Editing Rheumatoid arthritis (section)

==Signs and symptoms==
RA primarily affects [[joints]], but it also affects other [[Organ (anatomy)|organs]] in more than 15–25% of cases.<ref name="pmid12860726">{{cite journal | vauthors = Turesson C, O'Fallon WM, Crowson CS, Gabriel SE, Matteson EL | title = Extra-articular disease manifestations in rheumatoid arthritis: incidence trends and risk factors over 46 years | journal = Annals of the Rheumatic Diseases | volume = 62 | issue = 8 | pages = 722–727 | date = August 2003 | pmid = 12860726 | pmc = 1754626 | doi = 10.1136/ard.62.8.722 }}</ref> Associated problems include cardiovascular disease, [[osteoporosis]], [[interstitial lung disease]], infection, [[cancer]], feeling tired, depression, mental difficulties, and trouble working.<ref>{{cite journal | vauthors = Cutolo M, Kitas GD, van Riel PL | title = Burden of disease in treated rheumatoid arthritis patients: going beyond the joint | journal = Seminars in Arthritis and Rheumatism | volume = 43 | issue = 4 | pages = 479–488 | date = February 2014 | pmid = 24080116 | doi = 10.1016/j.semarthrit.2013.08.004 }}</ref>

===Joints===
[[File:Rheumatoid arthritis joint.gif|thumb|upright=1.2|A diagram showing how rheumatoid arthritis affects a joint]]
[[File:Swan neck deformity in a 65 year old Rheumatoid Arthritis patient- 2014-05-27 01-49.jpg|thumb|Hand deformity, sometimes called a ''swan deformity'', in an elderly person with rheumatoid arthritis]]

[[Arthritis]] of joints involves [[inflammation]] of the [[synovial membrane]]. Joints become swollen, tender and warm, and stiffness limits their movement. With time, multiple joints are affected ([[polyarthritis]]). Most commonly involved are the small joints of the [[hand]]s, [[foot|feet]] and [[cervical spine]], but larger joints like the shoulder and knee can also be involved.<ref name=Davidson2014/>{{rp|1098}} [[Synovitis]] can lead to [[Tether (cell biology)|tethering]] of tissue with loss of movement and erosion of the joint surface causing [[deformity]] and loss of function.<ref name=Majithia2007/> The [[fibroblast-like synoviocyte]]s (FLS), highly specialized mesenchymal cells found in the [[synovial membrane]], have an active and prominent role in these pathogenic processes of the rheumatic joints.<ref name="nygaard">{{cite journal | vauthors = Nygaard G, Firestein GS | s2cid = 218573182 | title = Restoring synovial homeostasis in rheumatoid arthritis by targeting fibroblast-like synoviocytes | journal = Nature Reviews. Rheumatology | volume = 16 | issue = 6 | pages = 316–333 | date = June 2020 | pmid = 32393826 | doi = 10.1038/s41584-020-0413-5 | pmc = 7987137 }}</ref>

RA typically manifests with signs of inflammation, with the affected joints being swollen, warm, painful and stiff, particularly early in the morning on waking or following prolonged inactivity. Increased stiffness early in the morning is often a prominent feature of the disease and typically lasts for more than an hour. Gentle movements may relieve symptoms in early stages of the disease. These signs help distinguish rheumatoid from non-inflammatory problems of the joints, such as [[osteoarthritis]]. In arthritis of non-inflammatory causes, signs of inflammation and early morning stiffness are less prominent.<ref>{{cite journal | vauthors = Suresh E | title = Diagnosis of early rheumatoid arthritis: what the non-specialist needs to know | journal = Journal of the Royal Society of Medicine | volume = 97 | issue = 9 | pages = 421–424 | date = September 2004 | pmid = 15340020 | pmc = 1079582 | doi = 10.1177/014107680409700903 }}</ref>
The pain associated with RA is induced at the site of inflammation and classified as [[nociceptive]] as opposed to [[neuropathic]].<ref>{{cite journal | vauthors = Gaffo A, Saag KG, Curtis JR | title = Treatment of rheumatoid arthritis | journal = American Journal of Health-System Pharmacy | volume = 63 | issue = 24 | pages = 2451–2465 | date = December 2006 | pmid = 17158693 | pmc = 5164397 | doi = 10.2146/ajhp050514 }}</ref> The joints are often affected in a fairly symmetrical fashion, although this is not specific, and the initial presentation may be asymmetrical.<ref name=Davidson2014>{{cite book| veditors = Walker BR, Colledge NR, Ralston SH, Penman ID |title=Davidson's principles and practice of medicine|date=2014|publisher=Churchill Livingstone/Elsevier|isbn=978-0-7020-5035-0 |edition=22nd}}</ref>{{rp|1098}}

As the pathology progresses the inflammatory activity leads to tendon tethering and erosion and destruction of the joint surface, which impairs range of movement and leads to [[deformity]]. The fingers may develop almost any [[deformity]] depending on which joints are most involved. Specific [[Deformity|deformities]], which also occur in [[osteoarthritis]], include [[ulnar deviation]], [[boutonniere deformity]] (also "buttonhole deformity", [[flexion]] of proximal interphalangeal joint and extension of distal [[Interphalangeal articulations of hand|interphalangeal joint]] of the hand), [[swan neck deformity]] (hyperextension at proximal interphalangeal joint and flexion at distal interphalangeal joint) and "Z-thumb." "Z-thumb" or "Z-deformity" consists of [[hyperextension]] of the interphalangeal joint, fixed flexion and [[subluxation]] of the [[metacarpophalangeal joint]] and gives a "Z" appearance to the thumb.<ref name=Davidson2014 />{{rp|1098}} The [[hammer toe]] [[deformity]] may be seen. In the worst case, joints are known as [[arthritis mutilans]] due to the mutilating nature of the deformities.<ref name="McGraw Hill">{{cite book | vauthors = Shah A |date=2012 |title=Harrison's Principles of Internal Medicine |publisher=McGraw Hill |location=United States |isbn=978-0-07-174889-6 |pages = 2738 |edition=18th}}</ref>

===Skin===
The [[rheumatoid nodule]], which is sometimes in the skin, is the most common non-joint feature and occurs in 30% of people who have RA.<ref name=Tur2013>{{cite journal | vauthors = Turesson C | title = Extra-articular rheumatoid arthritis | journal = Current Opinion in Rheumatology | volume = 25 | issue = 3 | pages = 360–366 | date = May 2013 | pmid = 23425964 | doi = 10.1097/bor.0b013e32835f693f | s2cid = 21462453 }}</ref> It is a type of inflammatory reaction known to pathologists as a "[[necrotizing]] [[granuloma]]". The [[initial]] pathologic process in nodule formation is unknown but may be essentially the same as the synovitis, since similar structural features occur in both. The nodule has a central area of [[fibrinoid necrosis]] that may be [[fissure (anatomy)|fissured]] and which corresponds to the [[fibrin]]-rich necrotic material found in and around an affected synovial space. Surrounding the necrosis is a layer of palisading [[macrophages]] and [[fibroblasts]], corresponding to the intimal layer in synovium and a cuff of [[connective tissue]] containing clusters of [[lymphocyte]]s and [[plasma cell]]s, corresponding to the subintimal zone in synovitis. The typical rheumatoid nodule may be a few millimetres to a few centimetres in diameter and is usually found over bony prominences, such as the [[olecranon|elbow]], the [[calcaneal tuberosity|heel]], the [[metacarpophalangeal joints|knuckles]], or other areas that sustain repeated mechanical stress. Nodules are associated with a positive RF ([[rheumatoid factor]]) [[titer]], ACPA, and severe erosive arthritis. Rarely, these can occur in internal organs or at diverse sites on the body.<ref>{{cite journal | vauthors = Ziff M | title = The rheumatoid nodule | journal = Arthritis and Rheumatism | volume = 33 | issue = 6 | pages = 761–767 | date = June 1990 | pmid = 2194460 | doi = 10.1002/art.1780330601 | doi-access = free }}</ref>

Several forms of [[vasculitis]] occur in RA, but are mostly seen with long-standing and untreated disease. The most common presentation is due to involvement of small- and medium-sized vessels. Rheumatoid vasculitis can thus commonly present with skin ulceration and vasculitic nerve infarction known as [[mononeuritis multiplex]].<ref>{{cite journal | vauthors = Genta MS, Genta RM, Gabay C | title = Systemic rheumatoid vasculitis: a review | journal = Seminars in Arthritis and Rheumatism | volume = 36 | issue = 2 | pages = 88–98 | date = October 2006 | pmid = 17023257 | doi = 10.1016/j.semarthrit.2006.04.006 }}</ref>

Other, rather rare, skin associated symptoms include [[pyoderma gangrenosum]], [[Sweet's syndrome]], drug reactions, [[erythema nodosum]], lobe [[panniculitis]], [[atrophy]] of finger skin, [[palmar erythema]], and skin fragility (often worsened by corticosteroid use).<ref>{{Cite web |last=Moriyama |first=Takahiro |title=Chronic Disease |url=https://www.immunotherapy-clinic-ikiru.com/chronic-disease/ |access-date=2024-05-09 |website=Immunotherapy cancer and chronic disease |language=en-US}}</ref>

[[Diffuse alopecia areata]] (Diffuse AA) occurs more commonly in people with rheumatoid arthritis.<ref name=":1" /> RA is also seen more often in those with relatives who have AA.<ref name=":1">{{cite book | vauthors = Khan P, Beigi M |s2cid=46954629 |date=2018|title=Alopecia Areata|doi=10.1007/978-3-319-72134-7|isbn=978-3-319-72133-0 }}</ref>

===Lungs===
{{Main|Rheumatoid lung disease}}
[[Lung fibrosis]] is a recognized complication of rheumatoid arthritis. It is also a rare but well-recognized consequence of therapy (for example with [[methotrexate]] and [[leflunomide]]). [[Caplan's syndrome]] describes lung nodules in individuals with RA and additional exposure to [[coal]] dust. [[Exudate|Exudative]] [[pleural effusion]]s are also associated with RA.<ref>{{cite journal | vauthors = Kim EJ, Collard HR, King TE | title = Rheumatoid arthritis-associated interstitial lung disease: the relevance of histopathologic and radiographic pattern | journal = Chest | volume = 136 | issue = 5 | pages = 1397–1405 | date = November 2009 | pmid = 19892679 | pmc = 2818853 | doi = 10.1378/chest.09-0444 }}</ref><ref>{{cite journal | vauthors = Balbir-Gurman A, Yigla M, Nahir AM, Braun-Moscovici Y | title = Rheumatoid pleural effusion | journal = Seminars in Arthritis and Rheumatism | volume = 35 | issue = 6 | pages = 368–378 | date = June 2006 | pmid = 16765714 | doi = 10.1016/j.semarthrit.2006.03.002 }}</ref>

===Heart and blood vessels===
People with RA are more prone to [[atherosclerosis]], and risk of [[myocardial infarction]] (heart attack) and [[stroke]] is markedly increased.<ref>{{cite journal | vauthors = Wolfe F, Mitchell DM, Sibley JT, Fries JF, Bloch DA, Williams CA, Spitz PW, Haga M, Kleinheksel SM, Cathey MA | title = The mortality of rheumatoid arthritis | journal = Arthritis and Rheumatism | volume = 37 | issue = 4 | pages = 481–494 | date = April 1994 | pmid = 8147925 | doi = 10.1002/art.1780370408 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Aviña-Zubieta JA, Choi HK, Sadatsafavi M, Etminan M, Esdaile JM, Lacaille D | title = Risk of cardiovascular mortality in patients with rheumatoid arthritis: a meta-analysis of observational studies | journal = Arthritis and Rheumatism | volume = 59 | issue = 12 | pages = 1690–1697 | date = December 2008 | pmid = 19035419 | doi = 10.1002/art.24092 }}</ref><ref>{{cite journal | vauthors = Alenghat FJ | title = The Prevalence of Atherosclerosis in Those with Inflammatory Connective Tissue Disease by Race, Age, and Traditional Risk Factors | journal = Scientific Reports | volume = 6 | pages = 20303 | date = February 2016 | pmid = 26842423 | pmc = 4740809 | doi = 10.1038/srep20303 | bibcode = 2016NatSR...620303A }}</ref>
Other possible complications that may arise include: [[pericarditis]], [[endocarditis]], left ventricular failure, valvulitis and [[fibrosis]].<ref name="Gupta">{{cite journal |vauthors=Gupta A, Fomberstein B |title=Evaluating cardiovascular risk in rheumatoid arthritis |journal=Journal of Musculoskeletal Medicine |volume=26 |issue=8 |pages=481–494 |year=2009 |url=http://www.musculoskeletalnetwork.com/rheumatoid-arthritis/content/article/1145622/1433094 |url-status=live |archive-url=https://web.archive.org/web/20120723164920/http://www.musculoskeletalnetwork.com/rheumatoid-arthritis/content/article/1145622/1433094 |archive-date=2012-07-23 }}</ref> Many people with RA do not experience the same chest pain that others feel when they have angina or myocardial infarction. To reduce cardiovascular risk, it is crucial to maintain optimal control of the [[inflammation]] caused by RA (which may be involved in causing the cardiovascular risk), and to use exercise and medications appropriately to reduce other cardiovascular risk factors such as blood lipids and blood pressure. Doctors who treat people with RA should be sensitive to cardiovascular risk when prescribing anti-inflammatory medications, and may want to consider prescribing routine use of low doses of aspirin if the gastrointestinal effects are tolerable.<ref name="Gupta"/>

===Blood===
[[Anemia]] is by far the most common abnormality of the blood cells which can be caused by a variety of mechanisms. The chronic inflammation caused by RA leads to raised [[hepcidin]] levels, leading to [[anemia of chronic disease]] where iron is poorly absorbed and also sequestered into [[macrophages]]. The red cells are of normal size and color (normocytic and Normochromic).<ref>{{cite journal | vauthors = Wilson A, Yu HT, Goodnough LT, Nissenson AR | title = Prevalence and outcomes of anemia in rheumatoid arthritis: a systematic review of the literature | journal = The American Journal of Medicine | volume = 116 | issue = Suppl 7A | pages = 50S–57S | date = April 2004 | pmid = 15050886 | doi = 10.1016/j.amjmed.2003.12.012 }}</ref>

A [[neutropenia|low white blood cell count]] usually only occurs in people with [[Felty's syndrome]] with an enlarged liver and spleen. The mechanism of neutropenia is complex. An [[thrombocytosis|increased platelet count]] occurs when inflammation is uncontrolled.<ref>{{cite journal | vauthors = Tramś E, Malesa K, Pomianowski S, Kamiński R | title = Role of Platelets in Osteoarthritis-Updated Systematic Review and Meta-Analysis on the Role of Platelet-Rich Plasma in Osteoarthritis | journal = Cells | volume = 11 | issue = 7 | pages = 1080 | date = March 2022 | pmid = 35406644 | pmc = 8997794 | doi = 10.3390/cells11071080 | doi-access = free }}</ref>

===Other===
The role of the circadian clock in rheumatoid arthritis suggests a correlation between an early morning rise in circulating levels of pro-inflammatory cytokines, such as [[interleukin-6]] and painful morning joint stiffness.<ref name="pmid23427807">{{cite journal | vauthors = Gibbs JE, Ray DW | title = The role of the circadian clock in rheumatoid arthritis | journal = Arthritis Res Ther | volume = 15 | issue = 1 | pages = 205 | date = February 2013 | pmid = 23427807 | pmc = 3672712 | doi = 10.1186/ar4146 | doi-access = free }}</ref>

==== Kidneys ====
Renal [[amyloidosis]] can occur as a consequence of untreated chronic inflammation.<ref>{{cite journal | vauthors = de Groot K | title = [Renal manifestations in rheumatic diseases] | journal = Der Internist | volume = 48 | issue = 8 | pages = 779–785 | date = August 2007 | pmid = 17571244 | doi = 10.1007/s00108-007-1887-9 | s2cid = 28781598 }}</ref> Treatment with [[penicillamine]] or [[gold salts]] such as [[sodium aurothiomalate]] are recognized causes of [[membranous nephropathy]].<ref>{{cite journal | vauthors = Moroni G, Ponticelli C | title = Secondary Membranous Nephropathy. A Narrative Review | journal = Frontiers in Medicine | year = 2020 | volume = 7 | pages = 611317 | pmid = 33344486 | doi = 10.3389/fmed.2020.611317 | pmc = 7744820 | doi-access = free }}</ref>

==== Eyes ====
The eye can be directly affected in the form of [[episcleritis]]<ref name=Schonberg>{{cite book | vauthors = Schonberg S, Stokkermans TJ | chapter = Episcleritis | date = January 2020 | pmid = 30521217 | url = http://www.ncbi.nlm.nih.gov/books/nbk534796/ | title = StatPearls | location = Treasure Island (FL) | publisher = StatPearls Publishing }}</ref> or [[scleritis]], which when severe can very rarely progress to perforating scleromalacia. Rather more common is the indirect effect of [[keratoconjunctivitis sicca]], which is a dryness of eyes and mouth caused by [[lymphocyte]] infiltration of [[lacrimal gland|lacrimal]] and [[salivary gland]]s. When severe, dryness of the cornea can lead to [[keratitis]] and loss of vision as well as being painful. Preventive treatment of severe dryness with measures such as [[nasolacrimal duct]] blockage is important.<ref>{{cite journal | vauthors = Dammacco R, Guerriero S, Alessio G, Dammacco F | title = Natural and iatrogenic ocular manifestations of rheumatoid arthritis: a systematic review | journal = International Ophthalmology | volume = 42 | issue = 2 | pages = 689–711 | date = February 2022 | pmid = 34802085 | pmc = 8882568 | doi = 10.1007/s10792-021-02058-8 }}</ref>

==== Liver ====
Liver problems in people with rheumatoid arthritis may be due to the underlying disease process or as a result of the medications used to treat the disease.<ref name="Selmi2011" /> A coexisting autoimmune liver disease, such as [[primary biliary cirrhosis]] or [[autoimmune hepatitis]] may also cause problems.<ref name="Selmi2011">{{cite journal | vauthors = Selmi C, De Santis M, Gershwin ME | title = Liver involvement in subjects with rheumatic disease | journal = Arthritis Research & Therapy | volume = 13 | issue = 3 | pages = 226 | date = June 2011 | pmid = 21722332 | pmc = 3218873 | doi = 10.1186/ar3319 | doi-access = free }}</ref>

==== Neurological ====
[[Peripheral neuropathy]] and [[mononeuritis multiplex]] may occur. The most common problem is [[carpal tunnel syndrome]] caused by compression of the median nerve by swelling around the wrist.<ref>{{Cite journal |last1=Chung |first1=Tae |last2=Prasad |first2=Kalpana |last3=Lloyd |first3=Thomas E. |date=2013-05-25 |title=Peripheral Neuropathy |journal=Neuroimaging Clinics of North America |language=en |volume=24 |issue=1 |pages=49–65 |doi=10.1016/j.nic.2013.03.023 |pmid=24210312 |pmc=4329247 |issn=1052-5149 }}</ref>

[[Rheumatoid disease of the spine]] can lead to [[myelopathy]].<ref>{{Cite journal |last1=Mukerji |first1=N. |last2=Todd |first2=N. V. |date=2011 |title=Cervical Myelopathy in Rheumatoid Arthritis |journal=[[Neurology Research International]] |language=en |volume=2011 |pages=1–7 |doi=10.1155/2011/153628 |doi-access=free |issn=2090-1852 |pmc=3238417 |pmid=22203899}}</ref><ref>{{Cite journal |last1=Janssen |first1=Insa |last2=Nouri |first2=Aria |last3=Tessitore |first3=Enrico |last4=Meyer |first4=Bernhard |date=2020-03-17 |title=Cervical Myelopathy in Patients Suffering from Rheumatoid Arthritis—A Case Series of 9 Patients and A Review of the Literature |journal=[[Journal of Clinical Medicine]] |language=en |volume=9 |issue=3 |pages=811 |doi=10.3390/jcm9030811 |doi-access=free |issn=2077-0383 |pmc=7141180 |pmid=32191997}}</ref> 
[[Atlanto-axial joint|Atlanto-axial]] [[subluxation]] can occur, owing to erosion of the [[odontoid process]] or [[transverse ligament]]s in the [[cervical spine]] connection to the skull. Such an erosion (>3mm) can give rise to [[vertebrae]] slipping over one another and compressing the spinal cord.<ref>{{Cite journal |last1=Yang |first1=Sun Y. |last2=Boniello |first2=Anthony J. |last3=Poorman |first3=Caroline E. |last4=Chang |first4=Andy L. |last5=Wang |first5=Shenglin |last6=Passias |first6=Peter G. |date=2014-05-22 |title=A Review of the Diagnosis and Treatment of Atlantoaxial Dislocations |journal=Global Spine Journal |language=en |volume=4 |issue=3 |pages=197–210 |doi=10.1055/s-0034-1376371 |issn=2192-5682 |pmc=4111952 |pmid=25083363}}</ref> Clumsiness is initially experienced, but without due care, this can progress to [[quadriplegia]] or even death.<ref>{{cite journal | vauthors = Wasserman BR, Moskovich R, Razi AE | title = Rheumatoid arthritis of the cervical spine--clinical considerations | journal = Bulletin of the NYU Hospital for Joint Diseases | volume = 69 | issue = 2 | pages = 136–148 | year = 2011 | pmid = 22035393 | url = http://hjdbulletin.org/files/archive/pdfs/222.pdf }}</ref>

[[Vertigo]] may be associated with rheumatoid arthritis via the following associations that can cause [[vertigo]]:
* [[Ménière's disease]]<ref name="pmid29287768">{{cite journal | last1=Caulley | first1=Lisa | last2=Quimby | first2=Alexandra | last3=Karsh | first3=Jacob | last4=Ahrari | first4=Azin | last5=Tse | first5=Darren | last6=Kontorinis | first6=Georgios | title=Autoimmune arthritis in Ménière's disease: A systematic review of the literature | journal=Seminars in Arthritis and Rheumatism | volume=48 | issue=1 | date=2018 | issn=1532-866X | pmid=29287768 | doi=10.1016/j.semarthrit.2017.11.008 | pages=141–147}}</ref><ref name="pmid22053211 ">{{cite journal | last1=Gazquez | first1=Irene | last2=Soto-Varela | first2=Andres | last3=Aran | first3=Ismael | last4=Santos | first4=Sofia | last5=Batuecas | first5=Angel | last6=Trinidad | first6=Gabriel | last7=Perez-Garrigues | first7=Herminio | last8=Gonzalez-Oller | first8=Carlos | last9=Acosta | first9=Lourdes | last10=Lopez-Escamez | first10=Jose A. | title=High prevalence of systemic autoimmune diseases in patients with Menière's disease | journal=PLOS ONE | volume=6 | issue=10 | date=2011 | issn=1932-6203 | pmid=22053211 | pmc=3203881 | doi=10.1371/journal.pone.0026759 | doi-access=free | page=e26759}}</ref>
* "Biologic disease-modifying antirheumatic drugs"<ref name="pmid29466539">{{cite journal | last=Roberts | first=Richard A. | title=Management of Recurrent Vestibular Neuritis in a Patient Treated for Rheumatoid Arthritis | journal=American Journal of Audiology | volume=27 | issue=1 | date=2018-03-08 | issn=1558-9137 | pmid=29466539 | doi=10.1044/2017_AJA-17-0090 | pages=19–24}}</ref> This may not happen in the absence of infection.<ref name="pmid24770796">{{cite journal | last1=Toktas | first1=H. | last2=Okur | first2=E. | last3=Dundar | first3=U. | last4=Dikici | first4=A. | last5=Kahveci | first5=O. K. | title=Infliximab has no apparent effect in the inner ear hearing function of patients with rheumatoid arthritis and ankylosing spondylitis | journal=Clinical Rheumatology | volume=33 | issue=10 | date=2014 | issn=1434-9949 | pmid=24770796 | doi=10.1007/s10067-014-2625-z | pages=1481–1487}}</ref>
* [[Atlanto-axial joint]] instability can cause symptoms including vertigo and sudden death.<ref name="pmid37841539">{{cite journal | last1=Subagio | first1=Eko Agus | last2=Wicaksono | first2=Pandu | last3=Faris | first3=Muhammad | last4=Bajamal | first4=Abdul Hafid | last5=Abdillah | first5=Diaz Syafrie | title=Diagnosis and Prevalence (1975-2010) of Sudden Death due to Atlantoaxial Subluxation in Cervical Rheumatoid Arthritis: A Literature Review | journal=TheScientificWorldJournal | volume=2023 | date=2023 | issn=1537-744X | pmid=37841539 | pmc=10569890 | doi=10.1155/2023/6675489 | doi-access=free | page=6675489}}</ref>
* Atypical Cogan's syndrome may be associated with rheumoatoid arthritis.<ref name="pmid24418297">{{cite journal | last1=Kessel | first1=Aharon | last2=Vadasz | first2=Zahava | last3=Toubi | first3=Elias | title=Cogan syndrome--pathogenesis, clinical variants and treatment approaches | journal=Autoimmunity Reviews | volume=13 | issue=4–5 | date=2014 | issn=1873-0183 | pmid=24418297 | doi=10.1016/j.autrev.2014.01.002 | pages=351–354}}</ref>

==== Constitutional symptoms ====
[[Constitutional symptoms]] including [[fatigue (medical)|fatigue]], low grade [[fever]], [[malaise]], [[morning stiffness]], [[loss of appetite]] and [[loss of weight]] are common systemic manifestations seen in people with active RA.

==== Bones ====
Local [[osteoporosis]] occurs in RA around inflamed joints. It is postulated to be partially caused by inflammatory [[cytokines]]. More general osteoporosis is probably contributed to by immobility, systemic cytokine effects, local cytokine release in bone marrow and corticosteroid therapy.<ref name="pmid16271143">{{cite journal | vauthors = Ginaldi L, Di Benedetto MC, De Martinis M | title = Osteoporosis, inflammation and ageing | journal = Immunity & Ageing | volume = 2 | issue = | pages = 14 | date = November 2005 | pmid = 16271143 | pmc = 1308846 | doi = 10.1186/1742-4933-2-14 | doi-access = free }}</ref><ref name="pmid25905202">{{cite book | vauthors = Ilias I, Milionis C, Zoumakis E | chapter = An Overview of Glucocorticoid-Induced Osteoporosis. | date = March 2022 | title = Endotext [Internet]. | location = South Dartmouth (MA) | publisher = MDText.com, Inc. | url = https://www.ncbi.nlm.nih.gov/sites/books/NBK278968/ | pmid = 25905202 | veditors = Feingold KR, Anawalt B, Blackman MR, Boyce A, Chrousos G, Corpas E, de Herder WW, Dhatariya K, Dungan K, Hofland J, Kalra S, Kaltsas G, Kapoor N, Koch C, Kopp P, Korbonits M, Kovacs CS, Kuohung W, Laferrère B, Levy M, McGee EA, McLachlan R, New M, Purnell J, Sahay R, Shah AS, Singer F, Sperling MA, Stratakis CA, Trence DL, Wilson DP, Ilias I, Milionis C, Zoumakis E | display-editors = 6 }}</ref>

==== Cancer ====
The incidence of [[lymphoma]] is increased, although it is uncommon and associated with the chronic inflammation, not the treatment of RA.<ref>{{cite journal | vauthors = Baecklund E, Iliadou A, Askling J, Ekbom A, Backlin C, Granath F, Catrina AI, Rosenquist R, Feltelius N, Sundström C, Klareskog L | title = Association of chronic inflammation, not its treatment, with increased lymphoma risk in rheumatoid arthritis | journal = Arthritis and Rheumatism | volume = 54 | issue = 3 | pages = 692–701 | date = March 2006 | pmid = 16508929 | doi = 10.1002/art.21675 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Franklin J, Lunt M, Bunn D, Symmons D, Silman A | title = Incidence of lymphoma in a large primary care derived cohort of cases of inflammatory polyarthritis | journal = Annals of the Rheumatic Diseases | volume = 65 | issue = 5 | pages = 617–622 | date = May 2006 | pmid = 16249224 | pmc = 1798140 | doi = 10.1136/ard.2005.044784 }}</ref> The risk of [[non-melanoma skin cancer]] is increased in people with RA compared to the general population, an association possibly due to the use of [[immunosuppression]] agents for treating RA.<ref>{{cite journal | vauthors = Assassi S | title = Rheumatoid arthritis, TNF inhibitors, and non-melanoma skin cancer | journal = BMJ | volume = 352 | pages = i472 | date = January 2016 | pmid = 26822198 | doi = 10.1136/bmj.i472 | s2cid = 45857932 }}</ref>

==== Teeth ====
[[Periodontal disease|Periodontitis]] and tooth loss are common in people with rheumatoid arthritis.<ref name="pmid19337286">{{cite journal | vauthors = de Pablo P, Chapple IL, Buckley CD, Dietrich T | s2cid = 7173008 | title = Periodontitis in systemic rheumatic diseases | journal = Nature Reviews. Rheumatology | volume = 5 | issue = 4 | pages = 218–224 | date = April 2009 | pmid = 19337286 | doi = 10.1038/nrrheum.2009.28 }}</ref>