今日の臨床サポート

ウイルス性関節炎

著者: 押川 英仁 熊本赤十字病院 リウマチ・膠原病内科

監修: 岸本暢将 杏林大学医学部 腎臓・リウマチ膠原病内科

著者校正/監修レビュー済:2021/03/31
患者向け説明資料

概要・推奨   

  1. C型肝炎に伴う関節炎では小関節の対称性関節炎が持続し、およそ5070%でRFも陽性となるため、RAとの鑑別が困難となるケースも少なくない。C型肝炎による関節炎では抗CCP抗体陽性や画像上の骨破壊などはみられないため、これらの所見はRAとの鑑別に有用である(推奨度2
  1. ヒトパルボウイルスB19の急性感染症の診断は通常、血清中の抗IgM抗体(ELISA法)で行うが、発症後3カ月以内に測定することが重要である(推奨度2
  1. ヒトパルボウイルスB19IgM抗体(ELISA)は偽陽性となることがあり、偽陽性が疑われる場合には、ウイルスDNAPCR)を確認する(推奨度3
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薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、林太祐、渡邉裕次、井ノ口岳洋、梅田将光による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
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尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※同効薬・小児・妊娠および授乳中の注意事項等は、海外の情報も掲載しており、日本の医療事情に適応しない場合があります。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適応の査定において保険適応及び保険適応外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適応の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
押川 英仁 : 特に申告事項無し[2022年]
監修:岸本暢将 : 講演料(田辺三菱製薬,アッヴィ,エーザイ,日本イーライリリー,旭化成ファーマ,ヤンセン,ノバルティス,中外製薬,UCB,アステラス製薬,アムジェン,ファイザー,BMS,あゆみ製薬,第一三共)[2022年]

改訂のポイント:
  1. 定期レビューを行い、疫学情報や検査項目について一部加筆修正を行った。

病態・疫学・診察

疾患情報(疫学・病態)  
  1. ウイルス性関節炎は、基本的に急性発症の対称性多発関節炎であり、多くは数週以内に自然軽快する一過性のものである。
  1. 例外的に、ヒトパルボウイルスB19や風疹ウイルス(あるいはワクチン)、アルファウイルスの一部で持続例や再発例がみられるほか、HCV関連関節炎では慢性の経過であることが多い。ウイルス性関節炎ではしばしば抗核抗体が陽性となり、ときにRFも陽性となることがある。関節リウマチ(RA)や全身性エリテマトーデス(SLE)の分類基準を満たす場合があり、RAやSLEとの鑑別が必要である。
  1. 日常診療において遭遇する可能性があるウイルスとしては、以下のものがある。ヒトパルボウイルスB19や風疹ウイルスによる関節炎は特に女性に多い。
  1. ヒトパルボウイルスB19
  1. B型肝炎ウイルス(HBV)
  1. C型肝炎ウイルス(HCV)
  1. 風疹ウイルス(あるいはワクチン)
  1. デングウイルス
  1. アルファウイルス(特にチクングニアウイルス)
  1. デングウイルスやチクングニアウイルスは今後わが国の日常診療でも遭遇する可能性があり、流行地への渡航歴などがあれば鑑別が必要である。
 
病歴・診察のポイント  
  1. 発症から数週以内のすべての関節炎において、ウイルス感染症の可能性を検討しなければならない。

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文献 

Mark H Wener, Kathleen Hutchinson, Chihiro Morishima, David R Gretch
Absence of antibodies to cyclic citrullinated peptide in sera of patients with hepatitis C virus infection and cryoglobulinemia.
Arthritis Rheum. 2004 Jul;50(7):2305-8. doi: 10.1002/art.20355.
Abstract/Text OBJECTIVE: To determine if antibodies to cyclic citrullinated peptide (anti-CCP) are found in chronic hepatitis C virus (HCV) infection.
METHODS: Rheumatoid factor (RF) and anti-CCP were measured in sera from 50 patients with HCV infection but without cryoglobulinemia, sera from 29 patients with mixed cryoglobulinemia (including 13 with rheumatic symptoms and 5 with arthritis), and sera from 20 normal blood donors. Anti-CCP was measured by second-generation enzyme-linked immunosorbent assay (ELISA).
RESULTS: No sera with elevated anti-CCP were found in patients with HCV infection without cryoglobulinemia, and in that population, the maximum anti-CCP was 10 units, well below the positive cutoff of 20 units. Positive findings on RF testing >13 IU/ml were present in 22 (44%) of the HCV patients, with RF >50 IU/ml in 8 (16%) and a maximum RF of 526 IU/ml. Of the cryoglobulinemia patients, 22 (76%) had positive results on tests for RF, including 18 (62%) with RF >50 IU/ml and a maximum RF of 5,540 IU/ml. Two (6.9%) of the cryoglobulinemia patients had borderline-positive findings on tests for anti-CCP (25 units and 37 units), which were false-positive results caused by nonspecific binding in the ELISA. No association between the RF and the anti-CCP concentrations was found.
CONCLUSION: Whereas RF was frequent in patients with HCV infection with and without cryoglobulinemia, anti-CCP was not observed in patients with uncomplicated HCV infection. Borderline-positive anti-CCP results were observed infrequently in patients with mixed cryoglobulinemia and were caused by nonspecific binding to plastic. Measurement of anti-CCP may help in diagnosing RA in patients with chronic HCV infection.

PMID 15248231
Michele Bombardieri, Cristiano Alessandri, Giancarlo Labbadia, Cristina Iannuccelli, Francesco Carlucci, Valeria Riccieri, Vincenzo Paoletti, Guido Valesini
Role of anti-cyclic citrullinated peptide antibodies in discriminating patients with rheumatoid arthritis from patients with chronic hepatitis C infection-associated polyarticular involvement.
Arthritis Res Ther. 2004;6(2):R137-41. doi: 10.1186/ar1041. Epub 2004 Jan 29.
Abstract/Text This study was performed to assess the utility of anti-cyclic citrullinated peptide (anti-CCP) antibodies in distinguishing between patients with rheumatoid arthritis (RA) and patients with polyarticular involvement associated with chronic hepatitis C virus (HCV) infection. Serum anti-CCP antibodies and rheumatoid factor (RF) were evaluated in 30 patients with RA, 8 patients with chronic HCV infection and associated articular involvement and 31 patients with chronic HCV infection without any joint involvement. In addition, we retrospectively analysed sera collected at the time of first visit in 10 patients originally presenting with symmetric polyarthritis and HCV and subsequently developing well-established RA. Anti-CCP antibodies and RF were detected by commercial second-generation anti-CCP2 enzyme-linked immunosorbent assay and immunonephelometry respectively. Anti-CCP antibodies were detected in 23 of 30 (76.6%) patients with RA but not in patients with chronic HCV infection irrespective of the presence of articular involvement. Conversely, RF was detected in 27 of 30 (90%) patients with RA, 3 of 8 (37.5%) patients with HCV-related arthropathy and 3 of 31 (9.7%) patients with HCV infection without joint involvement. Finally, anti-CCP antibodies were retrospectively detected in 6 of 10 (60%) patients with RA and HCV. This indicates that anti-CCP antibodies can be useful in discriminating patients with RA from patients with HCV-associated arthropathy.

PMID 15059277
M J Anderson, P G Higgins, L R Davis, J S Willman, S E Jones, I M Kidd, J R Pattison, D A Tyrrell
Experimental parvoviral infection in humans.
J Infect Dis. 1985 Aug;152(2):257-65.
Abstract/Text Healthy adult volunteers were inoculated intranasally with human parvovirus obtained from an asymptomatic blood donor. One week after inoculation, intense viremia was observed in seronegative volunteers, accompanied by a mild illness with pyrexia, malaise, myalgia, itching, and excretion of virus from the respiratory tract. In the following week hematologic studies revealed reticulocytopenia with an associated slight drop in hemoglobin concentration, lymphopenia, neutropenia, and a drop in platelet counts. At 17-18 days after inoculation a second-phase illness with rash and arthralgia lasting three to four days occurred in three of four infected volunteers. This study confirms the etiologic role of human parvovirus in erythematous rash illness, with the second-phase illness being consistent with adult cases of erythema infectiosum. Moreover, the hematologic changes associated with infection support the hypothesis that the same virus is responsible for the temporary arrest of erythropoiesis that leads to aplastic crisis in persons with chronic hemolytic anemia.

PMID 2993431
L J Anderson, C Tsou, R A Parker, T L Chorba, H Wulff, P Tattersall, P P Mortimer
Detection of antibodies and antigens of human parvovirus B19 by enzyme-linked immunosorbent assay.
J Clin Microbiol. 1986 Oct;24(4):522-6.
Abstract/Text Acute-phase serum from a patient with aplastic crisis provided sufficient human parvovirus B19 to make a monoclonal antibody against B19 and to develop antigen and immunoglobulin M (IgM) and IgG antibody detection enzyme-linked immunosorbent assays (ELISAs). The indirect capture antibody method was used for all three assays. Antigen was detected in 8 of 29 sera drawn within 2 days of onset of illness from patients with aplastic crisis. These sera had high titers of virus by electron microscopy and DNA hybridization and had no detectable B19 antibody. Antigen was not detected in serum specimens that had low titers of B19 DNA and had B19 antibody. With the IgM ELISA, we detected B19 IgM in over 85% of clinical cases of aplastic crisis and fifth disease and less than 2% of controls. The prevalence of B19 IgG antibodies increased with age. Approximately 2% of children less than 5 years of age and 49% of adults greater than 20 years of age had B19 IgG antibodies. The B19 antibody ELISAs are sensitive and specific tests to detect B19 infections.

PMID 3021807
Alice H Johnson, Andrew Gough
False positive parvovirus serology.
J Rheumatol. 2004 Mar;31(3):625-6.
Abstract/Text
PMID 14994423
J R Kerr, N Boyd
Autoantibodies following parvovirus B19 infection.
J Infect. 1996 Jan;32(1):41-7.
Abstract/Text This study was undertaken to assess the incidence and significance of autoantibody production following B19 infection, 53 patients with acute B19 infection (positive for serum anti-B19 IgM) were studied; symptoms were rash and arthralgia (n = 26), rash (n = 7), arthralgia (n = 16), aplastic crisis (n = 3), and intrauterine death (n = 1). These patients were followed for 26-85 months (mean 57 months) and re-assessed for persistent symptoms, serum anti-B19 antibodies, and serum autoantibodies. At follow-up, 14 test and two control patients had one or more serum autoantibodies (anti-nuclear antibody, anti-smooth muscle antibody, gastric parietal cell antibody, anti-reticulin antibody, anti-mitochondrial antibody, rheumatoid factor) at a titre of > or = 40 (P = 0.004). Seven test patients and no control patients had serum autoantibody at a titre > or = 160. Of these seven test patients, only one had persistent symptoms. At follow-up assessment, this woman was 48-year-old, had persistent arthralgia for 4 years following acute B19 infection, rheumatoid factor at a titre of 160 (1920 IU/ml), and had been independently diagnosed as having rheumatoid arthritis. In conclusion, results of the present study showed that low titre autoantibody production was common following symptomatic B19 infection, however, while interesting from a virological standpoint, this finding may be of little significance for future development of autoimmune disease.

PMID 8852550
Pascal Sève, Tristan Ferry, Martial Koenig, Pascal Cathebras, Hugues Rousset, Christiane Broussolle
Lupus-like presentation of parvovirus B19 infection.
Semin Arthritis Rheum. 2005 Feb;34(4):642-8. doi: 10.1016/j.semarthrit.2004.07.008.
Abstract/Text OBJECTIVES: To describe 2 cases of parvovirus B19 (B19) infection mimicking systemic lupus erythematosus (SLE) and to identify all cases of SLE imitated by and/or associated with B19 in the medical literature.
METHODS: A computer-assisted (PubMed) search of the medical literature from 1975 to 2003 was performed using the following key words: parvovirus, B19, SLE, lupus, antibodies, auto-immunity.
RESULTS: Thirty-eight patients were identified: 35 women, 3 men; mean age = 28.8 years. Clinical manifestations were as follows: fever (24 patients); articular involvement (36 patients); cutaneous lesions (28 patients); lymphadenopathy (9 patients); hepato- and/or splenomegaly (6 patients); serositis (6 patients); renal involvement (4 patients); cerebral impairment (10 patients). Cytopenia was observed in 23 cases. Antinuclear antibodies were detected in 34 patients, anti-double-stranded DNA antibodies in 20 patients, anti-Sm antibodies in 4 patients, antinuclear ribonucleoprotein antibodies in 5 patients, anti-Ro-SSA antibodies in 4 patients, anti-La-SSB antibodies in 4 patients, and anticardiolipin and/or anti-beta2-glycoprotein I antibodies in 8 patients. Hypocomplementemia was found in 15 of 26 patients. In 19 cases, the B19 infection had a self-limiting course. In 6 cases, B19 infection occurred in a context of previously established SLE, simulating SLE exacerbation. In 6 observations, symptoms persisted several months after the viral infection. In 7 cases, the exact relationship between SLE and B19 could not be determined.
CONCLUSIONS: B19 infection may present a clinical and serological tableau making it difficult to distinguish between a viral infection and the first episode of SLE. Although B19 may modulate the clinical and biological features of rheumatic disease, studies in large series do not support a causative role for B19 in the pathogenesis of SLE.

PMID 15692957
G Nesher, T G Osborn, T L Moore
Parvovirus infection mimicking systemic lupus erythematosus.
Semin Arthritis Rheum. 1995 Apr;24(5):297-303.
Abstract/Text There are striking similarities between human parvovirus B19 (HPV-B19) infection and systemic lupus erythematosus (SLE): both may present with malar rash, fever, arthropathy, myalgia, cytopenia, hypocomplementemia, anti-DNA, and antinuclear antibodies (ANA). Therefore, it is difficult at times to differentiate HPV-B19 infection from SLE presentation or exacerbation. We report 4 cases of HPV-B19 infection mimicking SLE and review 10 other reported cases, all of whom were women. The similarity to a typical SLE presentation was indeed striking: most patients presented with rash, arthropathy, myalgia, fever, and positive ANA. In some cases, HPV-B19 infection seemed to exacerbate SLE rather then resemble it, and differentiation was difficult. Nearly all patients improved within several weeks. However, a few patients had symptoms and laboratory abnormalities lasting more than 6 months. The possibility of HPV-B19 infection should be entertained in patients presenting with SLE-like features.

PMID 7604297
Dimitrios Vassilopoulos, Leonard H Calabrese
Virally associated arthritis 2008: clinical, epidemiologic, and pathophysiologic considerations.
Arthritis Res Ther. 2008;10(5):215. doi: 10.1186/ar2480. Epub 2008 Sep 18.
Abstract/Text Several viruses have been associated with the development of inflammatory arthritis, including the hepatitis viruses (hepatitis B virus and hepatitis C virus), HIV, the parvovirus B19, the human T-cell lymphotropic virus-I, and the alphaviruses. Here, we review the epidemiology, the pathophysiological mechanisms, the pertinent clinical and laboratory findings as well as the principles of therapy of the most common virus-associated arthritides. We believe that the knowledge of these key diagnostic and therapeutic features of virus-associated arthritides is important for the rheumatologist of the 21st century.

PMID 18828883
Jennifer Becker, Kevin L Winthrop
Update on rheumatic manifestations of infectious diseases.
Curr Opin Rheumatol. 2010 Jan;22(1):72-7. doi: 10.1097/BOR.0b013e328333b9f5.
Abstract/Text PURPOSE OF REVIEW: As infectious diseases continue to emerge, and as molecular techniques advance, the rheumatic manifestations of infectious diseases are increasingly recognized and better understood. Herein, we review important recent clinical, epidemiologic, and basic science advances within this area of rheumatology.
RECENT FINDINGS: We searched the U.S. National Library of Medicine PubMed database for relevant articles published since 1 January 2008. We identified a number of studies suggesting a potentially greater role for persistent viral and bacterial infections in the development of rheumatoid arthritis or rheumatoid arthritis-like syndromes. These include emerging pathogens like Chikungunya virus, as well as historically important pathogens like measles. New literature furthers the idea that antecedent infections with Chlamydia sp. could be causative in some cases of undifferentiated spondyloarthritis. Other studies document diagnostic methods capable of distinguishing between Hepatitis C virus and auto-immune driven arthritis allowing clinicians to better target therapy.
SUMMARY: Infectious pathogens are increasingly recognized in association with rheumatic disease. Rheumatologists should be aware of this trend as such recognition may alter the diagnosis and management of rheumatic symptoms, as well as trigger new research opportunities to better understand the causes of rheumatic disease.

PMID 19910794
Leonard H Calabrese, Stanley J Naides
Viral arthritis.
Infect Dis Clin North Am. 2005 Dec;19(4):963-80, x. doi: 10.1016/j.idc.2005.09.002.
Abstract/Text The role of viruses in the development of acute and chronic arthritis is complex, because viruses are ubiquitous, and all human beings are occasionally afflicted by viral infections. In general, most viral infections are acute and self-limiting and survive by infecting one susceptible host, then moving on to another. Some viruses establish prolonged latency in the host after acute infection, whereas other agents produce chronic infections following the primary stage. The mechanisms whereby these infections produce arthritis are diverse and still poorly understood, but are clearly influenced by both host and viral factors. This review addresses these and other common forms of viral arthritis, such as that caused by parvovirus B19.

PMID 16297742
Annelies Wilder-Smith, Eli Schwartz
Dengue in travelers.
N Engl J Med. 2005 Sep 1;353(9):924-32. doi: 10.1056/NEJMra041927.
Abstract/Text
PMID 16135837
Frank L Lanza, Francis K L Chan, Eamonn M M Quigley, Practice Parameters Committee of the American College of Gastroenterology
Guidelines for prevention of NSAID-related ulcer complications.
Am J Gastroenterol. 2009 Mar;104(3):728-38. doi: 10.1038/ajg.2009.115. Epub 2009 Feb 24.
Abstract/Text Guidelines for clinical practice are intended to indicate preferred approaches to medical problems as established by scientifically valid research. Double-blind, placebo-controlled studies are preferable, but compassionate use reports and expert review articles are used in a thorough review of the literature conducted through Medline with the National Library of Medicine. Only when data that will not withstand objective scrutiny are available is a recommendation identified as a consensus of experts. Guidelines are applicable to all physicians who address the subject, without regard to specialty training or interests, and are intended to indicate the preferable, but not necessarily the only, acceptable approach to a specific problem. Guidelines are intended to be flexible and must be distinguished from standards of care, which are inflexible and rarely violated. Given the wide range of specifics in any health-care problem, the physician must always choose the course best suited to the individual patient and the variables in existence at the moment of decision. These guidelines were developed under the auspices of the American College of Gastroenterology by a committee of experts in the field, reviewed by its Practice Parameters Committee, and approved by the Board of Trustees. The recommendations of these guidelines are therefore considered valid at the time of production based on the data available. New developments in medical research and practice pertinent to each guideline will be reviewed at an established time and indicated at publication to assure continued validity. Owing to the volume of new data on the subject of non-steroidal anti-inflammatory drug (NSAID)-related injury to the upper gastrointestinal tract, i.e., the advent of cyclooxygenase (COX)-2 inhibitors, new data on interactions between these agents, as well as traditional NSAIDs, with aspirin and H. pylori, it was elected by the Committee to confine these guidelines to upper gastrointestinal (GI) injury and to leave post-duodenal injury as the subject of a separate guideline.

PMID 19240698

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