Rheumatology Flashcards
MTX MOA
Where does: metabolism and clearance take place?
- MOA is folic acid antagonism: inhibits dihydrofolate reductase (competitively) which is required to convert folic acid -> tetrahydrofolate (reduced/functional/biologically active form)
- Hepatic metabolism
- Renally cleared
MTX Toxicity
- Toxicity sx/effects
- What agent causes toxicity?
- Antidote to toxicity?
Methotrexate toxicity effect
o Severe enteritis + mucositis
o Liver damage, dermatitis, stomatitis
o Myelosuppression
o Renal impairment/acute renal failure due to precipitation in tubules
Increased toxicity with Bactrim due to same MOA (dihydrofolate reductase inhibitors) and both renally excreted
Antidote to methotrexate toxicity is folinic acid
o Folinic acid is the reduced form of folic acid and does not require dihydrofolate reductase for conversion into tetrahydrofolate (reduced, active form)
o Therefore can enter cells and be converted into active form despite presence of MTX
Mx JIA
o Early intervention improves prognosis by preventing/delaying irreversible bony changes and loss of function
o PT, OT, podiatry – stretching, strength and function improvement, joint splinting, foot orthoses
o NSAIDs – sx control
o I/A steroid injections – mild-mod disease
o DMARDs (MTx/cyclosporine) – polyarticular, poorly controlled oligoarticular or systemic
o Biologics (etanercept or infliximab) – severe resistant disease
JIA xray changes
o Early: soft tissue swelling, osteopenia, periosteal new bone formation
o Late: Bony overgrowth, osteoporosis, subchondral bone erosions, joint space narrowing, collapse, deformity, fusion, subluxation
JIA
Definition
Sx
Definition:
o Chronic synovitis (>= 6 weeks)
o +/- extra-articular features
o Occurs BEFORE 16yo (‘juvenile’)
Symptoms
o Early morning joint stiffness
o Joint swelling, warmth; sometimes red and tender
o Limited painful movement
o Contractures and/or bony deformity can develop rapidly
Osgood-Schlatter disease
Front knee pain and painful lump just below knee cap in boys of late childhood/early adolescence (10-15y) who are highly active (running, jumping sports).
Worse with activity, improves with rest.
Resulting from inflammation at tibial tuberosity at patellar ligament insertion site. sx resolve when growth plate closes.
Xray: Bone fragmentation at the tibial tuberosity may be evident 3 to 4 weeks after the onset of sx.
Tx - RICE (PT, NSAIDs, brace)
What is an apophysis
What is apophysitis? Give an example of a common condition in children
Part of growth plate to which ligaments/tendons etc join. weaker than other parts of growth plate -> prone to traction/overuse injuries in growing children = apophysitis
ex - Osgood Schlatter disease (inflammation at tibial tuberosity at patellar ligament insertion site)
Spot diagnosis and potential complication:
Abrupt onset of reluctance to walk with severe symmetrical bilateral lower leg pain following a recent viral illness. Common prodromal symptoms of these viral illnesses include rhinorrhea, low-grade fever, sore throat, cough, and malaise.
OE: Wide based (tiptoe walking or stiff legged) and leg muscles tender to palpation. Normal neurological signs.
Diagnosis: Viral myositis
Sx: Sudden onset refusal to walk/symmetric bilateral lower limb (often calves) pain in a child presenting with a history of recent viral illness.
Gait might appear wide based (tiptoe walking or stiff legged)
Lasts ~3 days as inital illness resolves
Initial workup only in thsoe chlidren who won’t walk at all - CK (high), FBE [WCC and plt (high or low)]
If worsening/not improving after ~3-4 days: urine myoglobin, FBE, UEC, LFT, CRP
Complication: Rhabdomyolysis -> renal failure
What is transverse myelitis?
Classic sx
Causes
Ix workup
Inflammation of spinal cord resulting in acute onset of motor, sensory, and autonomic dysfunction:
- Back pain usually the first sign
- Urinary retention +/- bowel incontience or constipation
- B/L lower limb (+/- arms) weakness (paraplegia or quadriplegia)
- decr tone and reflexes acutely -> hyperreflexia w incr tone over time
- Sensory level - parasethesias etc
- Autonomic sx - temp, HR, RR variability
- *Causes:**
- Post-infectious most common - viral/bact/fungal/parasitic
- Autoimmune (multiple sclerosis, neuromyelitis optica, systemic lupus erythematous, Sjogren’s syndrome and sarcoidosis)
Ix
- Urgent MRI spine (r/o compressive lesion and confirm inflammation of spine)
- if confirmed TMS -> MRIB (r/o MS), LP for CSF, lots of blood tests looking for aetiology, opthal review (?NMO)
Polyarteritis nodosa
What is it?
Presentating features
Diagnosis
- Small and medium sized vasculitis (non-ANCA)
- Targets renal and visceral arteries
- often viral aetilogy: hep B/C, EBV, parvovirus B19, HIV
- Presentation
1. Systemic sx: malaise, fever, weight loss, myalgias
2. SKIN (purpuric rash, subcutaneous lesions, bullous vesicular lesions, livedo reticularis)
2. Migratory arthralgia, arthritis
3. Renal (renal artery involved -> infarction): haematuria, proteinuria, CRF, HTN
4. Neuro: Mononeuritis multiplex and peripheral neuropathy
5. CV: aneurysms, MI, cardiac failure
6. GI: non-specific abdo pain
Diagnosis is via vessel bx
Dermatomyositis
WHat is it?
Presenting features
Diagnosis
Mx
Inflammatory disease of skeletal muscle and skin
Presentation:
- SKIN: Rash to sun-exposed areas and face (malar rash) and eyelids (heloprope rash), subcutaneous calcium deposits which can extrude (look like exudate), gottron’s papules (red rash overlying DIP, PIP joints and knees) and nail fold capillaritis
- NEURO: Symmetrical proximal muscle weakness and pain (Gower sign and waddling gait); resp muscles weakness; dysphagia, dysphonia)
- LUNGS: Resp muscle weakness and fibrosis
Can also get joint, GI, cardiac, retinitis, renal involvement
Diagnosis - muscle bx of thick +/- pos ANA, neg RhF
Mx - systemic steroids, PT, OT/splinting, immunosuppressants (MTX, cyclosporin) or biologics in resistant cases
What is nodular panniculitis/WEber-Christian disease
WHat is it?
Cause?
PResentation
Inflammatory condition of subcutaneous fat characterised by one or multiple, recurrent, subcutaneous nodules. These commonly arise on the legs but can arise elsewhere on the body. Nodular panniculitis is associated with acute systemic symptoms such as fever, general malaise and abdominal pain.
Cause- unknown. only called nodular panniculitis when no other cause for presentation has been found (ie erythema nodosum, alpha 1 antitrypsin deficiency etc)
Presenting features
- Fever
- Malaise
- Painful nodules, 1–2 cm in diameter, on both thighs, lower legs and buttocks -> each nodule regresses after a few weeks. In some cases, the nodules can ulcerate and leak an oily, yellow discharge.
Limited Cutaneous systemic sclerosis
Features
Bloods
Formerly ‘CREST’ syndrome
- Calcinosis (Ca deposits in skin)
- Raynaud’s
- Esophageal dysmotility (GORD)
- Sclerodactyly (fibrous tissue deposition in hands -> contractures)
- Telangiectasia
Bloods: Anti-centromere ab and ANA positive; ESR normal
Systemic sclerosis
Features
Bloods
All ‘CREST’ sx as well as affecting internal organs
- CV: HTN, coronary artery
- Lung: fibrosis (gradual onset dry cough and SOB)
- Kidneys: ‘scleroderma renal crisis’ - ARF (CREST syndrome does not get renal failure)
Bloods: ANA positive and Anti-SCL 70 Ab positive
Systemic Scleroderma
-> Key skin features
Shiny, tight skin without normal skin folds
Most notably on hands and face
‘CREST’
Calcinosis
Reynaud’s phenomenon with ABNORMAL capillaries in nail beds (microhaemmhorages and avscular areas)
Esophageal dysmotility (swalloing difficulties, acid reflux, esophagus)
Sclerodactyly -> skin tighting around joints of hands -> restricted range of motion and loss of fat pads + ulceration due to tightened skin breaking
Telangiectasia - small visible blood vessels on hands
Localised scleroderma
Most common form of scleroderma in kids
Limited to SKIN (btu also tendons and joints -> joint stiffness and pain)
Features:
- Morphoea (discrete firm plaques) or linear lesions, initially erythematous but become atrophic and shiny with raised violaceous borders. Hyper OR hypopigmented.
Natural history - burns out after a number of gears but MTX and biologics can limit damage during the active yeas
Ankylosing spondylitis
What is it?
Presentation
Bloods
Classic xray finding
Inflammatory condition affecting spine (Sacroiliac and vertebral column joints) causing pain and stiffness
Presentation:
Young male in late teens
Lower back/buttox pain and stiffness
Worse with rest (first thing in morning) and improves w movement/throughout day
Can also present w
- Systemic sx (weight loss, fatigue)
- Chest pain
- Enthesitis (ankle pain/inflammation)
- Dactylitis (inflammation/pain of finger or toe)
- Anterior uveitis
Bloods:
- Anaemia of chronic disease
- ESR, CRP increased
- RHF and ANA negative
- HLA-B27 gene associated (90% of patients w ank spond) however only 2% of patients with HLA-B27 gene have ank spond
Can progress to fusion of joints in spinal column and/or SI joint -> leads to ‘bamboo spine’ xray finding
Psoriatic arthritis
What is it?
Signs
Inflammatory seronegative spondyloarthropathy associated with psoriasis
-> varying severity
Occurs in 10-20% of patients w psoriasis
Patterns:
- Symmetric polyarthritis
- Assymmetrical pauciarthritis
- Spondylitic (back, sacroiliac and antanto-axial/neck) - more in men
Signs
- Extensor surfaces/scalp - scaly salmon pink plaques
- Pitting of nails
- Dactylitis (inflammation of full finger or toe)
- Onycholysis (separation of nail from bed)
- Enthesitis: inflammation of tendon insertion site into bone (ex achilles)
- Uveitis/conjunctivities
- Aortitis
Rheumatoid arthritis
What is it?
sx
extra articular manifestatons
bloods
Autoimmune condition affecting synovial lining of joints
Symmetric polyarthritis affecting small joints (MCP, PIP, MTP) initially -> larger joints when it progresses
Flares -> warm, red, stiff, painful joints
Stiff/painful in morning/after rest, improves over course of day
Ulnar deviation
Boutonniere deformity
Bakers cysts
Extra-articular
- Systemic: fever, malaise, LOW, weakness
- SKIN: Rheumatoid nodules (elbows)
- Anaemia of chronic disease
- Lungs: interstitial fibrosis and pleural effusions
Bloods
- Anti-CCP ab
- Rh F
- HLA-DR1 and HLA-DR4
What is HLA-DR1 and HLA-DR4 assoc w
RA
What is HLA B27 assoc w
ankylosing spondylitis
reactive arthritis
Serum sickness/serum sickness like reaction
- Clinical features
- Time course
- Treatment
- Triggers
Clin ft TRIAD: Rash, fever and polyarthritis.
- Pruritic Rash - urticarial-type lesions (see images below)
Often appearing first in flexural areas and then becoming more generalised
Persist for days in same area (migate more slowly that true urticarial rash)
Lesions gradually expand, and may leave a central area of clearing or slight purpura.
Spare the oral mucosa
- Erythema and oedema of hands and feet is common
- Polyarthritis – acute joint pain, limp, inability to walk
- Fever – true serum sickness > 38.5 vs SSLR low-grade fever
- Lymphadenopathy
- Odema of hands, feet, facial, periorbital region
- Low C3 and C4 (type 3 HS reaction)
Time course: Signs and symptoms of true serum sickness occur 1-2 weeks after first exposure, while SSLRs usually develop after 5 to 10 days.
Treatment: Identification and removal of the causative agent is the key, but note treatment may have been ceased prior to appearance of rash.
- True Serum Sickness TRIGGERS :
• Snake anti-venom, equine and rabbit anti-thymocyte globulin (ATG)
• Monoclonal antibody drugs such as Rituximab are most often implicated.
• Insect stings eg: bees
• Antiserum – rabies and tetanus - Serum Sickness-Like Reaction (SSLRs) TRIGGERS
• Cefaclor and amoxicillin.
• Illnesses
• Immunisations
Scarlet fever
What is it caused by?
Sx
Ix
Mx
- Group A beta haemolytic strep
- Entry point is pharynx
- Follows 2-4 days after streptococcal pharyngitis infection
Clinical features
o Fever, headache, sore throat, rigors, vomiting, anorexia
o Swollen tonsils -> White coated tongue (peels) -> strawberry tongue
o Flushed cheeks with circumoral pallor
o Rough/‘Sandpaper’ rash starting on neck then spreading to rest of body (including face, palms, soles)
Ix
o Throat swab - PCR
o ASOT and anti-DNAse B present
Mx
o Oral penicillin for 10 days (erythromycin if penicillin allergy)
Osteogenesis imperfecta - what is it?
gene mutation
types 1-4
Autosomal Dominant condition featuring fragile bones, dentition due to defective or reduced type 1 collagen
Due to mutations in genes COL1A and COL1A2
4 different types
- 1 is mildest form; most common
- 2 is most severe, often fatal
- 3 is assoc w fractures at birth and severe early hearing loss
- 4 similar to 1
Features
- Skeletal:
- -> scoliosis, kyphosis etc
- -> multiple fractures before puberty
- -> barrel shaped chest, soft skull
- -> bowed legs and arms, joint hypermobility
- -> triangular face, small nose
- -> soft brittle discoloured teeth
- -> short stature
- Skin: loose, thin, smooth skin, easy bruising
- Eyes: blue-grey sclera
- Deafness in 50% from age 20
What is this picture diagnostic of?
Wormian bones -> Osteogenesis imperfecta
Also seen in:
- Craniosynosisis
- Rickets
- “Kinky-hair” Menke’s syndrome
- Hypothyroidism and hypophosphatasia
- Down syndrome
What is this condition?
Osteogenesis imperfecta - blue/grey sclera
