Rheumatology Flashcards
Most common complication of uveitis associated with oligoarticular JIA?
Cataracts
Oligoarthritis or dactylitis, family history of psoriasis?
Juvenile psoriatic arthritis
- psoriasis rash may not develop for up to 10 years after joint involvement
- nail pitting is another common feature
Heel spurs are often associated with which conditions?
Plantar fasciitis and ankylosing spondylitis
What is enthesitis?
Inflammation where joint capsules, ligaments and tendons attach to bone
- is the hallmark of ankylosing spondylitis
Mechanism of action of tocilizumab?
= recombinant humanised anti-human monoclonal antibody against the IL6 receptor
Used in treatment of systemic onset JIA and polyarticular JIA
Given via infusion
Mechanism of action of infliximab?
= chimeric monoclonal antibody that binds to TNF alpha
Used in treatment of refractory Kawasaki disease
(Etanercept also binds to TNF alpha but is a recombinant protein, not shown to be effective in KD)
Mechanism of action of anakinra?
= IL1 inhibitor, administered daily
Used in the treatment of systemic JIA
Canakinumab is also an IL1 inhibitor but given monthly, and rilonacept is also an IL1 inhibitor but given weekly
Overview of hydroxychlorquine?
Anti-malarial drug, used in treatment of cutaneous rheumatological disease such as SLE and dermatomyositis
- can lead to reversible corneal toxicity
- retinal toxicity is a rare but irreversible side effect
- most common SE is nausea
- toxicity is dose related, therefore lowest effective doses are administered
6 week history of arthritis, two week history of fever, rash which is worse when febrile, lymphadenopathy and hepatosplenomegaly?
JIA
- can be very unwell initially and can be misdiagnosed with septic arthritis or osteomyelitis, but fail to respond to ABx
- should always also consider malignancy
Differences between pseudoporphyria and porphyria cutanea tarda (PCT)?
Pseudoporphyria has normal porphyrin levels in plastma/erythrocytes/urine and stool (abnormal suggests PCT)
10% of children with JIA who are taking naproxen will develop pseudoporphyria, and increased risk with pale skin/if also taking chloroquine
PCT is associated with hyperpigmentation and hypertrichosis, but pseudoporphyria is not
Skin lesions take ~6 months to heal
Ankylosing spondylitis presentation?
Usually presents with SEA syndrome
- Rh factor seronegativity
- enthesitis around foot and knee
- oligoarthritis: legs >arms (esp hips), SI joint and axial skeleton usually affected later in the course
Overview of familial mediterranean fever (FMF)?
Caused by mutations in MEFV (most are missense)
Present with 1-3 days of fever, serositis, arthritis and an erysipeloid rash (appears over ankle or dorsum of the foot is characteristic)
90% of cases present before the age of 20
Most serious complication of FMF?
Amyloidosis
- colchicine is given as prophylaxis
- usually presents with proteinuria
- if untreated, leads to renal failure in 3-5 years
What is pyoderma gangrenosum associated with?
PAPA (pyogenic sterile arthritis, pyoderma gangrenosum and acne)
Role of complement C4a and C5a?
Anaphylatoxins - promote inflammation, stimulate smooth muscle contraction, increase vascular permeability and encourage mast cell degranulation to release further inflammatory mediators
Relevance of C5a with regards to leukocytes?
Chemotactic for monocytes and neutrophils, and stimulates leukocyte adherence to blood vessel walls at the site of infection, phagocytosis and bactericidal activities
Role of IL-1 and IL-2?
Produced by macrophages and polymorphs, and have a target effect on T/B/NK cells. Interleukins are generally produced by macrophages, neutrophils, Th1 and Th2 cells. Their target effect is usually on T/B/NK cells to proliferate, differentiate and class switch
Overview of TNF alpha
TNF alpha is produced by macrophages, mast cells and NK cells, and act on macrophages and tumour cells. The main effect is to direct macrophages to produce cytokines and cause cell death
Overview of TNF beta
TNF beta is produced by Th1 cells and acts on phagocytes and tumour cells, causing phagocytosis, NO production and cell death
What is ANCA?
Antineutrophil cytoplasmic autoantibodies - directed against antigens mainly within granules of neutrophils and monocytes, whereby they cause tissue damage
Subtypes of ANCA?
Typical immunofluorescence on fixed neutrophils using serum containing proteinase 3 (PR3)-ANCA reveals a cytoplasmic pattern (C-ANCA).
Serum containing anti-myeloperoxidase (MPO)-ANCA shows a perinuclear pattern (P-ANCA)
What type of autoantibodies is microscopic polyangiitis (MPA) associated with?
Primarily associated with anti-myeloperoxidase (MPO)-ANCA
What type of autoantibodies is eosinophilic granulomatosis with polyangiitis (EGPA)/Churg-Strauss associated with?
Almost always positive for MPO-ANCA
Drug-induced ANCAs are usually which subtype?
MPO-ANCA
What type of autoantibodies is granulomatosis with polyangiitis (GPA) associated with?
PR3-ANCA is mostly limited to being associated with GPA
Which autoantibody is most specific for SLE?
Anti-Sm - highly specific for SLE (96%) but with low sensitivity
ANA is highly sensitive but has low specificity as it may be positive in many other conditions as well as healthy controls
Antihistone antibody is commonly seen in which condition?
More common in drug induced lupus (sensitivity 95%, specificity high), and is mainly useful due to negative predictive value in drug induced lupus
Anti-Ro antibodies are reflective of?
25-30% sensitive and up to 94% specific for SLE patients
Also associated with Sjogren’s syndrome
Anti-Ro antibodies are seen in 90% of cases of neonatal lupus
Anti-ribonucleoprotein antibodies are suggestive of?
Seen in 30-40% of patients with SLE, but more commonly associated with Mixed Connective Tissue (MCTD), which is characterised by overlapping features of SLE, scleroderma and myositis (where they occur in 95-100% of patients)
ANA subtypes are defined by what?
Target antigens
Relevance of uveitis with presentation of arthritis?
Suggestive of JIA
Anterior uveitis is seen in 20% of patients (more common in oligarticular > polyarticular > systemic)
75% of oligoarticular arthritis patients test positive for ANA
Which type of JIA has the lowest risk for uveitis?
Systemic JIA
Nailfold changes in a history sounding like Raynaud phenomenon?
= Scleroderma
Nail fold changes make the diagnosis unlikely to be Raynaud phenomenon, and can be secondary to scleroderma or SLE (but not likely to be SLE in a normally grown child)
Features of Raynaud phenomenon?
Can be primary, or secondary to scleroderma/SLE
Affects fingers and toes, pain frequently
Blanching leads to cyanosis, leads to hyperaemia
Often begins in adolescence
Usually earliest manifestation of scleroderma
Primary Raynauds features: symmetric, no secondary disease, normal nail-fold capillaries, normal ESR, neg ANA
Skin finding associated with dermatomyositis?
Gottron’s papules - classic finding, found over dorsal aspect of interphalangeal joints and extensor surface of the elbows and knees, can coalesce to become patches
May be misdiagnosed as eczema
Second most common skin feature is heliotrope rash
Mechanism of folinic acid in the context of treating presumed methotrexate toxicity?
Provision of reduced folates for nucleic acid synthesis
Overview of juvenile chronic arthritis
Occurs before 16 year of age
Chronic synovitis +/- extra articular features
Features of involved joints include early morning stiffness, swelling, warm, restricted movement, contractures and bony deformities
Subtypes of arthritis
Oligoarticular
Polyarticular
Systemic onset (clinical diagnosis of exclusion)
Enthesitis related arthropathy
Reactive arthritis
Features of systemic onset JIA
Arthritis and fevers, PLUS one of:
- evanescent rash, lymphadenopathy, hepatosplenomegaly, serositis, polyarthritis
Overview of rheumatic fever
Inflammatory disease secondary to Group A strep
Polyarthritis, fever, malaise, cardiac symptoms
Diagnosis made based on Jones criteria
Major diagnostic criteria for rheumatic fever?
Carditis
Polyarthritis
Sydenham chorea
Erythema marginatum
Subcutaneous nodules
Minor diagnostic criteria for rheumatic fever?
Fever
Arthralgia
Long PR interval
Raised ESR, CRP
Leukocytosis
Previous rheumatic fever
Overview of Yersinia arthritis?
Reactive arthritis
Usually lower limb, asymmetric oligoarthritis
Clear preceding infection within 4 weeks
No clear clinical joint infection, no other arthritis cause
Yersinia, shigella, salmonella, campylobacter, mycoplasma, streptococcal
Can last weeks to months, with recurrences over several years
What is the Beighton score?
Assesses children for joint hypermobility
Maximum score is 9, a score of 4 or more indicates hypermobility
Criterion of Beighton score?
- hands flat on floor without bending knees
- oppose thumb to volar aspect of ipsilateral forearm
- passive dorsiflexion of the fifth MCP joint by at least 90 degrees
- hyperextend the knee by at least 10 degrees
- hyperextend the elbow by at least 10 degrees
What markers are the most useful for assessing disease activity in SLE?
C3/C4/CH50 (decreased in active disease)
What is the most common type of eye involvement in pauci-articular JIA?
Anterior uveitis = inflammation of the iris and anterior chamber (iris and ciliary body are affected)
- choroid affected in posterior uveitis
Overview of enthesitis-related arthritis (ERA)?
Accounts for 10% of JIA, more common in boys
Usually oligo-articular, affecting the lower limbs, pain at tendon insertion points
Associated with back pain and stiffness
HLA B27 positive in up to 80% of children, and associated with poorer prognosis
XR often normal at presentation
Overview of Osgood-Schlatter disease?
Traction apophysitis of the proximal tibial tubercle, at the insertion of the patellar tendon
Presents in children aged 9-14, often active in sports
Anterior knee pain, tibial tubercle tenderness
Overview of Sindig-Larsen-Johansson (SLJ) disease?
Patellar apophysitis caused by excessive jumping
Pain at lower pole of the patella
Resolves with time, can treat with rest/ice/NSAIDs
Overview of juvenile ankylosing spondylitis (JAS)?
Subcategory of ERA, requires radiological evidence of bilateral sacroilitis (abnormal XR)
HLA B27 can be positive
Overview of HSP?
Also known as IgA vasculitis
Purpuric rash (can be just erythematous initially)
Second most common presentation is joint pain, followed by abdominal pain
Renal involvement can eventually develop (need monitoring)
Arthritis in HSP is usually transient/migratory and more common in lower limbs than upper limbs, self-limiting
Overview of periodic fever with aphthous stomatitis, pharyngitis and adenines (PFAPA)?
Also known as Marshall syndrome
Begins 2-6 years of age
Symptoms include fever, malaise, exudative appearing tonsillitis with negative throat cultures, cervical lymphadenopathy and aphthae
Less common symptoms: headache, abdominal pain, arthralgia
Duration and frequency of PFAPA episodes?
Episodes last 4-6 days (regardless of antipyretics/antibiotics)
8-12 episodes per year
Both the frequency and intensity of episodes decrease over time
Examination/investigation findings in PFAPA?
Mild hepatosplenomegaly
Mild leukocytosis
Elevated acute phase reactants
Management of PFAPA?
Majority of patients respond dramatically to a single dose of prednisolone (1-2mg/kg) or betamethasone (0.3mg/kg) with prompt resolution of symptoms within 24 hours.
Some patients experience complete resolution after tonsillectomy
Spontaneous resolution over time with no long term issues (NO AMYLOIDOSIS)
Periodic fever syndromes
Familial Mediterranean Fever (FMF)
Periodic fever with aphthous stomatitis, pharyngitis and adenines (PFAPA)
Bony erosions in patients with rheumatoid arthritis are due to which cell type?
Osteoclasts
