Connective tissue disease explained

Connective tissue disease
Synonyms:	Connective tissue disorder, collagen vascular diseases

Connective tissue disease, also known as connective tissue disorder, or collagen vascular diseases, refers to any disorder that affect the connective tissue. The body's structures are held together by connective tissues, consisting of two distinct proteins: elastin and collagen. Tendons, ligaments, skin, cartilage, bone, and blood vessels are all made of collagen. Skin and ligaments contain elastin. The proteins and the body's surrounding tissues may suffer damage when these connective tissues become inflamed.^[1]

The two main categories of connective tissue diseases are (1) a set of relatively rare genetic disorders affecting the primary structure of connective tissue, and (2) a variety of acquired diseases where the connective tissues are the site of multiple, more or less distinct immunological and inflammatory reactions.

Diseases in which inflammation or weakness of collagen tends to occur are also referred to as collagen diseases. Collagen vascular diseases can be (but are not necessarily) associated with collagen and blood vessel abnormalities that are autoimmune in nature.

Some connective tissue diseases have strong or weak genetic inheritance risks. Others may be due to environmental factors, or a combination of genetic and environmental influences.

Classification

Connective tissue diseases can be classified into two groups: (1) a group of relatively rare genetic disorders affecting the primary structure of connective tissue; and (2) a number of acquired conditions where the connective tissues are the site of multiple, more or less distinct immune and inflammatory reactions.^[2]

Heritable connective tissue disorders

Hereditary connective tissue disorders are a diverse set of broad, single-gene disorders that impact one or more of the main components of connective tissues, such as ground substance (glycosaminoglycans), collagen, or elastin. Many result in anomalies of the skeleton and joints, which can substantially impair normal growth and development. In contrast to acquired connective tissue diseases, these conditions are uncommon.^[2]

• Marfan syndrome - inherited as an autosomal dominant characteristic, due to mutations in the FBN1 gene that encodes fibrillin 1.^[3]
• Homocystinuria - condition of methionine metabolism brought on by a cystathionine β-synthase deficit that causes a build-up of homocysteine and its metabolites in the urine and blood.^[4]
• Ehlers–Danlos syndrome - diverse collection of disorders distinguished by the fragility of soft connective tissues and widespread symptoms affecting the skin, ligaments, joints, blood vessels, and internal organs.^[5]
• Osteogenesis imperfecta - hereditary condition marked by reduced bone mass, weakened bones, increased brittleness, and short stature.^[6]
• Alkaptonuria - inborn error of metabolism caused by mutations in the HGO gene and homogentisate 1,2-dioxygenase deficiency.^{[7] [8]}
• Pseudoxanthoma elasticum - rare multisystem disease marked by gradual calcification and fragmentation of elastic fibres.^[9]
• Mucopolysaccharidosis - a class of hereditary illnesses distinguished by the excretion of mucopolysaccharide in the urine.^[10]
• Fibrodysplasia ossificans progressiva - rare and debilitating hereditary disorder characterized by progressive heterotopic ossification and congenital skeletal malformations.^[11]
• Familial osteochondritis dissecans - separation of the subchondral bone and cartilage from the surrounding tissue.^[12]
• Stickler syndrome - autosomal dominant disorder distinguished by skeletal, ocular, and orofacial abnormalities.^[13]
• Alport syndrome - hereditary kidney disease is distinguished by structural abnormalities and malfunction in the glomerular basement membrane, as well as basement membranes in other organs such as the eye and ear.^[14]
• Congenital contractural arachnodactyly - autosomal dominant disorder defined by arachnodactyly, multiple flexion contractures, abnormal pinnae, severe kyphoscoliosis, and muscular hypoplasia.^[15]
• Epidermolysis bullosa - hereditary, diverse grouping of rare genetic dermatoses that are marked by blisters and mucocutaneous fragility.^[16]
• Loeys–Dietz syndrome - autosomal dominant condition linked to a wide range of systemic manifestations, such as skeletal, cutaneous, vascular, and craniofacial abnormalities.^[17]
• Hypermobility spectrum disorder - a variety of connective tissue diseases that are marked by ongoing pain and joint hypermobility.^[18]

Autoimmune connective tissue disorders

Acquired connective tissue diseases share certain clinical features, such as joint inflammation, inflammation of serous membranes, and vasculitis, as well as a high frequency of involvement of various internal organs that are particularly rich in connective tissue.^[2]

• Rheumatoid arthritis - autoimmune disease with an unclear cause that manifests as symmetric, erosive synovitis and, occasionally, extraarticular involvement.^[19]
• Systemic lupus erythematosus - chronic, complex autoimmune inflammatory disorder that can affect every organ in the body.^[20]
• Scleroderma - diverse collection of autoimmune fibrosing conditions.^[21]
• Dermatomyositis and polymyositis - autoimmune myopathies that are clinically characterized by extramuscular symptoms, muscle inflammation, proximal muscle weakening, and oftentimes the detection of autoantibodies.^[22]
• Vasculitis - disease that results in blood vessel inflammation.^[23]
• Sjögren syndrome - a systemic autoimmune illness that mostly affects the exocrine glands and causes mucosal surfaces, especially those in the mouth and eyes, to become extremely dry.^[24]
• Rheumatic fever - multisystem inflammatory illness that develops after group A streptococcal pharyngitis.^[25]
• Amyloidosis - uncommon condition caused by protein mutations or changes in the body that result in twisted clusters of malformed proteins accumulating on organs and tissues.^[26]
• Osteoarthritis - common articular cartilage degenerative disease linked to hypertrophic bone abnormalities.^[27]
• Thrombotic thrombocytopenic purpura - uncommon and potentially fatal thrombotic microangiopathy characterized by severe thrombocytopenia, organ ischemia connected to diffuse microvascular platelet rich-thrombi, and microangiopathic hemolytic anemia.^[28]
• Relapsing polychondritis - uncommon multisystem autoimmune disease with an unclear etiology that is marked by progressive cartilaginous tissue loss and recurring episodes of inflammation.^[29]
• Mixed connective tissue disease - systemic autoimmune disease that shares characteristics with two or more other systemic autoimmune diseases, such as rheumatoid arthritis, polymyositis/dermatomyositis, systemic lupus erythematosus, and systemic sclerosis.^[30]
• Undifferentiated connective tissue disease - unclassifiable systemic autoimmune disorders that do not meet any of the current classification requirements for connective tissue diseases yet have clinical and serological signs similar to connective tissue diseases.^[31]
• Psoriatic arthritis - inflammatory musculoskeletal condition linked to psoriasis.^[32]

See also

• Overlap syndrome
• Connective tissue

Further reading

• Spagnolo . Paolo . Cordier . Jean-François . Cottin . Vincent . Connective tissue diseases, multimorbidity and the ageing lung . European Respiratory Journal . European Respiratory Society (ERS) . 47 . 5 . 2016-02-25 . 0903-1936 . 10.1183/13993003.00829-2015 . 1535–1558 . 26917611 . none.
• Baildam . Eileen . Rare connective tissue diseases in childhood . Paediatrics and Child Health . 24 . 2 . 2014 . 10.1016/j.paed.2013.12.005 . 51–57 . none.

External links

• Web site: Connective Tissue Disorders . National Library of Medicine . 2017-09-15 . none.
• Web site: Dunkin . Mary Anne . Connective Tissue Disease: Types, Symptoms, Causes . WebMD . 2023-10-10 . none.
• Web site: Connective tissue diseases . DermNet® . 2023-10-26 . none.

Notes and References

1. Web site: Connective Tissue Disorders . Cedars-Sinai . 2020-06-08 . 2024-07-16.
2. Web site: Benedek . Thomas G. . Rodnan . Gerald P. . Description, Types, & Symptoms . Encyclopedia Britannica . 1998-07-24 . 2024-07-15.
3. Pepe . Guglielmina . Giusti . Betti . Sticchi . Elena . Abbate . Rosanna . Gensini . Gian . Nistri . Stefano . Marfan syndrome: current perspectives . The Application of Clinical Genetics . 2016 . 9 . 55–65 . 1178-704X . 27274304 . 4869846 . 10.2147/TACG.S96233 . free .
4. Kumar . Tarun . Sharma . Gurumayum Suraj . Singh . Laishram Rajendrakumar . Homocystinuria: Therapeutic approach . Clinica Chimica Acta . Elsevier BV . 458 . 2016 . 0009-8981 . 10.1016/j.cca.2016.04.002 . 55–62. 27059523 .
5. De Paepe . A . Malfait . F . The Ehlers–Danlos syndrome, a disorder with many faces . Clinical Genetics . 82 . 1 . 2012 . 0009-9163 . 10.1111/j.1399-0004.2012.01858.x . 1–11. 22353005 .
6. Book: Marini . Joan C. . Cabral . Wayne A. . Genetics of Bone Biology and Skeletal Disease . Osteogenesis Imperfecta . Elsevier . 2018 . 978-0-12-804182-6 . 10.1016/b978-0-12-804182-6.00023-x . 397–420.
7. Bernardini . Giulia . Braconi . Daniela . Zatkova . Andrea . Sireau . Nick . Kujawa . Mariusz J. . Introne . Wendy J. . Spiga . Ottavia . Geminiani . Michela . Gallagher . James A. . Ranganath . Lakshminarayan R. . Santucci . Annalisa . Alkaptonuria . Nature Reviews Disease Primers . Springer Science and Business Media LLC . 10 . 1 . 2024-03-07 . 2056-676X . 10.1038/s41572-024-00498-x . 16. 38453957 .
8. Phornphutkul . Chanika . Introne . Wendy J. . Perry . Monique B. . Bernardini . Isa . Murphey . Mark D. . Fitzpatrick . Diana L. . Anderson . Paul D. . Huizing . Marjan . Anikster . Yair . Gerber . Lynn H. . Gahl . William A. . Natural History of Alkaptonuria . New England Journal of Medicine . 347 . 26 . 2002-12-26 . 0028-4793 . 10.1056/NEJMoa021736 . 2111–2121. 12501223 .
9. Laube . S . Pseudoxanthoma elasticum . Archives of Disease in Childhood . 90 . 7 . 2005-07-01 . 0003-9888 . 15970621 . 1720489 . 10.1136/adc.2004.062075 . 754–756.
10. Web site: Mucopolysaccharidoses (MPS) . Johns Hopkins Medicine . 2021-08-08 . 2024-07-15.
11. Kaplan . Frederick S. . Le Merrer . Martine . Glaser . David L. . Pignolo . Robert J. . Goldsby . Robert E. . Kitterman . Joseph A. . Groppe . Jay . Shore . Eileen M. . Fibrodysplasia ossificans progressiva . Best Practice & Research Clinical Rheumatology . Elsevier BV . 22 . 1 . 2008 . 1521-6942 . 10.1016/j.berh.2007.11.007 . 191–205. 18328989 . 2424023 .
12. Stattin . E.-L. . Tegner . Y. . Domellöf . M. . Dahl . N. . Familial osteochondritis dissecans associated with early osteoarthritis and disproportionate short stature . Osteoarthritis and Cartilage . Elsevier BV . 16 . 8 . 2008 . 1063-4584 . 10.1016/j.joca.2007.11.009 . 890–896. 18226555 .
13. Bennett . James . McMurray . Scott . Stickler Syndrome . Journal of Pediatric Orthopaedics . November 1990 . 10 . 6 . 760–763 . 10.1097/01241398-199011000-00010 . 2250061 . 15 July 2024.
14. Warady . Bradley A. . Agarwal . Rajiv . Bangalore . Sripal . Chapman . Arlene . Levin . Adeera . Stenvinkel . Peter . Toto . Robert D. . Chertow . Glenn M. . Alport Syndrome Classification and Management . Kidney Medicine . Elsevier BV . 2 . 5 . 2020 . 2590-0595 . 10.1016/j.xkme.2020.05.014 . 639–649. 33094278 . 7568086 .
15. Tunçbilek . Ergül . Alanay . Yasemin . Congenital contractural arachnodactyly (Beals syndrome) . Orphanet Journal of Rare Diseases . 1 . 1 . 2006 . 1750-1172 . 16740166 . 1524931 . 10.1186/1750-1172-1-20 . free . 20.
16. Bardhan . Ajoy . Bruckner-Tuderman . Leena . Chapple . Iain L. C. . Fine . Jo-David . Harper . Natasha . Has . Cristina . Magin . Thomas M. . Marinkovich . M. Peter . Marshall . John F. . McGrath . John A. . Mellerio . Jemima E. . Polson . Rex . Heagerty . Adrian H. . Epidermolysis bullosa . Nature Reviews Disease Primers . Springer Science and Business Media LLC . 6 . 1 . 2020-09-24 . 2056-676X . 10.1038/s41572-020-0210-0 . 78. 32973163 .
17. Gouda . Pishoy . Kay . Robert . Habib . Marina . Aziz . Amir . Aziza . Eitan . Welsh . Robert . Clinical features and complications of Loeys-Dietz syndrome: A systematic review . International Journal of Cardiology . 362 . 2022 . 10.1016/j.ijcard.2022.05.065 . 158–167. 35662564 . free .
18. Atwell . Karina . Michael . William . Dubey . Jared . James . Sarah . Martonffy . Andrea . Anderson . Scott . Rudin . Nathan . Schrager . Sarina . Diagnosis and Management of Hypermobility Spectrum Disorders in Primary Care . The Journal of the American Board of Family Medicine . 34 . 4 . 2021 . 1557-2625 . 10.3122/jabfm.2021.04.200374 . 838–848. 34312277 . free .
19. American College of Rheumatology Subcommittee on Rheumatoid Arthritis Guidelines . Guidelines for the management of rheumatoid arthritis: 2002 Update . Arthritis & Rheumatism . 46 . 2 . 2002 . 0004-3591 . 10.1002/art.10148 . 328–346. 11840435 .
20. COJOCARU . Manole . COJOCARU . Inimioara Mihaela . SILOSI . Isabela . VRABIE . Camelia Doina . Manifestations of Systemic Lupus Erythematosus . Mædica . Amaltea Medical, Editura Magister . 6 . 4 . 2024-03-14 . 330–336 . 22879850 . 3391953 .
21. Fett . Nicole . Scleroderma: Nomenclature, etiology, pathogenesis, prognosis, and treatments: Facts and controversies . Clinics in Dermatology . Elsevier BV . 31 . 4 . 2013 . 0738-081X . 10.1016/j.clindermatol.2013.01.010 . 432–437. 23806160 .
22. Mammen . Andrew L. . Dermatomyositis and polymyositis: Clinical presentation, autoantibodies, and pathogenesis . Annals of the New York Academy of Sciences . 1184 . 1 . 2010 . 0077-8923 . 10.1111/j.1749-6632.2009.05119.x . 134–153. 20146695 .
23. Web site: Cleveland Clinic medical professional . Vasculitis: Symptoms, Types & Treatment . Cleveland Clinic . 2024-05-01 . 2024-07-15.
24. Brito-Zerón . Pilar . Baldini . Chiara . Bootsma . Hendrika . Bowman . Simon J. . Jonsson . Roland . Mariette . Xavier . Sivils . Kathy . Theander . Elke . Tzioufas . Athanasios . Ramos-Casals . Manuel . Sjögren syndrome . Nature Reviews Disease Primers . Springer Science and Business Media LLC . 2 . 1 . 2016-07-07 . 2056-676X . 10.1038/nrdp.2016.47 . 16047. 27383445 .
25. Rullan . Eugenia . Sigal . Leonard H. . Rheumatic fever . Current Rheumatology Reports . 3 . 5 . 2001 . 1523-3774 . 10.1007/s11926-996-0016-4 . 445–452. 11564377 .
26. Web site: Cleveland Clinic medical professional . Amyloidosis: What It Is, Symptoms, Types & Treatment . Cleveland Clinic . 2022-07-05 . 2024-07-16.
27. Sinusas . Keith . Osteoarthritis: Diagnosis and Treatment . American Family Physician . 85 . 1 . 2012-01-01 . 49–56 . 2024-07-16.
28. Joly . Bérangère S. . Coppo . Paul . Veyradier . Agnès . Thrombotic thrombocytopenic purpura . Blood . 129 . 21 . 2017-05-25 . 0006-4971 . 10.1182/blood-2016-10-709857 . 2836–2846. 28416507 .
29. GERGELY . P . Relapsing polychondritis . Best Practice & Research Clinical Rheumatology . Elsevier BV . 18 . 5 . 2004 . 1521-6942 . 10.1016/j.berh.2004.05.012 . 723–738. 15454129 .
30. Tani . Chiara . Carli . Linda . Vagnani . Sabrina . Talarico . Rosaria . Baldini . Chiara . Mosca . Marta . Bombardieri . Stefano . The diagnosis and classification of mixed connective tissue disease . Journal of Autoimmunity . Elsevier BV . 48-49 . 2014 . 0896-8411 . 10.1016/j.jaut.2014.01.008 . 46–49. 24461387 .
31. Mosca . Marta . Tani . Chiara . Vagnani . Sabrina . Carli . Linda . Bombardieri . Stefano . The diagnosis and classification of undifferentiated connective tissue diseases . Journal of Autoimmunity . Elsevier BV . 48-49 . 2014 . 0896-8411 . 10.1016/j.jaut.2014.01.019 . 50–52. 24518855 .
32. Ocampo D . Vanessa . Gladman . Dafna . Psoriatic arthritis . F1000Research . F1000 Research Ltd . 8 . 2019-09-20 . 2046-1402 . 10.12688/f1000research.19144.1 . free . 1665. 31583079 . 6758836 .