Rhematologic Disorders of MSK Flashcards
What is a rheumatologist disorder? Basic concepts.
Rheumatology is the study of inflammatory disorders of the connecAve Assues • ConnecAve Assue – Skin, tendons, ligaments, bones, blood vessels, muscle, joints • Over 140 disorders • Most common presentaAons include disorders of the musculoskeletal system
Joints/bones: Arthralgia, ArthriAs
– Tendons, ligaments: TendoniAs/bursiAs
– Muscle: Myalgia, MyosiAs
Systemic problem
what comprises the MSK system?
.
RA definition
Definition – symmetric inflammatory peripheral
polyarthriAs characterized by destrucAon of joints
through erosion of carAlage and bone.
• Most common inflammatory arthriAs
– 1% of the populaAon
– 2:1 female to male raAo
– Peak incidence between ages 40 to 60
• Onset usually insidious over months.
Cause is not known
– Complex interacAon between genes and
environment
– Breakdown of immune tolerance and synovial
inflammaAon
How is rheumatoid arthritis treated?
Early treatment with a disease modifying drug is
standard of care
• Non-disease modifying
– NSAIDs
– Prednisone
• Disease modifying
– Methotrexate
– Hydroxychloroquine
– Sulfasalazine, leflunomide
– Biological agents: TNF-alpha blockers, abatacept, rituximab,
and tocilizumab.
Goal of treatment is clinical remission if possible
• Control of disease prevents bone erosions and
subsequent deformity and loss of funcAon
• All disease modifying drugs are
immunosuppressive and have side effects
• Joint arthroplasty for end-stage disease
Spondylarthropathies
Ankylosing SpondyliAs
- PsoriaAc ArthriAs
- Enteropathic ArthriAs and ReacAve ArthriAs
- UndifferenAated.
How is spondyloarthropathy treated?
.
How does crystalline arthropathy present?
.
how is crystalline arthropathy treated?
.
how to myositis treated?
.
How does myositis present?
.
How does relapsing polychondritis/PMR/CTD present.
.
How is relapsing polycrodritis/PRM/CTD treated
Case 1: 60 y/o woman presents for the first time with sudden onset of severe bilateral shoulder pain with difficulty moving her arm. She also complains of bilateral hip pain and sever stiffness. so stiff she cannot get out of bed w/o assistance. Fatigue, tiredness, overall not well. Controlled long term diabetes.
Systemic- shoulders and hips, overall fatigue
Case 2: 55 y/o M c/o sever r knee pain. Getting bilateral knee pain intermittently for past 5 yers. stiffness in the morning. lately right knee pain is worse. pain up and down stairs. smoker. hx of HTN.
Systemic or not systemic
non systemic
Case 3: 38 y/o F, stiff all over body, thought it was b/c of exercise but hands are especially stiff. takes 1.5 hours before they feel better. swelling in a few of her joints. relatively tired, hard to concentrate and type.
Systemic or not systemic
systemic
DD: RA
osteoarthritis most commonly in the …
inflammatory or not inflammatory?
Knees
also in hips
non-inflammatory
osteoarthritis most commonly in the …
inflammatory or not inflammatory?
What joints of the hands?
Knees
also in hips
non-inflammatory
PIP and first CMC joint
x-ray features: join stays
extra bones - burst
suchondral sclerosis
Osteoarthritis.
OA is a progressive disease represenAng the failed
repair of joint damage that, in the preponderance of
cases, has been triggered by abnormal intra-arAcular
stress.
• All of the Assues of the joint are involved, including
the arAcular carAlage, subchondral bone, ligaments,
menisci (when present), periarAcular muscles and
peripheral nerves.
• OA may be iniAated by an abnormality in any of
these Assues. Thus, OA is not a disease merely of
carAlage but is a failure of the synovial joint.
Osteoarthritis findings (epi)
Most common type of arthriAs
– OA of the knee, hand, or hip have a similar prevalence of
~20-30% of adults
– More than half of individuals over age 55 have
radiographic evidence, goes up to 90% at age 70
– Slight female predominance in older age, but both sexes
affected
OsteoarthriAs: Classification
Idiopathic
– Localized
– Generalized (3 or more sites)
• Secondary
– Trauma, congenital, crystalline arthropathy,
osteonecrosis, inflammatory arthriAs, sepAc
arthriAs, Paget’s disease, Diabetes, Charcot/
neuropathic arthropathy, hypothyroidism,
acromegaly, frostbite
Damage to normal arAcular carAlage by physical forces
(can be single events of macrotrauma or repeated
microtrauma)
– Chondrocytes react to this injury by releasing degradaAve
enzymes
– inadequate repair responses
• Fundamentally defecAve carAlage fails under normal
joint loading, thereby leading to osteoarthriAs.
– type II collagen gene defect
– ochronoAc carAlage that fails because of deleterious
pigment deposiAon
Osteoarthritis: diagnosis
History is important – gradual onset of symptoms,
lack of inflammaAon, someAmes history of prior
injury or overuse or other secondary trigger
• Physical exam – crepitance, hypertrophic changes,
lack of erythema or warmth, usually not much
tenderness
• X-ray will confirm diagnosis – asymmetric joint space
narrowing, sclerosis near the joint line, and spurring
are characterisAc
Osteoarthritis nodes - hands
Heberden’s nodes - DIP joint bony nodules
- Bouchard’s nodes - PIP joint bony nodules
- Both “nodes” are diagnosAc for hand OA
– 10 Ames more common in women than men,
and have a strong geneAc component
Base of thumb :1st CMC
joint
– Very commonly affected
• Treatment
– NSAIDs or Tylenol
– CorAcosteroid injecAons
parAcularly for base of
thumb
– Rarely ever surgery
Genetic factors for RA
GeneAc factors clearly important
– HLA “shared epitope” is strongest risk factor
– Non-HLA genes such as PTPN22, STAT4, TNFAIP3
• Environmental factors
– Cigareoe smoking increases both risk of disease
and severity of disease
RA Diagnosis
Symmetric pain and swelling in small joints of
hands, wrists, feet, ankles most common,
followed by knees, elbows, shoulders
– Morning sAffness – beoer with acAvity
– ConsAtuAonal symptoms – faAgue, even
weight loss are common, but fever is VERY
RARE
– Steady, progressive, addiAve onset is most
common presentaAon
Rheumatoid ArthriAs
Extra-arAcular features
Rheumatoid nodules
- Pleural effusions
- Atherosclerosis
- ScleriAs
- Rheumatoid vasculiAs (rare)
- Felty’s syndrome (neutropenia,
splenomegaly, recurrent infecAon)
RA presentation
High ESR or CRP common but not required
• Rheumatoid factor posiAve in about 50%
– RF usually indicates more severe disease, greater likelihood
of extra-arAcular manifestaAons
• AnA-CCP anAbodies
– Found in about 50% of paAents without much overlap with
rheumatoid factor
– Highly sensiAve – posiAve test almost always indicates
disease (>90% specificity for RA, even in mixed autoimmune
cohorts)
– So can “rule in”, but low sensiAvity prevents “rule out”
Classical findings of inflammatory arthriAs:
– PeriarAcular joint erosions
– PeriarAcular osteopenia
– Symmetric joint space narrowing
• Note that each of these is the opposite of OA!!
– Erosions instead of spurs
– Osteopenia instead of sclerosis
– Symmetric instead of asymmetric joint narrowing
Spondyloarthropathy
DefiniAon and Prevalence
Group of inflammatory condiAons affecAng the
axial skeleton (spine, pelvis)
– May also demonstrate asymmetric oligoarthriAs and
enthesiAs (inflammaAon of tendon inserAons)
- Prevalence about 1 per 1000 in US
- Ankylosing spondyliAs is characterized by a 3:1
male to female raAo
Spondylarthropathies
Paoerns of Disease
Inflammatory spinal involvement is typical
– differenAates from other arthriAdes
• EnthesiAs or inflammaAon of tendon
inserAons is classical
• Asymmetric oligoarthriAs is typical paoern of
peripheral joint arthriAs
Extra-arAcular ManifestaAons- spondylar..
Eye involvement (uveiAs) is common
- AorAAs with valvular insufficiency
- Apical lung fibrosis
- IgA nephropathy
- Secondary Amyloidosis
Ankylosing SpondyliAs
Symptoms are inflammatory back pain
• Can also affect hips and shoulders, rare to affect more
distal joints
- HLA-B27 in 90% of European ancestry
- Diagnosis – SacroiliiAs and anklyosis on X-ray
- Treatment – NSAIDs for mild disease, TNF-blockers,
IL17A inhibitors, JAKi
X-ray of sacroiliiAs
Ankylosing spondyliAs: lumbar vertebrae,
bamboo spine
PsoriaAc ArthriAs
ACR Image
PsoriaAc ArthriAs
A subset of paAents with psoriasis (5-7%) have psoriaAc
arthriAs
– Inflammatory spine disease
– Peripheral arthriAs
• Diagnosis
– Underlying psoriasis
– X-rays show erosive joint disease with destrucAve changes
such as “pencil-in-cup”
• Treatment - Steroids may result in flare of skin disease
when tapered, methotrexate and sulfasalazine
common, TNF-blockers, IL17 inhibitors, Il12/23
inhibitors
Enteropathic ArthriAs
SpondyloarthriAs associated with inflammatory
bowel disease
– Spine
– Peripheral joints: Type 1 and 2 arthriAs
– Therapy for IBD may work for arthriAs
– TNF alpha inhibitors, Il12/23 inhibitors
ReacAve ArthriAs
•
Spondylarthropathy following GI or GU
infecAon
- May have associated peripheral arthriAs
- Onen self-limited
– Can either be recurrent or persistent
– Classic triad: uveiAs, arthriAs, urethriAs
Reactive Arthritis
Crystalline Arthropathies- types
Gout
• Calcium pyrophosphate deposiAon disease
Gout
Gout is a heterogeneous group of diseases resulAng
from monosodium urate (MSU) crystal deposiAon in
Assues or from supersaturaAon of uric acid in
extracellular fluids
The metabolic disorder underlying gout is
hyperuricemia, defined as serum uric acid >2
SD above the mean
(> 7.0 mg/dL for men, > 6.0 for women)
• AsymptomaAc hyperuricemia in the absence
of gout is not a disease
Clinical manifestations gout
Acute Gout
- Chronic tophaceous gout
- Uric acid calculi, nephrolithiasis
- IntersAAal nephropathy with renal funcAon
impairment, called gouty nephropathy
Pathogenesis- gout
Uric acid is the normal end product of the
degradaAon of purine compounds:
5-Phosphoribosyl-1-pyrophosphate (PRPP) +
Glutamine to
5-Phosphoribosyl-1- amine
using PRPP synthetase
salvage pathway -gout
pathogenesis gout cont
Pathoegensis -gout explanation
Limit of solubility of MSU in plasma is 6.7 mg/dL
(normal, 5.1 in men; 4.0 in women)
• In humans, hyperuricemia and gout is consequence
of species wide lack of uricase i.e. uric acid is end
product of purine metabolism, rather than allantoin
• Major route of uric acid disposal is renal excreAon
(2/3); bacterial oxidaAon in gut (1/3)
Acute gouty arthriAs is triggered
Acute gouty arthriAs is triggered by the
supersaturaAon and precipitaAon of MSU crystals in
Assue i.e. joint
• Precise mechanism not known…
– Involves phagocytosis of crystals by neutrophils
– AccumulaAon of chemotacAc factors and cytokines (IL-1,
-6 and TNF), prostaglandins, leukotrienes and oxygen
radicals, acAvaAon of complement and lysosomal enzyme
release
• Why acute aoacks are self-limited also unclear.
Clinical ManifestaDons - gout
AsymptomaAc hyperuricemia
• Acute gouty arthriAs
-early episodes monarAcular, abrupt onset,
occur at night or early morning
- exquisite pain, erythema, swelling
- periarAcular pain, gouty celluliAs
- 1st MTP = podagra, instep, ankles, heels,
knees, wrists, fingers and elbows
-non-arAcular sites- olecranon bursa, Achilles
Chronic tophaceous gout
Aner 10 or more years of acute gout
– IntercriAcal periods not pain free
– Persistent pain, swelling deformiAes
– Bony erosions and joint destrucAon
– May be confused with Rh. ArthriAs
Diagnosis- gout
RecogniAon of Needle-shaped, NegaAvely
birefringent, moNosodium urate crystals present in
leukocytes or tophi
- Use of compensated polarizing light microscopy
- Crystals not always idenAfied, parAcularly if late in
aoack
• PresumpAve diagnosis made by signs and locaAon of
aoack, duraAon and presence of hyperuricemia
• N.B. Uric acid levels may be normal during aoackcheck
aner resoluAon of aoack
gout microscopy
Gout -diagnosis
Radiographic erosions typical of gout may be
suggesAve i.e. “rat bite”
• Synovial fluid is inflammatory i.e. 10-100,000
cells/mm3, but not specific
• Bacterial infecAons can co-exist with gout:
always send fluid for gram stain and culture
Treatment- gout
AsymptomaAc Hyperuricemia
-Usually not treated
• Acute Gouty ArthriAs
– NSAID’s
– Intra-arAcular steroid for 1-2 joints
– Systemic steroids (prednisone over 10-14 days)
– Colchicine used classically, but a toxic drug
- Must use early in the aoack
- Very effecAve as a prophylacAc agent - 0.6mg bid
Chronic (tophaceous) Gout
– frequent aoacks > 2-3 aoacks/year
– chronic gouty arthriAs with erosions
• Xanthine oxidase inhibitors: Allopurinol,
Febuxostat
- Uricase: PegloAcase (Krystexxa)
- Colchicine
- With compliance, and UA <6.0mg/dl, may
prevent aoacks, and tophi should resolve
Calcium Pyrophosphate Dihydrate
DeposiDon Disease
Calcium salt (Ca2P2O2-2H20) deposited in
carAlage (chondrocalcinosis on radiograph)
• CPPD released into joint, causing acute painful
arthriAs, called pseudogout
• Chondrocalcinosis occurs most commonly in
wrists, knees and shoulders
• Most chondrocalcinosis is asymptomaAc
Acute arthriAs/ pseudogout/ pseudo-rheumatoid
arthriAs can occur without chondrocalcinosis
• Rhomboid-shaped, weakly PosiAvely birefringent
Pyrophosphate crystals
– must rule out sepAc arthriAs
• Hyperparathyroidism, hemochromatosis, familial
form and aging
• NSAID’s, intra-arAcular or systemic steroids,
colchicine (acutely or prophylacAcally)
MYALGIA/MYOSITIS
Viral infecAons
- DermatomyosisAs/PolymyosiAs
- Polymyalgia rheumaAca
Inflammatory MyosiAs
•
DermatomyosiAs (DM) and polymyosiAs (PM)
are idiopathic inflammatory myopathies
– Proximal skeletal muscle weakness
– Muscle inflammaAon
• Incidence: 2 per 100,000 annually in the general
populaAon
- F:M raAo of 2:1
- Peak incidence in adults occurs between the
ages of 40 and 50].
DermatomyosiAs
Gooren’s Papules
Inflammatory MyosiAs
•
Proximal muscle weakness
- Cutaneous manifestaAons in dermatomyosiAs
- Other manifestaAons:
– IntersAAal pulmonary disease, Dysphagia,
PolyarthriAs, Raynaud’s phenomenon
– May overlap with other systemic rheumaAc disease
• Treatment:
– GlucocorAcoids
– Steroid sparing therapy: Methotrexate/ Azathioprine
Polymyalgia RheumaAca
Polymyalgia rheumaAca (PMR) is an
inflammatory rheumaAc condiAon characterized
by aching and morning sAffness in the shoulders,
hip girdle, and neck
• May be associated with giant cell (temporal)
arteriAs (GCA)
– The 2 disorders may represent different
manifestaAons of a shared disease process
- Affects adults > 50 yrs
- Prevalence increases with age
Cause is unknown
– Environmental and geneAc factors play a role
• Subacute or chronic onset of aching and
morning sAffness in the shoulders, hip girdles,
neck, and torso in paAents over the age of 50
- The diagnosis is made clinically
- PaAents will typically have an elevated ESR
>40mmHr
• Treatment: oral steroids
Relapsing PolychondriAs
Systemic inflammatory disorder
– CarAlage involvement –nose, ear, costal, tracheal
– Eyes, cardiovascular, renal and nervous system
involvement
• GeneAc predisposiAon, exposure of carAlage
(immune privileged Assue)
• Rare disease, can occur in all ages, sexes etc
Relapsing PolychondriAs
Relapsing PolychondriAs- treatment
NSAIDS
- Steroids
- DMARDs – Methotrexate
- Cyclophosphamide
