Alexandria Rheumatology

abir ali
Faculty of Medicine
Alexandria University
Internal
Medicine
Department
2022
Internal Medicine Book

Part I
Internal Medicine Notes – Part I

Head of Internal Medicine Department

Prof Dr Eman Yousef
Editors
Prof Dr Eman Al-Guohary
Prof Dr Abeer Abd-Elaaty

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CHAPTER 1
Rheumatology
By
Staff members of Rheumatology Unit

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Classification of Rheumatic Diseases
o There are between 100-150 rheumatic disease varieties
o The term rheumatism is a layperson term describing joint pain and
stiffness and not specifically rheumatic disorders.
o When describing the rheumatic disorders both inflammatory and non-
inflammatory forms may be included.
o Rheumatic disorders have two forms:
 Non-inflammatory
– Articular: such as osteoarthritis
– Non-articular: affect soft tissues or muscles and lead to pain
syndromes, i.e. Fibromylagia
 Inflammatory disorders affecting joints, muscles, bones, and
vessels.
– Affecting mainly the joints: rheumatoid arthritis, spondylitis, PsA….
etc.
– Affecting mainly muscles: as inflammatory myopathies
– Affecting mainly vessels: as Vasculitis

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Inflammatory rheumatic diseases: such as
o Rheumatoid Arthritis (RA)
o Systemic lupus erythematosus (SLE)
o Seronegative Spondylarthritides (SpA)
o Systemic Sclerosis (SSc)
o Sjögren’s syndrome (Sjs)
o Inflammatory Myopathies: Dermatomyositis & polymyositis (DM & PM)
o Juvenile idiopathic arthritis (JIA) is a form of rheumatoid arthritis that
affects children under the age of 16.
o Vasculitis
Non-inflammatory rheumatic diseases

o Osteoarthritis that may affect the major joints including hips, knees
and hands.
o Degenerative disease of the spine that affect the neck, back and
lumbar spine.
o Fibromyalgia syndrome or regional pain syndromes.
Approach to patient with Arthritis

We have to answer these points
 Articular or systemic
 Articular or periarticular
 Acute or chronic
 Inflammatory or non-inflammatory
 Pattern of articular involvement:
o Mono, oligo, or poly-articular
o Peripheral or axial
o Small or large joints
o Symmetrical or asymmetrical

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Some Rheumatology terms
Arthralgia = joint pain (subjective)
Arthritis = joint inflammation = tenderness, swelling, and/or stiffness
Periarthritis = inflammation of the periarticular structures
Dactylitis = (sausage digit), is a combination of synovitis, enthesitis,
tenosynovitis and soft tissue swelling.
Enthesitis = inflammation of entheses (the sites of attachment of tendons,
ligaments, fascia or joint capsules to bone
Morning stiffness = Slowness or difficulty moving the joints when getting
out of bed or after staying in one position too long, which gets better with
movement.
The duration of morning stiffness is a good indicator of disease activity,
and physicians should record this value as part of the clinical assessment.
The longer the duration of the stiffness, the more severe the inflammation
(≥ one hour is significant for inflammatory diseases).
Many patients take a hot shower to relieve the sensation.
Due to accumulation of pro-inflammatory cytokine, interleukin (IL-1, IL-6,
TNF) at site of inflammation(joints).
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Referred pain
o The most common sites of musculoskeletal pain of visceral origin
o Denotes symptoms felt at a distance from their
anatomical origin.
o Very wide, ill-defined area of pain.
o Accompanied by other more suggestive symptoms.
Not affected by joint movement
Rheumatology’s Golden Rules

 In acute Inflammatory monoarticular arthritis we MUST have joint
aspiration to rule out septic and/or crystalline arthropathy.
 Facts regarding RF
o Not all pts with (+) RF have RA
o A negative RF does not exclude the diagnosis of RA.
o RA patients with high RF titer tend to have more severe disease
(it has a prognostic value).
o Has Poor correlation with disease activity.
o No need to repeatedly measure RF to assess disease activity.
 Not all pts with (+) ANA have SLE

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Pathogenesis of most of autoimmune diseases

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Spondyloarthritis
Spondyloarthropathies
Group of disorders, with shared articular, extra-articular, and genetic
features.
Strong predeliction to spine, especially SI joints, often associated with HLA
B27, negative for RF, familial tendency and more common in White people.
Seronegative Spondyloarthropathy: a misnomer!!
 Historically, these disorders were thought to be “variants” of rheumatoid
arthritis, hence the term “seronegative”
SpA definition: A group of inflammatory arthropathies that share
distinctive clinical, radiographic and genetic features. These diagnoses
include:
 Ankylosing spondylitis
 Reiter's syndrome (reactive arthritis)
 Psoriatic arthritis
 Enteropathic arthritis (Crohns, Ulcerative colitis, Whipples)
Patients not fulfilling criteria for these individually may be classified more
generally as having a “spondyloarthropathy”.
Clinical subsets of Spondyloarthropathy
1. Ankylosing spondylitis
2. Psoriatic arthritis
3. Reactive arthritis &Reiter’s syndrome
4. Enteropathic arthritis
5. Undifferentiated SpA
Muscloskeletal features
• Sacroilitis
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• Spondylitis
• Enthesopathies:
 Achilles tendinitis
 Plantar fasciitis
• Asymmetrical peripheral arthritis
• Tenosynovitis.
Extra-skeletal features
• Inflammatory eye disease (conjunctivitis, uveitis)
• Psoriasis
• Inflammatory bowel disease (UC, CD)
• GU inflammation (e.g. urethritis, balantitis)
• Cardiovascular involvement
• Pulmonary involvement
• Renal impairment (second. amyloidosis)
European SpA Study Group criteria for spondyloarthropathy
{Sensitivity 77%, Specificity 89%}.

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HLA-B27
• Class I MHC, important in antigen presentation CD8 T cells
• Associated with the spondyloarthropathies: Ankylosing spondylitis,
Reiter's syndrome, Psoriatic arthritis, and enteropathic arthritis.
• HLA-B27 is a normal gene found in 8% of Caucasians
o 3-4% of African-Americans, 1% of Orientals.
 But not in American Orientals or Koreans
• Actual risk of developing AS in ANY HLA-B27(+) person is only 1-2%.
• Over 95% of patients with ankylosing spondylitis are B27+
• there is 20-30% risk to 1st degree relatives of AS patients
Seronegative Spondyloarthropathies - HLA-B27
• HLA-B27 may influence disease expression

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– B27-positive individuals are more likely to have an earlier onset,
sacroiliitis, spondylitis, acute anterior uveitis, and a more severe
clinical course.
– B27-negative patients are more likely to develop peripheral
arthropathritis, skin and nail disease, or inflammatory bowel
disease.
– Thus = Increased risk of spondylitis and uveitis.
• HLA-B27 Diagnostic Testing
– Not necessary to diagnose most patients with spondyloarthropathy
(eg Reitier’s, AS).
– May be useful in diagnosing patients with incomplete or
undifferentiated spondyloarthropathy.
– Not useful as a screening test for arthritis

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Ankylosing spondylitis
• Prevalence: occurs in 0.2% of general population, in 2% of B27+ve

population &20% of B27+ve individual with an affected family member.
• Age of onset: < 40 years of age (average 26 yrs)
• M:F ratio 3:1
• Inflammatory Back pain :
If 4 of 5 features are present:
1. Age at onset less than 4o yrs
2. insidious onset
3. Duration longer than 3 months
4. Associated with morning stiffness
5. Improves with exercises & increase with rest
Differentiating Inflammatory vs Mechanical Back Pain
Mechanical Back Inflammatory Back
Features
Pain Pain
AM Stiffness Minor < 45 min. Prolonged > 60min.
Max. Late in day Early AM

Pain/Stiffness
Exercise/activity Worsens Symptoms Improves Symptoms
Duration Acute or Chronic Chronic
Age at Onset 20-65 yrs. 9-40 yrs.

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Radiographs Osteophytes, Sacroiliitis, Vertebral
malalignment ankylosis,
syndesmophytes
Articular manifestations:
• The classic presentation occurs in a young man between 15 and 40
years old who experiences the insidious onset of intermittent or
persistent low back pain and stiffness that is often worse in the
morning hours and after prolonged rest. The pain is typically relieved
by physical activity. It is usually centered in the lumbosacral spine but
may also be present in the buttocks and hips and occasionally radiate
into the thighs.
• Chest pain. Thoracic involvement can lead to anterior chest pain that
may mimic angina pectoris.
• Peripheral arthritis occurs in one-half of patients during the course of
AS. Involved joints are usually large and proximal, such as the hips
and shoulders..
• Heel pain may occur secondary to local enthesopathy of the calcaneus;
Achilles tendinitis is also common
Extra-skeletal manifestations
• Cardiac: Aortic insufficiency, ascend. aortitis, conduction defects
• Kidney: secondary amyloidosis & IgA nephropathy
• Ocular: anterior uveitis (25-30% of patients)
• Pulmonary: upper lobe fibrosis, restrictive changes
• GIT: 30-60% of patients have asymptomatic –colitis
Pathology
1. Skeletal sites of inflammatory involvement in AS are

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• a. The axial skeleton (including sacroiliac joints, intervertebral disk
spaces, and apophyseal and costovertebral joints).
• b. The anterior central joints (e.g., manubriosternal joint,
sternoclavicular joint, and symphysis pubis).
• C. large proximal synovial joints (hips, knees, shoulders).
2. Extra skeletal sites of inflammation include the uveal tract, aortic root wall,
apical lung parenchyma, and heart valves.
3.Pathologic findings.
• Fibrocartilage is the primary site of inflammation in articular tissues.
• Other areas of inflammation include
• subchondral bone (osteitis),
• the annulus fibrosis of intervertebral disks,
• perispinal ligaments,
• periarticular ligamentous-bony junctions (enthesitis),
• periosteum (periostitis), and occasionally synovial membranes
(synovitis).
• In all these tissues, the initial cellular inflammatory changes are
followed by fibrosis and often ossification, which lead ultimately to
bony ankylosis.
Physical examination tests to assess spinal disease in AS
• Occiput-to-wall-test
• Chest expansion
• Schober’s test
• Sacro-iliac stress tests:
1. Lateral pelvic compression
2. Gaenslen’s test
3. Pump-handle
Laboratory studies
• HLA-B27 is present in 95% of white spondylitic patients.
• The erythrocyte sedimentation rate and CRP is elevated in many cases .

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• Hematologic tests. A mild normocytic anemia is seen in severe cases. The
white cell count is normal.
• Pulmonary function tests in patients with thoracic involvement usually
indicate a diminished vital capacity and total lung capacity and an
increased residual volume and functional residual volume. Flow
measurements are usually normal.
• Immunologic tests. RF –ve, no specific abnormalities.
Radiographs
The radiographic appearance of advanced AS is characteristic.
1.Sacroiliac joints.
The earliest radiographic changes are
a. Punched-out erosions.
b. “Pseudo-widening” of the joint.
c. Adjacent sclerosis.
d. Bony bridging of the joint with complete loss of joint space may develop.
Computed tomography (CT) and magnetic resonance imaging (MRI). These
scans may identify erosions in sacroiliac joints before they appear on
radiographs
Sacroiliitis: Scoring System
• Grade 0 : Normal
• Grade 1: Suspicious changes
• Grade 2: Minimal Change. Localized erosions or sclerosis not altering
joint width
• Grade 3: Definite moderate to severe change, with one or more of the
following:
• Erosions; Sclerosis; Joint Space Widening; Joint Space Narrowing;
Partial ankylosis
• Grade 4: Severe. Total Ankylosis

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2.Spine
a. Vertebral chondritis and adjacent subchondral osteitis followed by fibrosis
and ossification lead to bony bridging of adjacent vertebrae
(syndesmophytes). The advanced radiographic appearance of the
ossification process of AS is aptly named bamboo spine.
b. The Romanus sign.
c. Periostitis of the periphery of the vertebral body leads to early “squaring”
of vertebral bodies.

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Forty two year old male with ankylosing spondylitis:
• Demonstrating advanced disease with bilateral subchondral sclerosis, erosions, and
pseudo-widening of the sacroiliac joints. • The entire spine demonstrating bilateral SIJ’s
BME, fat metaplasia, and erosions as well as corner inflammatory lesions and fatty lesions
in the spine.
3.Peripheral joints.
There is a greater tendency in AS to central articular erosion, proliferative
new bone formation in periarticular tissues, and bony ankylosis. Concentric
joint space narrowing and lateral osteophytes are distinctive radiographic
signs of hip disease in AS.

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4.Ligamentous-bony junctions.
Inflammation and secondary ossification at these
junctions in areas such as the pelvis, the greater
trochanter of the femur, plantar fascia, and the Achilles
tendon lead to proliferative bone margins and whiskery
spicules.
Complications
• Patients with ankylosed spines have an increased susceptibility to
vertebral fractures, especially in the cervical region, after falls or even
minimal trauma because of the rigidity of the spine.
The cauda equina syndrome, which causes pain in the buttocks or lower
extremities, bladder or bowel dysfunction, and variable sensory loss is
sometimes seen in long-standing AS. It is a consequence of nerve root
compression by abnormal bony growths
Ankylosing Spondylitis - Mortality
– 1.5 – 4 fold increased
– Amyloidosis
– Spinal fractures
– Cardiovascular disease
– Gastrointestinal bleeding
– Nephritis
– Pulmonary diseases
– Colon cancer

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Modified New York Criteria for AS
Modified New York Criteria (1984) for Diagnosing Ankylosing
Spondylitis
Clinical Criteria
 Low back pain and stiffness for > 3 months that improves with exercise
but not with rest
 Limitation of lumbar spine mobility in both the sagittal and frontal planes
 Limitation in chest expansion as compared with normal range for age and
sex
Radiologic Criteria
 Unilateral sacroiliitis of grade 3-4 or
 Bilateral sacroiliitis of grade ≥2
Grading
Definite ankylosing spondylitis if the radiological criterion is associated
with at least one clinical criterion
Probable ankylosing spondylitis if
 Three clinical criteria are present or
 The radiologic criterion is present without any signs or symptoms
satisfying the clinical criteria
Treatment
The aims of management in AS are to control pain, maintain maximum
skeletal mobility, and prevent deformities.
• Physical therapy. All patients should be enrolled in a physiotherapy
program. Maintenance of erect posture is critical in all activities,
including sitting, standing, and walking.
• Drugs
The role of drugs is to relieve pain and inflammation so that posture
can be preserved and an exercise program maintained.
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• Indomethacin (25 to 50 mg three to four times daily is the most
commonly prescribed drug. .
• Sulfasalazine (500 mg to 1 g twice daily with meals) relieves spinal
symptoms and decreases acute-phase reactants. It is especially
useful early in disease
• Immunosuppressive agents, such as methotrexate
• Systemic steroids, used with extreme caution, may be helpful to
treat acute flares and systemic manifestations
• Intraarticular corticosteroids may occasionally be useful for acutely
inflamed joints.
• Biological Therapies :TNF alpha inhibitors is no specific therapy or
cure for AS.
SpA: Therapeutic Options
• Nonpharmacologic measures
– Patient education, joint protection, maintenance of function and
posture (Ankylosing Spondylitis Association, Arthritis Foundation)
– Exercise, rest, physical therapy, diet, vocational counseling
• Pharmacologic therapies
– Analgesic agents
• Use to control noninflammatory symptoms or “burnt out”
spondyloarthropathy
• Maybe useful as adjunctive therapy during active
inflammatory Dz
– NSAIDs - Mainstays for Sx therapy; Does not change course of SpA
– Corticosteroids - rarely used; rarely effective (occ intralesional use)
– DMARD: SSZ, MTX only effective with peripheral arthritis – not spine
– anti-TNF therapies: highly effective with inflammatory spondylitis

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NSAIDs
• May be useful in the control of: inflammatory back pain, spinal
stiffness, peripheral arthritis, enthesopathy
• No evidence that NSAIDs inhibit disease progression
• FDA-approved NSAIDs for AS: Indomethacin, indomethacin-SR, enteric
coated acetylsalicylic acid, naproxen, sulindac, diclofenac.
• Few controlled and antecdotal reports suggest that certain NSAIDs
may be more effective:
– indomethacin: especially in long acting form. CNS Sx?
– diclofenac: as effective as Indocin, less toxic, LFTs!
Corticosteroids
• Systemic corticosteroids are seldom used in the Spondyloarthropathies.
• No evidence to support the use of systemic low dose OR high (“pulse”)
dose therapy
• Most useful as local therapy:
– ophthalmic preparations: for ocular inflammation
– intralesional injections: for enthesitis or tendinitis
– intra-articular injection: for uncontrolled monarthritis
– intra-articular injection of sacroiliac joint: uncontrolled trials suggest
efficacy
NSAID Resistant AS/SpA
• Consider DMARDs when:
– Anti-inflammatory therapy is insufficient
– Progressive inflammatory axial disease
– Active persistent polyarthritis
– Uncontrolled extra-spinal/articular disease
• But Which DMARD?

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– None shown to be effective at Axial disease
– None FDA approved for AS, SpA
– MTX indicated in psoriasis - not psoriatic arthritis - Hepatotoxicity Issues
– Reliance on antecdotes and experience in RA
Ineffective DMARDs
• Gold - no proven benefit!
– Intramuscular (aurothioglucose, aurothiomalate)
– Dosing similar to that used in rheumatoid arthritis
– Primarily studied in psoriatic arthritis
• Hydroxychloroquine
– Controlled and uncontrolled trials in psoriatic arthritis, suggesting some
efficacy.
– Dermatology literature suggests it may exacerbate Psoriasis?
– Dose: 200-400 mg per day
• Azathioprine
– Uncontrolled and controlled trials in Reiters and psoriatic arthritis
– Dose: 1-2.5 mg/kg/day
DMARDs
• Methotrexate
– Controlled & uncontrolled trials in psoriatic arthritis and AS
– Dose: 7.5 - 20 mg per week
– AS: of no proven benefit
– Psoriatic Arthritis: effective against skin and joint disease
• High incidence of hepatotoxicity
• Guidelines require regular LFTs, avoid EtOH, Liver Bx q 1500 mg
• Sulfasalazine
– Well studied in AS, PsA, Reiters
– Effective against peripheral arthritis, NOT with axial disease

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– May work via Tx of asymptomatic ileitis often present
– Dose: 2000-4000 mg qd
Biological Therapies
Anti-TNF alpha blockers
– The goals of treating the patient with SpA or PsA are to

optimize long-term health-related quality of life and
– social participation through control of signs and symptoms,
prevention of structural damage.

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Psoriatic Arthritis (PsA)
• Chronic inflammatory arthropathy in setting of psoriasis
• Etiology and genotype unclear
• 1-5% of US population has Psoriasis: 5-42% of these will develop
psoriatic arthritis (skin usually precedes joints)
– Frequency of PsA increases with disease severity and duration
• Nail changes: pitting, dystrophy, onycholysis
• Course: chronic, destructive arthritis in 30-50%
Classification of Psoriatic Arthritis
Type Key Clinical Features Incidence
Asymmetric Morning stiffness, DIP and PIP
polyarthritis or involvement, nail disease, £ 4 40%
oligoarthritis joints involved
Symmetric Symmetric polyarthritis, RA-like
25%
polyarthritis distribution, but RF negative
Ankylosing spondylitis Inflammatory low back pain,
sacroilitis, axial involvement, 50% 20%
HLA-B27+
Distal interphalangeal Nail changes, often bilateral joint
15%
joint disease involvement
Arthritis mutilans Destructive form of arthritis,
telescoping digits, joint lysis,
<5%
typically in phalanges and
metacarpals

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Reactive Arthritis
• Acute inflammatory arthritis occurring 1-3 weeks after infectious event
(GU, GI, idiopathic)
• TRIAD: arthritis + urethritis (vaginitis) + conjunctivitis (classic triad
found in < one-third of patients)
• Usually asymmetric oligoarticular + extraarticular Sxs
– Arthritis recurrent in 15-30%, more in chlamydial arthritis
patients.
• HLA-B27+ in 75-80% Caucasians
• Post-venereal onset: more common Sex 5:1 M:F
• Post-dysenteric: less, equal M=F
• Course: self-limiting (< 6 mos), chronic, intermittent

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• Complications: Acute anterior uveitis 5%, carditis, fasciitis
Decreasing incidence in the HIV era (condom use)
Infectious Triggers for Reactive Arthritis
Common pathogens
• Enteric Infections
– Shigella flexneri, serotype 2a, 1b
– Salmonella typhimurium, S. enteritidis
– Yersinia enterocololitica (serotypes 0:3, 0:8, 0:9; SCANDINAVIA)
– Campylobacter jejuni
• Urogenital Infections
– Chlamydia trachomatis
– C.Pneumoniae
– Ureaplasma Urealyticum
Uncommon pathogens
• Bacterial:
– S. paratyphi, S heidelberg, S. abony, S. blocley, S. schwarzengrund,
S. haifa, S. manila, S. newport, S. bovis morbificans
– Y. pseudotuberculosis (outside of Scandinavia)
– C. fetus
– Vibrio parahemolyticus
– C. psittaci
– Streptococcal (Group A,G G)
– Clostridium difficile
– Propionibacterium Corynebacterium Acne
– Staphylococcus aureus (Toxic shock arthritis)
 Spirochetal: Borrelia burgdorferi
 Mycobacterium tuberculosis and avium intracellulare (Poncet's
disease)
 Parasitic: Giardia lamblia, Strongyloides stercoralis , Cryptosporidium,
Ascaris lumbricoides, Taenia saginata, Filaria

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 Immunotherapy/Immunization Related
– Bacillus Calmette-Guerin : intravesical injection
– Hepatitis A vaccine
Clinical presentation
Articular Manifestations
• asymmetric arthritis, typically oligoarticular and predominantly in the
lower extremities. Most common are knees, ankles, and
metatarsophalangeal joints.
• Acute sacroiliitis may present as a diffuse low back pain that is difficult
to localize but may be felt in the deep gluteal area.
• Enthesitis. Plantar fasciitis and Achilles tendinitis are quite specific for
RS
Extra-articular manifestations
• Mucocutaneous: - Circinate balantitis (30%)
- Keratoderma Blennorrhagica (20%)
- Painless oral ulcers (25%)
• Genitourinary: - Urethritis or cervicitis
• Gastro-intestinal: - Antecedent diarrhea
• Ocular - Conjunctivitis (60%)
- Uveitis (unilateral) (20%)

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Reiter’s syndrome (RS)
 Defines a clinical triad of arthritis, conjunctivitis, and urethritis,
 Most authors now accept the presence of a seronegative asymmetric
arthritis plus one characteristic extraarticular feature as sufficient for
the diagnosis

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Enteropathic arthritis
Arthropathies associated with
 Idiopathic inflammatory bowel disease (UC, CD)
 Enteropathic reactive arthritis
 Whipple’s disease
 Intestinal by-pass arthritis
5-20% of IBD patients (Crohn’s disease or Ulcerative colitis) will develop
inflammatory arthritis
Risk increases with extent of colonic disease and presence of other
extraintestinal manifestations: abscesses, E. Nodosum, uveitis,
pyoderma gangrenosum
Gut disease may be asymptomatic for years
Subsets:
1. Asymmetric oligoarthritis (intermittent or chronic)
2. Seronegative RA-like polyarthritis 20% of IBD patients
3. Spondylitis 10-15% (may be misdiagnosed as AS)
Peripheral arthritis parallels the gut! NOT THE SPINE!
Clinical manifestation and diagnosis
Peripheral arthritis
• Usually acute, migratory, and transient.
• Asymmetric and oligoarticular pattern, typically involving the large and
small joints of the lower extremities.
• Usually follows bowel symptoms. It tends to correlate with extent and
activity of gut inflammation and often coincides with other bowel
activity-related extra-intestinal manifestations (erythema nodosum,
enthesitis, aphthous oral ulcerations, finger clubbing, and possibly also
uveitis).
Axial involvement (sacroiliitis and spondylitis)

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• Clinically and radiographically indistinguishable from idiopathic AS.
• Occurs independently of bowel disease activity and extent, and
frequently precedes it by several years.
In as many as 6% of patients with ankylosing spondylitis, Crohn’s disease
may evolve.
Juvenile ankylosing
Arthritis and enthesitis , or arthritis or enthesitis with at least two of the
following:
-
B27 antigen.
History of ankylosing spondylitis, enthesitis related arthritis, sacroilitis with

inflammatory bowel disease, Reiter’s syndrome or acute anterior uveitis in a
first degree relatives. Affects males more than females at age more than 8
years
Acute Anterior uveitis
• Idiopathic Anterior uveitis
• There is HLA B27 positivity in 50% of cases
• Characterize by being recurrent and Unilateral > bilateral.

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What Cells can produce IL-17?
IL-17 Is Expressed by many Innate & Adaptive Immune Cells

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nt advances have been made in the treatment of axSpA.
-line
treatment for patients with axSpA, and non-pharmacological treatment
modalities continue to be important in the management of t
For the first time in many years a new therapeutic approach has been
approved (targeting IL-17) and others show promise in axSpA.
biologic treatment.
to establish which patients benefit the most from each drug is a
challenge for the future.

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Rheumatoid Arthritis
 Progressive, systemic, inflammatory deforming disorder

 Unknown etiology
 Characterized by
 Symmetric swelling
 Joint destructions
 Multi-system manifestations
 Affects about 2.0 % of the Egyptian population
 Two out of three patients are female
 Peak age of onset between the ages of 25 and 45 years
 Patients moderately disabled within two years of diagnosis and are
severely disabled by 10 years
 Prevalence 1% world wide
 Female / Male 2:1
Symmetrical, deforming, small and large joint polyarthritis often associated

with systemic disturbance and extraarticular disease features.

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Aetiology
I -Genetic background:
 Association HLA DR1, DR4, DRW14.
 Shared epitope: Increased susceptibility with a specific amino
acid sequence on B chain of HLA DR1. DR4.
 Increased In first degree relatives
2-Possible environmental factor antigen
 Virus (parvovirus, Epstein Barr)
 Retrovirus
 Mycoplasma
 Mycobacteria and Smoking
3-Self perpetuation through autoimmunity.
Pathogenesis
• Cell mediated Immunity through macrophage and TH1 lymphocytes,
• Some contribution of B lymphocytes  plasma cells antibodies 
immune complexes that may be responsible for some of extraarticular
features.
• Macrophage present processed antigen to TH1.
• Th1 produce: * IL2,  stimulates lymphocytes.
• IFN  : stimulate macrophage.
• Macrophage produce:
* IL6 : stimulates acute phase response ( ESR CRP).
* IL-8 chemotactic to polymorphs  * Toxic oxygen radicals
* Prostaglandins and leukotrienes
• IL1—TNF I. activate synovial fibroblasts and chondrocytes 

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a) Metalloproteinases  cartilage destruction.
b) PGE2  demineralization and destruction of bone.
II. Upregulation of adhesion molecules with cell recruitment.
III. Stimulation of angiogenesis to supply the proliferating synovium.

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Pathology
Joints:
1-Early change: injury to synovial microvasculature.
2-Swelling and congestion of synovial membrane - infiltration with TH1
lymphocytes , macrophages and some plasma cells ─ Effusion of synovial
fluid rich in polymorphs.
3-Hypertrophy of synovial membrane with villous formation – lymphoid
follicles may form.
4-Formation of inflammatory granulation tissue(pannus) spreading over and
under the articular cartilage which becomes eroded.
5-Fibrous and bony ankylosis may occur.
6-Atrophy of muscles adjacent to inflamed joints.
7-Inflammatory destruction of soft tissues  laxity of ligaments and tendons
–deformities.

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Clinical picture
Onset:
 gradual (usually)
 Acute in a minority
 Occasionally palindromic (pain , swelling , erythema that resolve but
recur 50% develop RA)
Systemic symptoms: Fatigue, malaise, weakness, low grade fever, loss of
weight.

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Joints:
 pain- swelling- tender on pressure
 Morning stiffness: due to edema and inflammatory mediator
accumulation
o During sleep or inactivity.
 Joints commonly involved: joints of hand (MCP-PIP-Wrist) foot joints-
knee.
 Also affected : shoulder- hip- ankle —sternoclavicular joints.
 Less commonly: Tempromandibular and cricoarytenoid joint.
o Spinal involvement is limited to upper cervical area, sacroiliac
joint is spared
 Symmetry and non-involvement of DIP is characteristic.

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The ACR criteria for diagnosis of R.A (1987)
1. Morning stiffness at least one hour and present for at least 6 weeks.
2. Swelling of 3 or more joints for at least 6 weeks.
3. Swelling of wrist, MCP or PIP for 6 weeks or more.
4. Symmetric joint swelling.
5. Hand x ray changes typical changes of RA (erosions or unequivocal bony
decalcification).
6. Rheumatoid nodules.
7. Serum RF by a method positive in less than 5% of normal
 4 or more criteria must be present for diagnosis.
 Criteria are not sensitive for diagnosis of early RA.
 6 weeks duration of symptoms is important.
 It prevents self-limiting or vial arthritis to be labeled as RA.
The New RA Criteria

Patients are definitively diagnosed with RA if they score 6 or more points
according to the following criteria

48
Specific joints:
Hands:
 Early sign: fusiform or spindle shaped appearance of fingers due to
swelling of PIP joints.
 Bilateral symmetrical swelling of MCP.
 Ulnar deviation of fingers at MCP joint associated with deviation at
radiocarpal Joints  Zig Zag deformity of the hand.
 Swan neck deformity: Hyperextension at PIP with flexion at DIP.
 Boutonniere deformity: Flexion at the PIP with extension at DIP.
 Z shaped deformity of thumb.
 MCP subluxation.
 Dorsal subluxation of ulnar styloid of the wrist
 Trigger finger:
– Inflamed flexor tendon sheath that prevents extension of finger
from a flexed position. A nodule formed in the tendon sheath 
locking

49
– Muscle atrophy with weak hand grip strength.
– Boggy synovium at the dorsum of the wrist.
– Early limitation of dorsiflexion of the wrist.
– Palmer erythema and prominent veins on the dorsum of hand
indicating increased blood flow.
– Thin atrophic skin due to underlying synovitis.
Feet:
 Changes similar to hand.
 MTP subluxation and flexion at PIP  cock-up deformity of toe
(hammer toe)  callosities.
 Hallux valgus deformity of big toe.
 Fibular deviation of toes.
 Flattening of the longitudinal arch.
 Valgus deformity of ankle.
The Knee:
 Swelling due to synovial hypertrophy and effusion.
 Quadriceps atrophy
 Backer’s cyst : effusion in semimembranous bursa at back of knee.
This cyst may dissect in the calf and rupture mimics DVT.
 Doppler ultrasound or arthrography for diagnosis.
 Ultrasound or MRI (noninvasive) can now replace arthrography
Extraarticular features:
Systemic:
 Fever, fatigue ,weight loss,
susceptibility to infection.
 Musculoskeletal: Muscle wasting
 Tenosynovitis
 Bursitis
 Osteoporosis

50
 Haematological
 Anaemia:
 Normochromic normocytic anaemia, of chronic disease,
 Fe-deficiency anaemia: GIT erosions from NSAIDs – steroids
eosinophilia
 Thrombocytosis: Active disease.
 Lymphatic:
 Splenomegaly
 Felty’s syndrome
 Subcutaneous nodules: in seropositive-soft and mobile or firm and
fixed found at sites of pressure or friction sites such as extensor surface
of forearm, sacrum, Achilles tendon and toes.
Vasculitis:
 Digital arteries: nailfold infarcts.
 Palpable purpura
 Ulcers
 Pyoderma gangrenosum.
 Mononeuritis multiplex.
 Medium sized arteries with mesenteric, renal, or coronary occlusion
(Uncommon).
Ocular:
 Episcleritis: red- painless-benign-no discharge.
 Scleritis: red- painful may lead to uveitis-secondary glaucoma –visual
impairment.
 Scleromalacia: painless bilateral thinning-blue colour of underling
choroid.
 Corneal melting; pain - redness - blurred vision - thinning -perforation.
 Sjogren’s syndrome.
Respiratory:
 Cricoarytenoid joint inflammation - laryngeal pain – dysphonia - pain
on swallowing.

51
 Pleurisy
 Pleural effustion with low glucose level - Elevated LDH.
o Males - seropositive - small and unilateral resolve spontaneously
or require steroids.
 Interstitial fibrosis: Most common pulmonary manifestation,
asymptomatic- lower lobes.
 Nodules : solitary or multiple - can cavitate
o Rheumatoid nodule + pneumoconiosis  Caplan’s syndrome.
 Bronchiolitis obliterans: dyspnea - hyperinflation may be fatal.
Cardiac:
 Pericarditis: asymptomatic - 30% - detected by echocardiography.
 Myocarditis - cardiomyopathy.
 Heart block.
 Endocarditis
 Aortic regurge.
 Coronary vasculitis.
Neurological:
 Entrapment neuropatby:
o Median nerve : carpal tunnel syndrome (C.T.S)
o Posterior tibial: tarsal tunnel syndrome (T.T.S)
o Ulnar at elbow
o Peroneal at head of fibula
 Peripheral neuropathy
 Mononeuritis multiplex
 Cervical cord compression due to atlantoaxial subluxation due to
erosion of transverse ligament around the posterior aspect of the
odontoid peg. On neck flexion, peg moves posteriorly indenting the
cord.
Symptoms: occipital headache, parathesia, electric shock in the arm,
motor weakness (Quadreparesis).
o Lateral x ray in flexion and in extention if in flexion distance
between odontoid peg and atlas > 3mm  subluxation.
52
Investigations and monitoring of RA
To evaluate diagnosis:
o Clinical criteria.
o Acute phase response: ESR: CRP.
o Serological tests : Rheumatoid factor.
o X ray joints.
o Synovial fluid analysis.
To monitor disease activity and drug efficacy
o Pain (visual analogue scale).
o Early morning siffness (Minutes).
o Joint tenderness (Number of inflamed joints, articular index).
o Acute phase response.
To monitor disease damage
o X rays
o Functional assessment: health assessment questionnaire.
To monitor drug safety
o Urine analysis
o Biochemistry
Haematology

53
o Acute phase response:
 Elevated in widespread disease.
 But may be normal in isolated small joint synovitis.
o Rheumatoid factor:
 Antiglobulin antibody of class 1gM, IgG, or IgA against Fc
fragment of IgG.
 Agglutination tests detect IgM RF
 Latex test: use polystyrene particles coated with human IgG.
 Rose waaler: use sheep red cells coated with rabbit
antierythrocyte antibody
 Rose waaler is less sensitive but more specific than latex test.
 RF titer has no prognostic significance.
 RF is positive in 85% of patients but early in 70% only
 It is also positive in:
 Sjogren’s syndrome.
 Other C.T. diseases.
 Chronic liver diseases.
 Sarcoidosis.
 Multiple myeloma.
 Chronic infections : TB, leprosy syphilis.
o Other serological tests:
Anticitrulline antibody.
 Elisa determination of antibodies to citrullinated antigens is now
used
 (Anticyclic citrullinated peptides or anti-CCP).
 Anti CCP antibodies are found in:

54
 Early RA as well as in preclinical phase.
 Some RF negative RA cases.
 Anti CCP are predictors of severity of RA.
 Sensitivity in RA is 40% to 70%.
 Specificity may be 98%.
X ray:
o Early: soft tissue swelling.
o Periarticular osteoporosis.
o More advanced:
o Narrowing of joint spaces
o Marginal erosions
o Subluxations (malalignment)
o Deformities
Svnovial fluid anaylsis :
o Differentiates inflammatory arthritis (as RA) from degenerative as
(O.A) or septic arthritis
o In inflammatory arthritis:
 Turbid.
 WBC’s 2000 - 50.000 % polymorph 20-70%
 Mucin. clot is poor: hyaluronic acid is degraded
 Synovial fluid / blood glucose difference :30
 No crystals.
 Decreased complement.
Treatment
 Early diagnosis and early treatment are needed as joint destruction occurs
in the first 1-2 years of onset.
 Aggressive treatment for patients with poor prognostic features as
 Early onset of severe synovitis (high disease activity) with
functional limitation.

55
 Joint erosions.
 Extra — articular manifestations.
 Rheumatoid factor positivity.
 Family history of severe RA.
Goals of therapy
 Treat early
 Treat to limit and/or prevent:
 Pain
 Joint damage
 Extra articular disease
 Disability
 Premature death
 Treat to target (remission)
Treatment includes:
 Synthetic Disease Modifying Anti-Rheumatic Drugs
 Methotrexate, leflunomide, sulfasalazine
 Biological agents (anti-cytokine)
 Anti-TNF, anti-B cell, anti-IL-6

56
 Physical therapy is important
1-Passive movement to maintain full range of movement.
2-Graded exercise program
3- Heat therapy : Warm pools — paraffin bath
4- Rest splints for v. painful joints.
5- Surgery and rehabilitation may be needed.

57
Non - Steroidal anti - inflammatory drugs (NSAIDS)
 They control inflammation and pain (analgesic effect).
 They do not prevent the structural damage.
 Individual variation in response and toxicity.
Mode of action:
1. Reduce prostaglandin (PG) levels through inhibition of cyclo-oxygenase
(COX) 2 isoforms of cox
2. COX -1 is constitutively expressed and produces PG necessary for
integrity of gastric mucosa, maintenance renal blood flow and platelet
aggregation.
3. COX - 2 is largely induced at sites of inflammation , producing
prostaglandins involved in peripheral inflammation and pain.
4. COX - 2 inhibition is largely responsible for analgesic, anti- inflammatory
and antipyretic of NSAIDs.
5. Selective COX-2 inhibitors (Celecoxib and rofecoxib)
6. Have no increased risk of gastroduodenal ulceration but produce other
NSAID side effects.
Side effects of NSAIDs:
1. Gastro intestinal toxicity
2. Gastric ulcer:
3. Increased risk of bleeding and perforation of gastric and duodenal ulcers.
 Low - risk: Ibuprofen, Etodolac, Meloxicam
 High risk: Piroxicam, Indomethacin
 Moderate: Naproxen, Diclofenac.
4. Fluid retention  circulatory overload  compromise heart.
5. May affect renal function by suppressing vasodilator PGE2 or induce
interstitial nephritis.
6. CNS: dizziness, headache, confusion.
7. Asthma and anaphylaxis are rare.
8. Prolonged treatment may hasten cartilage and bone damage.

58
Disease Modifing antirheumatic drugs (DMARDs)
 They decrease inflammatory synovitis and prevent or retard joint erosion
and destruction
 Should be used within 12 w of onset, as joint damage occurs early in
disease course
 They are used singly or in combination in severe disease.
Steroids
Have a very rapid and dramatic anti - inflammatory action. However the
doses required to maintain adequate symptomatic relief are accompanied by
unacceptable side effects as Cushinoid features , osteoporosis,
hyperglycemia, IHD, hypertension. peptic ulcers. Glucoma , Cataract.
Indications:
1- Rapid , short term (1-3m) in control of marked synovitis while awaiting
efficacy from DMARDs (Bridge therapy) Use low dose (7.5 mg) of
prednisolone or equivalent.
2- For vasculitis, eye or lung involvement.
3-During pregnancy when DMARDs are contraindicated
Intra-articular injections:
 For temporary control of synovitis of one or few joints.
 2-8 week duration of benefit.
 Frequent injections- joint damage (not more than 4/ year in a large
joint)
 Strict aseptic technique is a must.

59
60
Anticytokine treatment (Biological agents)
I-TNF- antagonists: (Infliximab, etanercept, adalimumab).
Only infliximab needs to be combined with methotrexate to prevent
development of antibodies to the mouse component of the drug.
Anti-TNFα Biologics for RA

61
Biologic Therapy: Major Safety Issues
• Infections
• Infusion/injection-site reactions
• Autoimmune diseases
• Malignancy
• Immunogenicity, blocking antibodies
• Use in pregnancy
• Use in patients with congestive heart failure
• Use in patients with cardiovascular diseases
A-Infliximab (Remicade)
 Chimeric IgG1 anti TNF antibody containing the antigen-binding
region of the mouse antibody (one fourth of the molecule) and
the constant region of the human antibody.
 It binds TNF- with high affinity impairing its binding to its
receptor.
 It also kills cells that express TNF- through antibody dependent
and complement dependent cytotoxicity
 Infliximab is given as 2 hour IV infusion.
 3 loading dose of 3 mg/kg at week 1, 2 weeks later and at week
6 followed by maintenance doses every 8 weeks in combination
with methatrexate.
 If no adequate response dose is increased. (It may reach 10
mg/kg every 4 weeks).
B-Etanercept (Enbrel)
 Soluble TNF receptor fusion protein

62
 Composed of two dimers each with an extracellular ligand
binding portion of type II TNF receptor (p75) linked to Fc portion
of human IgG1.
 This fusion protein binds both TNF- and TNFB preventing
interaction with receptors.
 Subcut once (50 mg) or twice (25mg) weekly as monotherapy or
combination with MXT.
C-Adalimumab (Humira)
 Recombinant human IgG1 monoclonal antibody
 Subcutaneous 40 mg every other week
Side effects of anti-TNF
1-Infections
 Serious bacterial infections, TB, fungal, atypical mycobacteria.
TB
 Reactivation of latent injection
 PPD screening
 If positive and chest X-ray normal: isoniazid (300 mg) and vit B6
(50mg) for 9 month with anti TNF.
 Upper Respiratory tract infection or skin infections and ulcer withheld
then restart.
 Withheld 1 or 2 weeks before surgery restarted 2 weeks later.
2-Lymphoma (Non-Hodgkin's)
 ?? RA or anti TNF
 Incidence of cancer is not increased
3-Autoantibodies:
 ANA and anti ds DNA but drug induced lupus is rare.
4-Multiple sclerosis:

63
 Exacerbation and development of new DS has been reported.
 Should be avoided in D.S.
5-Injection site reactions:
 (redness and itching) but serious anaphylaxis is uncommon.
6-Abnormal LFT and cytopenia
II- IL1-ra (Anakinra)
 Recombinant protein-Targets IL-1 receptor competing with IL-1.
 Less effective than anti TNF
 Daily injections are required.
 Adverse effects:
 Infections: Bacterial
 No opportunistic
 Injection site reactions.
 Reversible neutropenia and thrombocytopenia.
 With anti TNF: severe infection
III- CTLA4 -Ig or Abatacept
 Fully humanized
 Blocks activation of T lymphocytes by competing with binding of
costimulatroy molecule CD28 on surface of T cells to CD80/CD86 on
antigen presenting cells
 IV 10mg/kg initially 3 infusions every 2 weeks followed by monthly
infusion.
 Alone or with methotrexate-good safety profile but with anti TNF high
level of infections.
IV-Rituximab (Mabthera)
 There is abundance of B cells in the synovium of RA joints
 B cells have a critical role in pathogenesis of RA
 Antigen presentation.

64
 T cell activation.
 Antibody production.
 Cytokine production (TNF-, lymphotoxin, IL-7) that activate
macrophage to produce proinflammatory cytokines.
Rituximab is a chimeric monoclonal antibody against CD20
molecules on B lymphocytes.
 Used in non Hodgkin's lymphoma.
 Effective with methotrexate in refractory RA.
 It causes B cell depletion for more than 6 months.
 B cell depletion occurs via.
 Antibody dependent cell mediated cytotoxicity.
 Complement dependent cytotoxicity.
 Apoptosis.
 Pro B cells and plasma cells do not express CD20-They are spared,
Immunoglobulin level (esp IgM) is lowered but remains within normal.
 Single course of 2 IV infusions.
 1 g each- 2 weeks apart.
 Further courses after 7 to 23 months according to disease activity.
 Side effects
 Infection rates within range reported in RA. Common infections
– No TB- no opportunistic infections.
 Infusion reactions (mild to moderate) premedication with
steroids.
 Low incidence of human chimeric antibodies (HACA) with no
effect on efficacy.
V-Anti IL-6 receptor antibody (tocilizumab)
 It is a humanized IgG monoclonal antibody against human IL6
receptor.
 It prevents IL6 induced :

65
 B cell activation and antibody production
 T cell activation
 Induction of acute phase protein synthesis
 Neutrophil recruitment and pannus formation
 Neovascularisation (induction of VEGF )
 Improve anaemia through inhibition of IL6 induced hepcidin
production. (hepcidin stop ferroportin from releasing iron stores)
 Improve fatigue and mood through action on hypothalamic pituitary
adrenal axis.
 Improve osteoporosis through inhibition of osteoclast.
 Given with MXT or as monotherapy to patients who have failed or are
intolerant to one or more DMARM or anti TNF .
 Rapid clinical response :2 weeks
 Side Effects
 Infections including TB
 As immunomodulator may increase the risk of malignancy
 hypersensitivity reactions
 Hepatic transaminase elevation
 Hematological :neutropenia and thrombocytopenia .
 Lipids :elevation chol an TG
 complication of diverticulitis :perforations.
 Administration
 IV drip -8 mg\kg –no lower than 480 mg given once month .
Targeted Synthetic DMARDs
Janus kinase inhibitors (JAKi) belong to a new class of oral targeted disease-
modifying drugs

66
Characterized by a novel mechanism of action, consisting of the
intracellular interruption of the JAK-STAT pathway crucially involved in the
immune response.
I. Tofacitinib
II. Baricitinib
III. Upadacitinib
IV. Peficitinib

67
Counteracting the activation of JAKs, which are cytosolic enzymes presiding
over many biologic functions, including the activation of the inflammatory
cascade in immune cells
Treatment strategy
Combination therapy is superior to monotherapy
1-Step down approach
 Combination of 2 to 3 DMARD's  steroids to completely control
disease as early as possible.
 Then taper the patient off a number of these drugs and leave
him on the simplest possible long term maintenance therapy.
2-Rapid step up approach

68
 Advantage: use of combination for only those patients who need
it.
 First drug is usually methotrexate
 To "incomplete responders" or "suboptimal responders" or active
disease despite methotrexate after3-6 months of conventional
DMARDs
 Choices
Methotrexate
 + Leflunomide
 + Hydroxychloroquine
 + Salazopyrine
 + Both previous 2 drugs
 + Biological agents
3-Parallel and sequentional therapy

69
70
Systemic Lupus Erythematosus
Systemic lupus: inflammatory multisystem disease affects women>men -
9:1 ratio, African American>whites, 90% of cases are women of child
bearing age, onset usually between ages 15 and 45 years, but can occur in
childhood or later in life, highly variable course and prognosis, ranges from
mild to life threatening, characterized by flares and remissions and mediated
by tissue-binding autoantibodies and immune complexes.
Incidence and prevalence: increasing, improved survival, diagnosing milder
cases.
Geographical variability:
African-american>Caucasian(x3)
Asian-american and Hipanics>Caucasian
Age at diagnosis:
 16-55 years of age: 65% of the cases
 < 16: 20%
 >65:15%
Pathogenesis
Genetic factors
Twins: Monozygotic 57%
Dizygotic 5%
Familial aggregation:
• First degree relative 12%
• HLA: DR2, DR3
• C1q, C2, C4
Environmental factors
 UV light (A2 and b component)
 Gender (female > male,estrogen)

71
 EBV
 Vitamin D deficiency
 Other organic compounds: silica, dust, solvents, petroleum product,
smoking.
Drugs: long list—sulfonamide, hydralazine, isonazide, d-penicellamine,
antiarrythmic drugs, propafenone, procainamide, disopyramide----INF & TNF
inhibitors
Immunity
 Activation of innate immunity
 Lowered activation thresholds and abnormal activation pathways
 Ineffective regulation of CD4+ and CD 8+ T cells, B cells and myeloid
derived suppressor cells
 Reduced clearance of immune complexes and apoptotic cells

72
Organ damage
Cytokines involved in tissue injury/organ damage in lupus include:
 B cell maturation /survival cytokines B-lymphocyte stimulator(
BYLS/BAFF)
 Interleukin 6, 17,18
 proinflammatory type 1 and 2 interferons (IFNS)
Clinical relevance: autoantibodies
ANA:
 High sensitivity ,low specificity
 Best screening test
 Repeated negative tests makes SLE unlikely
 Can be positive in up to 10-15% of normal individuals
 Immunefluorescent technique more reliable than ELISA and/or Bead
assay
73
Anti-ds DNA
 High titre:specific
 60% sensitivity
 In some, correlate with disease activity (nephritis and vasculitis)
Anti-smith (anti-Sm)
 Specific to SLE
 More common in black and asian
 No definite clinical correlation
Antiphospholipid antibodies
 Women with child bearing potential and SLE should be screened by
both antiphospholipid ab and anti-Ro ab.
Anti Ro/SS-A
 Non specific
 Associated with: sicca syndrome, neonatal lupus, sub-acute cutaneous
lupus
 Decreased risk of nephritis
Anti RNP: nonspecific, association with RA(rhupus), black>white
Anti La/SS-B :decreased risk for nephritis, associated with anti Ro
Anti histone: drug induced lupus
Antierythrocyte: measured by DCT
Antiplatelet: not useful clinically
Antineuronal: positivity in CSF: active CNS lupus
Antiribosomal P: positivity in serum :depression, psychosis in lupus

74
Clinical Picture of SLE
Acute cutaneous lupus or subacute cutaneous lupus
 Acute cutaneous lupus: lupus malar rash (spare the nasolabial folds),
bullous lupus, TEN variant of SLE, maculopapular lupus rash,
photosensitive lupus rash (in the absence of dermatomyositis)
 Subcutaneous lupus: non-indurated psoriasiform and/or annular
polycyclic lesions that resolve without scarring.
Chronic cutaneous lupus: Classic discoid rash localized (above the neck)
or generalized (above and below the neck). Heals with scar formation and
can lead to discoid alopecia (scaring alopecia)
 Hypertrophic (verrucous) lupus
 Lupus panniculitis ( profundus)
 Lupus erythromatosis tumidus
 Chilblain lupus
 Discoid lupus/lichen planus overlap
Oral or nasal ulcers:
 Oral ; palate, buccal, tongue
 Nasal ulcers
 In the absence of vasculitis, behcet's disease, infection (herpes virus),
inflammatory bowel disease, reactive arthritis, and acidic food
Non-scarring alopecia: diffuse thinning or hair fragility with visible broken
hair, reversible, heal without scar, correlate with disease activity.
Vasculitis rash, urticarial rash
Serositis
 Typical pleurisy for > 1 day or pleural effusion or pleural rub
 Typical pericardial pain ( pain with recumbency improved by sitting
forward) for > 1day or pericardial effusion or pericardial rub or
pericarditis by electrocardiography.

75
Renal manifestations
 One of the most serious manifestations.
 Classification of lupus Nephritis is purely histologic.
 Renal biopsy indicated in every SLE patient with evidence of nephritis.
76
 Urine PCR (or 24-hour urine protein) > 500mg protein/24 hours or RBC
casts.
 Nephrotic syndrome.
 ESRD.
Class Description Clinical manifestations
I Normal Normal
II Mesangial nephritis Little clinical evidence
Normal or near normal urine analysis
and renal function
III Proteinuria-hematuria. Seldom
Focal proliferative GN nephritic range proteinuria or loss of
renal function.
IV Proteinuria, hematuria-progress to
Diffuse proliferative
renal failure and hypertension.
V Extensive proteinuria, minimal
Membranous
hematuria or renal function
nephropathy
abnormality
VI Advanced sclerosing
Manifestations of renal failure
glomerulonephritis
Neurologic manifestations
 Cognitive dysfunction
 Difficulty with memory and reasoning
 Headaches, when excruciating, often indicates SLE flare
 Psychosis: must be distinguished from glucocorticoid induced
psychosis
 Disabling myelopathy
 Stroke, TIAs
 Aseptic meningitis
 Seizures
 Mononeuritis multiplex
 Myelitis, peripheral or cranial neuropathy
 Acute confusional state (delirium).

77
Haematological
 Hemolytic anemia
 Leucopenia(<4000/mm3) or lymphopenia 9<100/mm3)
 Thrombocytopenia(<100,000/mm3)
Immunologic criteria
 ANA> reference negative value, anti-ds DNA, anti-Sm, anti-
phospholipid, low serum complement, positive direct comb's test
Musculoskeletal features:
 Polyarthritis: most common clinical features with mild morning
stiffness (30 minutes)
 Small joint arthritis mimics RA but non erosive non deforming
arthropathy and rarely lead to joint deformities in only 10%, when
deformities occur they are secondary to ligament loosening (Jaccoud`s
arthritis)
 Individuals having rheumatoid-like arthritis with erosions who fulfill
criteria for both RA and SLE ("rhupus") may be coded as having both
diseases.
 Osteonecrosis: mainly of hip due to disease activity or Steroid therapy.
 Muscle pain and weakness: True myositis may occur, usually with
MCTD.
 Drug induced myopathy may occur with steroids or antimalarial drugs
Cardiopulmonary
 Pleuritic chest pain, pleural effusion.
 Pericarditis, pericardial effusion, tamponade., myocarditis
 Coronary artery disease, lupus pneumonitis, interstitial fibrosis,
pulmonary HTN
 Alveolar hemorrhage, ARDs.
Gastrointestinal
 Nausea, vomiting , diarrhea, pain abdomen, transaminitis, mesenteric
vasculitis, pancreatitis

78
Hematologic
 Anemia (chronic disease), leucopenia, lymphopenia, lymphopenia,
thrombocytopenia, lymphadenopathy, splenimegaly and autoimmune
haemolytic anemia.
Life threarening complications
 Cutaneous digital gangrene, cutaneous necrosis, thrombocytopenia,
autoimmune hemolytic anemia, catastrophic antiphospholipid
syndrome, pericardial tamponade, myocarditis, pulmonary alveolar
hemorrhage, myelitis and mesenteric vasculitis
Systemic lupus international collaborating clinics(SLICC)
classification
 11 clinical and 6 immunological criteria
 The patient should satisfy at least four of the criteria including at least
one clinical criterion and one immunological criterion.
 Biopsy-proven nephritis compatible with SLE in the presence of other
lupus features is regarded as sufficient for a patient to be diagnosed
as having lupus.

79
Management of SLE
 No cure, complete sustained remission, rare.
 Maintay: suppress symptoms and prevent organ damage.
 Depends on severity of disease
 Prevention of complications of disease and its treatment.
Non life- or organ –threatening
 Non pharmacological conservative, risk factor modification
 Addition of low dose corticosteroids, belimumab.
Life- or organ- threatening
 Nephritis, myelitis, vasculitis
 High dose IV steroids+ immunosuppressant
Special; conditions
 Pregnancy, dermatitis, thrombotic crisis.
Non pharmacological management
 Sunscreens, SPF at least 30, preferred > 55.
80
 Smoking cessation, weight loss, exercise, optimal blood pressuse control,
supplemental Vit D.
 Avoid high-dose oestrogen therapy, oral contraceptive
 Avoids culprit meds : sulphonamides , avoid pregnancy
Pharmacological therapies
NSAIDs
 For minor symptoms: arthralgia, musculoskeletal, fever, headaches
and mild serositis.
 Short periods only
 Advers effects: aseptic meningitis, transaminitis, decreased renal
function, GI bleed, vasculitis.
 All esp. COX 2 inhibitors: increase risk of MI.
Glucocorticoids
 Rapidly reduce inflammation
 Moderate innate and adaptive immune response.
 Dosage : depend on severity
Low dose prednisone Cutaneous and
Mild SLE
(0.1-0.2 mg/kg ) muscloskeletal symptoms
Pleuropericarditis or
Medium dose
Moderate SLE Hematological
prednisone (0.5mg/kg)
manifestations
High dose oral
prednisone (1- 1.5
mg/kg) Renal or neuropsychiatric
Severe disease
or manifestations or vasculitis
IV methyleprednisolone
(1 g or 15 mg/kg)
Long-term adverse effects
 Infections, HTN, Hyperglycemia, Acne, Aseptic necrosis of bones,
cushing syndrome, CHF, fragile skin, Insomnia, Menstrual
irregularities, osteoporosis, psychosis

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 Add calcium (1500 mg/day) & vitamin D (800 IU/day), if prednisone
or equivalent > 5mg/day)
Anti-Malarial agents
 MAO : Inhibit endosome function ? Disrupt class II MHC…..Decreasing
antigen presentation.
Activates endosomal TLR: decrease IFN alpha
 Use: constitutional , muscloskeletal, skin and mild pleuritic symptoms
 Dose: 200-400 mg daily
 Adverse event: retinal damage, agranulocytosis, aplastic anemia,
cardiomyopathy, peripheral neuropathy , pigmentation of skin
Quinacrine: diffuse yellow skin
Cyclophosphamide
 In comparative study no significant difference between NIH and Euro
Lupus
 Adverse reactions: Severe infections, Alopecia, Lymphoma and bladder
cancer and infertility
 IV mesna decrease risk of bladder cancer
 Gonadotrophin releasing hormone use prevents premature ovarian
failure
Azathioprine
 Purine analogue, inhibits synthesis of xanthylic and adenylic acids ,
suppress DNA synthesis
 Use : systemic features of lupus and maintenance dose for lupus
nephritis , ISN class III and IV
 Option as induction agent in patients with LN , concerned with risk of
infertility with CPM
 Dosage:
For induction : 2-3 mg/ kg / day PO
For maintenance: BM suppression, GI intolerance, hypersensitivity and
hepatotoxicity. Induction therapy for selected
Mycophenolate Mofetil

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 Monophosphate dehydrogenase inhibitor, blocks synthesis of
guanosine nucleotides and proliferation of T and B cells
 Use: Induction and maintenance therapy in lupus nephritis& moderate
to severe SLE
 N.B: More effective in Hispanic, African Americans and non Asians, non
white aces with lupus nephritis, compared to CPM
 Dosage :
Induction : 2-3 g/d po
For maintenance: 1-2 g/d po
 Adverse effects: Nausea, abdominal pain, diarrhea, myelosuppression
and infection
Methotrexate
 Folate antimetabolite, inhibits DNA synthesis.
 Use: for muscloskeletal manifestations, also good for serositis and to
some extent for skin manifestations
 Dosage: 10-25 mg/week PO or SC along with folic acid. Requires dose
modifications in renal impairment
 Adverse Effects: stomatitis, bone marrow suppression , hepatitis,
alopecia and pneumonitis, pulmonary fibrosis
 Therapy for Specific Manifestations
 Mainstay of treatment for any inflammatory life- threatening or organ
threatening manifestations of SLE is systemic glucocorticoids
 Pulse, 1g of methyleprednisolone IV daily for 3 days followed by high
dose (0.5-1 mg/kg /day) Prednisone or equivalent
Lupus Nephritis
 In mild disease: start with hydroxychloroquine , RAAS blockers,
manage proteinuria and hypertension
 Treatment with hydroxychloroquine have higher rates of renal
response, fewer relapses, and reduced accrual of renal damage
Patients with ISN grade III or IV disease, treatment with GCs and
CPM reduce progression to ESRD and Death.

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 For Induction : GCs + CPM or MMF
 Both CPM and MMF were found to be equally effective
 MMF preferred in Hispanic , African Americans and non Asians , Non
white races
 Azathioprine (AZA) may be effective for induction but is slower to
influence response and associated with more flares
 For Maintenance : either MMF or AZA can be used, in some studies
MMF was found more efficacious
 For Refractory cases : consider Rituximab / alternative therapy
Crescentic Lupus Nephritis
 Crescents in glomeruli have got worse prognosis
 Currently only high dose CPM with high dose GC , in induction phase
is recommended
Membranous Lupus Nephritis
 Classified as ISN class V , have proliferative changes
 In pure membranous variant , immunosuppression is not
recommended unless proteinuria in nephrotic renge
 ACE Inhibitors and ARBs are recommended
 Alternate day GCs plus CPM/MMF/ cyclosporine all effective in reducing
proteinuria
Pregnancy and Lupus
 Lupus does not affect fertility
 Rate of fetal loss increased
 Demise is higher in mothers with
 High disease activity
 SLE nephritis
 APLA
 Women with Anti Ro SSA need additional monitoring for neonatal
lupus
 APLA with SLE treated with heparin and low dose Aspirin
Neonatal lupus

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 Trans-placental fluorinated corticosteroids, dexamethasone and
betamethasone.
 Hydroxychloroquine during pregnancy associated with reduced rates
of NLS.
 IVIg was reported to prevent recurrence of CHB in one study, but two
large RCTs failed to show any beneficial effect.
Drug induced lupus
 Appears during therapy
 Fever, malaise, arthritis, intense arthralgia, myalgia, serositis, and /or
rash(less common)
 ANA positivity very high
 Differs from SLE: White predominance, less female predilection, rare
involvement of kidneys or brain
Commonly anti-histone antibody positive, anti DsDNA and RNP rare
 Management
Withdraw offending drug
Low doses of systemic corticosteroids if severe disease
Microvascular thrombotic crisis
 Hemolysis, thrombocytopenia, and microvascular thrombosis in
kidneys, brain and other tissues
 High mortality
 LAB: PS shows schistocytes, LDH is elevated, antibodies to ADAMS13.
 Management: plasma exchange, along with GC therapy.
Lupus and antiphospholipid syndrome
 Repeated fetal losses, venous or arterial clotting, with at least 2
positive tests for APLA (12 weeks apart).
 Target INR
 Between 2.0-2.5 (one episode of venous clotting).
 Between 3.0-3.5 (recurring clots or arterial clotting)
 Heparin and warfarin
 Statins, hydroxychloroquine, and rituximab might be useful.

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Treatment of non-renal SLE—recommended drugs with respective grading of recommendation.
aPL, antiphospholipid antibodies; AZA, azathioprine; BEL, belimumab; BILAG: British Isles Lupus
Assessment Group disease activity index; CNIs, calcineurin inhibitors; CYC, cyclophosphamide;
GC, glucocorticoids; HCQ, hydroxychloroquine; IM, intramuscular; MMF, mycophenolate mofetil;
MTX, methotrexate; Pre, prednisone; PO, per os; RTX, rituximab; PLTs: Platelets; SLEDAI,
Systemic Lupus Erythematosus Disease Activity Index.

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Systemic sclerosis
Systemic Sclerosis
C.T disorder characterized by degenerative and inflammatory changes with
subsequent intense fibrosis; affecting skin, synovium, blood vessels,
skeletal muscles, GIT, heart, lung, kidney.
Etiopathogenesis

87
88
89
According to the American Rheumatism Association (ARA), features
characteristic for scleroderma are divided into 2 groups:
 Major features include centrally located skin sclerosis that affects the
arms, face, and/or neck.
 Minor features include sclerodactyly, erosions, atrophia of the
fingertips, and bilateral lung fibrosis.
 SSc is diagnosed when a patient has 1 major and 2 minor criteria.
 Malignant scleroderma most often occurs in men, usually in elderly
men. An accelerated course of malignant scleroderma leads to death.

90
Classification
I. Systemic sclerosis
A. With diffuse cutaneous scleroderma
 Symmetric widespread thickening of the skin affecting distal, proximal
extremities, trunk and face. Areas of skin hyperpigmentation and
hypopigmentation
 Rapid progression of skin changes
 Early appearance of visceral changes lungs, kidneys, digestive system,
and heart
 Tendon friction rubs
 Raynaud’s (75%) precedes the development of skin changes by
approximately 1 year:
 Antiscleroderma 70 (+ve)
 Nail-fold capillary dilatation and capillary destruction

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B. With limited cutaneous scleroderma
• Symmetric skin involvement restricted to distal extremities and face.
Atrophic changes of the ala nasi and lips, facial amimia .Telangiectasia
of the skin .
• Slow progression of skin affection
• Late appearance of visceral involvement . Late involvement of the
lungs and late development of pulmonary hypertension .
• Raynaud's (universal, may preceed skin lesion by several years).
• Dilated capillary loops in nail folds .Cutaneous calcification .
• Anti-centromere Ab (+ve)

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Subtypes
1. Pb-pulmonary hypertension + biliary cirrhosis.
2. CREST-cutaenous calcinosis, raynaud's + esophagus lesion + sclerodactyly
+ telangiectasia.
II. Localized scleroderma
- Skin without visceral lesion
1. Morphea-plaque like or generalized.
2. Linear scleroderma.
Clinical picture
 It has insidious onset with worldwide distribution.
 Mainly Female to Male ( 4 : 1 )
 More common on 4th and 5th decades.
 Rarely visceral scleroderma occurs in absence of the skin changes.
Forms of Systemic Sclerosis
• Limited Scleroderma
 Skin thickening is distal to elbows and knees, not involving trunk
 Can involve perioral skin thickening (pursing of lips)
 Less organ involvement
 Seen in CREST syndrome
 Isolated pulmonary hypertension can occur
• Diffuse Scleroderma
 Skin thickening proximal to elbows and knees, involving the trunk
 More likely to have organ involvement
 Pulmonary fibrosis and Renal Crisis are more common.
• Limited Scleroderma
CREST Syndrome

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A) Constitutional Manifestations
It may be associated with mild fever.
B) Organ Involvement Manifestations
 Skin
 Musculoskeletal
 Pulmonary
 Renal
 Gastrointestinal
 Cardiac

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Skin Manifestations
Musculoskeletal
 Arthritis: in > 50% with swelling, stiffness, and pain in the joints of the
hands.
 Carpal Tunnel Syndrome.
 Contractures: related to skin thickening.
 Polymyositis: may occur as part of mixed connective tissue disease or
overlap.
Pulmonary
 leading cause of death since we are better at control of renal disease.
 Symptoms: exertional dyspnea
 Types of lung Involvement:
 Interstitial lung disease.
 Isolated pulmonary hypertension.
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Renal Manifestations
Scleroderma Renal Crisis
• Abruptly developing severe hypertension
– Rise in SBP by > 30 mmHg, DBP by > 20 mm Hg
• One of the following:
 Increase in serum creatinine by 50% over baseline or creatinine >
120% of upper limit.
 Proteinuria > 2+ by dipstick.
 Hematuria > 2+ by dipstick or > 10 RBC/HPF
 Thrombocytopenia < 100
 Hemolysis (schisctocytes, low platelets, increased reticulocyte count).
• Can cause headache, encephalopathy, seizures, LV failure.
• 90% with blood pressure > 150/90.
• Can occur also with lower blood pressures < 140/90 and this confers
worse prognosis.
• Risk Factors for Renal Crisis
 Rapidly progressive skin thickening within the first 2-3 years.
 Steroid use (prednisone > 15 mg)
 Anti-polymerase III Ab.
 Pericardial Effusion.
Cardiac Manifestations
Forms of cardiac involvement
• Pericardial Effusion
– symptomatic pericarditis in 20%
• Microvascular CAD:
– recurrent vasospasm of coronary arteries
– Necrosis
– patchy myocardial fibrosis; leads to diastolic > systolic dysfunction.
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• Myocarditis
– Inflammation which leads to fibrosis
• Arrhythmias and conduction abnormalities
– Fibrosis of cardiac conduction system.
– AV conduction defects and arrhythmias.
Cardiac
Prevalence Diagnosis Treatment
Manifestation
Cardiac MRI, Cytoxan +
Myocarditis Rare
Biopsy steroids
Pericardial None; NSAIDs
5-16% Echocardiogram
effusion if symptomatic
Microvascular MRI/nuclear Calcium channel

> 60%
CAD medicine blockers
Macrovascular Coronary Stenting/medical
25%
CAD Angiogram tx
Bradyarrhythmias Rare EKG/Holter Pacemaker

Diltiazem,
Tachyarrhythmias 15% EKG/Holter ablation,
defibrillator
Gastrointestinal
 Disordered peristalsis of the lower two thirds of the esophagus presents
as dysphagia
 Impaired function of the lower esophageal sphincter
 chronic esophageal reflux include erosive esophagitis with bleeding,
Barrett's esophagus, and lower esophageal stricture

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 Involvement of the stomach occurs in systemic sclerosis and presents
clinically as ease of satiety and on occasion as either functional gastric
outlet obstruction or acute gastric dilatation.
 Small bowel involvement
 Intermittent bloating with abdominal cramps, intermittent or chronic
diarrhea, and presentations suggestive of intestinal obstruction.
 Malabsorption occurs
 Bacterial overgrowth in areas of intestinal stasis occurs frequently
Investigations
Lab:
• ↑ ESR (rare or mild).
• CBC: anaemia (↓ iron, autoimmune, traumatic microangiopathic).
Thrombocytopenia .
• Increased creatine phosphokinase levels in patients with muscle
involvement
• Increased urea and creatinine levels in patients with kidney
involvement.
• Serology
1. Anticentromere (limited type)
2. Anti-scl 70 (Diffuse type)
3. Antinucleolar (Diffuse type)
4. Anti PM-Scl (overlap)
5. Hypocomplementaemia, anti dsDNA rare (overlap)
6. + ve Rf (overlap).
7. ↑  globulin.
Synovial fluid
↑ WBCs (less than 10,000), ↑ plasma cells, ↑ lymphocytes, fibrin deposits,
↓ mucin, ↓ viscosity.
Wide field nailfold capillary microscope

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 Is a non-invasive, cheap and useful method used to differentiates the
primary Raynaud’s phenomenon from the secondary one.
 It can be used for early diagnosis of SSc and observation of development
of microangiopathy in SSc.
 The overall changes are classified into ‘early’, ‘active’, and ‘late’
scleroderma patterns.
 Nailfold capillaroscopy (NFC) is recommended as part of screening and
monitoring the process of SSc
 In patients with scleroderma, the capillary changes usually include:
o Dilated giant capillaries, dilatation & tortusity
o Enlarged capillaries are observed in all 3 portions of the capillary
nail fold–arterial, apical, and venous– and especially at the edge of
the nail fold. Adjacent areas are avascular.
o Hemorrhages,
o Disorganized vascular arrays,
o Ramified/bushy capillaries,
o Capillary losses

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Treatment
I. Immunosuppressive agents
 Cyclophosphamaide with plasma exchange or glucocorticoid
 Glucocorticoid (restricted to pts with myositis, active fibrosing
alveolitis, symptomatic serositis, early edematouse phase of the
skin, refractory arthritis, and tenosynovitis)
 Cyclosporine
 MTX
 MMF
 Rapamycin
 Autologous stem cell transplantation
II. Antifibrotic drugs
 D-penicillamine
 Interferon alpha
 Relaxin
 Prostacyclin analouge (Aloprost)
 Anticytokine therapy (CAT-192 = anti TGF-β1)
III. Drugs under investigation
 Imatinib (protein tyrosine kinase inhibitor)
 B cell depletion (rituximab)

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 IVIG
 Epigenetic effects (proetin de acytilase enzyme inhibitor)
 Immune tolerance induction (induction of T cell tolerence by
adminstration of oral bovine type 1 collagen)
IV. Other targeted biologic agents

 IL-6 receptor antagonist (tociluzumab)
 Abatacept
V. Treatment of systems
I. Cutaneous manifestations
 Pruritis: anti histaminic drugs
 Lubricant skin cream
 Lanoline based
 Counter irritant: cabsaicin
 Telangectasia: green foundation, laser, and light therapy
 Calcinosis cutis: menocycline, MTX, infleximab, rituximab, or
surgical removal
II. Raynaud’s phenomenon
 Calcium channel blockers, ARB blocker (lozartan), prostacycline
analouges, phosphodiestrase inhibitors, nitroglycerine patch and
chemical and digital sympathectomy
 Digital ulcers: endothelin receptor antagonist and atorstatin
III. Arthritis
 Acetaminophen and NSAID, low dose CS, MTX, antimalarial drugs,
anti TNF, and IL-6R inhibitor
IV. Myositis
 Steroids, MTX and azathioprine
V. GIT

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 PPI, and prokinetic agents
VI. Scleroderma renal crisis
 ACE inhibitors
 Antihypertensives
 Dialysis
 Renal transplant
VII. Pulmonary hypertension

 Calcium channel blockers
 Prostacyclin analogues
 Endothelin receptor blockers
 Phosphodiestrase inhibitors
 Combination therapy
 Imatinib
 Lung transplant
VIII. Interstitial lung disease
 Immunosuppressives (steroids, cyclophosphamide, MMF , and
azathioprine)
 Imatinib
 Lung transplant
IX. Advanced stage multisystem disease
 Immunosuppressives (ATG, ALG , and MMF)
 Autologous stem cell transplant

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Idiopathic Inflammatory Myopathies
Skeletal Muscle Disorders
• I. Inflammatory muscle disorders
• II. Non-inflammatory:
1. Hereditary: douchene
2. Endocrinal: cushing, hypothyroidism
3. Metabolic: storage diseases,
4. Electrolyte disturbance as hypoK, hypoCa
5. Others
Inflammatory Muscles Diseases
I. Idiopathic inflammatory myopathies
1. Polymyositis.
2. Dermatomyositis
3. Juvenile DM-PM
4. Myositis with other connective tissue and inflammatory disorders
(e.g., systemic lupus erythematosus, rheumatoid arthritis,
scleroderma, sarcoidosis).
5. Myositis with malignancy.
6. Inclusion body myositis.
II. Myositis secondary to infectious agents.
III. Drug- and toxin-induced myositis.
Idiopathic Inflammatory Myopathies
• Heterogeneous group of disorders characterized by:
 Proximal muscle weakness
 Non-suppurative inflammation of skeletal muscle with predominantly
lymphocytic infiltrates

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Epidemiology
• 2-8 cases per million per year
• Female: male = 2:1
• Bimodal distribution:
– 7-10 years
– 45- 60 years
• Age of onset for myositis associated with another condition is similar
to that in the other condition
• IBM and myositis associated with malignancy are common after the
age of 50 years
Pathogenesis
• The etiology of IIM is unknown.
• Aberrations in the immune system that give rise to an increased
susceptibility to infectious agents
• Modifications of cellular immunity that lead to the development of
mononuclear cells capable of injuring muscle.
• Complement may play a role in tissue injury in DM.
Clinical picture of PM
Muscles:
• Proximal muscle weakness is the presenting feature in 90% to 95% of
patients with PM. Usually of an insidious onset.
• Limb girdle muscles:
 Shoulder girdle --- difficulty in hair coombing
 House-hold duties, lifting objects.
 Pelvic girdle muscles---difficulty in climbing stairs, standing from
sitting position.
• Neck flexors:

104
 neck extension position, later flexion due to exhaustion
 Eventually, be unable to raise their heads.
• Respiratory muscles:
 Diaphragm &intercostals
 Pharynx &upper third oesophagus --- dysphagia
• Cardiac muscles: dilated cardiomyopathy
• Ocular ms are never involved.
Extra-muscular manifestations
• Cardiac disturbances
 Asymptomatic ECG changes
 Conduction disturbances
 Supraventricular arrhythmias
 Cardiomyopathy
 Congestive heart failure
• Respiratory involvement
 Interstitial fibrosis
 Interstitial pneumonitis
• Systemic symptoms
 Arthralgias
 Fever, malaise
 Raynaud’s phenomenon

105
Dermatomyositis
• Rash is the primary presenting feature in 95%.
• Only 50% to 60% of patients have proximal muscle weakness at
presentation.
• Follow-up of patients with a rash is therefore essential, as most
eventually manifest proximal weakness.
• Arthralgia, Raynaud’s phenomenon, and dysphagia are seen in 10% to
25% of DM patients.
• Rarely interstitial pneumonitis, cardiomyopathy, and heart block
Skin in DM
1. Heliotrope rash: violaceous discoloration of eyelids, often associated with
periorbital edema
2. Gottron’s sign/ papules: symmetric, scaly, violaceous or erythematous,
macular or raised eruption over extensor surfaces of MCP and IP joints,
elbows, knees, medial malleoli.
3. Mechanic's Hands: dark or dirty appearing horizontal lines over palmar
and lateral aspects of fingers.
4. Shawl sign: Macular erythema over the posterior shoulders and chest
5. V sign: Macular erythema over anterior neck and upper chest

106
Diagnosis of PM&DM
1. Symmetric, progressive proximal muscle weakness.
2. Elevation of serum levels of muscle associated enzymes: CK, aldolase,
LDH, and AST
3. Typical electromyographic triad
107
4. Evidence of chronic inflammation in muscle biopsy
5. Characteristic rashes of dermatomyositis
Childhood myositis
• Childhood DM-PM appears most commonly between ages 7 and 10 years.
• Slightly more often in girls than in boys.
• Most have the characteristic rash of DM at presentation.
• About 90% present with proximal muscle weakness.
• Distinctive features of the myopathy are atrophy, contractures, and tissue
calcifications.
• Visceral involvement is more frequent than in the adult form. (Abnormal
pulmonary function, esophageal motility, and gastrointestinal absorption).
• Some may present with an acute myositis with fever, malaise, and
abdominal pain.
• Gastrointestinal ulcerations caused by a diffuse necrotizing arteritis may
occur and lead to hemorrhage.

108
Myositis with CTD
• Overlap syndromes as defined here consist of PM or DM that fulfills the
previously mentioned criteria and another connective tissue disease
that fulfills a separate set of diagnostic criteria.
• The presenting features reflect the underlying connective tissue
disease.
Myositis with Malignancy
• The possibility of malignancy in an elderly patient with PM-DM is four
times greater than in an age-matched control.
• Between 10% and 20% of patients with PM-DM may have an
underlying malignancy.
• DM has a higher association with malignancy than does PM.
• Myositis precedes malignancy by an average of 1 to 2 years in 70% of
patients and follows it in 30%.
Inclusion Body Myositis
• Mainly affects older men
• Symptoms begin insidiously
• Differs from Polymyositis in that IBM:
 May include focal, distal or asymmetric weakness
 only borderline elevation of enzymes.
 Neurogenic or mixed neurogenic / myopathic changes on EMG and
 poor response to therapy
• May continue to progress slowly & steadily; in others, symptoms
plateau
Investigations
1.Acute phase reactants: (ESR and CRP) …. ESR is normal in 50%
2. ANA:
o may be + in over 50% of patients with IIM..
109
o in low titer and are non-specific in nature.
o The presence of high titer may indicate an associated CTD
3. Muscle enzymes:
o Elevation of CK sometime during course of disease (often >10 times
normal)
o AST, ALT, and LDH are elevated in most cases
4.EMG Findings:
o EMG classically reveals the following triad:
1. Increased insertional activity, fibrillations and sharp positive
waves
2. Spontaneous, bizarre, high frequency discharges
3. Polyphasic motor-unit potentials of low amplitude and short
duration
o Complete triad seen in 40% of patients
o 10-15% of patients have completely normal EMGs
5.Myositis-Specific Autoantibodies

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6.Muscle Biopsy:
Dermatomyositis Polymyositis IBM
B cells, Mononuclear cells Same as PM; also:
macrophages CD8 T cells Rimmed vacuoles
CD4 T cells Endomysial infiltrate Eosinophilic
Decreased Myonecrosis cytoplasmic
capillaries inclusions
Patchy, focal
Perifascicular
atrophy
Perivascular
infiltrate

111
Treatment
• The majority of IIM patients improve with corticosteroid treatment.
• However, immunosuppressive agents are both steroid sparing and
effective in treating the serious extra muscular manifestations.
• Regardless of the choice of initial therapy, early treatment limits muscle
damage and atrophy.
• MTX is first-line therapy after corticosteroids in steroid-refractory myositis
• studies demonstrate the effectiveness of azathioprine in myositis
• the combination of azathioprine and MTX proved efficacious when either
agent was ineffective alone
• Others
 Cyclosporine and Tacrolimus
 Intravenous Immunoglobulin
 Mycophenolate Mofetil

112
Septic arthritis
Arthritis: the word arthritis literally means joint inflammation; but it’s often
used to refer to group of more than 100 rheumatic diseases that can cause
pain, stiffness and swelling in the joints.
Synovial membrane: membrane surrounding joint cavity, produces
synovial fluid and contains rich capillary network for phagocytic and
hyaluronate-producing function.
Septic arthritis: is inflammation of a synovial membrane with purulent
effusion into the joint capsule, due to infection.
-50% of cases –children less than 5 years.
-30% of cases –children less than 2 years.
Most common joints involved in adult: Knee 53%, Hip 20%, Elbow 17%
and Shoulder 10%.
Most common joints involved in children: Knee 39% and Hip 32%
Common organisms involved:
Can be bacterial, fungal, mycobacterial or viral.
Bacterial divided into gonococcal and nongonococcal
 Gonococcal: more common but less morbidity and mortality.
 Staphylococcus.
 Streptococcus.
-Non- gonococcal septic arthritis, the most destructive type, generally is
monoarticular and most often affects the knees (85%). Shoulders, wrists,
hips, ankle joints can be involved.
-Staphylococcus aureus (50%) is the most common pathogen in non-
gonococcal septic arthritis , but non-group-A beta-hemolytic streptococci
(Strept Viridans , Strept Pneumoniae), Gram-negative bacilli, E-Coli ,
Pseudomonas , Proteus species present in only (10%) of cases.

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-Anaerobic and gram-negative infections are common in immuno-
compromised persons .
-Inflammation of a single large joint, especially the knee, may be present in
Lyme disease.
-Mycobacterial, fungal, and viral infections are rare.
-Bacterial arthritis is divided into gonococcal and non -gonococcal
infection .
-Gonococcal arthritis is the most common type of non-traumatic acute mono-
arthritis in young. It is three to four times more common in women than in
men
Modes of spread:
1. Direct invasion.
2. Local spread from adjacent tissues.
3. Spread from metaphyseal osteomyelitis.
4. Hematogenous spread.
5. Penetrating damage by puncture or cutting.
Risk factors for joint affections:
1. Previous arthritis.
2. Trauma.
3. Diabetes mellitus.
4. Immunosuppression.
5. Bacteremia.
6. Sickle cell anemia.
7. Prosthetic joint.
Clinical manifestation: fever, acute severe pain, swelling of the joint,
tenderness, warmth, limited joint mobility.

114
Clinical features differ according to age
In newborn: more on septicaemia rather than joint pain, baby is irritable &
refuse to feed, tachycardia with fever, joints are warmth, tenderness,
resistance to movement. Umbilical cord and inflamed IV site should be
suspicious source of infection.
In children: acute pain in single large joint, pseudoparesis, child is ill, rapid
pulse and swinging fever, overlying skin looks red & superficial joint swelling
may be obvious, local warmth and marked tenderness, all movement are
restricted by pain or spasm. (Look for source of infection from septic toe or
discharge ear).
In adults: often in the superficial joints( knee, wrist or ankle), joint painful
swollen& inflamed, warmth and marked local tenderness& movement
restriction. Look for gonococcal infection or drug abuse. Patients with
rheumatoid arthritis and especially on corticosteroid may develop silent joint
infection.
Any acute inflammatory process with rapid onset over hours to days usually
indicates an infection till proved otherwise
Pathogenesis
• Synovial membrane is highly vascularized-----bacteria can easily enter
synovial joint via blood stream------there will be inflammatory reaction
with seropurulent exudate and increase in synovial fluid------as pus appear
in the joint, the articular cartilage is eroded and destroyed. Partly by
bacterial enzymes and partly by enzymes released from synovium,
inflammatory cells and pus---lead to
 Infant ---destroy the epiphysis which is still largely cartilaginous
 Children-----vascular occlusion leads to necrosis of epiphyseal bone
 Adults----effect confined on articular cartilage. Extensive erosion can
occur due to synovial proliferation and in growth.
• If left untreated, it will spread to the underlying bone and out of the joint
to form abscess and sinus

115
Healing with
1. Complete resolution
2. Partial loss of articular cartilage and fibrosis of the joint
3. Loss of articular cartilage and bony ankylosis
4. Bony destruction and terminal deformity
Physical examination:
1. Decreased or absent range of motion.
2. Signs of inflammation: joint swelling, warmth, tenderness and
erythema.
3. Joint orientation to minimize pain(position of comfort)
 Hip: abducted, flexed and externally rotated.
 Knee, ankle and elbow: partially flexed.
 Shoulder: abducted and internally rotated.
Complications
1. Bone destruction and dislocation of the joints especially hip.
2. Cartilage destruction: may lead to either fibrosis or bony ankylosis.
In adult partial destruction of the joint will result in secondary osteoarthritis.
3. Growth disturbance: presenting as either localized deformity or
shortening of the bone.
Investigations
1. Leukocytosis > 12,000
2. ESR > 40 mm/hr.
3. CRP elevated
4. Blood culture may be positive
Leukocyte counts vary widely in septic and sterile synovial fluid , If the
history and diagnostic studies suggest an infection, aggressive treatment can

116
prevent rapid joint destruction. When an infection is suspected, culture and
Gram staining should be performed and antibiotics should be started.
Synovial fluid analysis:
 Aseptic technique is used during aspiration of synovial fluid.
 Avoid taken from infected site of skin.
 The fluid is then analyzed by gross, microscopic examination and
culture.
 Gross examination include appearance, volume, viscosity, mucin
clotting (amount of proteoglycans)
 Microscopic examination include leukocyte count, staining of smears,
serum glucose ratio and protein.
 Finally, culture and sensitivity for definitive diagnosis and treatment.
Imaging
X-Ray:
Early stage: normal
Look for soft tissue swelling, loss of tissue planes, widening of joint space
and slight subluxation due to fluid in the joint. Gas may be seen with E coli
infection
117
Late findings: (2-3 weeks)
1. Joint space narrowing
2. Blurring of fat planes
3. Increased density of fatty marrow.
4. Periosteal reaction.
5. Cortical erosion or destruction.
Ultrasonography
 More reliable in revealing joint effusion in early cases.
 Widening of space between capsule and bone of > 2 mm indicate
effusion.
 Echo free- transient effusion, positively echogenic – septic arthritis.
 Ultrasound can detect joint swelling.
 Being a non-ionizing, easily available, non-invasive and relatively cheap
modality, ultrasound should be first line of investigation in a suspected
case of infective arthritis.
CT scan: Soft tissue swelling, joint effusions, abscess formation, guide joint
aspiration, monitor therapy and planning operative approaches.
MRI: extent of infection, diagnosing infections that are difficult to access,
better anatomical detail.
 MRI findings: synovial enhancement, perisynovial edema and joint
effusion, single or multiple radiolucent abscesses and assessment of
the extend of tissue affected
Bone scan: detect localized areas of inflammation.
Nuclear medicine imaging: can detect septic arthritis 10 to 14 days
before changes are visible on plain radiographs.
 Highly sensitive but not specific, inexpensive, focal hyperperfusion,
focal hyperemia and focal bone uptake.
Differential diagnosis
Acute osteomyelitis, trauma, irritable joint, hemophilic joint, rheumatic fever,
gout and pseudo gout, gaucher’s disease.
118
Reactive Arthritis Septic Arthritis
Definition Arthritis developing soon Arthritis in which variable
after infection elsewhere in micro-organisms enter the
which the variable micro- joints and synovial fluid
organisms don’t enter the cultures are thus positive .
joints . Synovial fluid
cultures are negative .
Causative Urogenital : Chlamydia . Common organism is
Organism Enteric : Shigella ,
Staphylococcus aureus .
Salmonella ,Yersinia,
Streptococci , Haemophilus
Campylobacter . influenzae ,
Gram Negative Bacteria.
Risk Factors Patients who are HLA-B27  Joints may become infected
Family History of Psoriasis, by direct injury or by blood
IBD , SpA . born infection from an
infected skin lesion .
 Chronically inflamed joints as
RA , individuals who are
immunosuppressed by AIDS ,
diabetes , drugs , alchohol
abuse , elderly , and those
with artificial joints .
Clinical Picture : Usually there is a delay of 1- It is a medical emergency :
2 weeks from infection till Young patient , previously fit
start of arthritis . Primary arthritis with dramatic
young adults , aged 20-40 presentation .
years .
Articular Typically there is acute Acute , tender , hot , swollen ,
manifestations asymmetrical oligo-arthritis erythematous with marked
Peripheral mainly of LL . Most limitation of active and possive
Joints : common are knees, ankles, joint movement .
and MTP joints . Commonly monoarticular (80 -
90 %), oligo or polyarticular (10
-20 %)
Common sites : knee joint
(55%), hip joint (11%) .

119
Acute May present as an NO
Sacroilitis : inflammatory low back
pain .
Enthesitis : Planter Fasciitis and Achilis NO
Tendinitis .
Extra-articular Mucocutanoeus:Circinate NO
Manifestations balanitis (30%) ,
Keratoderma ,
Blennorrhagica , Painless
oral ulcer , Erythema
nodosum .
Ocular :Conjunctivitis ,
Uveitis.
Laboratory
Investigation Reactive Arthritis Septic Arthritis
s
Demonstrati During the acute phase Synovial fluid analysis and
on of the Urine Culture , Genital culture .
infection swabs, Stool Culture . After
arthritis developed, sero-
diagnosis to detect
antibodies against the
triggering organism .
Blood Negative . Positive .
Culture
Joint
Aspiration
Synovial Fluid  WBCs less than  WBCs more than 50.000
Analysis, 50.000 cmm3. cmm3.
 PNLs less than 75%  PNLs more than 90 % .
.

120
Culture and Culture is positive .
Gram staining . Culture is negative .
Treatment
General supportive care
analgesics , IV fluids
Splintage
 The joint must be rested either on a splint or in a widely split plaster.
 In neonates and infants, with hip infection the joint is held abducted
and 30 degree flexed, on traction to prevent dislocation
Antibiotics
 Treatment is started once the blood and samples are obtained without
waiting for a detail results.
 Choice of antibiotics depend on the most likely pathogen.
Surgical management
Surgical drainage:
Indications
 Joints that don not respond to antimicrobial therapy and daily
arthocentesis.

121
 Any joint with limited accessibility including the sternoclavicular or the
hip joint
 Patients with underlying disease (DM, Rheumatoid arthritis,
immunosuppression, etc.)
 Need more aggressive treatment with earlier surgical intervention.
 Arthoscopic debridement and copious irrigation with normal saline-
more frequently with Knee joint septic arthritis.
Gonococcal arthritis
 is the most common type of septic arthritis in young .
 It is three to four times more common in women than in men
 Results from gonococcal (colonization of urethra, cervix or pharynx)
 Sexually active healthy person, congenital complement component
deficiency.
Clinical features
 Disseminated gonocaccal infection-fever ,chills, rash, small n. of papules
that progress to hemorrhagic pustules present on trunk and extensor
surfaces of distal extremities.
 Migratory arthritis and tenosynovitis of the knee, hand ,wrist, feet and
ankles.
 Cultures of synovial fluid are negative, blood cultures positive < 45%,
synovial fluid are difficult to obtain, usually contain 10000 to 20000
leucocytes/micro L
 Gonococcal arthritis: acute illness with fever, chills, malaise, tenosynovitis,
generalized arthralgia and dermatitis pustular or vesicopustular.
Treatment
 Initially ceftriaxone (1gm IV every 24 hours).
 Local and systemic signs resolve, oral antibiotic ( ciprofloxacin 500mg BD)
should be started
 Penicillin susceptible- amoxicillin 500mg TDS
 Suppurative arthritis usually respond to needle aspiration and antibiotic
treatment for 7 to 10 days

122
Mycobacterial arthritis
1 % of all cases of TB and 10% of extrapulmonary cases.
Pathology
 Enter the body via lung (droplet infection) or the gut ( swallowing
infected milk products), rarely through the skin.
 It causes granulomatous infection associated with tissue necrosis and
caseation.
 Primary complex-initial lesion in the lung, pharynx or gut with
lymphatic spread to regional lymph nodes
 Secondary spread- widespread dissemination via blood stream giving
rise to extrapulmonary lesions
 Tertiary lesions-foci developing to destructive lesions
 Once they get foothold they elicit a chronic inflammation
Clinical features
 Previous history of infection or recent contact with T.B
 A long history of pain and swelling, Marked synovial thickening,
Involvement of only one joint, severe muscle wasting, enlarged and
matted regional lymph nodes, night cries, fever, night sweats and loss
of weight.
Investigation
 X-Ray—soft tissue swelling, periarticular osteoporosis, articular space
narrowing, epiphyseal enlargement in children, erosion of subarticular
bone, little or no periosteal reaction
 ESR elevated, Mantoux test is positive
 Synovial fluid contains average cell count of 2000 micro L with 50%
neutrophils. AFB staining may be positive.
 Culture of synovial tissue taken at biopsy is more reliable.
Treatment
-Rest.
-Therapy:

123
Two months course of Isoniazide 600 mg , Pyrazinamide 1500 mg ,
Ethambutol 1200 mg three times weekly and then four months course
of Isoniazide , Ethambutol , Rifampicine .
Fungal arthritis
 Infection causes granulomatous reaction, often lead to abscess
formation, tissue destruction and ulcer formation
 Superficial and deep infections
 Superficial myosis-primarily infection of the skin and mucus membrane
e.g madurmucosis, sportothrix, candida, actinomycosis.
 Deep mycosis-blastomyces, histoplasma, Cryptococcus, coccidioides,
aspergillus. Gain entry through lung
 Cut in the foot -----spred through subcutaneous tissue and along
tendon sheaths-----bones and joints are infected by direct invasion,
local abscesses form and break through the skin as multiple sinuses.
Clinical features
 Subcutaneous nodule, tender. Swollen foot, indurated. Discharging
sinuses and ulcers.
 X-Ray –multiple bone cavities, progressive bone destruction
 Organism can be identified in sinus discharge or biopsy
Treatment
 Intravenous amphotericin b advocated
 Necrotic tissue-excised
 Amputation may be necessary
Candidiasis
 Normal commensal organism
 Immunosuppression predisposing factor
 Gain entry through direct contamination during surgery or other invasive
procedures
 Diagnosis is usually made by tissue sampling and culture
 Treatment – joint irrigation, curettage, IV amphotericin B

124
Viral arthritis
 Infects synovial tissue during systemic infections or by provoking an
immunologic reaction that involves joints
 Rubella –arthralgia, frank arthritis within 3 days of rash following natural
infection with rubella.
 Parvovirus B 19—arthritis , arthropathy, stiffness of joints.
 Acute HBV---arthralgia, fever, urticarial 2 weeks before onset of jaundice.
 Hepatitis- B : Sudden symmetrical polyarthritis of the small joints of
hands in one third of patients .
 HIV infection : Infective arthritis , minimal , or no symptoms. Some recent
anti-viral agents causes arthritis (Crystallization in joints).
 Arthralgia is common in AIDS , it is usually sero-negative , in LLs , similar
to Reiter’s or Reactive arthritis .

125
Degenerative Joint Diseases (Osteoarthritis)
Osteoarthritis (OA) was previously thought to be a normal consequence
of aging, thereby leading to the term degenerative joint disease. However,
it is now realized that osteoarthritis results from a complex interplay of
multiple factors, including joint integrity, genetic predisposition, local
inflammation, mechanical forces, and cellular and biochemical processes.
Why important?
Osteoarthritis (OA) is the leading cause of arthritis, Joint pain is a frequent
symptom that often prompts a patient to seek medical attention
Essentials of Diagnosis
 Joint pain brought on and exacerbated by activity and relieved with
rest.
 Stiffness that is self-limited upon awakening in the morning or when
rising from a seated position after an extended period of inactivity.
 Absence of prominent constitutional symptoms ( no systemic
manifestations)
 Examination:
1- increased bony prominence at the joint margins
2- crepitus or a grating sensation upon joint manipulation
3- tenderness over the joint line of the symptomatic joint.
4- Joint swelling with evidence of inflammation in inflammatory OA.
Clinical Presentation
 Characteristic sites of involvement in the peripheral skeleton include
the hand (distal interphalangeal joint and first carpometacarpal joint),
knees and hips .
 Other sites includes: the spine, feet, ankle and wrists.
 Constitutional symptoms are absent

126
Investigations
 Erythrocyte sedimentation rate normal for age.
 Non-inflammatory synovial fluid (<1000 WBC/mm3), no crystals
 Negative serologic tests for antinuclear antibody and rheumatoid factor
 Radiographic evidence of osteoarthritis (non-uniform joint space
narrowing, osteophyte formation, subchondral cysts, and eburnation
[bony sclerosis])
 osteoarthritis of the distal interphalangeal (DIP), proximal
interphalangeal (PIP) & 1st carpometacarpal (CMC) joints.
 Joint space narrowing of the DIP and PIP joints and bony sclerosis
(eburnation) of all joints involved by the osteoarthritis process.

127
128
Knee osteoarthritis with medial joint space narrowing and osteophytes.
Clinical criteria for the diagnosis of OA of the Knee
The classic criteria for OA of the knee is based upon the presence of knee
pain plus at least three of the following six clinical characteristics :
 Greater than 50 years of age
 Morning stiffness for less than 30 minutes
 Crepitus on active motion of the knee
 Bony tenderness
 Bony enlargement
 No palpable warmth
Risk factors for osteoarthritis
 Increasing age (all sites)
 Female sex or gender (some sites, particularly knee and hand)
 Race or ethnicity (variable at different joint sites)
 Genetic predisposition (all sites)

129
 Obesity (most sites, but more marked for the knee than other joints)
 Trauma, and some occupations involving repetitive activities
Types Of Osteoarthritis
1- Primary (nodular type, erosive, inflammatory)
2- Secondary
 Congenital disorder (hip) : Legg-Calvé-Perthes disease, Acetabular
dysplasia , Slipped capital femoral epiphysis
 Inborn error of connective tissue : Ehlers-Danlos syndrome, Marfan
syndrome
 Post traumatic (knee): Anterior cruciate ligament tear, Meniscus
tear .
 Metabolic disorders : Hemochromatosis , Wilson disease
 History of a septic joint: Post-inflammatory
 Underlying rheumatoid arthritis

130
131
Treatment
The goals of medical therapy are to:
1- control pain
2- improve function
3- minimize disability
4- enhance health-related quality of life (HQO)
Treatment of Osteoarthritis
The treatment options given to the individual varies and is designed
specifically for that individual based on the stage and severity of
osteoarthritis.
Treatment options include the following:
 Education
 Moderate exercises

132
 Weight loss programs
 Physiotherapy for the joints
 Mechanical aids or appliances
 Medications
 Surgery
 The affected individual is taught about the disease process and the risk
factors associated with it.
 Aerobics and mild flexing of the affected joints are taught to prevent
the changes occurring due to immobility of the joints.
 Obese people have obtained significant relief after undergoing weight
loss, which reduces the pressure on the affected joints.
 Shock absorbing footwear and walking sticks help the reduction of the
impact on the joints while walking and makes it easier for the affected
individual to walk around
Pharmacological Treatment
 Multiple medications that include simple painkillers, steroid injections
and other medications are available for pain relief.
133
Surgical treatment
 Surgery that involves the clearing of the diseased tissues of the
joints or insertion of graft materials is some of the options available
for individuals who are not relieved with nonsurgical procedures.
 Joint replacement is the ultimate treatment protocol, which provides
relief of up to 20 years
Alternative Therapy of Osteoarthritis
 The alternative therapies that are available include ginger and other
herbal supplements, mind–body interventions, counselling and
acupuncture. However, these options are usually advised as an
adjunct to the ongoing therapy with other options and are not
efficient enough while used alone.

134
 A doctor’s opinion must always be taken before initiation of such
therapies.
EULAR Recommendations for the treatment of Knee OA

 We suggest patients with symptomatic OA of the knee be encouraged to
participate in self-management educational programs (e.g. walking
instead of running)
 We recommend patients with symptomatic OA of the knee, who are
overweight (as defined by a BMI>25), should be encouraged to lose
weight (a minimum of five percent (5%) of body weight) and maintain
their weight at a lower level with an appropriate program of dietary
modification and exercise.
 We recommend patients with symptomatic OA of the knee be encouraged
to participate in aerobic fitness exercises.
 We suggest quadriceps strengthening for patients with symptomatic OA
of the knee.
 We suggest patients with symptomatic OA of the knee use patellar taping
for short term relief of pain and improvement in function.
 We recommend glucosamine and/or chondroitin sulfate or hydrochloride
not be prescribed for patients with symptomatic OA of the knee.
 We suggest patients with symptomatic OA of the knee receive one of the
following analgesics for pain unless there are contraindications to this
treatment:
 Acetaminophen [not to exceed 4 grams per day]
 Non-steroidal anti-inflammatory drugs (NSAIDs)
 We suggest patients with symptomatic OA of the knee and increased GI
risk (Age >= 60 years, comorbid medical conditions, history of peptic ulcer
disease, history of GI bleeding, concurrent corticosteroids and/or
concomitant use of anticoagulants) receive one of the following analgesics
for pain:
 Acetaminophen [not to exceed 4 grams per day]
 Topical NSAIDs

135
 Non selective oral NSAIDs plus gastro-protective agent
 Cyclooxygenase -2 inhibitors
 We suggest intra-articular corticosteroids for short-term pain relief for
patients with symptomatic OA of the knee.
 We cannot recommend for or against the use of intra-articular hyaluronic
acid for patients with mild to moderate symptomatic OA of the knee.
 We suggest that needle lavage not be used for patients with symptomatic
OA of the knee.
Future Directions: Biomechanical Treatments
 Identify biomarkers—of bone and cartilage turnover—that may identify
those at risk for osteoarthritis and those at risk for disease progression.
 Availability of drug therapy that may inhibit the adverse effects of
degradative enzymes or promote the growth of deficient cartilage.
 Genetic therapy to prevent the occurrence of the disease.

136
Approach to patient with Arthritis
Symptoms of rheumatic diseases

 Pain
 Stiffness
 Limitation of movement
 Swelling
 Weakness
 Functional disabilities
 Sleep disturbances
 Constitutional symptoms: in systemic diseases
 (fever, loss of weight or appetite)
Signs of rheumatic diseases
 Signs of inflammation (swelling, hotness, redness, tenderness….)
o Swelling
o Tenderness
o Limitation of motion
 Crepitation
 Deformity
 Nodules
 Enthesis
 Dactylitis
 Joint Instability
 Muscle wasting
To Solve any problem …….. Ask yourself
o Articular or Systemic
o Articular or Periarticular
o Acute or Chronic
o Inflammatory or Non-inflammatory
Pattern of articular involvement
o Mono oligo Poly-articular
o Peripheral or Axial
137
o Small or Large joints
o Symmetrical or Asymmetrical
Extra-articular signs & symptoms ( systemic ) i.e.
 Constitutional symptoms
 Skin rashes
 Mucous membrane lesions
 Ocular
 Nails
 Raynaud’s phenomenon
 Serositis
 Any other cardiac, respiratory, renal, neurological manifestations
Articular
 Deep or diffuse pain.
 Painful or limited range of movement - both active and passive
 Swelling of joint
 Crepitation
 Joint instability
 Locking of joint
 Deformity
Non-articular
 Localised pain
 Point or local tenderness
 Painful active movements but not on passive
 Physical findings are remote from joint capsule
 Swelling, crepitation, joint instability, deformity are rare
Acute arthritis
o Duration of ≤ 6 weeks
Chronic arthritis
o Duration of > 6 weeks
 Inflammatory:
o Prolonged morning stiffness ≥ 1 hr
o Signs of inflammation: Redness, hotness, tenderness, swelling, LOM
138
o Elevated inflammatory markers: (ESR/ CRP)
 Non-inflammatory:
o Short duration of MS (<30 min) or non
o No signs of inflammation
o Normal inflammatory markers
Monoarthritis = One joint affection
Oligoarthritis = 2-4 joint affection
Polyarthritis ≥ 4 joint affection
Rheumatologic History
o H/o presenting complaints
 Onset
 Progression
 Distribution of disease
 Stiffness
 Aggravating or relieving factor
 Diurnal variation
 Other systemic feature
 Functional disability
o General systematic medical history.
o Past medical and surgical history.
o Family history.
o Drug history.

139

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abir ali

Internal Medicine Book

Internal Medicine Notes – Part I

Head of Internal Medicine Department

Internal Medicine Notes – Part I

Internal Medicine Notes – Part I

Internal Medicine Notes – Part I

Non-inflammatory rheumatic diseases

Approach to patient with Arthritis

Internal Medicine Notes – Part I

Rheumatology’s Golden Rules

Internal Medicine Notes – Part I

Internal Medicine Notes – Part I

Internal Medicine Notes – Part I

Internal Medicine Notes – Part I

Internal Medicine Notes – Part I

• Prevalence: occurs in 0.2% of general population, in 2% of B27+ve

Max. Late in day Early AM

Exercise/activity Worsens Symptoms Improves Symptoms

Duration Acute or Chronic Chronic

Age at Onset 20-65 yrs. 9-40 yrs.

Internal Medicine Notes – Part I

Internal Medicine Notes – Part I

Internal Medicine Notes – Part I

Internal Medicine Notes – Part I

Internal Medicine Notes – Part I

Internal Medicine Notes – Part I

Internal Medicine Notes – Part I

Internal Medicine Notes – Part I

Internal Medicine Notes – Part I

Internal Medicine Notes – Part I

– The goals of treating the patient with SpA or PsA are to

Internal Medicine Notes – Part I

Internal Medicine Notes – Part I

Internal Medicine Notes – Part I

Internal Medicine Notes – Part I

Internal Medicine Notes – Part I

Internal Medicine Notes – Part I

Internal Medicine Notes – Part I

History of ankylosing spondylitis, enthesitis related arthritis, sacroilitis with

Internal Medicine Notes – Part I

Internal Medicine Notes – Part I

Internal Medicine Notes – Part I

 Progressive, systemic, inflammatory deforming disorder

Symmetrical, deforming, small and large joint polyarthritis often associated

Internal Medicine Notes – Part I

Internal Medicine Notes – Part I

Internal Medicine Notes – Part I

Internal Medicine Notes – Part I

Internal Medicine Notes – Part I

Internal Medicine Notes – Part I

The New RA Criteria

Internal Medicine Notes – Part I

Internal Medicine Notes – Part I

Internal Medicine Notes – Part I

Internal Medicine Notes – Part I

Internal Medicine Notes – Part I

Internal Medicine Notes – Part I

Internal Medicine Notes – Part I

Internal Medicine Notes – Part I

Internal Medicine Notes – Part I

Internal Medicine Notes – Part I

Internal Medicine Notes – Part I

Anti-TNFα Biologics for RA