなどの筋原性酵素の上昇はなく，筋電図・筋生検は正常である．
　治療は側頭動脈炎の合併がない場合，プレドニゾロン10～20 mg/日程度の低用量で筋痛は数日以内に劇的に改善する．しかし同薬剤の減量・中止による再燃例が多く，長期間にわたって少量のステロイド薬の投与が必要である．なお，側頭動脈炎を合併している場合は，眼動脈の炎症による視力低下を防ぐ目的で，初期からステロイドパルス療法を含めた大量ステロイド療法を行う．【⇨10-2-4）】
f．全身性強皮症（scleroderma，systemic sclerosis：SSc）
　神経筋の合併症は比較的まれであるが，20％前後に末梢神経障害を生じる．末梢神経障害は絞扼性障害が多いとされるが，虚血性の要因で生じる可能性も考えられる．筋症状はしばしばみられる合併症で，多くは，筋力低下やCKの上昇を伴わず，筋生検でも筋周膜の線維化は認めるものの，筋細胞壊死や炎症細胞浸潤の所見は乏しい．多発筋炎の重複症候群と思われる筋力低下の目立つ例もある．治療は血管拡張薬，d-ペニシラミン，または少量のステロイド薬が使用される．【⇨10-5】
g．混合性結合組織病（mixed connective tissue disease：MCTD）
　混合性結合組織病は，全身性エリテマトーデスと全身性強皮症および多発筋炎/皮膚筋炎の症状が同時または経過とともに同一患者に出現し，血清中に抗U1 snRNP 抗体が検出される疾患である．Raynaud現象が初発症状であることが多く，手指に限局した皮膚硬化や浮腫状に腫脹したソーセージ様指は全経過を通じてみられる．関節炎は関節破壊を伴わない軽度な場合が多い．その他，全身性エリテマトーデス様皮疹，発熱，肝脾腫，筋痛・筋力低下，リンパ節腫脹，漿膜炎，白血球減少，貧血，食道蠕動不良，無菌性髄膜炎，三叉神経痛などがみられる．　抗U1 snRNP抗体，特にfirst stem-loopの70 kDaに反応する抗体がMCTDの診断に特異的マーカーとなる．検査データとしてはその他，高ガンマグロブリン血症，血中免疫複合体の存在，補体価の低下，リンパ球減少，RF陽性などを認める．
　治療は症状に応じて選択する必要があるが，末梢循環改善薬，血小板凝集抑制薬，非ステロイド系抗炎症薬，関節炎・筋炎などの急性炎症症状に対しては副腎皮質ステロイドを使用する．【⇨10-7】［池田修一］
■文献
膠原病に伴う神経・筋障害．日本内科学会雑誌，99(8), 2010.
膠原病と神経疾患—基礎から臨床まで．Clinical Neuroscience, 28(2), 2010.

膠原病(ほかの疾患に伴う肝障害)

（3）膠原病
　膠原病に伴う肝障害の多くは軽症である．膠原病自体による障害，ステロイド剤による脂肪肝，免疫抑制薬や抗炎症薬による薬物性肝障害，膠原病類似疾患の合併による障害，アミロイドーシスのような膠原病に続発した病態による障害などがある．
a.全身性エリテマトーデス
（systemic lupus erythematosus：SLE）　SLEでは30～60％の症例に血清トランスアミナーゼや胆道系酵素の上昇，20～50％に肝腫大がみられる．肝障害の原因はSLE自体によるものとステロイドなどの治療薬によるものが多い．SLEの肝組織像は，脂肪肝と非特異的反応性肝炎（non specific reactive hepatitis：NSRH）がそれぞれ40％程度を占め，活動性肝炎や肝硬変は少ない．まれに血管炎や結節性再生性過形成（nodular regenerative hyperplasia：NRH）の像がみられる．肝障害を伴ったSLEとの鑑別を要する疾患としてLE細胞現象が陽性の自己免疫性肝炎（autoimmune hepatitis：AIH）があげられる．AIHはSLEよりもガンマグロブリン値が高く，抗平滑筋抗体が陽性で，抗ds-DNA抗体が陰性の症例が多い．AIHでは形質細胞浸潤と肝細胞壊死を伴う慢性活動性肝炎が認められるが，SLEの肝病変は軽度で門脈域に非特異的なリンパ球浸潤を伴う非特異的反応性肝炎を呈する．
b.関節リウマチ（rheumatoid arthritis：RA）
　関節リウマチの20～50％に肝障害を認める．肝組織の検討では，非特異的反応性肝炎を40％に，脂肪肝を20％に認め，肝アミロイドーシスを合併することもある．関節リウマチに自己免疫性肝炎や原発性胆汁性肝硬変（primary biliary cirrhosis：PBC）が合併することは少ないが，AIHとPBCにおける関節リウマチの合併は，それぞれ10％と5％程度とされている．関節リウマチ，脾腫，白血球減少を3主徴とするFelty症候群では高率に肝障害がみられ，AST，ALTやALP値の上昇などを40～60％に，肝腫大を70％に認める．門脈圧亢進症が出現することも比較的多く，組織像では門脈域の線維化を伴う結節性再生性過形成を認める症例が多い．発熱，皮疹，関節痛を３主徴とする成人Still病においても肝障害が高率にみられ，肝腫大を50％，脾腫大を65％，肝障害を85％に認める．
c.Sjögren症候群（SjS）
　Sjögren症候群の10～30％に肝障害がみられ，約1/4の症例に脾腫大を伴う．Sjögren症候群からみれば原発性胆汁性肝硬変や自己免疫性肝炎の合併は低率であるが，原発性胆汁性肝硬変と自己免疫性肝炎におけるSjögren症候群の合併は比較的高く，それぞれ20％と10％であると報告されている．
d.全身性強皮症（systemic scleroderma）
　全身性強皮症は皮膚硬化が全身に及ぶ汎発型と手指に限局する限局型に分類される．消化管病変を高率に認めるが，肝障害の頻度は低い．限局型のCREST症候群ではPBCの重複が注目されており，重複例では抗セントロメア抗体の陽性率が90％以上ときわめて高い．
e.結節性多発動脈炎（polyarteritis nodosa：PN）
　剖検ではPNの約半数に肝動脈の病変を認めるが，臨床的に肝障害をきたすことはまれである．しかし，血管炎により動脈瘤を形成し，破裂や肝梗塞を起こし重症化することがある．［西口修平］

出典　内科学第10版内科学第10版について　情報

<<: High Sword Father - Kou Kenfu

>>: Antigen recognition