Trends in LIMS

Posted on February 21, 2024 By onQ Software Blog

Mixed connective tissue disease
Other namesMCTD, connective tissue disease overlap syndrome, mixed collagen vascular disease, sharp syndrome.[1]
SpecialtyImmunology, rheumatology Edit this on Wikidata

Mixed connective tissue disease (MCTD) is a systemic autoimmune disease that shares characteristics with at least two other systemic autoimmune diseases, including systemic sclerosis (Ssc), systemic lupus erythematosus (SLE), polymyositis/dermatomyositis (PM/DM), and rheumatoid arthritis.[2] The idea behind the "mixed" disease is that this specific autoantibody is also present in other autoimmune diseases such as systemic lupus erythematosus, polymyositis, scleroderma, etc. MCTD was characterized as an individual disease in 1972 by Sharp et al.,[3][4] and the term was introduced by Leroy[5] in 1980.[6]

Some experts consider MCTD to be the same as undifferentiated connective tissue disease,[7] but other experts specifically reject this idea[8] because undifferentiated connective tissue disease is not necessarily associated with serum antibodies directed against the U1-RNP. Furthermore, MCTD is associated with a more clearly defined set of signs and symptoms.[8]

Signs and symptoms

The early clinical features of MCTD are nonspecific and may include fatigue, low-grade fever, myalgias, Raynaud phenomenon, swelling of the fingers or hands, arthralgia, esophageal reflux or dysmotility, acrosclerosis (also known as sclerodactyly), mild myositis, and various forms of pulmonary involvement.[9][10] MCTD can affect nearly any organ system.[11][12]

Skin involvement

Skin involvement is common in most people with MCTD and is frequently a presenting characteristic.[13] The most prevalent skin change is Raynaud's phenomenon, which usually appears early in the course of the disease.[14] Swollen digits are a common sign, and on occasion, the complete hand swells.[15][16] Acrosclerosis, also known as sclerodactyly, can develop with or without proximal scleroderma and is usually a later symptom of the condition.[10]

Rashes are found in 50-60% of patients.[10] Common symptoms include photosensitivity and malar rashes, similar to those seen with SLE.[17] Discoid lesions are also occasionally seen.[10] Some patients with MCTD may have scleroderma-like symptoms such as squared telangiectasia on the hands and face, periungual telangiectasia, sclerodactyly, and calcinosis cutis.[18][10]

Like systemic sclerosis, aberrant nailfold capillaroscopy with enormous capillaries, atypical forms, and low capillary density is a common hallmark of MCTD, and this can accumulate over time.[19][20][21]

Joint involvement

Approximately 60% of MCTD patients develop visible arthritis, frequently with rheumatoid arthritis (RA) deformities such as boutonniere deformities and swan neck alterations.[16][22] Other features include tiny marginal erosions[23][24] and destructive arthritis, such as arthritis mutilans.[25][26]

Pulmonary involvement

The lungs are commonly affected in MCTD, with around 75% of patients having lung involvement.[27][28] The most prevalent pulmonary complications of MCTD are interstitial lung disease (ILD) and pulmonary hypertension, however a wide spectrum of other pulmonary problems have been recorded, including pleural effusions, pleuritic discomfort, alveolar hemorrhage, and thromboembolic illness. Early indications of pulmonary involvement include dyspnea, dry cough, and pleuritic chest pain.[29]

Muscle involvement

Diagnosing MCTD involves identification of inflammatory myopathy that is histologically and clinically identical to polymyositis (PM).[30][31][32] The majority of persons with MCTD do not experience clinical weakness. People with MCTD typically have mild myositis, with normal muscle enzymes and electromyographic results. In fact, some people may be completely asymptomatic. Myositis can be severe and difficult to differentiate from conventional dermatomyositis.[10] Myalgia is a prevalent complaint among patients with MCTD.[33]

Cardiac involvement

About 30% of MCTD patients have symptomatic heart disease, whereas up to 40% have subclinical cardiac illness. The most common ECG abnormalities are hemiblock, bundle branch block, and atrioventricular block. Pericarditis is the most common clinical indication of cardiac involvement, affecting up to 40% of patients.[34]

Kidney involvement

Renal involvement is a key complication of MCTD. Some studies show that it affects around 25% of people and is generally asymptomatic.[35] The most prevalent finding is membranous nephropathy,[36] however nephrotic range proteinuria may also occur.[37] Tubulointerstitial nephritis, mesangioproliferative glomerulonephritis, and hypertensive episodes resembling scleroderma renal crisis have also been observed.[38][39][40]

Gastrointestinal involvement

Gastrointestinal involvement is prevalent and overlaps with systemic sclerosis.[41] Esophageal dysfunction is the most common gastrointestinal manifestation. The condition is initially asymptomatic, with difficulty swallowing (dysphagia) being the most prevalent symptom.[42]

Nervous system involvement

The original clinical criteria of MCTD stressed the absence of CNS involvement.[43] For instance, people with MCTD do not suffer serious problems such as cerebritis, psychosis, or seizures. However, roughly 25% of individuals have a some form of CNS illness.[44][45] The most common central nervous system manifestation is trigeminal (fifth cranial) nerve neuropathy, which may be a patient’s first symptom.[46][47] Headaches are prevalent and are typically vascular in origin.[48] Headaches can also be due to aseptic meningitis.[49] Sensorineural hearing loss is frequently overlooked, however it is estimated to occur in 50% of MCTD patients.[50]

Hematologic involvement

Hematologic abnormalities are prevalent in MCTD. Mild lymphadenopathy affects 25–50% of patients, and it is frequently an early symptom of the disease. This usually subsides over time, however it may reappear during flares. Between 50% and 75% of people with MCTD will experience anemia, lymphopenia, or leukopenia. Anemia of chronic disease is the most common type of anemia seen in MCTD.[10] Thrombocytopenia can develop in MCTD but is less common than leukopenia or anemia.[18][43]

Systemic involvement

Malaise and low-grade fever may develop with MCTD. The condition can cause elevated body temperatures without a clear cause.[10] Sicca symptoms are frequent in MCTD, affecting 25-50% of individuals.[17]

Causes

Genetic and environmental factors both influence susceptibility to MCTD. The condition is associated with aberrant immunological regulation and immune-effector pathways.[10]

Triggers

Several environmental factors have been postulated to modify illness susceptibility or induce disease; the most persuasive of these is the role of female sex hormones, as evidenced by the disease's significant female-to-male ratio and other data.[51] Furthermore, investigations indicate that Epstein-Barr virus, retroviruses, or other viruses may play a role in causing disease in some patients. Cytomegalovirus has also been proposed as capable of eliciting anti-RNP antibody responses in the absence of illness. Environmental exposure to vinyl chloride has been linked to the development of an MCTD-like condition.[10]

Genetics

In MCTD, major histocompatibility complex (MHC) and non-MHC genes have been linked to disease vulnerability.[10] HLA-DR4 in the MHC is linked to both anti-RNP antibody responses and MCTD.[52][53] The HLA class II phenotype/genotype most closely connected with scleroderma, HLA-DR5, and its subgroups, has been demonstrated to have a negative connection with MCTD.[54][55]

Another genetic feature of MCTD is the presence of anti-RNP antibodies. However, these antibodies are not present in all patients.[56] Genome-wide association studies have revealed that there are parts of a patient’s genetic material which cause production of these anti-RNP antibody. The mechanism is not yet thoroughly defined.[57][10]

Mechanism

Several immunological variables have been linked to MCTD and may play a role in disease etiology.[58][51] The 70-kD peptide of the U1-RNP antigen appears to be a dominant autoantigen in MCTD, consisting of a 437 residue polypeptide that noncovalently binds with U1-RNA via an RNA binding region on the polypeptide spanning residues 92-202.[59] The U1 70-kD polypeptide and RNP undergo a range of potential and demonstrated structural alterations, each of which may influence the antigenicity of the RNP complex.[60][61]

Autoantibodies are generally recognized as a feature of several rheumatic illnesses, including MCTD.[62] Two investigations have provided evidence that anti-RNP antibodies have a role in the development of MCTD by linking antibody emergence to clinical illness.[63][64] Beyond antibody formation, B cells can serve in a variety of other important immunological pathways, including as antigen presentation, pathogenic cytokine secretion, and tissue harm via antibody-directed mechanisms.[51]

T cells appear to have a key role in the pathophysiology of MCTD. RNP-reactive CD4+ T cells have been detected in the peripheral blood of MCTD patients. Both anti-RNP and anti-U1-RNA antibodies identified in patients' serum have typically undergone isotope shift to immunoglobulin G (IgG) subtypes. In addition, there is intense lymphocyte infiltration, with many T cells detected in the locations of tissue injury at autopsy and in patient biopsy specimens.[65] In vitro studies have also revealed that human RNP reactive T cells can aid in the generation of anti-RNP autoantibodies.[51][62]

Vascular changes cause some of the most severe clinical signs of MCTD. Adult MCTD patients had uncontrolled overexpression of endostatin and vascular endothelial growth factor (VEGF), two angiostatic and angiogenic factors. VEGF levels were higher in MCTD individuals who had pulmonary arterial hypertension and myositis, which may indicate a more severe course of disease.[65]

Diagnosis

Because of the vast range of clinical symptoms in MCTD, diagnosis is not often straightforward.[12] Different types of connective tissue disease, such as transitory illnesses and the early stages of characterized connective tissue diseases that will become completely defined in a few months or years, should be considered in the differential diagnosis.[66] There are also uncompleted versions of recognized connective tissue diseases, in which clinical and serological symptoms allow for a diagnosis but classification criteria are not met.[67] The most prevalent strategy to diagnosis in clinical practice combines serological criteria with at least three clinical criteria.[68]

Classification

Four commonly accepted criteria for classifying patients with MCTD have been published, the Sharp criteria (1987), the Alarcón-Segovia criteria (1987), the Kasukawa criteria (1987), and the Kahn criteria (1991). The Alarcon-Segovia and Kahn criteria have equivalent sensitivity and specificity, and a comparison of the four diagnostic criteria suggests that the Kasukawa criteria provide the best sensitivity, while both Alarcon-Segovia and Kahn criteria have the maximum specificity.[69]

Sharp criteria

The Sharp criteria require at least four major criteria, as well as anti-U1-RNP antibody titer of at least 1:4000, or two major criteria from criteria 1, 2, and 3, and two minor criteria, plus anti-U1-RNP antibody titer of at least 1:1000. The sharp criteria also excludes anyone with a positive anti-Sm antibody.[69] It has a sensitivity of 42%[70] and a specificity of 87.7%.[32]

Major criteria:[69]

  1. Myositis
  2. Pulmonary involvement:
  3. Raynaud's phenomenon or esophageal hypomotility
  4. Swollen hands
  5. Anti-ENA antibody N 1:10,000 and anti-U1 RNP antibody positive and anti-Sm negative

Minor criteria:[69]

  1. Alopecia
  2. Leukopenia
  3. Anemia
  4. Pleuritis
  5. Pericarditis
  6. Arthritis
  7. Trigeminal neuropathy
  8. Malar rash
  9. Thrombocytopenia
  10. Mild myositis
  11. History of swollen hands

Alarcón-Segovia criteria

The Alarcón-Segovia criteria require serological criteria and at least three clinical criteria including either synovitis or myositis to qualify for a diagnosis of MCTD.[69] It has a sensitivity of 62.5% and a specificity of 86.2%.[31]

Serological criteria:[69]

Clinical criteria:[69]

  1. Edema in hands
  2. Synovitis
  3. Myositis
  4. Raynaud's phenomenon
  5. Acrosclerosis

Kasukawa criteria

The Kasukawa criteria require a minimum of one of the common symptoms, a positive anti-RNP antibody, as well as one or more symptoms of the mixed symptoms in at least two of the three disease categories to qualify for a diagnosis of MCTD.[69] It has a sensitivity of 75%[70] and a specificity of 99.8%.[32]

Common symptoms:[69]

  1. Raynaud's phenomenon
  2. Swollen fingers or hands anti-RNP antibody positive

Mixed symptoms:[69]

  1. SLE-like symptoms:
  2. SSc-like findings:
  3. PM-like findings:
    • Muscle weakness
    • Elevated serum levels of muscle enzymes (CPK)
    • Myogenic pattern on EMG

Kahn criteria

The Kahn criteria require serological criteria in addition to Raynaud's phenomenon and two out of the three symptoms listed below (swelling of the fingers, myositis, and synovitis) to qualify for a diagnosis of MCTD.[69] It has a sensitivity of 63% and a specificity of 86%.[31]

Serological criteria:[69]

  • Presence of high titer anti-RNP antibody corresponding to speckled ANA at titer ≥ 1 : 2000

Clinical criteria:[69]

  1. Raynaud's phenomenon
  2. Synovitis
  3. Myositis
  4. Swollen fingers

Treatment

MCTD has no specific treatment. Management should address the individual's primary issues, such as arthritis, skin disease, or visceral involvement. Low-dose glucocorticoids, nonsteroidal anti-inflammatory medications, hydroxychloroquine, or a combination of these therapies can effectively treat many patients.[65]

Fever, tiredness, unspecific arthralgias, or myalgias are commonly treated with nonsteroidal anti-inflammatory medications (NSAIDs), hydroxychloroquine, or a low dose of prednisone, depending on the severity.[68]

Mild joint involvement can be effectively treated with NSAIDs, hydroxychloroquine, and oral prednisone.[71][44][25] Methotrexate has been observed to be useful in more severe cases.[72] If methotrexate is contraindicated, alternative disease-modifying medications for RA, such as leflunomide or azathioprine, may be used.[68] High dosages of corticosteroids are typically effective in treating acute severe myositis.[44][73]

Topical steroids, prednisone, and/or hydroxychloroquine are useful in treating SLE-like skin rash, oral ulcers, and photosensitivity.[44][25] Steroid treatment is often effective in treating sclerodermatous skin symptoms. Raynaud's phenomenon in MCTD typically responds to vasodilator therapy such as calcium channel blockers, as well as preventive measures including avoiding cold temperatures, smoking, and sympathomimetic drugs. Warming and protecting the fingers are also important.[68]

Recent breakthroughs have increased the therapy choices available to people with pulmonary hypertension.[68] To ensure early detection, all individuals with MCTD must have screening echocardiography and high-resolution computed tomography upon diagnosis.[74] Mild cases require regular testing to monitor for progression.[68] Traditional therapies such as calcium channel blockers, ACE inhibitors, immunosuppression, and heart failure medications can be used.[75][76] Pericarditis is typically treated with NSAIDs and/or corticosteroids based on severity. For moderate to severe myocarditis, high-dose steroid therapy should be combined with standard congestive heart failure treatment.[68]

Treatment for gastrointestinal problems in MCTD is identical to that for systemic sclerosis. First-line treatment for chronic reflux symptoms includes proton-pump inhibitors, H2-receptor antagonists, lifestyle changes, and oesophageal PH monitoring. Kidney involvement can lead to nephrotic syndrome, which may be treated with high-dose corticosteroid therapy. Corticosteroids are used to treat nervous system involvement in low-dose oral, high-dose oral, or high-dose intravenous regimens, depending on the severity of the potential harm.[68]

Outlook

The long-term course of MCTD may vary. Long-term follow-up studies have shown that MCTD can progress to a moderate disease with a favorable prognosis, or patients can acquire a significant condition with vascular alterations driven by pulmonary hypertension and increased mortality. Approximately one-third of people with MCTD have a benign course and go into remission, while the other one-third have a more aggressive course with a poor response to treatment. Approximately one-third of MCTD patients improved with immunosuppressive medication but continued to require immunosuppressive therapy after several years. The prevalence of pulmonary hypertension was related with the worst prognosis and a high mortality rate, making it the most significant complication in MCTD.[37]

Epidemiology

There is currently very little epidemiologic data on MCTD.[10] Japan's statewide multicenter collaborative survey found a prevalence of 2.7% for MCTD.[77] Globally, the prevalence of MCTD has been reported to be significantly lower.[10] While there are ethnic differences in the development of anti-RNP antibodies and the prevalence of MCTD, the rate of clinical manifestations among patients from different ethnic groups remains consistent.[78] MCTD is more frequent in women than men. A Japanese nationwide survey indicated a 16:1 female-to-male ratio for MCTD,[77] while a longitudinal prospective clinical series from a tertiary referral institution in the midwestern US found an 11:1 ratio of women to men.[44][71]

History

Gordon C. Sharp first described mixed connective tissue disease (MCTD) in 1972 as an entity with mixed features of systemic sclerosis (SSc),  systemic lupus erythematosus (SLE),  polymyositis/dermatomyositis (PM/DM), and rheumatoid arthritis (RA) along with an elevated level of high-titre anti-U1small nuclear (sn) anti-ribonucleoprotein (anti-RNP) antibodies.[43]

See also

References

  1. ^ "Mixed connective tissue disease". Monarch Initiative. Retrieved 2024-07-16.
  2. ^ Tani, Chiara; Carli, Linda; Vagnani, Sabrina; Talarico, Rosaria; Baldini, Chiara; Mosca, Marta; Bombardieri, Stefano (2014). "The diagnosis and classification of mixed connective tissue disease". Journal of Autoimmunity. 48–49: 46–49. doi:10.1016/j.jaut.2014.01.008. PMID 24461387.
  3. ^ Ungprasert, Patompong; Crowson, Cynthia S.; Chowdhary, Vaidehi R.; Ernste, Floranne C.; Moder, Kevin G.; Matteson, Eric L. (December 2016). "Epidemiology of Mixed Connective Tissue Disease 1985-2014: A Population Based Study". Arthritis Care & Research. 68 (12): 1843–1848. doi:10.1002/acr.22872. ISSN 2151-464X. PMC 5426802. PMID 26946215.
  4. ^ Sharp GC, Irvin WS, Tan EM, Gould RG, Holman HR (February 1972). "Mixed connective tissue disease--an apparently distinct rheumatic disease syndrome associated with a specific antibody to an extractable nuclear antigen (ENA)". The American Journal of Medicine. 52 (2): 148–59. doi:10.1016/0002-9343(72)90064-2. PMID 4621694.
  5. ^ Tsokos GC, Gordon C, Smolen JS (2007). Systemic lupus erythematosus: a companion to Rheumatology. Elsevier Health Sciences. pp. 429–. ISBN 978-0-323-04434-9.
  6. ^ LeRoy EC, Maricq HR, Kahaleh MB (March 1980). "Undifferentiated connective tissue syndromes". Arthritis and Rheumatism. 23 (3): 341–3. doi:10.1002/art.1780230312. PMID 7362686.
  7. ^ Rapini RP, Bolognia JL, Jorizzo JL (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. ISBN 978-1-4160-2999-1.
  8. ^ a b Hoffman RW (1 June 2009). "Mixed Connective Disease". In Stone J (ed.). Pearls & Myths in Rheumatology. Springer. pp. 169–172. ISBN 978-1-84800-933-2. Retrieved 26 June 2010.
  9. ^ Farhey, Yolanda; Hess, Evelyn V. (1997). "Mixed connective tissue disease". Arthritis & Rheumatism. 10 (5). Wiley: 333–342. doi:10.1002/art.1790100508. ISSN 0004-3591. PMID 9362600.
  10. ^ a b c d e f g h i j k l m n Hoffman, Robert W.; Greidinger, Eric L. (2013). "Mixed Connective Tissue Disease and Undifferentiated Connective Tissue Disease". Dubois' Lupus Erythematosus and Related Syndromes. Elsevier. pp. 506–517. doi:10.1016/b978-1-4377-1893-5.00041-8. ISBN 978-1-4377-1893-5.
  11. ^ Rasmussen, E. K.; Ullman, S.; Høier-Madsen, M.; Sørensen, S. F.; Halberg, P. (1987). "Clinical implications of ribonucleoprotein antibody". Archives of Dermatology. 123 (5): 601–605. doi:10.1001/archderm.1987.01660290069018. ISSN 0003-987X. PMID 3495241.
  12. ^ a b Bodolay, E.; Csiki, Z.; Szekanecz, Z.; Ben, T.; Kiss, E.; Zeher, M.; Szücs, G.; Dankó, K.; Szegedi, G. (2003). "Five-year follow-up of 665 Hungarian patients with undifferentiated connective tissue disease (UCTD)". Clinical and Experimental Rheumatology. 21 (3): 313–320. ISSN 0392-856X. PMID 12846049.
  13. ^ Sen, Sumit; Sinhamahapatra, Pradyot; Choudhury, Supriyo; Gangopadhyay, Anusree; Bala, Sanchaita; Sircar, Geetabali; Chatterjee, Gobinda; Ghosh, Alakendu (2014). "Cutaneous manifestations of mixed connective tissue disease: Study from a tertiary care hospital in Eastern India". Indian Journal of Dermatology. 59 (1). Medknow: 35–40. doi:10.4103/0019-5154.123491. ISSN 0019-5154. PMC 3884926. PMID 24470658.
  14. ^ Grader-Beck, Thomas; Wigley, Fredrick M. (2005). "Raynaud's Phenomenon in Mixed Connective Tissue Disease". Rheumatic Disease Clinics of North America. 31 (3). Elsevier BV: 465–481. doi:10.1016/j.rdc.2005.04.006. ISSN 0889-857X. PMID 16084319.
  15. ^ Pope, Janet E. (2005). "Other Manifestations of Mixed Connective Tissue Disease". Rheumatic Disease Clinics of North America. 31 (3). Elsevier BV: 519–533. doi:10.1016/j.rdc.2005.04.011. ISSN 0889-857X. PMID 16084323.
  16. ^ a b Venables, P JW (2006). "Mixed connective tissue disease". Lupus. 15 (3). SAGE Publications: 132–137. doi:10.1191/0961203306lu2283rr. ISSN 0961-2033. PMID 16634365.
  17. ^ a b Setty, Yatish N.; Pittman, Cory B.; Mahale, Adit S.; Greidinger, Eric L.; Hoffman, Robert W. (2002). "Sicca symptoms and anti-SSA/Ro antibodies are common in mixed connective tissue disease". The Journal of Rheumatology. 29 (3): 487–489. ISSN 0315-162X. PMID 11908561.
  18. ^ a b Singsen, Bernhard H.; Bernstein, Bram H.; Kornreich, Helen K.; King, Karen Koster; Hanson, Virgil; Tan, Eng M. (1977). "Mixed connective tissue disease in childhood". The Journal of Pediatrics. 90 (6): 893–900. doi:10.1016/S0022-3476(77)80555-6.
  19. ^ Blockmans, D.; Vermylen, J.; Bobbaers, H. (1993). "Nailfold Capillaroscopy in Connective Tissue Disorders and in Raynaud's Phenomenon". Acta Clinica Belgica. 48 (1). Informa UK Limited: 30–41. doi:10.1080/17843286.1993.11718282. ISSN 1784-3286. PMID 8388601.
  20. ^ Furtado, R NV; Pucinelli, M LC; Cristo, V V; Andrade, L EC; Sato, E I (2002). "Scleroderma-like nailfold capillaroscopic abnormalities are associated with anti-U1-RNP antibodies and Raynaud's phenomenon in SLE patients". Lupus. 11 (1). SAGE Publications: 35–41. doi:10.1191/0961203302lu144oa. ISSN 0961-2033. PMID 11899953.
  21. ^ Todoroki, Yasuyuki; Kubo, Satoshi; Nakano, Kazuhisa; Miyazaki, Yusuke; Ueno, Masanobu; Satoh-Kanda, Yurie; Kanda, Ryuichiro; Miyagawa, Ippei; Hanami, Kentaro; Nakatsuka, Keisuke; Saito, Kazuyoshi; Nakayamada, Shingo; Tanaka, Yoshiya (2022-03-14). "Nailfold microvascular abnormalities are associated with a higher prevalence of pulmonary arterial hypertension in patients with MCTD". Rheumatology. 61 (12). Oxford University Press (OUP): 4875–4884. doi:10.1093/rheumatology/keac165. ISSN 1462-0324. PMID 35285493.
  22. ^ Fairley, Jessica L.; Hansen, Dylan; Proudman, Susanna; Sahhar, Joanne; Ngian, Gene-Siew; Walker, Jenny; Strickland, Gemma; Wilson, Michelle; Morrisroe, Kathleen; Ferdowsi, Nava; Major, Gabor; Roddy, Janet; Stevens, Wendy; Nikpour, Mandana (2021-04-03). "Clinical Features of Systemic Sclerosis–Mixed Connective Tissue Disease and Systemic Sclerosis Overlap Syndromes". Arthritis Care & Research. 73 (5). Wiley: 732–741. doi:10.1002/acr.24167. hdl:11343/298420. ISSN 2151-464X. PMID 32058672.
  23. ^ O'Connell, D. J.; Bennett, R. M. (1977). "Mixed connective tissue disease—clinical and radiological aspects of 20 cases". The British Journal of Radiology. 50 (597). Oxford University Press (OUP): 620–625. doi:10.1259/0007-1285-50-597-620. ISSN 0007-1285. PMID 901973.
  24. ^ Ramos-Niembro, Francisco; Alarcóan-Segovia, Donato; Hernández-Ortíz, Jorge (1979). "Articular manifestations of mixed connective tissue disease". Arthritis & Rheumatism. 22 (1). Wiley: 43–51. doi:10.1002/art.1780220107. ISSN 0004-3591. PMID 758918.
  25. ^ a b c Bennett, R M; O'Connell, D J (1978-10-01). "The arthritis of mixed connective tissue disease". Annals of the Rheumatic Diseases. 37 (5). BMJ: 397–403. doi:10.1136/ard.37.5.397. ISSN 0003-4967. PMC 1000265. PMID 718271.
  26. ^ Halla, James T.; Hardin, Joe G. (1978). "Clinical features of the arthritis of mixed connective tissue disease". Arthritis & Rheumatism. 21 (5). Wiley: 497–503. doi:10.1002/art.1780210502. ISSN 0004-3591. PMID 666870.
  27. ^ SULLIVAN, WILLIAM D.; HURST, DANIEL J.; HARMON, CATHERINE E.; ESTHER, JAMES H.; AGIA, GARY A.; MALTBY, JAMES D.; LILLARD, STEPHEN B.; HELD, CHARLES N.; WOLFE, J. FREDERICK; SUNDERRAJAN, E. V.; MARICQ, HILDEGARD R.; SHARP, GORDON C. (1984). "A Prospective Evaluation Emphasizing Pulmonary Involvement in Patients with Mixed Connective Tissue Disease". Medicine. 63 (2). Ovid Technologies (Wolters Kluwer Health): 92–107. doi:10.1097/00005792-198403000-00003. ISSN 0025-7974. PMID 6700436.
  28. ^ Prakash, Udaya B.S. (1992). "Lungs in mixed connective tissue disease". Journal of Thoracic Imaging. 7 (2). Ovid Technologies (Wolters Kluwer Health): 55–61. doi:10.1097/00005382-199203000-00007. ISSN 0883-5993. PMID 1578526.
  29. ^ Bull, Todd M.; Fagan, Karen A.; Badesch, David B. (2005). "Pulmonary Vascular Manifestations of Mixed Connective Tissue Disease". Rheumatic Disease Clinics of North America. 31 (3). Elsevier BV: 451–464. doi:10.1016/j.rdc.2005.04.010. ISSN 0889-857X. PMID 16084318.
  30. ^ Bennett, Robert M.; O'Connell, Dennis J. (1980). "Mixed connective tissue disease: A clinicopathologic study of 20 cases". Seminars in Arthritis and Rheumatism. 10 (1). Elsevier BV: 25–51. doi:10.1016/0049-0172(80)90013-x. ISSN 0049-0172. PMID 7414333.
  31. ^ a b c Amigues, J. M.; Cantagrel, A.; Abbal, M.; Mazieres, B. (1996). "Comparative study of 4 diagnosis criteria sets for mixed connective tissue disease in patients with anti-RNP antibodies. Autoimmunity Group of the Hospitals of Toulouse". The Journal of Rheumatology. 23 (12): 2055–2062. ISSN 0315-162X. PMID 8970041.
  32. ^ a b c Alarcón-Segovia, D.; Cardiel, M. H. (1989). "Comparison between 3 diagnostic criteria for mixed connective tissue disease. Study of 593 patients". The Journal of Rheumatology. 16 (3): 328–334. ISSN 0315-162X. PMID 2724251.
  33. ^ Hall, Stephen; Hanrahan, Patrick (2005). "Muscle Involvement in Mixed Connective Tissue Disease". Rheumatic Disease Clinics of North America. 31 (3). Elsevier BV: 509–517. doi:10.1016/j.rdc.2005.04.003. ISSN 0889-857X. PMID 16084322.
  34. ^ Ungprasert, Patompong; Wannarong, Thapat; Panichsillapakit, Theppharit; Cheungpasitporn, Wisit; Thongprayoon, Charat; Ahmed, Saeed; Raddatz, Donald A. (2014). "Cardiac involvement in mixed connective tissue disease: A systematic review". International Journal of Cardiology. 171 (3). Elsevier BV: 326–330. doi:10.1016/j.ijcard.2013.12.079. ISSN 0167-5273. PMID 24433611.
  35. ^ Kitridou, Rodanthi C.; Akmal, Mohammad; Turkel, Susan B.; Ehresmann, Glenn R.; Quismorio, Francisco P.; Massry, Shaul G. (1986). "Renal involvement in mixed connective tissue disease: A longitudinal clinicopathologic study". Seminars in Arthritis and Rheumatism. 16 (2). Elsevier BV: 135–145. doi:10.1016/0049-0172(86)90047-8. ISSN 0049-0172. PMID 3563525.
  36. ^ Yoshida, A.; Morozumi, K.; Takeda, A.; Koyama, K. (1994). "[Nephropathy in patients with mixed connective tissue disease]". Ryumachi. [Rheumatism]. 34 (6): 976–980. ISSN 0300-9157. PMID 7863388.
  37. ^ a b Lundberg, Ingrid E. (2005). "The Prognosis of Mixed Connective Tissue Disease". Rheumatic Disease Clinics of North America. 31 (3). Elsevier BV: 535–547. doi:10.1016/j.rdc.2005.04.005. ISSN 0889-857X. PMID 16084324.
  38. ^ Celikbilek, Mehmet; Elsurer, Rengin; Afsar, Baris; Ozdemir, Handan B.; Sezer, Siren; Ozdemir, Nurhan F. (2006-11-21). "Mixed connective tissue disease: a case with scleroderma renal crisis following abortion". Clinical Rheumatology. 26 (9). Springer Science and Business Media LLC: 1545–1547. doi:10.1007/s10067-006-0442-8. ISSN 0770-3198. PMID 17119864.
  39. ^ Cheta, Jordana; Rijhwani, Suresh; Rust, Harlan (2017). "Scleroderma Renal Crisis in Mixed Connective Tissue Disease With Full Renal Recovery Within 3 Months: A Case Report With Expanding Treatment Modalities to Treat Each Clinical Sign as an Independent Entity". Journal of Investigative Medicine High Impact Case Reports. 5 (4). SAGE Publications: 232470961773401. doi:10.1177/2324709617734012. ISSN 2324-7096. PMC 5637966. PMID 29051891.
  40. ^ Madieh, Jomana; Khamayseh, Iman; Hrizat, Alaa; Hamadah, Abdurrahman; Gharaibeh, Kamel (2021-01-06). "Scleroderma Renal Crisis in a Case of Mixed Connective Tissue Disease Treated Successfully with Angiotensin-Converting Enzyme Inhibitors". Case Reports in Nephrology. 2021. Hindawi Limited: 1–6. doi:10.1155/2021/8862405. ISSN 2090-665X. PMC 7808802. PMID 33505743.
  41. ^ Gutierrez, Fernando; Valenzuela, Jorge E.; Ehresmann, Glenn R.; Quismorio, Francisco P.; Kitridou, Rodanthi C. (1982). "Esophageal dysfunction in patients with mixed connective tissue diseases and systemic lupus erythematosus". Digestive Diseases and Sciences. 27 (7). Springer Science and Business Media LLC: 592–597. doi:10.1007/bf01297214. ISSN 0163-2116. PMID 7083997.
  42. ^ Doria, A.; Bonavina, L.; Anselmino, M.; Ruffatti, A.; Favaretto, M.; Gambari, P.; Peracchia, A.; Todesco, S. (1991). "Esophageal involvement in mixed connective tissue disease". The Journal of Rheumatology. 18 (5): 685–690. ISSN 0315-162X. PMID 1865414.
  43. ^ a b c Sharp, Gordon C.; Irvin, William S.; Tan, Eng M.; Gould, R.Gordon; Holman, Halsted R. (1972). "Mixed connective tissue disease-an apparently distinct rheumatic disease syndrome associated with a specific antibody to an extractable nuclear antigen (ENA)". The American Journal of Medicine. 52 (2). Elsevier BV: 148–159. doi:10.1016/0002-9343(72)90064-2. ISSN 0002-9343. PMID 4621694.
  44. ^ a b c d e MA, Burdt; RW, Hoffman; SL, Deutscher; GS, Wang; JC, Johnson; GC, Sharp (1999). "Long-term outcome in mixed connective tissue disease: longitudinal clinical and serologic findings". Arthritis and Rheumatism. 42 (5). Arthritis Rheum: 899–909. doi:10.1002/1529-0131(199905)42:5<899::AID-ANR8>3.0.CO;2-L. ISSN 0004-3591. PMID 10323445. Retrieved 2024-07-28.
  45. ^ Bennett, Robert M.; Bong, David M.; Spargo, Benjamin H. (1978). "Neuropsychiatric problems in mixed connective tissue disease". The American Journal of Medicine. 65 (6). Elsevier BV: 955–962. doi:10.1016/0002-9343(78)90747-7. ISSN 0002-9343. PMID 217265.
  46. ^ Hojaili, Bernard; Barland, Peter (2006). "Trigeminal Neuralgia as the First Manifestation of Mixed Connective Tissue Disorder". JCR: Journal of Clinical Rheumatology. 12 (3). Ovid Technologies (Wolters Kluwer Health): 145–147. doi:10.1097/01.rhu.0000222045.70861.a5. ISSN 1076-1608. PMID 16755246.
  47. ^ Hagen, Neil A.; Stevens, J. Clarke; Michet, Clement J. (1990). "Trigeminal sensory neuropathy associated with connective tissue diseases". Neurology. 40 (6). Ovid Technologies (Wolters Kluwer Health): 891–896. doi:10.1212/wnl.40.6.891. ISSN 0028-3878. PMID 2161090.
  48. ^ Bronshvag, Michael M.; Prystowsky, Stephen D.; Traviesa, Daniel C. (1978). "Vascular Headaches in Mixed Connective Tissue Disease". Headache: The Journal of Head and Face Pain. 18 (3). Wiley: 154–160. doi:10.1111/j.1526-4610.1978.hed1803154.x. ISSN 0017-8748. PMID 669945.
  49. ^ Okada, J; Hamana, T; Kondo, H (2003). "Anti-U1RNP antibody and aseptic meningitis in connective tissue diseases". Scandinavian Journal of Rheumatology. 32 (4). Informa UK Limited: 247–252. doi:10.1080/03009740310003767. ISSN 0300-9742. PMID 14626633.
  50. ^ HAJAS, AGOTA; SZODORAY, PETER; BARATH, SANDOR; SIPKA, SANDOR; REZES, SZILARD; ZEHER, MARGIT; SZIKLAI, ISTVAN; SZEGEDI, GYULA; BODOLAY, EDIT (2009-08-14). "Sensorineural Hearing Loss in Patients with Mixed Connective Tissue Disease: Immunological Markers and Cytokine Levels". The Journal of Rheumatology. 36 (9): 1930–1936. doi:10.3899/jrheum.081314. ISSN 0315-162X. PMID 19684145.
  51. ^ a b c d Hoffman, Robert W.; Maldonado, Marcos E. (2008). "Immune pathogenesis of Mixed Connective Tissue Disease: A short analytical review". Clinical Immunology. 128 (1). Elsevier BV: 8–17. doi:10.1016/j.clim.2008.03.461. ISSN 1521-6616. PMID 18439877.
  52. ^ Genth, E; Zarnowski, H; Mierau, R; Wohltmann, D; Hartl, P W (1987-03-01). "HLA-DR4 and Gm(1,3;5,21) are associated with U1-nRNP antibody positive connective tissue disease". Annals of the Rheumatic Diseases. 46 (3). BMJ: 189–196. doi:10.1136/ard.46.3.189. ISSN 0003-4967. PMC 1002098. PMID 2953314.
  53. ^ Kaneoka, Hidetoshi; Hsu, Kou-Ching; Takeda, Yoshihiko; Sharp, Gordon C.; Hoffman, Robert W. (1992). "Molecular Genetic Analysis of HLA—DR and HLA—DQ Genes Among Anti—U1-70-kd Autoantibody Positive Connective Tissue Disease Patients". Arthritis & Rheumatism. 35 (1). Wiley: 83–94. doi:10.1002/art.1780350113. ISSN 0004-3591. PMID 1370621.
  54. ^ Hoffman, Robert W.; Rettenmaier, Lawrence J.; Takeda, Yoshihiko; Hewett, John E.; Pettersson, Ingvar; Nyman, Ulf; Luger, Alan M.; Sharp, Gordon C. (1990). "Human autoantibodies against the 70-kd polypeptide of u1 small nuclear rnp are associated with hla-dr4 among connective tissue disease patients". Arthritis & Rheumatism. 33 (5): 666–673. doi:10.1002/art.1780330509. ISSN 0004-3591. PMID 2140681.
  55. ^ Gendi, Nagui S. T.; Welsh, Ken I.; Van Venrooij, Walther J.; Vancheeswaran, Rama; Gilroy, Jill; Black, Carol M. (1995). "Hla type as a predictor of mixed connective tissue disease differentiation ten-year clinical and immunogenetic followup of 46 patients". Arthritis & Rheumatism. 38 (2): 259–266. doi:10.1002/art.1780380216. ISSN 0004-3591. PMID 7848317.
  56. ^ Hoffman, R. W.; Sharp, G. C. (1995). "Is anti-U1-RNP autoantibody positive connective tissue disease genetically distinct?". The Journal of Rheumatology. 22 (4): 586–589. ISSN 0315-162X. PMID 7791147.
  57. ^ CERVINO, ALESSANDRA C. L.; TSINOREMAS, NICHOLAS F.; HOFFMAN, ROBERT W. (2007). "A Genome-Wide Study of Lupus". Annals of the New York Academy of Sciences. 1110 (1). Wiley: 131–139. doi:10.1196/annals.1423.015. ISSN 0077-8923. PMID 17911428.
  58. ^ Hoffman, Robert W.; Greidinger, Eric L. (2000). "Mixed connective tissue disease". Current Opinion in Rheumatology. 12 (5). Ovid Technologies (Wolters Kluwer Health): 386–390. doi:10.1097/00002281-200009000-00006. ISSN 1040-8711. PMID 10990174.
  59. ^ Kastner, B; Kornstädt, U; Bach, M; Lührmann, R (1992-02-15). "Structure of the small nuclear RNP particle U1: identification of the two structural protuberances with RNP-antigens A and 70K". The Journal of Cell Biology. 116 (4). Rockefeller University Press: 839–849. doi:10.1083/jcb.116.4.839. ISSN 0021-9525. PMC 2289330. PMID 1531145.
  60. ^ Greidinger, Eric L.; Foecking, Mark F.; Ranatunga, Sriya; Hoffman, Robert W. (2002). "Apoptotic U1–70 kd is antigenically distinct from the intact form of the U1–70-kd molecule". Arthritis & Rheumatism. 46 (5). Wiley: 1264–1269. doi:10.1002/art.10211. ISSN 0004-3591. PMID 12115232.
  61. ^ Hall, John C; Casciola-Rosen, Livia; Rosen, Antony (2004). "Altered structure of autoantigens during apoptosis". Rheumatic Disease Clinics of North America. 30 (3). Elsevier BV: 455–471. doi:10.1016/j.rdc.2004.04.012. ISSN 0889-857X. PMID 15261336.
  62. ^ a b Greidinger, Eric L.; Hoffman, Robert W. (2005). "Autoantibodies in the Pathogenesis of Mixed Connective Tissue Disease". Rheumatic Disease Clinics of North America. 31 (3). Elsevier BV: 437–450. doi:10.1016/j.rdc.2005.04.004. ISSN 0889-857X. PMID 16084317.
  63. ^ EL, Greidinger; RW, Hoffman (2001). "The appearance of U1 RNP antibody specificities in sequential autoimmune human antisera follows a characteristic order that implicates the U1-70 kd and B'/B proteins as predominant U1 RNP immunogens". Arthritis and Rheumatism. 44 (2). Arthritis Rheum: 368–375. doi:10.1002/1529-0131(200102)44:2<368::AID-ANR55>3.0.CO;2-6. ISSN 0004-3591. PMID 11229468. Retrieved 2024-08-01.
  64. ^ Arbuckle, Melissa R.; McClain, Micah T.; Rubertone, Mark V.; Scofield, R. Hal; Dennis, Gregory J.; James, Judith A.; Harley, John B. (2003-10-16). "Development of Autoantibodies before the Clinical Onset of Systemic Lupus Erythematosus". New England Journal of Medicine. 349 (16). Massachusetts Medical Society: 1526–1533. doi:10.1056/nejmoa021933. ISSN 0028-4793. PMID 14561795.
  65. ^ a b c Pepmueller, Peri H.; Lindsley, Carol B. (2016). "Mixed Connective Tissue Disease and Undifferentiated Connective Tissue Disease". Textbook of Pediatric Rheumatology. Elsevier. p. 418–426.e3. doi:10.1016/b978-0-323-24145-8.00029-6. ISBN 978-0-323-24145-8.
  66. ^ Mosca, Marta; Tani, Chiara; Talarico, Rosaria; Bombardieri, Stefano (2011). "Undifferentiated connective tissue diseases (UCTD): Simplified systemic autoimmune diseases". Autoimmunity Reviews. 10 (5). Elsevier BV: 256–258. doi:10.1016/j.autrev.2010.09.013. ISSN 1568-9972. PMID 20863913.
  67. ^ Mosca, Marta; Tani, Chiara; Bombardieri, Stefano (2007). "Undifferentiated connective tissue diseases (UCTD): a new frontier for rheumatology". Best Practice & Research Clinical Rheumatology. 21 (6). Elsevier BV: 1011–1023. doi:10.1016/j.berh.2007.09.004. ISSN 1521-6942. PMID 18068858.
  68. ^ a b c d e f g h Ortega-Hernandez, Oscar-Danilo; Shoenfeld, Yehuda (2012). "Mixed connective tissue disease: An overview of clinical manifestations, diagnosis and treatment". Best Practice & Research Clinical Rheumatology. 26 (1): 61–72. doi:10.1016/j.berh.2012.01.009.
  69. ^ a b c d e f g h i j k l m John, Kevin John; Sadiq, Mohammad; George, Tina; Gunasekaran, Karthik; Francis, Nirmal; Rajadurai, Ebenezer; Sudarsanam, Thambu David (2020-01-29). "Clinical and Immunological Profile of Mixed Connective Tissue Disease and a Comparison of Four Diagnostic Criteria". International Journal of Rheumatology. 2020. Hindawi Limited: 1–6. doi:10.1155/2020/9692030. ISSN 1687-9260. PMC 7204172. PMID 32411251. This article incorporates text from this source, which is available under the CC BY 3.0 license.
  70. ^ a b Cappelli, Susanna; Bellando Randone, Silvia; Martinović, Dušanka; Tamas, Maria-Magdalena; Pasalić, Katarina; Allanore, Yannick; Mosca, Marta; Talarico, Rosaria; Opris, Daniela; Kiss, Csaba G.; Tausche, Anne-Kathrin; Cardarelli, Silvia; Riccieri, Valeria; Koneva, Olga; Cuomo, Giovanna; Becker, Mike Oliver; Sulli, Alberto; Guiducci, Serena; Radić, Mislav; Bombardieri, Stefano; Aringer, Martin; Cozzi, Franco; Valesini, Guido; Ananyeva, Lidia; Valentini, Gabriele; Riemekasten, Gabriela; Cutolo, Maurizio; Ionescu, Ruxandra; Czirják, László; Damjanov, Nemanja; Rednic, Simona; Matucci Cerinic, Marco (2012). ""To Be or Not To Be," Ten Years After: Evidence for Mixed Connective Tissue Disease as a Distinct Entity". Seminars in Arthritis and Rheumatism. 41 (4). Elsevier BV: 589–598. doi:10.1016/j.semarthrit.2011.07.010. ISSN 0049-0172. PMID 21959290.
  71. ^ a b Sharp, Gordon C.; Irvin, William S.; May, Charles M.; Holman, Halsted R.; McDuffie, Frederic C.; Hess, Evelyn V.; Schmid, Frank R. (1976-11-18). "Association of Antibodies to Ribonucleoprotein and Sm Antigens with Mixed Connective-Tissue Disease, Systemic Lupus Erythematosus and Other Rheumatic Diseases". New England Journal of Medicine. 295 (21). Massachusetts Medical Society: 1149–1154. doi:10.1056/nejm197611182952101. ISSN 0028-4793.
  72. ^ Kowal-Bielecka, O.; Distler, O. (2010). "Use of methotrexate in patients with scleroderma and mixed connective tissue disease". Clinical and Experimental Rheumatology. 28 (5 Suppl 61): S160–163. ISSN 0392-856X. PMID 21044452.
  73. ^ Nimelstein, S. H.; Brody, S.; McShane, D.; Holman, H. R. (1980). "Mixed connective tissue disease: a subsequent evaluation of the original 25 patients". Medicine. 59 (4): 239–248. doi:10.1097/00005792-198007000-00001. ISSN 0025-7974. PMID 6967141.
  74. ^ Devaraj, Anand; Wells, Athol U.; Meister, Mark G.; Corte, Tamera J.; Wort, Stephen J.; Hansell, David M. (2010). "Detection of Pulmonary Hypertension with Multidetector CT and Echocardiography Alone and in Combination". Radiology. 254 (2). Radiological Society of North America (RSNA): 609–616. doi:10.1148/radiol.09090548. ISSN 0033-8419. PMID 20093532.
  75. ^ Lang, Irene; Gomez-Sanchez, Miguel; Kneussl, Meinhard; Naeije, Robert; Escribano, Pilar; Skoro-Sajer, Nika; Vachiery, Jean-Luc (2006). "Efficacy of Long-term Subcutaneous Treprostinil Sodium Therapy in Pulmonary Hypertension". Chest. 129 (6). Elsevier BV: 1636–1643. doi:10.1378/chest.129.6.1636. ISSN 0012-3692. PMID 16778286.
  76. ^ Oudiz, Ronald J.; Schilz, Robert J.; Barst, Robyn J.; Galié, Nazzareno; Rich, Stuart; Rubin, Lewis J.; Simonneau, Gérald (2004). "Treprostinil, a Prostacyclin Analogue, in Pulmonary Arterial Hypertension Associated With Connective Tissue Disease". Chest. 126 (2). Elsevier BV: 420–427. doi:10.1378/chest.126.2.420. ISSN 0012-3692. PMID 15302727.
  77. ^ a b Kotajima, L.; Aotsuka, S.; Sumiya, M.; Yokohari, R.; Tojo, T.; Kasukawa, R. (1996). "Clinical features of patients with juvenile onset mixed connective tissue disease: analysis of data collected in a nationwide collaborative study in Japan". The Journal of Rheumatology. 23 (6): 1088–1094. ISSN 0315-162X. PMID 8782145.
  78. ^ ME, Maldonado; M, Perez; J, Pignac-Kobinger; ET, Marx; EM, Tozman; EL, Greidinger; RW, Hoffman (2007-11-28). "Clinical and immunologic manifestations of mixed connective tissue disease in a Miami population compared to a Midwestern US Caucasian population". The Journal of Rheumatology. 35 (3). J Rheumatol: 429–437. ISSN 0315-162X. PMC 2919224. PMID 18260175.

Further reading

  • Aringer, Martin; Smolen, Josef S. (2007). "Mixed connective tissue disease: what is behind the curtain?". Best Practice & Research Clinical Rheumatology. 21 (6): 1037–1049. doi:10.1016/j.berh.2007.10.002. PMID 18068860.
  • Gunnarsson, Ragnar; Hetlevik, Siri Opsahl; Lilleby, Vibke; Molberg, Øyvind (2016). "Mixed connective tissue disease". Best Practice & Research Clinical Rheumatology. 30 (1): 95–111. doi:10.1016/j.berh.2016.03.002. PMID 27421219.
source: https://en.wikipedia.org/wiki/Mixed_connective_tissue_disease

    by onQ Software

    Website

    Related Posts