Spondyloarthropathies:

Ankylosing Spondylitis, Psoriatic

Arthritis, Reactive/Enteropathic
Arthritis and HLA-B27……and
Adult Still’s Disease….2020
Mark Stillwell, MD, FACP
 Learning Objectives for this Session
• Define spondyloarthritides, spondylitis and sacroiliitis.
• Discuss the findings and management of:
• A. Ankylosing spondylitis
• B. Psoriatic arthritis
• C. Reactive arthritis/Reiter’s syndrome
• D. Post-Streptococcal reactive arthritis and how it is different from acute
rheumatic fever
• E. Enteropathic reactive arthritis
• F. Celiac disease arthritis
• G. Adult Still’s Disease
• Review the meaning of HLA-B27 and the diseases associated with it
Oh my aching back!......back pain is sometimes due to more than just myofascial strain or degenerative disc/joint disease
Source: ankylosingspondylitisnews.com
 Case-
• CC- An 85 yo male comes in for joint pain of 7 days, to the point he cannot care for himself
any longer.
• HPI-
• O- 7 days ago, fairly abrupt onset, no trauma
• L- R knee, L ankle, R 2nd MCP
• D- pain is persistent, non-migratory
• C- pain is sharp
• A- Better with non-use or weight bearing on joints, worse with use of the joints
• R- none
• T- worse at night
• S- knee 10/10, ankle 9/10, MCP 7/10
• A- Positive- fevers to 100 degrees, had a “URI” 2-3 weeks ago with sinus congestion, sore
throat and mild cough.
• Negative- chills, mental status changes, chest pain, dyspnea, rash, h/o microcrystalline
disease, dysuria
 Case-
• Past Hx-
• Childhood- Had Measles, Mumps, Rubella, Chicken pox, Roseola,
Scarlet fever, Whooping cough and Diphtheria.
• Med- Hypertension, Cataracts
• Surg- Tonsillectomy age 6 for recurrent tonsillitis.....no transfusions
• Screenings- Last colonoscopy 8 yrs ago was nl, prostate exam 1 year
ago nl
• Vaccines- UTD on Pneumovax (1998), Prevnar (2015), Shingrix (2019
x 2), TDaP (2015), Hep B (1988 x 3), Hep A (1998 x 2)
• FHx- M- died of pneumonia age 92, F- died of MI at 86, bro- died of
lung cancer at 62, children healthy
 Case-

• SHx- Widowed, lives alone in town, no family in the area, no tick/insect

bites, no travel, no exposures to sick people, no EtOH/Tob/drug abuse.
• Meds- HCTZ 25 mg/d and Lisinopril 10 mg/d, compliant, on no
OTC/vit/herbals
• All- none to meds, latex, environment or food
• ROS- unremarkable except HPI.
• PE- unremarkable except for hot, red, effused R knee/L ankle/R 2nd
MCP. T 100.5, BP 145/95, P 94, RR 16, O2 sat 95% on RA.
 Case-

• Lab-
• CBC- WBC 14k (82% polys, 5% bds)
• CMP- unremarkable, Uric acid nl
• ESR 55 (nl < 20)
• Blood cx x 2, Urine cx, Urethral GC/Chlamydia NAAT all negative
• UA- unremarkable
• ANA/RF/CCP/RPR/ANCA/HLA-B27 all negative
• Knee joint aspirate- 12,000 WBCs (100% polys), 50 RBC, glucose nl,
crystals negative, GS- no organisms, aerobic/anaerobic/GC cx negative
• Echo- no vegetations or significant valve abnormalities
 Case-

• A diagnostic procedure was done. Rest of the case to be discussed at

the end of the hour.
 Spondyloarthritides

• Definitions-
• A. Spondyloarthritides- a group of arthritic, inflammatory diseases
that attack the spine, sacro-iliac joints, peripheral joints, tendons and
where the tendons/ligaments attach to the bone (entheses). These
diseases may also affect almost any organ system in the body,
especially the eyes, skin/mucous membranes/soft tissues, GI and GU
tracts.
• B. Spondyloarthritis- inflammatory arthritis of the spine.
• C. Sacroiliitis- inflammatory arthritis of the sacroiliac joints.
What is HLA-B27?
Source: viplab.in
 HLA-B27 peptide (chain A green, chain B yellow) on a cell surface complexed to an antigen (orange) it presents to a T cell
(CD8+) Source: wikipedia.org
HLA-B27
HLA-B27- Intro
• A. The MHC (major histocompatibility complex) on chromosome 6
encodes for various cell surface antigens that present other antigens to
various T cells.
• 1. MHC Class I HLA (human leukocyte antigen) antigens are present on
most nucleated cells and present other antigens to CD8+ lymphocytes and
NK cells.....mediates destruction of infected and malignant cells (cellular
immunity).
• 2. MHC Class II HLA antigens reside on B lymphocytes, dendritic cells,
macrophages, monocytes and endothelial cells and present other antigens
to CD4+ cells and present antigens to CD4+ cells (adaptive, humoral
immunity immunity).
• 3. MHC Class III HLA antigens include several secreted proteins
including complement, cytokines and heat shock proteins.
HLA-B27
HLA-B27- Intro
• B. HLA-B27 (subtypes B2701-2759) is an MHC Class I
encoded cell surface antigen strongly associated with certain
inflammatory diseases (however HLA-B27+ does not
necessarily mean there will be an associated disease develop).
• 1. **8% of Caucasians, 5% of Latinos, 25% of
Alaskan/Canadian Inuits (50% of the Haida tribe in the Alaskan
panhandle), 4% of North Africans, 2% of African-Americans,
24% of Northern Scandinavians, 2-9% of Chinese and 0.1-0.5%
of Japanese persons possess the gene encoding HLA-B27.
 HLA-B27
HLA-B27- Associated diseases (esp. the “sero-negative” spondyloarthropathies)
• A. Ankylosing spondylitis- >/= 90% are HLA-B27+.....1-2% of HLA-B27+ people will get
this.......21% of HLA-B27+ relatives of HLA-B27+ patients with spondylitis will get this
• 1. With uveitis or aortitis.......100%
• B. Reactive arthritis......30-80% are positive.....associated in Caucasians but not in
those of Sub-Saharan Africa heritage.
• C. Psoriatic arthritis
• 1. With spondylitis.......50% are positive
• 2. With peripheral arthritis.......15% are positive
• 3. Without arthritis........not increased
• D. Acute anterior uveitis....50% are positive
• E. Enteropathic arthritis/IBD......50-75% are positive
• F. Juvenile spondyloarthritis....70% are positive
• G. Undifferentiated spondyloarthritis......70% are positive
• H. Wipple’s disease.....30% are positive
• I. Common among the < 0.5% of HIV+ patients that are long-term nonprogressors
Common disease associations from one 2002 study
Source: medscape.org
6th century skeleton with Ankylosing Spondylitis
Source: wikipedia.com
Ankylosing spondylitis over 25 years
Source: chicagoarthritis.com
 Ankylosing Spondylitis (AS)
Ankylosing Spondylitis- Intro
• A. Also known as Marie-Strumpell disease, Bechterew’s disease, seronegative
spondylitis (meaning RF-negative, no specific autoantibodies for this disease have
yet been identified), *bamboo spine and axial spondyloarthritis
• B. ****>/= 90% are HLA-B27+
• C. Thought *autoimmune (from autoantibodies) and *autoinflammatory
(activated immune cells, due to dysregulated secretion of pro-inflammatory
cytokines, leading to consequent damage of host tissues) in nature
• D. TNF-alpha and IL-1 have been implicated in this disease.
• E. *At 60% increased risk for cerebrovascular mortality and 50% increased risk
for vascular mortality.
• F. *Most common in those of Northern European descent with a *male:female
ratio of 3:1......usually presenting with chronic back pain before the age of 40.
• G. Many with this disease have high IgA levels.
• H. Occurs in 1.4% of the US population.
 Ankylosing Spondylitis (AS)
Ankylosing Spondylitis- Clinical
• A. Musculoskeletal
• 1. **Low back pain- typically has at least 4 of the following 6:
• a. Onset < 40 yo
• b. Insidious onset
• c. *Improvement with exercise
• d. No improvement with rest
• e. Pain at night (with improvement upon rising)
• f. Morning stiffness
• 2. Neck pain- more prominent with disease progression
• 3. Impaired spine mobility
 Ankylosing Spondylitis (AS)
Ankylosing Spondylitis- Clinical
• A. Musculoskeletal
• 4. **Impaired posture- with hyperkyphosis (hunchback), often even in the first 10
years.....atlanto-axial subluxation at C1-C2 can occur spontaneously too.
• 5. Buttock pain- can be bilateral, common to be alternating side to side, due to
sacroiliitis.
• 6. Hip pain- felt most in inguinal regions, sometimes leading hip flexion deformities.
• 7. Peripheral arthritis- most common in ankles, knees, hips, shoulders,
sternoclavicular and TMJs.
• 8. *Enthesitis- pain/inflammation at attachment of tendons/ligaments to bone,
especially where the Achilles tendon attaches at the heel.
• 9. *Dactylitis- “sausage digits” with diffuse swelling of toes/fingers.
• 10. ***“Bamboo spine”- the classic finding, develops when the outer fibers of the
intervertebral discs ossify, forming *marginal syndesmophytes between adjoining
vertebrae.
• 11. Osteopenia with fragility fractures
Hyperkyphosis with AS
Source: rheumexamatlas.com
Easy to see why there can be respiratory compromise in late AS.....diaphragms won’t help much with this body habitus
Source: pinterest.com
Dactylitis in AS
Source: epainassist.com
Dactylitis of L D1/D4 and R D3
Source: the-rheumatologist.org
Enthesitis, inflammation at a tendon insertion, common site is the Achilles tendon insertion…seen above in R heel
Source: rheumainkaernten.at
Enthesitis, bilateral here……this person has real “Achilles heels”
Source: researchgate.net
Progressive boney fusion in AS, leading to the characteristic “bamboo spine”
Source: faceyourback.com
Gross section of spine in AS
Source: cram.com
AS doesn’t just affect the spine
Source: spondylitis.org
 Ankylosing Spondylitis (AS)
Ankylosing Spondylitis- Clinical
• B. Extra-articular disease
• 1. *25-30% get acute anterior uveitis (inflammation of the pigmented layer of the
eye that lies between the inner retina and the outer sclera/cornea....includes the iris,
ciliary body and choroid).....presents with acute eye pain, photophobia and blurred
vision, tends to be unilateral and recurrent....can lead to glaucoma and cataracts.
• 2. Inflammatory bowel disease- ileal and colonic mucosal inflammation, frequently
asymptomatic, can be found histologically in 50%.
• 3. Psoriasis in 10%, and these patents tend to have concomitant peripheral arthritis
issues too.
• 4. Cardiovascular disease- aortic root issues cause AI in 10% and increased
conduction abnormalities, coronary artery disease plus venous thromboembolism.....see
“E” in the intro section.
• 5. Pulmonary- Mechanical restrictive lung disease is common, and apical fibrosis is
common to see radiographically.
• 6. Occasional IgA nephropathy and renal amyloidosis may develop.
• 7. Low-grade fevers may be present intermittently or chronically
AS problems develop from head to toes, and not just in bones and joints
Source: creakyjoints.org
 Ankylosing Spondylitis (AS)
Ankylosing Spondylitis- Diagnosis
• A. Lab-
• 1. *50-75% have elevated ESR/CRP
• 2. **Positive HLA-B27 in most cases
• 3. Elevated alkaline phosphatase (from bone) in 13%
• 4. Occasional normo/normo anemia of chronic disease
• B. Radiologic tests
• 1. Sacro-iliac joints with joint space narrowing, sclerosis or erosive change.
• 2. Spine- *squaring of vertebral bodies from bone erosion,
*syndesmophytes and *ankylosis of facet joints.......eventual “bamboo
spine”.........up to 14% can get atlanto-axial subluxation C1-C2
AS with fusion on both AP and lateral Xrays
Source: researchgate.net
 AS on AP Xray with lateral fusion (white arrows), “dagger sign” of apical fusion between spinous processes by calcification of
supraspinous ligament (orange arrows) and SI joint fusion (yellow arrows) Source: svuhradiology.ie
AP CT scan of AS with lateral fusions
Source: 52.62.202.235
Lateral CT scan with fusion
Source: pinterest.com
Lateral CT images of AS, including 3d reconstruction (center)....fusion anteriorly (small arrows) and between spinous processes
(thick arrows) Source: researchgate.net
AS with sacroiliitis, which tends to start on the ilium side of the join (CT scan with coronal view)
Source:uwmsk.org
AS with sacroiliitis, which tends to start on the ilium side of the joint (CT scan with transverse view)
Source:uwmsk.org
AS with sacroiliitis, and SI joint is starting to fuse (CT scan with transverse view a, coronal view b)
Source:researchgate.net
 Ankylosing Spondylitis (AS)
Ankylosing Spondylitis- Treatment
• A. Non-pharm-
• 1. Smoking cessation
• 2. PT
• 3. Depression screening/psychosocial support
• B. Pharm-
• 1. *NSAIDs
• 2. DMARDs- not helpful
• 3. *TNF-alpha inhibitors (see Rheumatologic Drugs PowerPoint)
• 4. IL-17 monoclonal antibodies
• 5. JAK inhibitors
• 6. Thalidamide
• C. Surgery- a big time proceedure to go through with this disease
Intra-op stabilization of AS
Source: link.springer.com
Before and after surgery.......massive stabilization rods and giant screws
Source: ipsurgery.com
Psoriatic Arthritis
Source: charlottedermatologypa.com
 Psoriatic Arthritis (PA)
Psoriatic arthritis- Intro
• A. Psoriasis + musculoskeletal symptoms
• B. Male = females in frequency
• C. *2% of the population has psoriasis, and 20-40% of people with psoriasis will have
PA (you would think it is much more prevalent based on all the adds for meds on TV
and in magazines!).......the longer or more severe the psoriasis, the more likely PA will
develop......**psoriasis tends to precede PA by 7-10 years......in 10-15% of PA the
arthritis comes first, however......those with psoriasis also have 4-8x increased risk to
get Crohn’s disease.
• D. Most with PA develop it between 30-55 yo
• E. *80-90% of those with PA have psoriatic nail changes (**nail pitting, separation of
nail from nail bed = *onycholysis, *horizontal/vertical ridging and cracking, red spots
in the lunula = mottled lunula, nail plate crumbling, *nail thickening = hyperkeratosis,
areas of whitish discoloration = leukonychia or even loss of nail)........*only 40% of
those with psoriasis alone have nail changes......can look like onychomycosis.
 Psoriatic Arthritis (PA)
Psoriatic arthritis- Clinical
• A. Asymmetric, inflammatory oligoarthritis (1-5 joints)
• 1. Most common joints involved are commonly the *DIP > PIP and
MCP joints....”peripheral arthritis”......but can involve more central
joints too
• 2. Symmetric, deforming arthritis (arthritis mutans) similar to
RA.........+/- flexor tenosynovitis
• 3. Morning stiffness in 50%, with fatigue
• B. *Dactylitis and enthesitis (esp. Achilles tendon) like AS.......+/-
pitting edema
• C. Nail changes....see Intro section for details
• D. +/- Spondylitis or sacroiliitis
Source: slideshare.net
Skin, nail and joint changes in PA
Source: wjgnet.com
Inflammatory enthesitis in PA at Achilles tendon insertion (MRI)
Source: wikipedia.org
Nail changes in PA
Source:creakyjoints.org
A. Onycholysis, B. dystrophy with oil spots, C. hyperkeratosis, D. pitting in PA
Source: researchgate.net
Nail onycholysis and pitting in PA
Source: medicalnewstoday.com
Leukonychia in PA
Source: e-ijd.org
Crumbling, hyperkeratotic nails in PA, can look like onychmycosis
Source: medpage.com
Ridges and leukonychia in PA
Source: healthline.com
Pitting (closeup), ridges and onycholysis in PA…….**pitted nails on Boards, or when asked about on ward rounds, always think
of Psoriasis or PA! Source: healthline.com
Mottled lunula, onycholysis, ridging, onycholysis and pitting in PA
Source: pinterest.com
 Psoriatic Arthritis (PA)
Psoriatic arthritis- Clinical
• E. Ocular-
• 1. Uveitis
• 2. Conjunctivitis
• F. Skin- 2% of the population has psoriasis (80% have just mild-mod disease......</= 5%
body surface area). In 85% the rash starts many years before the arthritis appears.
• 1. Red patches/plaques of skin with silvery scales, with most common sites being
elbows/knees, low back and back of neck, scalp/face, palms/soles
• a. *Plaque psoriasis- is the most common (85-90%).
• b. Guttate psoriasis- causes many small, oval patches first appearing on the chest.
• c. Inverse psoriasis- smooth, red patches in skin folds (inguinal, breasts, axillae)
• d. Pustular psoriasis- rarer, with small, fluid filled blisters/pustules
• e. Erythrodermic psoriasis- rare, severe, affecting most of the body.
•
Types of Psoriasis
Source:apexskin.com
Typical plaque psoriasis, with silvery-white scales
Source: psoriasis.com
Plaque psoriasis on knees
Source: clevelandclinic.org
Plaque psoriasis on elbow
Source: mdedge.com
Plaque psoriasis is common on the back, especially low back
Source: wikipedia.org
Plaque psoriasis on scalp
Source: webmd.com
Plaque psoriasis in scalp and on back of neck
Source: fbresearch.org
Plaque psoriasis on hand, can be confused with eczematous dermatitis
Source: medicalnewstoday.com
Plaque psoriasis on hand, can be confused with eczematous dermatitis
Source: photos.com
Plaque psoriasis of foot
Source: rheumnow.com
Guttate psoriasis
Source: healthline.com
Guttate psoriasis
Source: psoriasismedication.org
Inverse psoriasis can be confused with Candida dermatitis
Source: psoriasis.org
Inverse psoriasis can be confused with Candida dermatitis
Source: mayoclinic.org
Pustular psoriasis
Source: webmd.com
Pustular psoriasis- closeup
Source: healthline.com
Erythrodermic psoriasis
Source: dermnetnz.org
 Psoriatic Arthritis (PA)
Psoriatic arthritis- Lab
• A. ESR/CRP elevated in 40%
• B. WBC elevation in 1/3
• C. HLA-B27
• 1. 50%+ with spondylitis
• 2. 15%+ with arthritis alone
• D. Less than 20% have a positive ANA, RF, anti-dsDNA or anti-CCP
antibody
 Psoriatic Arthritis (PA)
Psoriatic arthritis- Treatment
• A. Exercise, PT, OT with weight reduction.
• B. NSAIDs
• C. DMARDs for refractory or severe disease
• D. Biologics if “C” fails, especially Apremilast ( Otezla), also used
for psoriasis alone, which acts as a selective inhibitor of the
enzyme phosphodiesterase 4 and inhibits spontaneous production
of TNF-alpha from synovial cells.
 Classic Reactive Arthritis
Classic reactive arthritis- Intro
• A- Definition- *an arthritis which develops soon after, or during,
an infection elsewhere in the body......but which the
microorganisms cannot be recovered from the joint.
• B. Two major clinical features:
• 1. An interval ranging from several days to weeks before
antecedent infection and arthritis.
• 2. Typically mono- or oligoarticular asymmetric pattern of
arthritis, often involving the lower extremities, and sometimes
associated with dactylitis or enthesitis.
 Classic Reactive Arthritis
Classic reactive arthritis- Intro
• C- Historically this syndrome referred to a triad (Reiter’s
syndrome, Reactive Arthritis Triad) of **post-infectious arthritis,
**urethritis and **conjunctivitis. However, there are many other
issues that can develop that will be discussed later.
• D. Typically occurs in young adults
• E. **30-80% are HLA-B27 positive......and HLA-B27 tends to be
associated with the more severe and chronic forms of reactive
arthritis.
 Classic Reactive Arthritis
Classic reactive arthritis- Infectious etiologies
• A. **Chlamydia trachomatis- the most common associated disease
• B. *Salmonella of various servovars
• C. *Shigella flexneri > S. dysenteriae > S. sonnei
• D. *Campylobacter jejuni
• E. *Yersinia enterocolytica and Y. pseudotuberculosis
• F. *Clostridiodes (Clostridium) difficile
• G. Others, less commonly associated, Chlamydia pneumoniae,
Ureaplasma urealyticum, Mycoplasma genitalium, E. coli, Bacillus
Calmette-Guerin (BCG)
 Classic Reactive Arthritis
Classic reactive arthritis- Mechanism
• A. Typically triggered by certain Gram-negative bacteria that have
lipopolysaccharide as an integral component of their outer
membrane, tend to attack mucosal surfaces, invade host cells and
survive intracellularly. HLA groups (e.g. B27) may modulate
interaction between triggering bacteria and immune cells.
Bacterial antigens may still reside in affected areas once the
bacteria have died, but LPS and nucleic acids may still be present
and the reaction, such as synovitis, may be against these antigens
(speculation).
 Classic Reactive Arthritis
Classic reactive arthritis- Clinical
• A. Peripheral arthritis
• 1. Acute onset **asymmetric, oligoarthritis of lower > upper
extremities (esp. knees) or **sacroiliitis/spondylitis. This usually
resolves in 3-5 months, but occasionally lasts chronically (15%).
• B. GU- **urethritis/dysuria is typical. There may also be pelvic
pain, cervicitis, salpingo-oophoritis, prostatitis or cystitis.
• C. Ocular- **conjunctivitis.....less frequently anterior uveitis,
episcleritis and keratitis.
• D. Constitutional- fever, fatigue, malaise or weight loss.
 Classic Reactive Arthritis
Classic reactive arthritis- Clinical
• E. Skin and soft tissue-
• 1. **Keratoderma blennorrhagicum- hyperkeratotic red skin
lesions, waxy nodules, on palms and soles resembling psoriasis.
• 2. **Circinate balanitis- painless erythematous, serpiginous
lesions beginning as vesicles then forming small shallow ulcers on
the glans penis.
• 3. Nail lesions similar to psoriasis
• 4. *Dactylitis- “sausage” fingers and toes.....up to 40% of cases
• 5. *Enthesitis- common, especially in the heel
 Classic Reactive Arthritis
Classic reactive arthritis- Lab (in the face of an antecedent or
concomitant indicator infection).
• A. Elevated ESR/CRP
• B. HLA-B27+ in 30-80%
• C. Joint fluid with high WBC/predominately neutrophils
indicating synovitis
 Classic Reactive Arthritis
Classic reactive arthritis- Treatment
• A. NSAIDs initially.
• B. If fails NSAIDs, then intra-articular or systemic steroids are
given.
• C. DMARDs for refractory cases.
 Post-Streptococcal Reactive Arthritis
Post-Streptococcal Reactive Arthritis- Intro
• A. Immune, reactive scenarios after Strep infections that can occur
***after Group A Streptococcus, and *occasionally after Group C and
Group G Streptococcus, infections. Due to molecular mimicry or
immune complex disease. These include:
• 1. **Acute Rheumatic Fever (ARF)- 10-28 days after pharyngitis,
*see pre-reading primer on ARF......associated with migratory arthritis.
• 2. **Post-Streptococcal Arthritis- 1-10 days after pharyngitis,
associated with non-migratory arthritis.
• 3. Post-Streptococcal Glomerulonephritis- 1-3 weeks after
pharyngitis or 3-6 weeks after skin/soft tissue infection.
• 4. PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders
Associated with Streptococcal infections) 1-4 weeks after pharyngitis.
 Post-Streptococcal Reactive Arthritis
Post-Streptococcal Reactive Arthritis- Clinical
• A. **Non-migratory (*unlike migratory arthritis seen in ARF) acute reactive
arthritis presenting 7-10 days after GAS pharyngitis.....asymmetric in 60-
70%.....50% resolve in 6 weeks.
• B. Has no other Jones criteria for ARF.
• C. Often more severe than that seen in ARF......may have fever.
• D. *Can be either persistent or recurrent, can be additive over time, and can
affect large, small or axial joints (ARF predominately large joints)......usually
mono- or oligoarthritis......sacroiliitis in only 1-2%.....enthesitis/dactylitis in < 1%.
• E. *Bimodal age group spikes....8-14 yo and 21-37 yo (c/w 5-15 for ARF)........I
have seen it in people up to their 80s!
• F. *Minimal response to NSAIDs (unlike ARF that has a good response).
• G. Associated erythema nodosum and erythema multiforme are common
(30%).
 Post-Streptococcal Reactive Arthritis
Post-Streptococcal Reactive Arthritis- Lab
• A. Recent documented GAS infection.
• B. If GAS was suspected but not proven, there may be an
elevated ASO (anti-streptolysin O) or streptozyme titer.
• C. Elevated ESR/CRP.
• D. Leukocytosis common.
• E. HLA-B27+ in only 17%
• F. Caveat- must have no evidence of active septic arthritis or
other autoimmune disease.
 Post-Streptococcal Reactive Arthritis
• Post-Streptococcal Reactive Arthritis- Treatment
A. NSAIDs (slow, less satisfactory than in ARF)
B. Steroids
• C. Prophylaxis against recurrence with antibiotics for >/= 1 year
(c/w ARF, given for >/= 10 years).

• ***monitor closely for 1 year, some may eventually develop

cardiac issues (6% develop mitral valve disease) or other
symptoms/signs to fit them into an ARF or other diagnosis
(autoimmune, Lyme dis, etc).
 Enteropathic Reactive Arthritis
Enteropathic Reactive Arthritis- Intro
• A. Ulcerative colitis and Crohn’s disease (regional enteritis) are the most common IBDs
(inflammatory bowel diseases) associated with arthritis and spondylitis. Of those with
IBD:
• 1. 6-46% have arthritis.
• 2. 1-26% have spondylitis.
• B. Pathogenic pathways leading to this remain to be defined:
1. ? molecular mimicry- immune response to a gut-derived antigen cross-reacts with a
normal host protein (such as in synovium).
2. ? Circulating immune complexes, initiated by an immune response to gut
microbes.
C. Arthritis is more likely to be present in IBD patients with:
1. Large bowel involvement.
2. Those with other extra-intestinal features such as erythema nodosum, stomatitis,
uveitis or pyoderma gangrenosum.
D. 50-75% are HLA-B27+........males = females......happens in both children and adults
with IBD.
 Enteropathic Reactive Arthritis
Enteropathic Reactive Arthritis- Clinical
• A. Associated arthritis-
• 1. Peripheral arthritis-
• a. Type I arthropathy- *acute and *oligoarticular, nonerosive and
often involves large joints such as the *knees.....self-limited, in 90%
lasts under 6 months......*often associated with IBD flares....occurs in
5% of those with IBD.
• b. Type II arthropathy- *polyarticular and nonerosive with MCPs
being the most commonly affected joints, but can involve almost any
joint......half of episodes are migratory......can be recurrent on and off
for years.....*not associated with IBD flares....occurs in 3-4% of those
with IBD.
 Enteropathic Reactive Arthritis
Enteropathic Reactive Arthritis- Clinical
• A. Associated arthritis-
• 2. Spondylitis and sacroiliitis- stiffness and back pain often in
the morning and after rest, made better with exercise. In 4-18% of
those with IBD.
• 3. Enthesitis/dactylitis- in 20% and 4-6% respectively
 Enteropathic Reactive Arthritis
Enteropathic Reactive Arthritis- Lab
• A. IBD patients with arthritis issues are HLA-B27+ 50-75% of the
time.
• B. ESR/CRP are elevated, but tend to be that way anyhow due to
the underlying IBD, so may not be helpful.
• C. Synovial fluid is compatible with synovitis (5-15,000 WBCs,
mostly neutrophils)
 Enteropathic Reactive Arthritis
Enteropathic Reactive Arthritis- Treatment
• A. Steroids
• B. DMARDs
• C. TNF-alpha antagonizing biologics
 Celiac Disease Arthritis
Celiac Disease Arthritis- Intro
• A. Celiac disease ( = gluten enteropathy, celiac sprue) is an autoimmune disease
predominately affecting the small intestine caused by a reaction to gluten (a protein
found in wheat, barley, rye....but not typically in oats). Found in < 1% of the
population, women > men, highest prevalence in Caucasians and found in 10% of
first-degree relatives......can present anywhere from the first year of life until the 9th
decade.
• 1. Path- villous atrophy (shortening of the villi) in the small intestine leading to
steatorrhea (greasy BMs) due to malabsorption......as the bowel gets more damaged a
degree of lactose intolerance may develop.
• 2. Increased risk for lymphoma (RR 4.8-15) and adenocarcinoma of the small
bowel.
• 3. Symptoms- fatigue, anemia, diarrhea, abdominal pain/cramps, bloating (often
confused initially with irritable bowel syndrome), weight loss......*dermatitis
herpetiformis, neuropathy (from vitamin malabsorption) and growth failure can be
seen.
 Celiac Disease Arthritis
Celiac Disease Arthritis- Clinical
• A. Arthritis associated with it 10-20%
• 1. Usually non-erosive
• 2. Peripheral 10%, axial 8% and combined 9% in one
study.....some studies show lower arthritis frequency
• 3. There appears to be increased risk for later development of
JRA and RF+/anti-CCP+ RA.
 Celiac Disease Arthritis
Celiac Disease Arthritis- Diagnosis
• A. Small bowel biopsy
• B. Serology (Can be ordered as a “Celiac Panel”, with many of the following tests, or
they can be ordered separately too)
• 1. Anti-endomysial IgA antibody (sens 85-98% and spec 97-100%)
• 2. Anti-tissue transglutamase IgA antibody (sens 90-98%, spec 97-100%)
• 3. Anti-deamidated gliadin peptide antibody
• a. IgA- sens 94%, spec 99%
• b. IgG- sens 92% and spec 100%
• 4. Anti-gliadin antibody IgA and IgG (sens 85%, spec 85%)

• ****path improves and antibodies resolve on a gluten-free diet.....in patients with IgA
deficiency (3% with Celiac dis) more reliance should be placed on IgG tests.
 Celiac Disease Arthritis
Celiac Disease Arthritis- Treatment
• A. Gluten avoidance, +/- lactose avoidance
• B. NSAIDs
Normal small bowel path L, celiac dis path R (flattening. blunting of villi)
Source: pathologyoutlines.com
Normal small bowel path L, celiac dis path R (flattening. blunting of villi)
Source: pedsinreview.aapublications.org
Normal small bowel path L, celiac dis path R (flattening. blunting of villi)
Source: painepodcast.com
 **Dermatitis herpetiformis should suggest celiac disease (Board”s!), can be chronic or intermittent, flaring after gluten
exposure Source: coeliac.org.uk
Dermatitis herpetiformis vesicles L, post-vesicle breakdown R
Source: coeliac.org.nz
 Adult Still’s Disease
Adult Still’s Disease- Intro
• A. An inflammatory disorder characterized by **daily fevers (a
cause of FUOs), **arthritis/arthralgias and an **evanescent rash
(each in 75-95% of cases)…..originally described by George Still in
1896…..used to describe adults with features similar to JRA, but
who do not fulfill criteria for classic RA.
• B. Etiology- unknown…? Molecular mimicry response to infection
(proposed causes have included genetic pre-disposition,
Mycoplasma pneumoniae, Yersinia enterocolitica, viruses….but no
consistent associations found in studies).
 Adult Still’s Disease
Adult Still’s Disease- Patterns of illness
• A. Patterns:
• 1. Monophasic- (1/3) lasting weeks to months
• 2. Intermittent- (1/3) with complete remissions
• 3. Chronic- (1/3) persistently active disease leading to
destructive arthritis
 Adult Still’s Disease
Adult Still’s Disease- Clinical
• A. **Fever- usually once daily fever spikes (quotidian),
sometimes twice daily (double quotidian)
• B. **Rash- evanescent ***salmon-colored (Boards!) mac/mac-
pap, nonpruritic…..tends to come on with fever and go away with
defervescence. Usually on trunk/extremities….can involve
palms/soles and face. May have a “Koebner phenomenon” where
rash may come on in areas where skin is stroked or in areas of
pressure from tight clothes (beltline, bra strap regions).
 Adult Still’s Disease
Adult Still’s Disease- Clinical
• C. **Arthralgia/arthritis- can evolve over months into a
destructive polyarthritis…knees > wrists (may fuse) > ankles >
elbows > PIPs > shoulders.
• D. Other manifestations:
• 1. Myalgias- without weakness, often worse during fevers
• 2. Pharyngitis- severe, nonsuppurative is common…..may be
associated with cricothyroid perichondritis on MRI
• 3. Liver disease- common to see modest LFT elevations, +/-
hepatomegaly
• 4. Card-pulmonary disease- pericarditis, pleural effusions,
transient pulmonary infiltrates with symptoms of serositis
 Adult Still’s Disease
Adult Still’s Disease- Clinical
• D. Other manifestations:
• 5. Lymphadenopathy- ½, mild, slightly tender, reactive hyperplasia
on histopath
• 6. Splenomegaly- 1/3-1/2
• 7. Macrophage activation syndrome- can be seen in around 12%,
also termed *hemophagocytic lymphohistiocytosis HLH/reactive
hemophagocytic syndrome…..associated sometimes with disease
flares…..may have pancytopenia and very high triglycerides (*on path of
bone marrow or liver RBCs can be seen phagocytized by macrophages)
• 8. GI- abd pain in 50%....nausea, anorexia and weight loss can be
seen
Adult Still’s Disease
Source: periodicfevers.com
Evanescent, salmon-colored rash of Adult Still’s Disease
Source: dermnetnz.org
Evanescent, salmon-colored rash of Adult Still’s Disease
Source: dermnetnz.org
Evanescent, salmon-colored rash of Adult Still’s Disease
Source: dermnetnz.org
Evanescent, salmon-colored rash of Adult Still’s Disease……Koebner phenomenon at left
Source: jmedicalcasereports.biomedcentral.com
Adult Still’s Disease with non-erosive narrowing of carpo-metacarpal and intercarpal joints
Source: hindawi.com
 Adult Still’s Disease
Adult Still’s Disease- Lab
• E. Lab findings:
• 1. **ESR/CRP- marked elevations
• 2. **Ferritin- marked elevations in 70% (hepatocytes reacting to
inflammatory cytokines can increase ferritin synthesis), it is an acute phase
reactant….*on Boards, if they present a febrile patient and give you a super high
ferritin result, then think adult Still’s disease! (ferritin not typically something
checked unless Fe deficiency, iron overload or Still’s disease is suspected)
• 3. *Usually leukocytosis, >/= 15k, *poly predominance……leukopenia with
associated HLH
• 4. *Anemia with Hgb of </= 10 in most patients
• 5. *Increased LFTS and LDH in 75%
• 6. *Positive RF/ANA/CCP in < 10%
• 7. Inflammatory synovial fluid (mean WBC 13k)
• 8. X-rays show non-erosive narrowing (esp c-mc and intercarpal joints)
 Adult Still’s Disease
Adult Still’s Disease- Diagnosis
• F. Diagnosis:
• 1. ***A diagnosis of exclusion!

• **Please see next slide for criteria

Adult Still’s Disease is a diagnosis of exclusion
Source: scielo.br
 Adult Still’s Disease
Adult Still’s Disease- Treatment
• G. Treatment:
• 1. With mild disease NSAIDs can be effective 20% of the time
• 2. Steroids are necessary in most patients
• 3. Otherwise see fow diagram on next slide
Treatment of Adult Still’s Disease
Source: dovepress.com
 Case
ASO titer- 800 units (nl < 200 units)

Dx- Post-Streptococcal Reactive Arthritis

Therapy- Amoxicillin 500 mg po TID x 10 days, then Penicillin VK 500 mg

po BID for 1 year
- No improvement on Naprosyn 500 mg po BID for several days,
but his inflammatory arthritis quickly improved with a Medrol
(Methylprednisolone) dosepak
-No recurrence of illness or development of cardiac abnormality
when followed for the next 2 years
Source: pinterest.com
Source: cheezburger.com
Source: inspirationalweb.org
 Valley of Pain (where you’re walking when you
have arthritis)
• Bonnie Raitt
• Released- 2002
• Album- Silver Lining
• Active- 1971-present
• Genre- Blues rock
• Achievements- 11 Grammys and 16 nominations, inducted into the Rock and
Roll Hall of Fame in 2000. One of Rolling Stone Magazine’s 100 Greatest Singers
and 100 Greatest Guitarists
• First hit- Runaway 1977
• Other hits: Thing Called Love, Have A Heart, Something to Talk About, I Can’t
Make You Love Me, Angel From Montgomery, Love Me Like A Man, Nick of
Time, Love Has No Pride, Runaway, Not the Only One, Love Sneakin’ Up On You,
Source: discogs.com