Rheumatology

Dr Arif Rahim Khan

Associate Professor
Nishtar medical university
and hospital Multan
Polyarthritis
Osteoarthritis

Inflammatory arthritis
◦ Rheumatoid arthritis
◦ Systemic Lupus Erythmatosis (SLE)
◦ Rheumatic fever
◦ Spondylarthritis (Ankylosing spondylitis)
◦ Crystal arthritis (Gout)
◦ Gonococcal arthritis
◦ Psoriatic arthritis
◦ Enteropathic arthritis
◦ Reiter’s syndrome
Monoarthritis
Osteoarthritis

Tuberculous arthritis
Pyogenic arthritis
Gonococcal arthritis
Gouty arthritis
Pseudogout
Neuropathic arthritis
RHEUMATOID
ARTHRITIS

A chronic, inflammatory, multisystem

disease of unknown etiology
characterized by symmetric peripheral
polyarthritis.
Epidemiology

It affects .5-1% of population.

It has a world wide distribution.
Prevalence is lowest in black
Africans and Chinese people.
Female to male ratio is 2-3:1.
It can present from early
childhood to late old age.
Most common age of onset is 25-
55 years.
Juvenile rheumatoid arthritis
involves inflammation and
stiffness for more then 6 weeks
under 16 years.
Aetiology and
Pathogenesis
The cause is multifactorial and a
complex interplay of genetic,
environmental and immunologic factors
play a role.

Genetic factors:
◦ There is increased incidence in first degree
relatives (2 – 10 times).
◦ High concordance among monozygotic twins
upto 15% and dizygotic twins 3.5%.
◦ There is strong association with certain HLA
haplotypes; HLA DR4, HLA DRB1.
Environmental factors:
◦ Smoking (relative risk is 1.5 – 3 times)
◦ Infectious agents (EBV, CMV, parvo
virus, mycoplasma) have been found
in the synovial fluid).

Immunologic factors:
◦ Autoantibodies like rheumatoid factor
and anti citrullinated peptide are
found in the sera of patients.
Rheumatoid factor(RF) and anti-
citrullinated peptide (ACPAs)
antibodies.
◦ RF are circulating autoantibodies
(usually of IgM type) that have Fc
portion of IgG as their antigen.
◦ The term seronegative RA is used for
patients with persistently –ve test for
RA.

◦ ACPA are antibodies against

deaminted peptides.
Genetic,environmental and
immunologic factors produce
dysregulation of the immune
system.

What is the initial trigger and

precise event that disrupts the
immunity remains a mystery.
Pathology
 Chronic synovitis

 Formation of a pannus

 Erosions
of bones, cartilage, ligaments
and tendons

 Fibrousankylosis
 Bony ankylosis in late stages
 osteoporosis
Clinical Features
Onset
◦ Slowly progressive, symmetric
peripheral arthritis (70%)
◦ Acute with florid morning stiffness,
polyarthritis (15%)
◦ Palindromic/relapsing remitting,
usually monoarthritis, lasting for
hours to days(5%)
Symptoms
Pain and joint swelling
Morning stiffness lasting more
than one hour
Systemic systems and extra
articular features may also occur.
Typically small joints of hands,
feet, wrists
Large joint involvement may also
occur
Cervical spine may be involved
but thoracic and lumber spine are
not affected.
 Examination
Symmetric swelling of PIP and MCP
(spindle shaped fingers)
Tender and warm on palpation
There is muscle wasting
Erythema is absent
Pain on passive movement
Characteristic deformities with
long standing uncontrolled disease
(due to destruction of joints and
soft tissue). Less common now
with aggressive treatment.

◦ Swan neck deformity - fixed

hyperextension of PIP + flexion of DIP
◦ Boutonniere deformity - fixed
flexion of PIP + hyperextension of DIP
◦ Z deformity of thumb - subluxation
of 1st MCP + hyperextension of 1st IP
◦ Ulnar deviation of fingers
◦ Palmer subluxation of MCPs
◦ Hammer toe deformity
◦ Cock up toe deformity – dorsal
subluxation MT
◦ Flat foot – loss of longitudnal arch of
foot
Clinical course
◦ Persistent and progressive activity
that waxes and wanes
◦ Intermittent and recurrent attacks
◦ Spontaneous remission occurs in10%
cases.
◦ Rarely the process may cease (burnt-
out RA)
Extra articular features
More common in long standing,
erosive and seropositive disease.

Systemic
◦ Fever
◦ Anorexia, weight loss
◦ Fatigue
◦ Susceptibility to infections
Musculoskeletal
◦ Muscle wasting
◦ Osteoporosis
◦ Tenosynovitis, bursitis
◦ Baker’s cyst
Hematological
◦ Anemia (most common)
◦ Thrombocytosis
◦ Eosinophilia

Lymphatic
◦ Felty’s syndrome (neutropenia,
splenomegaly, RA)
◦ Splenomegaly
◦
Ocular
◦ Episcleritis, scleritis
◦ Keratoconjunctivitis sicca (dry eyes)
◦ Scleromalacia
Vasculitis(in long standing
disease)
◦ Digital arteritis-infarcts
◦ Ulcers
◦ Pyoderma gangrenosum
Cardiac
◦ Pericarditis, pericardial effusion
(most common)
◦ Myocarditis
◦ Endocarditis
Pulmonary
◦ Pleurisy
◦ Pleural effusions (most common)
 Exudative with monocytes and
neutrophills
◦ ILD - Fibrosing alveolitis UIP
◦ Bronchiolitis
◦ Caplan’s syndrome (rheumatoid
nodules + pneumoconiosis)
Neurological
◦ Cervical cord compression due to
atlantoaxial subluxation
◦ Entrapment neuropathy
 Median nerve entrapment at wrist – carpal
tunnel syndrome
 Ulnar nerve compression at elbow
 Posterior tibial nerve entrapment at ankle
– tarsal tunnel syndrome
◦ Peripheral neuropathy
◦ Mononeuritis multiplex
Subcutaneous nodules
◦ Firm and non tender,
◦ develop on areas subject to repeated
trauma (forearm, sacrum, achilles
tendon)
◦ occur in 30-40% cases in patients
with active disease.
◦ consist of a central area of fibrinoid
necrosis surrounded by a palisade of
mononuclear cells.
◦ may get complicated with ulceration
and secondary infection.
Amyloidosis Nephrotic
syndrome
Investigations

Diagnosis of RA is based on
clinical grounds but
investigations are useful in
confirming the diagnosis and
assessing the disease activity
ESRand CRP are usually raised.
Anemia and thrombocytosis
RA factor
◦ Found in 75-80 % cases called
seropositive arthritis.
◦ Specificity is 50%.
◦ It is present in other autoimmune
diseases, chronic infections and also
in some normal individuals.
Anti CCP antibodies
◦ 95% specificity
◦ 70% sensitivity

ANA is found in 20% cases.

Synovial fluid analysis
◦ Fluid is turbid with low viscosity
◦ Cell count ranges from 5000-
50,000/µL
◦ Cells are mostly polymorphonuclear
leucocytes.
Radiological findings
Plain X-ray
◦ Soft tissue swelling
◦ Symmetric narrowing of joint space
◦ Periarticular osteoporosis
◦ Subcortical bony erosions

USG
MRI (more sensitive)
Approach Considerations for
Rheumatoid Arthritis
• Diagnosis Overview:
• No single test is pathognomonic for RA.
• Diagnosis relies on clinical,
laboratory, and imaging features.
• ACR and EULAR established criteria for
RA diagnosis.
• Disease activity assessed through
patient reports, clinician evaluations,
and laboratory findings.
• Treat-to-target approach for
managing RA activity.
Laboratory Studies in RA
Diagnosis
Markers of Inflammation:
ESR (Erythrocyte Sedimentation
Rate)C-reactive protein (CRP):
Correlates with disease activity
and radiographic progression.
• Hematologic Parameters:CBC:
Anemia of chronic disease,
thrombocytosis, and leukocytosis
may indicate disease activity.
• Thrombocytopenia and
Leukopenia: Rare adverse
events of therapy or part of Felty
syndrome.
• Immunologic Parameters:
• Rheumatoid Factor (RF): Present
in 60-80% of RA patients, associated
with radiographic progression.
• Anti-CCP Antibodies: Highly
specific and sensitive for RA,
especially in early disease.
 Immunologic Parameters in RA
• Rheumatoid Factor (RF):
• IgM antibody targeting Fc fragment of IgG.
• Non-specific: also present in infections, other
autoimmune disorders, and some healthy individuals.
• Predicts progression of bone erosions in RA.
• Antinuclear Antibodies (ANA):
• Positive in about 40% of RA patients.
• Negative for most nuclear antigen subsets.
• Anti-Citrullinated Protein Antibody (ACPA /
Anti-CCP):
• Used for RA diagnosis, sensitive and specific.
• ACPA-positive patients tend to have a more erosive
disease course.
Considerations in Special Populations

• RA in Pregnancy:
• RA often goes into remission during
pregnancy.
• RF levels do not predict outcomes
during pregnancy.
• ESR values are not reliable in
pregnancy due to physiological
changes.
2010 ACR/EULAR Classification
Criteria for RA
Patients to be tested:
At least 1 joint with definite
clinical synovitis. Synovitis should
not be explained by other
diseases (e.g., lupus, psoriatic
arthritis, gout).
A score-based system based on
four factors:
Joint involvement, Serology
results, Acute-phase reactants,
Joint Involvement in RA
Classification

•Points Allocation:
•1 large joint = 0 points
•2-10 large joints = 1 point
•1-3 small joints = 2 points
•4-10 small joints = 3 points
•More than 10 joints (at least 1 small) = 5 points
•Large joints: Shoulders, elbows, hips, knees, ankles.
•Small joints: MCP, PIP, wrist, thumb IP, and MTP joints.
Serology in RA
Classification
• At least 1 serology test result is required:
• Negative RF and anti-CCP = 0 points
• Low-positive RF or low-positive anti-CCP
= 2 points
• High-positive RF or high-positive anti-CCP
= 3 points
• Low-positive: IU values > ULN but ≤ 3x
ULN.
• High-positive: IU values > 3x ULN.
• If RF is reported only as positive/negative,
consider a positive result as low-positive
RF.
•Acute-phase reactants:
•Abnormal CRP or ESR = 1 point.
•Normal CRP and ESR = 0 points.
•Symptom duration:
•≥6 weeks = 1 point.
•<6 weeks = 0 points.
Scoring and Diagnosis
of RA
• Total Score: Maximum score = 10
points.
• Patients with a score of 6 or higher are
classified as having definite RA.
• Key Points:
• Early detection and accurate
classification are critical for optimal
patient management.
• Focus on joint involvement,
serology, inflammation markers,
and symptom duration.
 ACR/EULAR criteria for RA
 Joints affected
◦ 1large joint
◦ 2-10 large joints ◦ 0
◦ 1-3 small joints ◦ 1
◦ 4-10 small joints ◦ 2
 ◦ 5
Serology
◦ Negative RF and ACPA
◦ 0
◦ Low positve RF and ACPA
◦ 2
◦ High positive RF and ACPA
◦ 3
 Duration of symptoms
◦ < 6 weeks
◦ > 6 weeks ◦ 0
 Acute phase reactants ◦ 1
◦ Normal ESR and CRP
◦ Abnormal ESR and CRP ◦ 0
◦ 1
Patients with a score of ≥ 6 are considered to have definite
RA
Morbidity and Mortality
 40% of RA patients are disabled
within 3 years of onset, 80% are
disabled within 20 years.
Mortality rate is two times greater
than in general population.
Ischemic heart disease and infection
are the most common causes of
death.
Median life expectancy is reduced
by 8-15 years.
Poor Prognostic Features
Female gender
Low socioeconomic status
Low education
Disability at presentation
Involvement of MTP joints
Smoking
Positive RF or ACPA
Radiographic damage at presentation
Chronic steroid use
DAS 28
No of tender joints
No of swollen joints
ESR or CRP
Patient global health assessment
• > 5.1 active disease

• < 3.2 low disease

activity

• < 2.6 remission

Management
DRUGS
◦ Non steroidal antiinflammatory drugs
(NSAIDs)
◦ Glucocorticoids
◦ Conventional DMARDs
◦ Biological DMARDs
Main stay of treatment is early
use of small molecule disease-
modifying antirheumatic drugs
(DMARDs) and corticosteroids for
induction of remission.

Early use of DMARDs improves

the clinical outcome.
Non steroidal anti-inflammatory
drugs

Analgesic and anti-inflammatory

effects effects
Side effects: gastritis, peptic
ulcer, renal impairment
Corticosteroids

Control the disease before the

onset of action of DMARDs which
can take several weeks or
months.
Regimes:
◦ Low dose (5-10 mg daily) for 6-24
months slows the progression of
disease
◦ 60 mg daily and then stop gradually
over 3 months.
◦ Intramuscular dopot injections
◦ Intraarticular injections in
oligoarthritis
Side effect: osteoporosis
DMARDs
They are so named because they
slow or prevent the structural
progression.

Delayed onset of action of 6-12

months
Methotrexate is of first choice,
usually well tolerated and onset
of action 1-2 months.
HCQ is used for early and mild
disease.
Gold, Penicillamine and
Ciclosporin are sparingly used
now due to less efficacy and toxic
effects.
 COMMONLY USED DMARDS IN RA

Drug Mechanism Maintenance Side effects Monitorin

of action dose g

Methotrexate Inhibit DNA 5-25 mg/week GI upset, FBC, LFTs

synthesis stomatitis,
hepatotoxicity,
rash, pneumonitis

Sulfasalazine Unknown 2-4 gm/day GI upset, rash, FBC, LFTs

hepatitis,
neutropenia

Hydroxychlor Unknown 200-400 Rash, Corneal Visual

oquine mg/day deposits, acuity,
retinopathy fundoscop
y
Leflunomide Blocks T cell 10 20 mg/day Hepatitis, FBC, LFTs
division hypertension, GI
upset, rash,
alopecia
Biologic therapy
(biologics)
Anti TNF therapy (first line)

◦ Infliximab
Expensive
◦ Etanercept
TNF blockade can
◦ Adalimumab cause serious
◦ Cetrolizumab infections,
reactivation of
◦ Golimumab latent TB,
malignancies like
lymphoma, basal
cell carcinoma
Rituximab (monoclonal Ab
abainst CD20)
Abatacept (fusion protein that
inhibits T cell stimulation)
Tocilizumab (IL-6 receptor
antagonist)
Anakinra (IL-1receptor
antagonist)
Janus Kinase (JAK) Inhibitors
◦ Alternate to biologics
◦ For severe RA resistant to
methotrexate

 Tofacitinib
 Baricitinib
Non pharmacological measure
◦ Adequate rest when active arthritis
◦ Exercise/physiotherapy
◦ Psychological support

Surgery
◦ Synovectomy
◦ Arthroplasty
◦ Joint replacement
Follow-Up Criteria for
Rheumatoid Arthritis Patients

•Frequency of Follow-Ups:
•Every 1-3 months during active
disease or treatment adjustments.
•Every 3-6 months during stable
disease.
•More frequent visits if symptoms
worsen or medication changes are
made.
Goals of Follow-Up:

•Monitor disease activity (joint pain,

swelling, stiffness).
•Assess treatment efficacy (response
to DMARDs, biologics).
•Track functional status (mobility, daily
activities).
•Prevent disease progression (joint
deformities, damage).
Follow-Up Investigations in RA
Patients
•Clinical Assessment:
•Joint examination for swelling, tenderness,
and range of motion.
•Patient-reported outcomes (pain, fatigue,
functional limitations).
•Laboratory Monitoring:
•ESR/CRP to assess inflammation levels.
•CBC and liver function tests (monitor
DMARD/biologic therapy side effects).
•Kidney function and lipid profile (monitor
complications of long-term treatment).
Follow-Up Investigations in RA
Patients

•Imaging:
•Periodic X-rays, ultrasound, or MRI to evaluate
joint damage or erosion progression.
•Adjustments in Therapy:
•Modify treatment based on disease activity and
side effects.
•Consider switching or adding DMARDs/biologics
if remission or low disease activity isn't
achieved.
Thank You