Arthritis Flashcards

Question

Osteoarthritis Risk Factors

Answer 1

* **↑ risk with ↑ age** * **Hand and knee OA are more common among women** * **Genetic predisposition** * Esp. in women with nodular disease in hands * Strong family predilection * **Obesity** ⇒ **↑** stress on weight-bearing joints * **Diseases that alter cartilage** * Hemochromatosis, gout, pseudogout * **Joint instability** from neuro problem or ligamentous laxity * **Prior infection of the joint** * **Trauma** (micro-trauma/macro-trauma) * **Abnormal joint anatomy** * Congenital, Rheumatoid Arthritis, etc. * **Hemophilia**

Answer 2

* Hallmark features are **chronic joint pain and joint stiffness** * Pain worsens w/ activity and relieved w/ rest * "**Gelling**" ⇒ joint stiffness brought on by rest and relieved rapidly with activity * Frequently monoarticular but multiple joints can be involved

Answer 3

* **Bony enlargement** * **Crepitus** ⇒ creaking /cracking of the joint heard or felt when palpating the joint during ROM * **↓ Range of motion (ROM)** * No signs of inflammation or thickened synovium

Answer 4

Decreased ROM with internal rotation occurs before external rotation. Groin pain with rotation may also be seen.

Answer 5

* **Crepitus** * **Tenderness along joint line** * **Varus or valgus deformity** (due to asymmetric loss of cartilage)

Answer 6

* Tenderness / bony enlargement @ **1st carpometacarpal joint** * **DIP \> PIP \> MCP** involvement * Osteophytes at _DIP_ ⇒ **Heberden’s nodes** * Osteophytes at _PIP_ ⇒ **Bouchard’s nodes**

Answer 7

* Distinguish from inflammatory joint diseases by H&P * _Characteristic radiographic features include:_ * **Subchondral sclerosis** * **Subchondral cysts** * **Narrowing of joint space** * **Osteophytes**

Answer 8

* _Non-pharmacologic:_ * **Weight loss** * **Avoid excessive use of joint** * **Physical therapy** * **Assistive devices** ⇒ ↓ weight on joint * **Knee brace** and/or **supportive footwear** * _Pharmacologic:_ * **Alters symptoms not course of disease** * Weigh pros and cons and potential issues with tx options * _Potential options include:_ * **Acetaminophen** * **NSAIDs** ⇒ avoid in elderly and others with risk factors (kidney disease, CHF, etc) * **Topical NSAIDs and capsaicin** ⇒ limit systemic toxicity issues * **Glucosamine/chondroitin sulfate** ⇒ no clear evidence from trials but seem to be safe * Anecdotal reports of ↓ pain for some patients * **Intra-articular corticosteroid injection** ⇒ short-term benefit * Need to carefully consider **narcotic/opioid** use * _Surgical options:_ * **Arthroscopic surgery** ⇒ probably ineffective * **Total joint replacement** * ↓ pain/disability and improves function * Should be delayed as long as possible ⇒ ↓ need for future revisions

Answer 9

* OA is the most common cause of arthritis * Consider it early when a patient present with a non-inflammatory joint complaint * Diagnosis is clinical, but can be confirmed with typical x-ray findings

Answer 10

Systemic, symmetric inflammatory polyarthritis that leads to joint destruction, deformity and loss of function.

Answer 11

Pathology of RA involves s**ynovial membranes and periarticular structures of multiple joints.** _Resulting in:_ * **Pain** * **Swelling** * **Uncontrolled inflammation** ⇒ irreversible damage and deformity * **Stiffness** * **Functional limitation** * **Pannus formation**

Answer 12

* Interaction between **APCs, T-cells, and B-cells** * ⊕ Helper T-cells ⇒ TNF-α and other soluble factors ⇒ ⊕ MΦ ⇒ secrete TNF-α, IL-1, and IL-6 * **TNF-α plays a central role in the inflammation process** * Current therapies intervene at each one of these steps in the inflammation process

Answer 13

* Prevalence is 1% of adults worldwide * **Women affected 2-3x more than men** * Peak age of onset is **30-50 y/o** * Most pts are dx under 65 yrs of age

Answer 14

* **Joint destruction** * Functional and work disabilities * **Treatment side effects** * Psychosocial dysfunction * Comorbidities * ↓ quality of life * ↓ life expectancy * Total estimated annual cost in US ⇒ $9 billion * Lifetime costs for RA rival those of CVD or CVA

Answer 15

* **Etiology of RA is unknown** * May be multifactorial * _Genetic susceptibility?_ * **HLA-DR4 and -DR1** Class II MHC leukocyte antigen types * **Enhanced T-cell responses** to inflammatory stimuli * Intrinsic abnormalities in synovial responses * _Environmental factors?_ * Unclear if either environmental and/or genetic effects account for ethnic differences in prevalence of RA

Answer 16

* _Onset is:_ * **Usually insidious ⇒ 70%** * Subacute onset ⇒ 20% * Acute ⇒ 10% * Rarely episodic course w/ migratory involvement * **Peripheral joints of the hands and feet are involved in almost everyone** * Hands ⇒ **MCPs, PIPs and wrists (DIPs are spared)** * Feet ⇒ **MTPs and ankles** * **Axial and central joints** * C-spine (C1-2), hip, shoulder, TM

Answer 17

* _Early rheumatoid arthritis (RA)_ * Swelling of **MCPs and PIPs joints** * **Fusiform or spindle-shaped enlargement of PIP joints** * Tenderness and limited range of motion * _Late rheumatoid arthritis (RA)_ * Massive diffuse swelling * Deformities such as the **Boutonnière, swan neck, and unstable PIP joint** * Caused by synovitis in that joint * _Long-standing RA_ * **Severe deformities** resulting from joint destruction * **Ulnar deviation** * **MCP joint subluxation** * **Rheumatoid nodules**

Answer 18

Progression of disease includes: * _Early in disease_: **peri-articular osteopenia w/ preserved joint space** * _Progression shows_: **joint space narrowing and irregularity** * _Later findings_: **joint erosions, ulnar deviation**

Answer 19

* _General_ – **weight loss, fatigue, fever** * _Ocular_ – Keratoconjunctivitis Sicca, Episcleritis, Scleritis, Scleromalacia Perforans * _Pulmonary_ – **interstitial fibrosis, pulmonary nodules**, pleuritis, pleural effusions, Brochiolitis obliterans, Caplan’s syndrome * _Dermatologic_ – **subcutaneous nodules**, Leukocytoclastic vasculitis, palmar erythema, ischemic ulcers * _Neurologic_ – **peripheral neuropathy**, entrapment syndromes, cervical myelopathy, mononeuritis multiplex * _Hematologic_ – anemia, lymphoma, **Felty’s syndrome** * _Cardiac_ – **pericarditis, myocarditis, coronary vasculitis**

Answer 20

* **Life expectancy ↓ by 10-15 yrs in pts w/ severe disease** * Mortality may approach 50% over 5 yrs in cases of severe disability * Pts w/ **extra-articular involvement 2x more likely to die** vs those w/ articular disease only * **Comorbid conditions and drug toxicity** account for majority of deaths in RA

Answer 21

* **Synovial fluid analysis ⇒ inflammatory** * 5,000-50,000 WBC/mm3 (\>50% PMNs) * No crystals * ⊖ cultures * **↑ ESR/CRP** * **⊕ rheumatoid factor, anti-CCP** * CBC, CMP, LFTs * **⊕ ANA in 30%** * **Hep B, Hep C, parvovirus if onset \< 6 weeks** * **XR** of hands, wrists, feet

Answer 22

* **70% ⇒ ⊕ RF @ disease onset** * 10-15% ⇒ become ⊕ w/in 2 yrs * 15-20% ⇒ remain seronegative throughout * **RF not specific for RA** * _Can be ⊕ in many conditions including:_ * Hep B and C, HIV, chronic infections, SABE * RF present in 44% of HCV * 76% in HCV w/cryoglobulin * SLE, Sjogren’s, MCTD, PBC * Sarcoidosis, IPF, asbestosis, age \> 65 years, malignancy

Answer 23

* Citrulline ⇒ post-translationally modified arginine residue * Anti-CCP Abs as detected by ELISA ⇒ useful adjunct in RA dx * Sensitivity 47-90% * Specificity 90-98% * Low incidence of anti-CCP found in Hep C * **⊕ Anti-CCP early in course of RA** predicted progression of radiographic joint scores at 5 yrs better than RF

Answer 24

_Classifies subtypes based on clinical features:_ * Systemic arthritis * Polyarthritis * Pauciarthritis or oligoarthritis * Enthesitis-related arthritis * Psoriatic arthritis

Answer 25

Previously called Still’s disease * **Least common JIA presentation** * Men = women * **Age of onset is \< 17 y/o** * **Any joints may be involved** * **Ass. w/ destructive arthritis** * **Presents w/ fever, rash, lymphadenopathy, hepatosplenomegaly** * Lab abnormalities include leukocytosis, anemia, ↑ ESR * **⊖ ANA** * **Rheumatoid Factor is rare** * Treated w/ disease modifying drugs

Answer 26

* **Most common JIA presentation** * **Female \> male predominance** * **Peak onset is 2-3 y/o** * Rare after age 10 yrs * **Large joints affected but rarely hips** * **No systemic sx** * ± Mildly ↑ ESR * **⊖ RF** * **Low titer ANA ⊕ is common** * A subset of those w/ ⊕ ANA will have **uveitis**

Answer 27

* Peak onset is **2-5 yrs** and **10-14 yrs** * More similar to adult RA ⇒ **multiple joint involvement; destructive arthritis** * Mild anemia * ± Mildly ↑ ESR * **Low titer ANA ⊕ is common** * **10-20% of those \> 10 yrs have ⊕ RF** * Disease modifying drugs used for treatment

Answer 28

* ⊕ ANA, especially in pauciarticular * Ass. w/ ↑ incidence of uveitis * ESR/CRP usually normal * RF usually ⊖

Answer 29

* Occur early in RA * Up to 93% of pts w/ \< 2 yrs of RA ⇒ ± radiographic abnormalities * Erosions detected by MRI w/in 4 months of RA onset * Rate of progression is significantly more rapid in the 1^st yr vs 2^nd and 3^rd yrs * Goal of early treatment is to prevent progression of disease

Answer 30

* Education * Build a cooperative long-term relationship * Use materials from arthritis foundation and ACR * Assistive devices * Exercise ⇒ ROM, conditioning, and strengthening * Medications * Analgesic and/or anti-inflammatory * Immunosuppressive, cytotoxic, and biologic * Balance efficacy and safety w/ activity

Answer 31

* _Two drug classes used to ↓ inflammation_ ⇒ **NSAIDs and glucocorticoids** * ↓ inflammation but do not slow disease process * Long-term use of corticosteroids ⇒ weight gain, diabetes, cataracts, osteoporosis * Low dose corticosteroids ↓ joint destruction * **Disease Modifying Anti-Rheumatic Drugs (DMARDS)** can slow progression

Answer 32

* **Slow disease progression** * Take some time to exert their action * Fall into two major categories * Older agents ⇒ non-biologics * Newer agents ⇒ mostly, but not exclusively Ab’s or recombinant proteins (“biologics”)

Answer 33

* **Group of inflammatory arthropathies** * Share common clinical, pathophysiologic and immunogenetic factors * Related to and may form a disease spectrum w/ **psoriasis and inflammatory bowel disease**

Answer 34

* Originally thought to be variants of rheumatoid arthritis * Later defined as a distinct group * Named **seronegative spondyloarthropathies** * Lack of rheumatoid factor * **Characteristic spinal involvement**

Answer 35

SpA encompasses several identifiable diseases Undifferentiated form or isolated features that suggest they fall into this group _Diseases include:_ * **Ankylosing spondylitis (as)** * **Reactive arthritis (ReA)** * **Psoriatic arthritis (PA)** * **Arthritis associated w/ inflammatory bowel disease (EA)** * **Undifferentiated spondyloarthritis (UspA)**

Answer 36

Features vary among the different entities and among individuals: * **Inflammatory back pain or asymmetric synovitis** * **Enthesopathy** ⇒ inflammation of tendon/ligament attachments * **Dactylitis** ⇒ swelling of a whole finger or toe * **Asymmetric arthritis** * Fhx of the same or a related disease * **Ocular inflammation** ⇒ uveitis or conjunctivitis * **Psoriasis** * **Bowel inflammation**

Answer 37

* **Enthesitis** ⇒ the attachment of ligaments and tendons to bone * Major site of inflammation in SpA * Enthesis attaches w/ a fibrocartilage component w/ fibers implanting in the bone * **Synovitis different pathologically to RA** * **Bone erosion @ sites of inflammation** * **New bone formation** can occur along the spine, fusing joints, or at tendon attachments * Unlike RA where erosion occurs w/o bone formation

Answer 38

**HLA B27 ⇒ major genetic marker** Not seen in all pts Not associated w/ all conditions of SpA family * Ankylosing spondylitis ⇒ 90% * Reactive arthritis ⇒ 30-50% * Enteropathic spondylitis ⇒ 35-75% * Psoriatic spondylitis ⇒ 40-50% * Undifferentiated spondyloarthritis ⇒ 70% * Anterior uveitis ⇒ 50% * Aortic insufficiency/heart block ⇒ 80%

Answer 39

* No diagnostic lab studies ⇒ estimates of incidence difficult * Overall incidents ~ 0.1-1.4 * Influenced by ethnicity of the population

Answer 40

An inflammatory disease primarily of the axial skeleton

Answer 41

* Onset typically in early 20’s w/ rare exceptions starting before age 45 * 2:1 M to F ratio * Incidence follows B27 incidence in population in the US * 1% of non-Hispanic of self-reported European ancestry * Includes non-radiographic axial spondylarthritis

Answer 42

* **Inflammatory ∆ start in sacroiliac joints and at enthesis** * Cytokine production @ inflammatory site * TNF ⇒ **cartilage and bone erosion** * Later development of **ossification w/ new bone formation** * Response to inflammation * Lack of inhibitors of signaling of bone formation

Answer 43

* **Axial pain** ⇒ key sx * Often described as stiffness * Worse in the morning for ≥ 1hour * Improves w/ activity * Worsens w/ rest * Pattern is called _inflammatory back pain_ * Not exclusively seen in SpA but very suggestive * Important to recognize pts early in their course * Pain and involvement tends to **start at the sacrum** * Proceeds to **involve the spine in an ascending fashion** over a period that can be yrs ⇒ sacrum to cervical * Pts may complain of **pain in the posterior leg** * From **irritation of the sciatic nerve** by the piriformis muscle * **Chest pain** can occur from: * Referred pain from the thoracic spine * Involvement of the manubriosternal joint * **Peripheral arthritis** tends to involve _shoulders or hips_ * Can occur in an asymmetric lower extremity pattern * Similar to that seen w/ ReA

Answer 44

* **Early loss of motion of lumbar spine** * Normally forward flexion L-spine ⇒ lordotic curvature reversal to kyphotic & an expansion of ~ 5 cm * Assessed w/ the Shoeber maneuver * Occurs before any XR ∆ * **± Early loss of chest expansion** * Normal chest expansion measured @ nipples is 2 inches or 5 cm * Easier to measure in men

Answer 45

_Characteristic radiologic ∆_ ⇒ necessary for dx of as until recently ∆ always bilateral in AS * **Initial ∆ in sacroiliac joints (SIJ)** * Smudging of the subchondral bone * Widening of the joint w/ cartilage erosions * Joint fusion * **Ascending ∆ in spine w/ squaring of vertebral bodies** * Subsequent ossification along spinal ligaments * Called **Syndesmophyte** on radiographs * Leads to _fusion of the spine_ * XR appearance called **bamboo spine** * Progression varies and does not advance in all pts * Time from onset of sx → XR ∆ ~ 5-10 yrs * Led to delayed dx in the past * Inflammatory ∆ can be seen much earlier by MRI * **Bone edema around the SIJs** * **Edema at ligament attachment sites or discs in the spine**

Answer 46

* No specific abnormalities * ± Anemia of chronic inflammation * ↑ ESR/CRP * **↑ CRP is the better marker** * **~ 90% of pts of European ancestry w/ HLA B27** * Never a dx test but ↑ likelihood of disease in the proper setting

Answer 47

* **Anterior uveitis (AU)** * Occurs in ~ 25% * Feature of all SpA * Also associated w/ many other diseases and occurs idiopathically * ~ 50% of idiopathic AU pts are B27 ⊕ so likely is a “forme fruste” of SpA * A minor feature of a disease presenting in isolation * **Heart block and aortic insufficiency** * Results from inflammation @ aortic root involving the conduction system and aortic valve * Seen in ~ 3% at 10 yrs of disease and 10% at 30 yrs * **Upper lobe pulmonary fibrosis** * **Cauda equine syndrome** * Impingement of the spinal nerves past the end of the cord * Causes numbness over the sacrum (saddle anesthesia), leg weakness, and bowel and bladder sphincter dysfunction * **Bowel inflammation** * ~ 60% of pts have subclinical ∆ in terminal ilium consistent w/ Crohn’s disease * Some will eventually develop symptomatic inflammatory bowel disease

Answer 48

_Dx made from clinical features and radiologic findings:_ * **Bilateral sacroiliitis** by XR or MRI almost pathognomonic * **↑ CRP** and **⊕ B27** can be suggestive * **Uveitis** and fhx can also suggest dx * Long delay in XR ∆ and MRI * ∆ can come and go

Answer 49

* Long delay in XR ∆ and MRI & ∆ can come and go * Non-Radiographic Axial Spondyloarthritis now recognized * **Defined by having inflammatory back pain** and several other features including: * Family history * ↑ ESR/CRP, B27 * Other SpA features such as psoriasis * By this definition, more pts identified w/ equal gender incidence

Answer 50

* Course very variable * From persistent sx w/o XR progression ⇒ non-radiologic axial spondyloarthritis * To complete fusion of the spine and potentially progressive deformity and disability * Complications of spinal fusion * Potential for fracture w/ trauma * Osteoporosis

Answer 51

* **NSAIDs** improve sx and may affect progression of fusion * **TNF inhibitors** have substantially ↓ sx and ↓ functional impairment of axial disease * **Physical therapy** ⇒ maintain function and prevent spinal deformity

Answer 52

Previously called **Reiter’s syndrome** * **An inflammatory disease occurring following infection** * Originally thought that organisms were not participating in the process but had provoked an Inflammatory response

Answer 53

* Urethritis which is sexually acquired ⇒ Chlamydia trachomatis * Bacillary dysentery * Shigella * Salmonella * Yersinia * Campylobacter fetus

Answer 54

* Generally M:F is 5:1 in post-urethritis * Equal incidence post-dysentery * Incidence and prevalence difficult to establish * Least common SpA

Answer 55

* **Sx occur days to weeks and occasionally months after infection** * Infectious event may be forgotten and at times sx were not dramatic * I.e., mild dysuria and discharge or diarrhea w/o fever or bleeding

Answer 56

Clinical features occur in variable combinations and time course: * **Arthritis/enthesitis** * _Asymmetric_ joint involvement * _Predominantly lower extremity_ w/ involvement of knees, ankles, toes * Most characteristic is **enthesitis** * @ Achilles attachment ⇒ **achilles tendonitis** * @ Attachment of the plantar fascia to the calcaneus ⇒ **plantar fasciitis** * ± Back pain from **sacroiliitis** (may be unilateral) * Other important causes of unilateral sacroiliitis is infection ⇒ bacteria, mycobacteria, and brucella * **Urethritis** * Urethra is the target & portal of entry of organism * Usually mild dysuria and discharge * **Conjunctivitis/uveitis** * Most typical eye involvement is conjunctivitis ⇒ erythema and discharge which may be mild * **Anterior uveitis** ⇒ same as seen w/ AS * **Mucocutaneous disease** * **Painless mouth ulcers** * **Keratoderma blennorhagicum** * Lesions typically on _palms and soles_ * Histology is typical of psoriasis * **Circinate balanitis** * In circumcised men ⇒ hyperkerotic lesion on the glans * In uncircumcised men ⇒ shallow ulcers around the glans * Can occur in isolation from the rest of syndrome

Answer 57

* After urethritis ⇒ disseminated Neisseria gonorrhea infection * Diarrhea and arthritis ⇒ inflammatory bowel disease * Initiating event unclear ⇒ other causes of acute arthritis and enthesitis

Answer 58

* **No specific diagnostic study** * _If possible:_ * **PCR for chlamydia** from urethra or other mucous membrane site * **Culture of a typical organism from stool** * **Synovial fluid** is inflammatory w/ \> 2,000 WBCs * **HLA-B27** reported in 40-80% ⇒ supportive of dx in the proper setting

Answer 59

* **Attacks last weeks to months and recurrences occur** * Some pts (9- 19%) develop chronic sx * **More common after Chlamydia \> bowel infection** * Over yrs, pts can develop symptomatic spondylitis & heart lesion as in as

Answer 60

* **Now known that chlamydia persists in a dormant intracellular form in synovia of pts w/ ReA** * Ag from bowel organisms, but not intact organisms exist in the joints * Relation to enthesitis and other features is unknown

Answer 61

* **NSAIDs** are used for symptomatic therapy * Other agents have been used for ongoing sx * **Methotrexate, sulfasalazine and TNF inhibitors** * May be possible to _eradicate chlamydia and disease_ w/ **combo of doxycycline or azithromycin and rifampin**

Answer 62

A characteristic arthritis that occurs in pts w/ psoriasis

Answer 63

* Occurs in 10-30% of pts w/ psoriasis * **M:F ratio is 11:1** * Age of onset typically **40-50s** * Can occur in childhood or much later * Relationship to the skin disease varies

Answer 64

* 70% ⇒ psoriasis (skin involvement) occurs before arthritis * ~15% ⇒ arthritis before skin findings * ~15% ⇒ skin findings dx @ the time of arthritis * No relation between extent of skin disease and arthritis

Answer 65

Usually described by onset and pattern of joint disease Patterns seen early, less distinct later in course * **Asymmetric arthritis** * Typically in hands and feet * Involved: **DIPs, PIPs, MCPs**, usually few joints * Can involve **large joints** * **Inflammation of DIP joints** * Very characteristic of PA \> other SpA * DIPs not involved in RA * Common in OA in the hands * **Characteristic psoriatic nail ∆ occur in the involved digit** * **Dactylitis** (sausage digit) ⇒ almost pathognomonic * Swelling and pain in a whole digit from flexor tendon and multiple joint involvements * **Enthesitis** such as achilles tendonitis * **Symmetric arthritis** * Same appearance as RA but RF and cyclic citrullinated peptide Ab are absent * **Spondylitis** * Sacroiliitis and spondylitis similar to as * **Arthritis mutilans** * Highly destructive form of PA * Produces the characteristic XR ∆ known as **“pencil and cup”** * Joint destruction and telescoping of digits * _Extra-articular features_ * **Uveitis and subclinical bowel disease**

Answer 66

* **Relationship to psoriasis is unknown** * **Majority of inflammatory process occurs @ enthesis** w/ less being actual synovitis * Synovial membrane in PA w/ **↑ vascularity** and **↓ Mφ compared to RA** * Multiple inflammatory cytokines including TNF ↑ in synovial fluid * Relationship b/t BMI to arthritis severity ⇒ ? Role of leptin and other adipose derived hormones

Answer 67

No lab abnormality characteristic of PA * **± ↑CRP/ESR** * **HLA B27** is ↑ to 50% w/ spondylitis but not w/ peripheral arthritis * **Dx made w/ characteristic clinical findings and presence of psoriasis** * Fhx is helpful in pts not exhibiting psoriasis at presentation * Psoriasis has a strong genetic component

Answer 68

* PA tends to have remissions and exacerbations * 40-50% have destructive and deforming disease * 20-40% have spondylitis

Answer 69

**TNF inhibitors** Best therapy for symptomatic disease and prevention of joint destruction

Answer 70

**Arthritis and spondylitis occurring in the presence of ulcerative colitis (UC) or Crohn’s disease (CD)** Occurs in ~ 10% of UC and CD

Answer 71

* **Usually involves a few joints in the lower extremities** * Become symptomatic w/ activity of the bowel disease * More common w/ colonic involvement * Previously when colectomy was done for UC, it abolished the peripheral arthritis * **Arthritis usually occurs in pts w/ established IBD** * **Can precede clinical bowel disease** * Subclinical bowel inflammation common in other SpA's * Spondylitis present in 10% of pts w/ IBD * A larger number have lower back pain related to sacroiliitis * **Course of spondylitis independent of bowel disease**

Answer 72

* **HLA-B27** in 50% of pts w/ IBD and spondylitis, not ↑ in peripheral arthritis * Evidence that **IL-23 stimulated by bowel bacteria** may be a driver of arthritis * **Multiple cytokines are ↑** * **TNF important** in both bowel disease and arthritis * Given response to inhibition of TNF

Answer 73

**Pts w/ features of SpA who do not fit a specific entity** * Related to typical clinical features ⇒ dactylitis, asymmetric arthritis * ↑ frequency of HLA B27 ⇒ idiopathic anterior uveitis, chronic achilles tendonitis, or plantar fasciitis * 65% of pts w/ undifferentiated SpA have subclinical bowel inflammation * Led to another classification scheme for SpA ⇒ includes axial and peripheral spondyloarthritis

Answer 74

* **HLA-B27** ⇒ best recognized etiopathologic factor in SpA * All subtypes of B27 except 06 and 09 ass. w/ AS and other SpA * B27 frequency in populations determines frequency of SpA * No difference between B27 ⊕ and B27 ⊖ disease * Only a small proportion of B27 ⊕ people develop SpA * _In AS, genetics account for 80-90% of susceptibility_ * 50-75% concordance rate in MZ twins and a 15% in DZ * Relative risk of disease is 94 for 1st-degree, 25 for 2nd-degree, and 34 for 3rd-degree relatives * B27 accounts for 30-50% of inheritance * Other candidate genes ⇒ **endoplasmic reticulum amino peptidase 1 (ERAP1) and IL-23 receptor**

Answer 75

**IL-23/IL-17** * IL-23/IL-17 axis ⇒ major driver of all the spondyloarthridities * Also important in psoriasis and inflammatory bowel disease * Bowel flora ⇒ ⊕ IL-23 from dendritic cells and Mφ ⇒ ⊕ IL-17 cells ⇒ ⊕ IL-17, IL-22, TNF and INF-𝛾 * Associated w/ findings of SpA

Answer 76

* **Non-steroidal agents** to ↓ pain and swelling * Useful, particularly in axial inflammation * Agents used to treat RA w/ limited or no benefit * Methotrexate, sulfasalazine, and lefunimide * **TNF inhibitors ⇒ most effective agents** * Infliximab, etanercept, and adalimumab * **IL-12/23 and IL-17 inhibitors now available**