RHEUMATOLOGY

1. Gout
 Def: It is a metabolic disease caused by hyperuricemia which may crystalize and result in clinical manifestation. It
most often affects middle-aged to elderly men and postmenopausal women. Plasma and ECF becomes
supersaturated with uric acid. About 1-2% of the population in the western world gets affected.
 Pathogenesis:
i. Uric acid is the end-product of purine nucleotide degradation
ii. It is excreted primarily by the kidney through glomerular filtration, tubular excretion and reabsorption.
iii. It occurs du to overproduction, reduced excretion or both
iv. Drugs that increases the risk:
- Thiazides (diuretics) - Niacin - Aspirin - ACE-inhib/ARBs
v. Acute gouty arthritis:
1. Monosodium urate (MSU) crystals in the joint are phagocytosed by leukocytes
 Release of inflammatory mediators and lysosomal enzymes
 recruitment of more phagocytes into the joint
 Synovial inflammation - Synovitis
 Clinical manifestation: Middle aged ♂, obese, alcoholic, HT and postmenopausal ♀
i. Acute arthritis: - Early manifestation of gout
1. Initially affects one joint, but may become polyarticular later (Other
joints: ankles, knees)
2. The 1st MTP joint (podagral) if often involves
3. It begins at night with dramatic pain, swelling, warmth and
tenderness.
4. It goes away spontaneously after 3-10 days
5. May be a single attack or recurrent episodes
6. It may be precipitated by:
- Dietary excess (meat, seafood, beer)
- Trauma, surgery, serious illness (ex. MI, stroke)
- Excessive alcohol ingestion
- Hypouricemic therapy
ii. Chronic arthritis:
1. Chronic non-symmetrical synovitis
2. Periarticular tophi if longstanding (Tophi = ”stone” in the joints, cartilage, bones and other
places)
3. Bone destruction
iii. Extra-articular tophi:
1. Often in:
- Olecranon bursa
- Achilles tendon
- Helix and antihelix of ears
- Ulnar surface of forearm
 iv. Tenosynovitis
v. Urate nephropathy
1. Deposit of monosodium urate crystals in interstitium (interstitial nephritis) and pyramids
2. Can cause chronic renal insufficiency
vi. Acute uric acid nephropathy (ATN)
1. Reversible cause of acute renal failure due to precipitation of urate in the tubules
2. Patients receiving cytotoxic (CTH) are at risk of this
vii. Uric acid nephrolithiasis
 Dx:
i. Synovial fluid analysis
- To confirm gout, even if it is clinical strongly suggestive
- Joint aspiration – cloudy with  leukocytes
- Presence of needle shapes monosodium urate crystals in polarizing microscopy
- Gram staining and culture to rule out infection
ii. Serum uric acid  Normal levels do NOT rule out gout
iii. Urine uric acid  >800mg/day on regular diet  suggest overproduction
iv. Screening for RFs of sequelae
- Urinalysis, serum creatinine, glucose and lipids
v. If overproduction is suspected: measure erythrocyte hypoxanthine guanine phosphoribosyl-transferase
(HGPRT)
vi. Joint x-ray – cystic changes and erosion with sclerotic margins
vii. Renal stones symptoms
 Tx:
i. Dietary changes:
- Cut out meat, seafood and alcohol
ii. Physical activity, Vit. C and coffee may reduce the risk
iii. Initial tx is to reduce symptoms of attach:
- NSAIDs
- Colchicine – alternative for those who does not tolerate NSAIDs (esp. GIT upset)
- Steroids – Joint infection must be excluded to not worse the condition
iv. Prevention and tx of chronic:
- Allopurinol – Decrease uric acid levels and prevent kidney stones
- Febuxostat -
- Probenecid -  Uric acid excretion

2. Osteoporosis
 Def: A systemic metabolic bone disease with a reduction in bone mass (or density) or presence of fragility fx.
Defined optionally as a bone density that falls 2,5 SD below the mean for a young normal individual. It’s a systemic
disease of the whole skeleton. (Most frq. Vertebrae, hip, wrist (colles fx))
 Affect >200 mill ♀ WW. And 2/3 over 80 years
 Clinical consequences:
i. Kyphosis, loss of height, bulging abdomen
 ii. Acute and chronic pain, Breathing difficulties, depression
iii. Fractures, esp. vertebrae and hip
 Aetiology:
i. Low peak bone mass (at age 20-22) or increased bone loss.
-  Osteoclatogenesis,  Osteoblastogenesis
ii. Modifiable RFs:
- Cigarette smoking, low body weight (<58kg) / BMI (<18), Anorexia, hyperthyroidism
iii. Non-modifiable RFs:
- Female, age (>65y), Caucasian, history of fractures (paternal and maternal
- Genetic disorders: Vit D/oestrogen/Ca++ receptors,
iv. Early menopausal bone loss  loss of bone mass and structure
1. Oestrogen  Inhibits osteoclastic activity
v. Ca++/Vit D def.:
1. Dietary Ca++ nutrition is poor in elderly
2. Impaired renal function   Vit D synthesis  Decreased Ca absorption  Secondary
parathyroid hyper production
vi. Drugs: Glucocorticoids (GIOP), anticonvulsants, cyclosporine, cytotoxic drugs,
 Types
i. Primary
1. Monogenous
2. Idiopathic – Vertebral fx
3. Involutional – Cortical bone fx
4. Juvenile
ii. Secondary – Disease associated
1. Endocrine: Hyperthyroidism, hyperparathyroidism, hypogonadism, Cushing sy.
2. Nutritional
3. Rheumatology: RA, ankylosing spondylitis
4. Drug-induced: Glucocorticoids (esp. before peak of bone mass), anticonvulsants
5. Immobilization, pregnancy, lactation
6. Others: Tumours
 Clinical features:
i. Patients with multiple vertebral crush fx and may have height loss, kyphosis and secondary pain
ii. The vertebrae are usually first affected before the femur.
- “Fun fact”: More women die of hip fx than cervix and ovaria cancer.
iii. Thoracic fx  restrictive lung disease
iv. Lumbar fx  abdominal sx, compression of nerves (sciatica)
 Dx
i. Medical history and physical examination:
- Ex. Low trauma fracture (usually the first sx)
- Cervical kyphosis
- Shrink of height
ii. Bone mineral density: dual x-ray absorptiometry (DEXA scan) #1
 1. Low dose x-ray.
2. Measuring the lumbar spine, head of femur and distal radius
a. The lumbar vertebras are usually the first bone to lose its density
3. Gives g/cm2 and compare it:
a. T-score compares the bone density on the basis of STD deviations to a normal 25-30
years old adult at his/her “bone peak mass”
b. Z-score compares figures to figures of the same age and sex
Normal= -1, Osteopenia= -1 to -2,5, Osteoporosis= < -2,5
iii. Lab tests: Blood count, Serum Ca++, Urine Ca++ 24 hours, serum phosphate, creatinine, Mg++, Alkaline
phosphatase, TSH, testosterone, 25OH vit D, PTH intact, N-telopeptide, Bone specific alk.phos., Protein
electrophoresis
iv. Biochemical markers: NTX, CTX, Osteocalcin, Bone spec. alk.phos.
 Ddx: Metastasis, Multiple Myeloma, Osteoporotic fx
 Prevention:
i. Vit D 400-800 IU
ii. Ca++ 1,5 g/day
iii. Smoking cessation
iv. Physical activity
 Tx: See next question!

3. Treatment of osteoporosis (2)

 Tx
- Counselling on the risk of osteoporosis and related fx  manage acute fractures
- Check secondary causes; ex. Drugs
- Active treatment is recommended if T-score is <-2,5, of
- Advise on oral intake of Ca++ (1-1,5g/day) and Vit D (800-100 IU/day)
- FRAX WHO – Fracture Risk Assessment Tool
- Regular physical activity, smoking cessation
- Minimal alcohol intake
i. Pharmacological – IF DEXA verified osteoporosis or osteopenia with fx
1. Anti-catabolic – Increase strength of bones and reduces fx risk – (Reduces further breakdown)
a. #1 – Bisphosphonates  Prevent formation of ruffled borders on osteoclasts
i. Alendronate, 70 mg PO weekly
ii. They are poorly absorbed and should be taken I the morning on empty
stomach
iii. SE: Acute phase response, Upper GIT, Rash, Jaw osteonecrosis
b. HRT (oestrogen)  Decreases the rate of bone reabsorption
i. ONLY in case of menopausal syndrome; indicated by gynaecologist
ii. Consider risk of CVD and breast cancer
c. SERMs/Raloxifene  Selective oestrogen receptor modulator   bone density
i. Decreased total LDL cholesterol without stimulating endometrial hyperplasia
 ii. SE: Hot flushes
d. Anti RANKL  Monoclonal Ab´s inhibiting osteoclasts
i. Denosumab  Osteoclast formation and function is reduced
ii. RANK ligand is the most important mediator of production and function of
osteoclasts
iii. Expression of rankle is stimulated by many mediators: interleukins, TNF-a, low
vit D levels…
2. Anabolic – Increases mass of bone tissue and reduce fx risk – (Bone formation)
a. 1-34 PTH
b. 1-84 PTH – Teriparatid, very expensive and only for patients with very high risk of fx
- Chronic elevated PTH  Deplete bone stores
- Intermittent elevated PTH  Activate osteoblasts more than osteoclasts

4. Metabolic osteopathies. Paget disease

 Talk mostly about osteoporosis and mention the other diseases with some information
 Metabolic osteopathies
i. Def: It is diseases caused by disturbance between bone formation, reabsorption and mineralization. It is
caused by dysfunction of bone cells, gene abnormalities (collagen 1), renal disorders, endocrinopathies
and tumors affecting the metabolism. Resulting in:
1. Osteopenia and bone loss (osteoporosis and osteomalacia)
2. Bone sclerosis
3. Bone marrow (Paget´s disease and osteopetrosis)

 Osteoporosis – Se Q above

 Osteomalacia/Rickets
i. Def: “Soft bone” (rickets is in children). It is a condition that results in weak or soft bones due to various
of cause. Osteomalacia means loss of inorganic bone (#1 hydroxyapatite) in adulthood. The amount of
osteoid is maintained.
ii. Aetiology:
1. Congenital
- 1# = Vit D deficiency
- Primary congenital: Vit D deficiency in mother’s blood   Mineralization
- Maternal osteomalacia, untreated celiac disease, malabsorption, pre-eclampsia
2. Too little sun-exposure
3. Exclusive breast feeding without supplementation
4. Hypocalcaemia related
- Low Ca++ intake
- Chronic renal failure
5. Hypophosphatemia related
- Primary – Vit D resistant rickets
- Secondary – Malabsorption
 - Falconi´s syndrome
6. Hydroxylase deficiency
- Type 1 (enzyme mutation)
- Type 2 (calcitriol receptor mutation)
iii. Sx:
- Bone pain and susceptible for bone fx – esp. greenstick fx (one bone broken the other bend)
- Bowed legs in young children
- Stunted growth
- Large forehead – Thin skull, delayed closure of fontanelles
iv. Complications:
1. - Fx - Muscle spasms ( Ca++) - Curved spine -  Intellectual ability
v. Dx:
1. Lab
-  Ca++,  PO4,  ALP (alkaline phosphatase)
- 25-D, 1,25-D, PTH, FGF-23
2. X-ray
- Metaphysis widening in femur
- Bending
- Fractures and pseudo-fractures
3. Pseudofractures
vi. Tx
1. Depends on the cause
2. Vit D and Ca++ supplements. Esp. Vit D to children exclusively bread-feeding
3. Calcitriol tbl  Increase Ca++ absorption
4. Phosphates in x-linked hypophosphatemia

 Osteitis fibrosa cystica – von Recklinghausen´s disease of bone

i. Def: A disease caused by  PTH which stimulated osteoclasts  Bone resorption  Ca++ are replaced
with fibrous tissue and formation of cyst-like brown tumors.
ii. Aetiology:
1. Parathyroid adenoma:
- #1 cause. Benign but metabolic active
2. Men 1 and hyperparathyroidism
3. ESRD (end stage renal disease)
- Kidneys fail to produce Calcitrol (active Vit. D)   PTH
4. Parathyroid carcinoma - rare
iii. Sx:
- Muscle weakness
- Bone pain and tenderness, bone fx, skeletal deformities
-  PTH may cause kidney stones, nausea, constipation
iv. Dx:
- Lab tests:
 -  Ca++
-  PTH
-  ALP
- X-ray:
- Extremely thin bones, often bowed and fx
- Brown tumors in hands, face, legs
v. Tx:
1. Vit D – Calcitriol (IV)
2. Surgery – Parathyroidectomy

 Osteopetrosis – Morbus Albers-Schönberg

i. Def: “Stone bone”, Marble bone disease. Genetic osteoclast abnormality leading to failure of bone
resorption failure and excessive bone is formed
ii. Aetiology:
- Genetic mutations in genes related to osteoclast function. Usually with their acidification of
resorption pits, ex. carbonic anhydrase enzymes.
- There exists AD, AR and XR forms
iii. Sx:
- Despite excess bone formation, ppl with osteopetrosis then to have more brittle bones.
- Mild forms are asymptomatic and causes no problems
- Stunted growth, deformities and higher chance of fx
- Anaemia, recurrent infection and hepatosplenomegaly due to bone expansion and less BW 
extramedullary haematopoiesis.
- Can lead to blindness, facial paralysis and deafness due to increased pressure at nerves
iv. Dx:
1. Clinical picture
2. Specific DNA mutations

v. Ddx:
1. Disorders that causes osteosclerosis
vi. Tx:
1. No specific treatment
2. In children: Give Vit D
3. Gamma interferon improves WBC functions leading to less infections
4. EPO and steroids for anaemia

 Paget´s disease of bone

i. Def: Disease of bone remodelling involving one or more bones  Deformity of bone. There is an
extremely high resorption and formation of bone  Disorganization
ii. Aetiology: Genetic and environmental factors. Not completely understood. Might also be viral influence
iii. Sx:
1. Weakness, deformities, fractures
 2. Bone pain. Mostly found in skull, spine, pelvis, femur
3. Loss of hearing in one or both ears due to nerve compression
iv. Dx: Very hard to diagnosed. X-ray bone scintigraphy, high S-bone ALP, biopsy
v. Ddx: Metastatic bone disease
vi. Complication: 1% risk for osteosarcoma
vii. Tx:
1. Bisphosphonates
2. Ca++ and Vit D to reduce chances of osteoporosis osteomalacia.
 Ddx of the involvemt of the joint in the hand

5. Osteoarthritis and spondylarthritis (2)

 Osteoarthritis
i. Def: Joint disease due to breakdown of joint cartilage and underlying bone. It is a process rather than a
disease and is NOT accompanied with any systemic illness.
- It is the most common joint disease, affecting both sexes and all races (50% > 60 years)
- It is one of the most common causes of physical impairment.
ii. Pathophysiology:
- It is NOT primarily an inflammatory but that’s a result of the process
- It is a loss of normal cartilage quality (degenerative – “wear and tear”)  Reactive changes in
adjacent tissue, and “ineffective reparation”:
-Bone Vascular congestion (“bone hypertension”)
- Cartilage repair and bone formation  Osteophytes and bone remodelling
- Exposure of subchondral trabecula
- Capsular fibrosis
- It also differs from simple “wear and tear”:
- Not necessarily age-related
- Asymmetrical distribution, often only one part of the joint
- More related to impact load then to frictional wear
iii. RF:
-Systemic:
 - Obesity - Gender (♀) - Age - Family history - Metabolic disorders
- Nutrition - Genetic predisposition
-Local:
- Joint dysplasia - Trauma - Chronic inflammation - Mechanical load
iv. Classification:
1. Primary
a. Localized: Knee OA, Hip OA, Hand OA, Foot OA, Spine OA… - Monoarthritis
b. Generalized: > 3 joint groups - Polyarthritis
2. Secondary
v. Sx:
1. Pain
- Due to: Synovitis,  vascular pressure, capsular fibrosis, fx osteophytes
- “Starting pain” – Pain on motion
- “After motion” – After physical activity
- “Secondary” – Due to secondary inflammation
2. Stiffness
- Initially: when a staring activity after a period of rest, 10-15 min
- Later stages: Permanent capsular fibrosis
3. Swelling, deformation and deformity
- Swelling due to effusion
- Deformation: Osteophytes (Herberden´s
nodes)
- Deformity
4. Limited range of motion
5. Loss of function
vi. Dx:
1. Disturbance of gait
2. Swelling and deformity, muscle wasting
3. Tenderness/pain on palpation
4. Marginal osteophytes
5. Loss of movement
6. X-ray, must be accompanies w/ pain, since all
older will have degenerative changes
a. Asymmetrical narrowing
- Not in inflammatory diseases
b. Subchondral sclerosis
c. Osteophytes
vii. Tx:
1. Lifestyle modifications
- Weight loss (if obese)
- Physical exercise
2. NSAIDs, COX-2 selective, glucosamine sulphate
  Spondylarthritis
i. Def: An umbrella term for inflammatory diseases involving both the joints and entheses. The most
common of these diseases is ankylosing spondylitis

6. Ankylosing spondylitis – Bechterev disease/Marie-Stumpell disease

 Def: Chronic inflammatory disease of unknown cause that primarily affects axial skeleton
 Spondylitis
 Sacrolitis
 Epidemiology/aetiology:
- ♂:♀= 10:1, Onset 2-3 decade
- HLA-B27 +ve in 90%
 Sx:
i. Inflammatory back pain
- Gradual onset, deep in lower lumbar/gluteal region
- Accompanied with morning stiffness (up to hours)
- Improves with activity and returns when inactive
ii. Loss of spinal mobility
- Gradual; Loss of lumbar lordosis and progressive shortening
- Forwarded C-spin
- Chest respiratory limitations
iii. Bony tenderness (enthesitis) – Sites where the tendons/ligament inserts to bone
- Costosternal junctions, Spinous processes, ischial tuberosity, tibial tubercles
iv. Arthritis of peripheral joints
- Hip and shoulders (Hip in children – onset of JIA)
- Frequently knee effusions
- Small joints are less effected
 Dx:
i. Tests:
1. Schuber test – Measure of lumbar spine flexion
 - Patient stands erect and marks are made at L5 and 10 cm above L5
- Patients bends forward maximally and distance between the marks are measured
-  by less than 5 cm is abnormal
2. Stibor test – Similar to Shuber test but:
- L5 – C7
-  by less than 7,5cm is abnormal
3. Tomayer test – patient bends forward maximally with arms hanging down
- Distance between fingertips and ground is measured
4. There are also others test for lateral flexion and chest excursion
ii. Extra-articular manifestations:
1. Eye: acute anterior uveitis
2. Heart: Aortitis, fibrosis
3. Kidney: Amyloidosis
4. Lungs: Apical lobe fibrosis
5. Urogenital: Non-specific urethritis
6. GIT: Colitis
iii. Dx criteria – Radiologic (Socialites/spondylitis) + > 1 clinical criteria:
- Lower back pain with stiffness, lasting > 3 months, relived by exercising, not by rest
- Limited motion of lumbar spine in 2 plains
- Decreased chest excursion according to normal values
 Tx:
i. NSAIDs - #1
- Good efficacy, administrated continuously
ii. Sulfasalazine – anti-inflammatory and immunosuppressive effect
- Esp. in peripheral arthritis
iii. Anti-IL-17a – Secukinumab
iv. Anti-TNF – Methotrexate, Sulfasalazine

7. Reactive arthritis and psoriatic arthritis

 Def: Acute non-purulent arthritis complicating an infection elsewhere in the body. Formerly known as Reiter´s sy.
 Aetiology:
i. Post-enteric infection: Salmonella, Yersinia, Shigella, Campylobacter
ii. Post-venereal infection: Chlamydia, Ureoplasma urealyticum
iii. Reiter´s sy. – Arthritis following urethritis/cervicitis, conjunctivitis) – The formerly name of reactive
arthritis
 Pathogenesis:
i. Triggering organisms produce LPS (Lipopolysaccharide – Endotoxin) which attack mucosal surface,
invades host cells and survive intracellularly.
ii. Bacterial antigens are present in synovium/synovial fluid leukocytes for longer periods after acute attack
iii. T-cells (most CD4+) are found in inflamed synovium, but not in peripheral blood.
iv. HLA-B27 (80%) – More severe and chronic form (prolonged intracellular survival)
 Clinical features:
 i. An infection 1-4 weeks before onset of sx. of the reactive disease
ii. Mnemonic: “Can´t see, can´s pee, can´t climb a tree” – Classical triad
1. Conjunctivitis
- Transient conjunctivitis or anterior uveitis
2. Non-gonococcal urethritis
- Urethritis/cervicitis, Prostatitis/Salpingitis
3. Asymmetric oligoarthritis (few joints involved)
- Peripheral – Knee, ankle, subtalar, MTP
- Sarcoiliitis
iii. Other sx:
1. Entesitis – Achilles tendinitis, Plantar facitis
2. Mucocutaneous
- Oral ulcers
- Keratoderma blenorrhagium: Vesicles on palms and soles (hyperkeratotic)
 Dx:
i. Clinical
- Episodes of stomach (diarrhoea) or urethritis (dysuria)
- Acute inflammatory asymmetric arthritis/tendonitis
ii. Physical exam
- Joint/tendon involvement
- Extra-articular involvement – Eyes, mucous membranes, skin, genitalia
iii. Culture/serology to find trigger – CPR, leukocytes, Stool, venerology
iv. HLA-B27 typing – Prognostic significance – Severity, chronicity
 Ddx:
- Disseminated gonococcal infection – NO back sx., symmetrical in extremities
- Psoriatic arthritis
- Gradual onset
- Primary upper extremities
- NO associated oral ulcers, urethritis, bowel symptoms
 Tx: - Mostly self-limiting
i. ATB – in case of present infection
ii. NSAIDs
iii. Sulfasalazine
iv. Corticosteroids - Intraarticular

8. Rheumatoid arthritis and juvenile idiopathic arthritis (2)

 Rheumatoid Arthritis
i. Def: A long term autoimmune disorder that primarily affects joints with pain, deformities and loss of
function. It decreased functional ability and may even lead to invalidity. It decreases quality of life and
usually shortens lifetime by 5-10 years (ass. with Hodgkin´s disease and CHD).
1. Clinical:
- Symmetrical polyarthritis
 - Involving mostly small joints of hands and RC
2. Anatomical:
- Persisting synovitis
- Local destruction of joint cartilage
- Bone erosion
- Extra-articular changes
3. Aetiology:
- Interaction of unknown antigen with impaired immune system
- Genetic susceptibility
- Acquired gene mutations
ii. Epidemiology:
- ♀:♂ = 3:1. Prevalence 1%, manifestation most often ages between 30-40
- Yearly incidence up to 50:100.000.
iii. Immuno-pathogenesis:
- Initially there is a molecular reaction (HLA, TCR, antigenic peptide)
 Activate immune-cells (macrophages)  Cells go into joints (chemokines)  Activation of
structural cells (osteoclasts)  Damage of joint tissue (cartilage, bone, soft tissue)
iv. Clinical manifestation:
1. Subjective:
- Small joint pain at rest
- Morning stiffness, >1hour
2. Objective:
a. Hand:
- Early changes: Periarticular swelling of soft tissue
- Chronic changes:
- Z-deformities (radial deviation at wrist and ulnar deviation of
digits, with palmar subluxation of proximal phalanges)
- Swan neck deformity (hyperextension of PIP w/ flexion of
DIP)
- Boutonnière deformity (Flexion of PIP w/ extension of DIP)
- Muscle atrophy (interossei)

b. Foot
- Medial foot:
- Valgus deformity (talo-calcanear, talo-navicular j. and spasm of
peroneal muscle)
- Pes planus (destruction of bone and cartilage  collapse of medial
foot)
- Frontal foot:
- Hallux valgus
- Hammer toe
 c. Cervical spine: Atlanto-axial subluxation
v. Extra-articular sx:
- Rheumatoid nodule/”Necrotizing granuloma”
- Lung fibrosis
- Prone to atherosclerosis and MI
- Anaemia, Leukopenia, thrombocytosis
- Renal amyloidosis
vi. Dx: Criteria (American College of Rheumatology)
- At least 4 of the following criteria:
- Morning stiffness >1hours
- Arthritis of > 3 joint regions  For
- Arthritis of hand joints (PIP, MCP, RC)  at least 6 weeks
- Symmetrical arthritis
- Rheumatoid nodules
- Serum RF
- X-ray changes (erosions)
- New marker: Anti-CCP (Cyclic citrullinate peptide)
- In Undifferentiated arthritis  Classifies arthritis as rheumatoid
- Predicts severe course of disease
vii. Staging – Based on type (large/small) the amount of joint involved
 Tx: Goal is to achieve clinical remission. To do that we need early and aggressive tx
i. NSAIDs
- Depresses sx of inflammation with rapid onset
1. Traditional (Non-selective)  Ibux, diclofenac
2. Selective Cox-2 inhibitors  Celecoxib, Meloxicam
- Decreased risk of GI side effects, BUT higher risk of CV events
ii. DMARDs – Disease-Modifying anti-rheumatic drug
- Immunosuppressive/immunomodulatory effect with delay of 3-6 months.
- Decreases disease activity in most patients, but may induce remission in a few ppl
- Don’t have direct analgesic effect
- SE: Oculotoxicity, hepatotoxicity, nephrotoxicity, myelosuppression, teratogenic
- Ex: Methotrexate, Sulfasalazine, Cyclosporine (nephrotoxic), Antimalarials
iii. Glucocorticoids
- Huge anti-inflammatory effect with quick onset (most effect in beginning of disease)
- SE: Osteoporosis, GI-ulcers, DM
iv. Biological therapy
- Modulates the immune system on the levels of Cytokines, co-molecules and B-cells
1. Anti-cytokine:
- Anti-TNF-a: Infliximab (SE: infections and lymphoma)
- Anti-IL1: Anakinra
- Anti-IL6: Tocilizumab
2. Inhibition of co-stimulatory molecules: Block interaction between T-cells and APCs
 - Orentia
3. Blockade of B-cells (anti-CD20)
- Rituximab
 Juvenile idiopathic arthritis - JIA
i. Def: “Juvenile”  Onset before age 16, “Idiopathic”  No defined causes, “Arthritis”  Inflammation of
the synovium of a joint. It occurs mostly from the age of 1 to 6 and may be transient and self-limited or
chronic.
ii. It differs significantly form arthritis commonly seen in adults (OA, RH)
iii. Etiopathology: Similar to RA, bur less cartilage erosion and usually absent rheumatoid factor.
iv. Signs and symptoms:
1. Initially it has non-specific symptoms like flue and persistent swelling of joints (commonly ankle,
knee and wrist and small joint of hands and feet)
2. Later also pain and morning stiffness develops
3. Extra-articular
a. Anterior uveitis (might progress to blindness), growth disturbance and bone deformities
v. Dx:
1. Done by exclusion: Blood tests, X-ray and RF (some have +ve)
vi. TX
1. Physiotherapy + same as RH

9. Extra-articular rheumatism
 Def: Diseases affecting extra-articular soft tissues of the musculoskeletal system (ex. muscles, tendons, enthesis,
fascia, bursae)
 Aetiology: Vary, but mostly due to local overuse, acute/repeated trauma and micro-trauma during
sport/activity/work, incorrect gait, inflammation
 Forms:
i. Generalized: Fibromyalgia, Chronic fatigue sy., Myofascial sy.
ii. Regional: Complex shoulder pain sy. (Humeroscapular periarthropathy) and hip periarthropathy
iii. Localized: Bursitis, tendinitis
 Fibromyalgia
i. Def: It is a longs-term condition that causes:
- Widespread musculoskeletal pain all over the body
- Increased sensitivity to pain - Paraesthesia
- Easy fatigue
- Muscle stiffness
- Sleep disturbances
- Frq. associated with depression, anxiety and PSD
ii. Aetiology – Unknown – Genetics and environmental triggers
- Genetic – The condition runs in families
- Environment – Triggers might include stress, trauma, and certain infections (HCV, HIV, Lyme
dis)
- Disorders commonly associated with fibromyalgia:
 - Irritable bowel sy.
- Irritable bladder
- Headache/Migraine
- Dysmenorrhea
iii. Epidemiology: ♀ > 50 years, Prevalence increases with age
iv. Pathogenesis:
- Disruption of stage 4 sleep (NREM)
- Serotonin deficiency (regulates pain and sleep)
- GH deficiency (secreted during NREM)
-  Levels of substance P  Spreading muscle pain
- Autonomic dysfunctions – orthostatic hypotension, Raynaud’s phenonomen…
- Psychological abnormalities – Depression, anxiety, somatization
v. Clinical manifestation:
- Generalized musculoskeletal pain – With activity, but some degree is always present
- Stiffness – Usually in the morning and improving out the day
- Fatigue
- Headache
1. Sx worsens by: stress, anxiety, cold weather, overexertion
2. Sx improves with: warmer weather, vacation
vi. Dx:
1. Some sites/points are more tender/painful than in
normal individuals
- Suboccipital muscle insertion
- Around transverse processes at C5-C7¨
- Above and medial border of scapula
- Lateral epicondyle
- Medial fat pads of knee

vii. Tx – No universally accepted treatment, but by sx:

- Improve quality of life!!!
- Behavioural therapy
- Exercise  Reduce pain and fatigue
- Pharmacotherapy:
- Anti-seizure: Pregabalin (Lyrica) – Neuropathic pain
- Antidepressants: SSRIs, TCAs (Amitriptyline) – Works only for a small %
- NSAIDs
- Opioids – Controversial

10. SLE
 Def: An inflammatory autoimmune multisystemic disease of unknown aetiology with heterogeneous clinical and
lab features. Virtually any organ of the body may be involved.
 Epidemiology:
 - 0,1% of the population, 10.000 patients in the Cz
- More frq in woman (1:10), mostly in 2-3 decade, rarely seen in older population (10%)
- With good management, the survival may be over 90%
 Aetiology – Unknown
- Not totally clear, but a mix of:
- Immune regulation 
- Environmental stimuli 
- Super antigens   Autoimmune disease
- Viruses - EBV 
- UV-light 
- Genetics 
- Hormonal – Estogen
 Causes of death
i. Severe disease manifestation – Renal, CNS, vasculitis
ii. Complication – Thrombosis, infections
iii. Accelerated atherosclerosis
iv. Treatment toxicity
 Pathogenesis: Autoantibodies (non-organ specific)
i. Immune complex disease – deposition in tissues and vital organs
ii. B-cell hyperactivity   Ig´s
iii. Excess antibody formation
iv. Development of autoantibodies years before onset of clinical features
 Classification criteria for SLE – Not necessary to know!!!
- Erythema in face
- Discoid erythema
- Photosensitivity
- Mouth ulcers
- Arthritis
- Serositis (pleuritic, pericarditis)
- Renal (proteinuria, casts)
- Neurological involvement (seizures, psychosis)
- Haematology (anaemia, leuco-, thrombocytopenia
- Immunology (Anti-dcDNA, anti-Sm… over 300 Atb´s)
- Antinuclear antibodies
 Clinical picture
- Variable course (usually relapsing-remitting) and prognosis
- Systemic features – At onset and during flares
- Fever, loss of weight, fatigue, catabolism, cachexia
- Organ specific symptoms: Underlines sx are the most common
- Skin:
- Rashes exacerbated by UV-light
- Lupus specific:
- Acute: - Subacute: - Chronic
- Malar (butterfly) rash - Annular (polycyclic) - Discoid – on check,
- Generalized erythema - Papulosquamous (psoriatiform) neck, scalp
- Bullous lupus erythematous

- Lupus non-specific:
- Vasculitis – fingertips
- Raynaud´s pheromone
- Alopecia, oral ulcers, livedo reticularis
- Musculoskeletal:
- Polyarthralgia (polyarthritis)
- Non-erosive
- MCP, OIP
- Fibromyalgia
- Complication: hip osteonecrosis, septic arthritis
- Kidney: (lupus nephritis)
- Proteinuria, haematuria
- Untreated  Nephrotic sy., renal failure
- Renal biopsy for verification of dx:
- Class 4: Diffuse proliferating GN
- Lung:
- Pleuritis (pleural effusion)
- Interstitial lung disease (Diffuse interstitial pneumonitis and fibrosis)
- Progressive dyspnoea on exertion, basal crepitation
- HRCT, pulmonary function tests
- Alveolar haemorrhage
- Heart:
- Pericarditis
- Myocarditis
- Libman-Sacks endocarditis
- CAD
- Haematology:
- Anaemia (lower production or haemolytic)
- Leukopenia
- Thrombocytopenia
- Abnormalities in coagulation
 Dx:
i. Based and clinical picture and:
ii. Lupus band test – Immunofluorescence staining – Ig and complement deposition at dermoepidermal
junction on non-sun-exposed skin
iii. Laboratory
 1. Leukopenia, thrombocytopenia
2. Hypergammaglobinaemia, autoantibodies
3. Coagulation inhibitors
 Poor prognostic factors:
i. Organ involvement (esp. lung, kidney)
ii. Low creatinine clearance and high serum creatinine
iii. Pulmonary hypertension
iv. Thrombosis and bleeding
v. Low complement levels
vi. Positive ant-dsDNA
 Tx:
i. Depends on the severity of disease
ii. CNS and renal involvement  aggressive Tx
iii. Emergencies
1. Severe CNS involvement
2. Systemic vasculitis
3. Profound thrombocytopenia
4. Rapid progressive nephritis
5. Diffuse alveolar haemorrhage
iv. Pharmacotherapy:
- NSAIDs  Depresses sx of inflammation with rapid onset
- Glucocorticoids  Huge anti-inflammatory effect
- DMARDS  Disease-Modifying anti-rheumatic drug
- Methotrexate, Cyclosporine, antimalarials
- When DMARDS fails 
- Cyclophosphamide (chemotherapy and immunosuppressant)
- Azathioprine (immunosuppressant)
- Biological – Modulates the immune system at different levels
- Rituximab (experiment) Blockade of B-cells (Anti-CD20)

11. Sjögren’s syndrome

 Def: A chronic, slowly progressive autoimmune disease characterized by lymphocytic infiltration of the exocrine
glands  xerostomia and dry eyes.
 Epidemiology:
i. Seen in females, usually in 40-60 years old
ii. Affecting 0,6-2,7%  60.00-270.000 in the Cz
 Types:
- Primary – Disease presents alone
- Secondary – Disease occurs in association with other autoimmune rheumatic disease – RA, SLE, SSc)
 Aetiology: Unknown
 Pathogenesis:
i. Infection – CMV, EBV
 ii. HLA
iii. Environmental – dust
iv. Hormones – female sex hormones
v. Associated with lymphomas – esp. extranodal low-grade marginal zone B cell lymphoma
 Clinical manifestation:
1. Eyes: 2. GIT: 3. ENT: 4. Lungs:
- Keratocinjunctivitis (tearing) - Xerostomia - Dryness in nose - Chronic bronchitis
- Dryness, itching - Enlarged parotid - Epistaxis - Dry cough
- Photophobia - Gastritis and pancreatitis - Carries ( protecting factors in saliva)

5. UGT: 6. Skinn: 7. Extraglandular:

- Vulvitis - Xeroderma - Non-erosive arthritis
- Colpitis - Pruritus - Raynaud´s phenomenon
- Dysparenuia - Eczema - Lymphadenopathy
- Vasculitis
 Dx:
i. Clinical features and:
ii. LAB
1.  ESR, BUT normal CRP
2. Mild normochromic, normocytic anaemia
3. Hypergammagobulinemia
4. Immunology:
- RF - ANA - ENA - SSa(Ro) (specific) - SSB (La) (specific) - AMA
iii. Additional exams:
1. Eyes:
- Schirmer´s I test – Measure of tear flow
- Slit lamp exam of cornea and conjunctive
2. Salivary glands:
- Sialometry
- Sialography
- Biopsy  Lymphocytic infiltrates
 Tx:
i. Glandular (only symptomatic treatment!):
- Eye drops
- Frequent drinking
- Chewing gums
- Lubricative jellies
ii. Extra-glandular:
- Methotrexate (arthritis) – 10-20 mg/week
- Prednisone + cyclophosphamide (vasculitis)
12. Systemic sclerosis, polymyositis, dermatomyositis
 Systemic sclerosis/Scleroderma:
i. Def: Generalized chronic CT (connective tissue) disease involving skin and visceral organs with fibrotic
sclerotization or peripheral and visceral vessels. The disease can be localized to the skin or involve other
organs in addition.
ii. Aetiology: Unknown – autoimmune (genetic and environmental factors)
iii. Pathogenesis:
1. Circulating autoantibodies, endothelial cells, fibroblasts, smooth muscles cells, lymphocytes,
monocytes, eosinophils and mastocytes and their complex interaction.
2. It is caused by genetic and environmental factors. Mutations in HLA genes seems to play a crucial
role, but other factors like silica, aromatic and chlorinated solvents +++ seems to contribute in
some of the affected persons.
3. In general:  Synthesis of collagen  Sclerosis  damage to vessels/endothelium  apoptosis
 vascular leakage (edema) – Th1-cells seems to play a role at this stage of disease.
- Impaired angiogenesis and vasculogenesis related to antiendothelial autobodies
results in a net vasoconstriction  ROS formation and ischemia – Th2-cells play a role
at this stage.
- B-cells  Plasma cells  further autoimmune reaction
- Fibroblasts and myofibroblasts are recruited by cytokines and GF´s  excessive
collagen deposition  Fibrosis
iv. Clinical picture:
1. Vascular phase:
- Raynaud´s phenonomen (episodic vasoconstriction of fingers and toes)
- First pallor and ischemia then erythema (when re-perfused)
- Ischemic changes in fingers (ulceration/gangrene) and visceral organs (renal crisis)
- Changes in microvasculature (nailfold capillaroscopy) – widened and irregular loops
2. Skin phase:
- Edema of fingers  arthralgia and morning stiffness
- Further scleroderma – Sclerodactyly (Glossy tight skin)
- “Salt and pepper” appearance
- Skin atrophy  Ulcers
- Face
- Expressionless face – loss of wrinkles
- Micro-stomia
- Calcinosis cutis
- Calcium hydroxyapatite crystal deposition in skin – fingers, palms, olecranon,
prepatellar bursae
v. Classification:
1. Localised scleroderma – Isolated patches of hardened skin on face, hands, and feet (or
anywhere else), but NO interal organ involvement
2. Systemic scleroderma – With internal organ involvement
a. CREST sy.
 b. Progressive systemic sclerosis
vi. Systemic sx:
1. GIT:
- Esophagus: regurgitation and heartburn, erosive esophagitis, strictures
- Stomach: Gastroparesis, bloating
- Small intestine: Colic, malabsorption, diarrhoea
- Colon: Constipation, diarrhoea
2. Cardiovascular:
- Raynaud´s phenonomen
- Palpitations
- Hypertension
- Congestive heart failure
3. Pulmonary:
- Pulmonary HT, dry persistent cough
- Interstitial lung disease
4. Musculoskeletal:
- Joint and muscle pain and weakness
- Carpal tunnel syndrome
5. Genitourinary:
- Erectile dysfunction, renal crisis, kidney failure
vii. Dx:
1. Clinical picture
2. Symmetrical skin thickening with 70% with Raynaud´s phenonomen, nail-fold capillary changes
and antinuclear antibodies
3. There is NO single test, but often a matter of exclusion.
4. Lab test can show:
- Antitopoisomerase antibodies
- Anti-scl70
- Anticentromere antibodies (Ass. with CREST sy.)
5. CREST syndrome (limited cutaneous form of systemic sclerosis) – Multisystem CT disease
- Calcinosis
- Raynaud’s phenonomen
- Esophageal dysmotility
- Sclerodactyly
- Telangiectasia
viii. Tx:
- No cure, only relief of symptoms
- Immunosuppressant – Methotrexate, cyclophosphamide, rituximab….
- Raynaud´s  Ca++ channel blockers
- Interstitial lung disease  Cyclophosphamide +/- corticosteroids
- Pulmonary HT  Phosphodiesterase inhibitors (Sildenafil)
- Kidney crisis  ACE-inhibitors or ARBs
 Inflammatory myopathies
i. Def: A heterogeneous group of condition characterized by proximal muscle weakness and non-
suppurative inflammation of skeletal muscle. Muscle weakness is the most common sx.
ii. Classification criteria:
1. Symmetric limb-girdle muscle weakness (dysphagia and resp. muscles involvement)
2. Elevation of serum skeletal muscle enzymes
3. Electromyography changes
4. Skeletal muscle histology
5. Typical skin rash
iii. What similarities do the 2 types have?
1. Clinical features
a. Progressive and symmetric muscle weakness increasing difficulty with everyday tasks
requiring use of proximal muscles (ex. getting up from a chair, combing hair, climbing
steps)
b. Sparing of ocular and facial muscles
c. Involvement of pharyngeal and neck flexor muscles  Dysphagia, “head-drop”
d. Weakness progresses subacutely (weeks-months)
e. Extramuscular manifestation (NO rash in PM)
2. Dx:
a. Myopathic muscle weakness
b. Skeletal muscle enzymes (CK)  (up to 50x)
c. In PM:
i. EMG: Myopathic (short duration and lower amplitude)
ii. Muscle biopsy: Inflammation complex located endomysially
3. Tx – Corticosteroids and symptomatic treatment
iv. Polymyositis – Endomysial inflammatory infiltrate surrounding and invading non-necrotic muscle fibres
1. Epidemiology:
a. Age at onset > 18 years.
b. NO familial association
2. Clinical features - NO RASH!!!
a. Associated with CT disease/systemic autoimmune disease, viral/bacterial infection,
drugs.
b. Extramuscular manifestation:
i. GIT - Dysphagia
ii. Systemic symptoms – Fever, malaise, weight loss, arthralgia, Raynaud´s p.
iii. Heart – CHF, conduction defects (blocks and arrhythmias)
iv. Lung – Interstitial lung disease, weakness of resp. muscles
v. Dermatomyositis – Perifasicular inflammatory infiltrate and atrophy
1. Epidemiology:
a. Age at onset: Childhood and adulthood. Mostly females
b. NO familial association
 2. Clinical features – RASH!!!
a. Associated with CT disease and scleroderma
b. Associated with malignancy – ovarian, breast, colon, melanoma…
c. Extramuscular manifestation:
i. Similar to PM, plus:
1. Subcutaneous calcification
2. Dilated capillary loops on finger nail-bed
ii. Rash: Usually precedes muscle weakness
1. Heliotrope rash – Blue on upper eyelids with edema
2. Gottron´s sign – Erythema on knuckles
3. “V sign” – Red rash on chest formed as a “V”

13. Systemic vasculitis

 Def: Inflammatory disease of blood vessels – Destruction of vessel wall, proliferation and occlusion. Clinical
syndromes result from tissue ischemia with general symptoms
 Types:
- Primary: Idiopathic inflammation of vessel wall
- Secondary: Accompanying RA, SLE, Juvenile DM, SS, SSc
 Dx – Based on pathological findings and imaging methods
 Classification of all vasculitis (Jeanette et al. 1993)
i. Large vessel vasculitis:
1. Giant cell (temporal) arthritis
 2. Takayasu´s arthritis
ii. Medium vessel vasculitis:
1. Polyarthritis nodosa
2. Kawasaki disease
iii. Small vessel vasculitis:
1. Wegner´s granulomatosis/ Granulomatosis with polyangiitis (GPA)
2. Churg-Strauss sy.
3. Henoch–Schönlein purpura (HSP)/ IgA vasculitis/Purpura rheumatica
 Giant cell (Temporal) arthritis:
i. Def: Arthritis of branches of carotid artery occurring in middle and old age
ii. Epidemiology: >50years, ♀, Scandinavia
iii. Pathogenesis:
- Ig and complement deposition
- Pathogenic T lymphocyte response to granuloma
iv. Clinical picture:
- General: Fever, fatigue, anorexia, headache, anaemia
- Jaw claudication
- Weak pulse
- Swelling of temporal artery
- Claudication of upper extremities and Raynaud´s phenonomen
- Arthritis
- Blindness
- Brain bleeding
- Death due to: Cerebrovascular events, MI, aortic aneurysms
v. Dx:
1. Lab:  ESR, Anaemia (normochromic),  ALP, -ve immunological tests
2. Biopsy  Granulomatous inflammation
vi. Complications:
1. Polymyalgia rheumatic. Def: Pain and stiffness on muscles of arm and pelvic girdles, possible
associated with giant cell arthritis.
vii. Tx:
1. Prednisone for 1 month, then tapering down for 2 years
2. Substitution: Cyclophosphamide, Azathioprine
 Wegener´s granulomatosis/Granulomatosis with polyangiitis (GPA)
i. Def: Long term systemic disorder that involves granulomatosis and polyangiitis. The vasculitis affects
small and medium sized vessels, mainly in respiratory tract and kidneys (glomerulonephritis (GN))
ii. Epidemiology: ♂, middle-aged
iii. Pathogenesis:
- Hypersensitivity, immune complexes
- Pathogenic T lymphocyte response and granuloma formation
iv. Sx: Initial sx can be extremely variable and non-specific.
- Rhinitis can be a typical first sx – Nosebleed, stuffiness…
 - Conjunctivitis is seen in more than 50%
- Rapidly progressive GN  Chronic kidney failure
- Arthritis (60%) – Often first dx as RA
v. Dx:
- Clinical features
- 90% have +ve Anti-Neutrophilic Cytoplasmic Antibodies (ANCAs)
- Biopsy of kidneys
vi. Tx:
- Severe disease: Rituximab/Cyclophosphamide + Corticosteroids
- Limited disease: Methotrexate + Corticosteroids
vii. Prognosis: With modern Tx  5-year survival is >80%
14. Treatment of rheumatic diseases; biological therapy
 Non-Pharmacotherapy
i. Lifestyle modifications
1. Weight loss
2. Physical exercise
 Pharmacotherapy used in Rheumatic diseases:
i. NSAIDs
- Depresses sx of inflammation with rapid onset
1. Traditional (Non-selective)  Ibux, diclofenac
2. Selective Cox-2 inhibitors  Celecoxib, Meloxicam
- Decreased risk of GI side effects, BUT higher risk of CV events
3. Colchicine (NOT NSAID)  Used in Gout for those unable to tolerate NSAIDs
ii. DMARDs – Disease-Modifying anti-rheumatic drug
- Immunosuppressive/immunomodulatory effect with delay of 3-6 months.
- Decreases disease activity in most patients, but may induce remission in a few ppl
- Don’t have direct analgesic effect
- SE: Oculotoxicity, hepatotoxicity, nephrotoxicity, myelosuppression, teratogenic
- Methotrexate
- Sulfasalazine
- Cyclosporine (SE: nephrotoxic)
- Antimalarials
iii. Glucocorticoids
- Huge anti-inflammatory effect with quick onset (most effect in beginning of disease)
- SE: Osteoporosis, GI-ulcers, DM +++
iv. Biological therapy
- Modulates the immune system on the levels of Cytokines, co-molecules and B-cells
1. Anti-cytokine:
- Anti-TNF-a: Infliximab (SE: infections and lymphoma)
- Anti-IL1: Anakinra (SE: BW suppression)
- Anti-IL6: Tocilizumab
2. Inhibition of co-stimulatory molecules: Block interaction between T-cells and APCs
 - Orentia
3. Blockade of B-cells (anti-CD20)
- Rituximab
v. Anti-uric acid decreasing drugs: Xanthine oxidase inhibitor
- SE: Itchiness and rash
- Allopurinol - Decrease uric acid levels and prevent kidney stones
- Probenecid -  Uric acid excretion

 Specific for the different diseases:

NSAIDS Glucocorticoids DMARDs Biological Allopurinol

- Gout x x x
- OA x
- Ankyl. Spond. X Sulfasalazine Infliximab
- Reactive arthritis x x Sulfasalazine
- Rheumatoid arth. X x Sulf., Metho., Cyclo. AntiMal. Inflix, Anakinra, Tocilizumab
- Extra-articular rheum. X (+ Anti-seizure (Pregabalin), antidepressants (TCAs, SSRIs)
- SLE x x Metho., Cyclo. AntiMal. Rituximab (+Cyclophosphamide)
- Sjøgren´s x Methotrexate (+Cyclophosphamide)
- Systemic sclerosis Methotrexate (+Cyclophosphamide)

15. Systemic and topical corticosteroid therapy; side-effects of the therapy

 There are 2 main classes of corticosteroids
i. Glucocorticoids – Cortisol:
- Carbohydrate, fat and protein metabolism
- Anti-inflammatory  Block inflammatory mediators
- Immunosuppressive  Suppress hypersensitive reactions (on T-cells)
- Anti-proliferative  Inhibits DNS synthesis
- Vasoconstriction  Inhibiting Histidine
ii. Mineralocorticoids – Aldosterone
- Increases Na+ uptake in kidneys  electrolyte and volume balance
 Drugs used
i. Systemic – Systemic diseases: Inflammatory, immune-disorders, adrenal deficiency +++
1. Cortisol – Hydrocortisone (Adrenal insufficiency)
2. Glucocorticoids – Dexamethasone
3. Glucocorticoid + some Mineralocorticoids – Prednisone
4. Mineralocorticoids – Fludrocortisone
ii. Topical – Rash, eczema and dermatitis
1. Weak – Hydrocortisone
 2. Very potent (600x stronger than hydrocortisone) – Clobetasol
iii. Injections – Inflammation of joint/tendon

 Considerations before starting oral corticosteroids:

i. Are they really necessary and have safer alternatives ex. NSAIDs been tried?
ii. Are there any relative contraindications or precautions? Ex. DM, HT, Osteoporosis
iii. Duration of treatment – Short or long term?
iv. Timing of dose – early morning if possible, as there is less HPA axis suppression. But in severe disease and
active disease, a split dose in morning and evening may be necessary.
v. Aim for the lowest dose and time of use
vi. Patients need to be advised of adverse effects against ceasing corticoids suddenly and about wearing
medical-alert badges while on long-term treatment
 Contra indications:
i. Absolute CI:
1. Pregnancy: Low but significant teratogenic effect
2. Infectious arthritis
3. Bacteraemia
4. Osteomyelitis
5. Bacterial endocarditis
ii. Relative CI:
1. Uncontrolled DM
2. Uncontrolled HT
3. Osteoporosis
4. Glaucoma
5. Joint instability
6. Congestive HF
7. Psychosis
 SEs:
i. Osteoporosis
ii. DM (hyperglycaemia, insulin resistance)
iii. Peptic ulcers, colitis
iv. HT (Na+ retention)
v. “Moon face”
vi. Vulnerability for infections

16. Infectious arthritis

 Def: Inflammation caused by presence microorganism in the joint (verified by cultivation)
 Aetiology:
- Bacterial
- Mycobacterial
- Fungi (candida, Coccidiosis immitis)
- Viruses (HBV, Parvovirus B19, Rubella virus, HIV)
 - Parasites (Dracunulus medinensis, Echinococcus granulosus)
 Pathogenesis:
- Microorganisms enter joint from:
- Bloodstream (Haematogenous from primary site)
- Adjacent structure (Bone, soft tissue)
- Direct contamination (Surgery, injection, trauma)
i. Bacterial arthritis
1. Non-gonococcal (Septic)
a. Aetiology:
- S. Aureus - Coagulase –ve staphylococci (prostatic joint) - Strep Pyogenes
- Skin anaerobes - Gram –ve bacilli
b. Sx:
i. Acute onset
ii. Systemic signs – Fever
iii. Local inflammation – Pain, Swelling,  Function (ROM), Erythema, Heat
iv. Mostly mono-articular and knee
c. Dx:
i. Non-specific:
-  ESR, CRP - Leucocytosis - Sepsis - Synovial fluid: Neutrophils
ii. Specific:
- Microbes in blood (50%) - Microbes in synovial fluid (90% sensitivity)
d. Tx:
i. ATB
1. Staph  Oxacillin
2. Strep  Penicillin G
3. G –ve Ceftriaxone
ii. Arthrocentesis –Drainage - Surgery – Arthrotomy
iii. Physiotherapy
2. Gonococcal
a. Aetiology – Neisseria gonorrhoea
b. Sx:
- Polyarthritis – Knee, hands, wrists, feet, ankles
- Dermatitis – Papules
- Tenosynovitis
- Genitourinary sx (in 25%)
c. Dx:
i. Non-specific: Similar to non-gonococcal arthritis
ii. Specific: Cultivation/DNA (PCR)
d. Tx:
i. ATB – Ceftriaxone (1g IV/24h), then ciprofloxacin 1-2 weeks
ii. Arthrocentesis –Drainage
iii. Surgery – Arthrotomy
 iv. Physiotherapy
ii. Mycobacterial arthritis
a. Aetiology: Mycobacterium tuberculosis
b. Pathogenesis:
- Reactivation of latent TB
- Hematogenic/lymphatic spread of primary infection