Children Rheum - MSK, PMR/GCA and SLE Flashcards
What can cause MSK pain in children?
Can be serious lifethreatening conditions such as malignancy, sepsis, vasculitis, and NAI Also rheumatic disorders IBD, cystic fibrosis Ortho syndromes etc etc
Localised pain in a well child - possible DDX x5
Strains and sprains Bone tumours JIA (oligoarthritis) Localised idiopathic pain syndromes Growing pains
Localised pain in an unwell child - DDX x2
Septic arthritis
Osteomyelitis
Diffuse pain in a well child - DDX x2
Hypermobility
Diffuse idiopathic pain syndromes
Diffuse pain in an unwell child x6
Leukaemia Neuroblastoma JIA (SA and PA) SLE Juvenile dermatomyositis Vasculitis
Red flags in children with back pain x3
Painful scoliosis
Neurological symptoms suggestive of nerve root entrapment or cord compression
Systemic findings suggesting malignancy or sepsis
What can inflammatory back pain in children be a sign of?
Late feature of enthesitis-related arthritis
Often presents in late adolescence
Strong HLA-B27 expression association
What is osteochondrosis?
Developmental derangement of normal bone growth
Aseptic ischaemic necrosis
What is osteochondritis?
Inflammation of the cartilage or bone of a joint
What is Osgood-Schlatter disease?
One of commonest causes of knee pain in adolescents - overuse injury causing inflammation (osteochondritis) of the tibial tubercle causing swelling just below the knee
What is Sever’s disease
Calcaneal apophysitis
Inflammation of growth plate in the heel of growing children
Especially adolescents
What are non-benign causes of hypermobility?
Marfans syndrome
Sticklers syndrome
Ehlers-Danlos syndrome
What is arthritis of SLE like?
Usually polyarticular, non-deforming and non-erosive
Presentation of juvenile dermatomyositis?
May present at any age with characteristic skin involvement and proximal muscle weakness
What are severe complications of juvenile dermatomyositis?
Risk of aspiration pneumonia and interstitial lung disease
Treatment of Juvenile dermatomyositis
High dose corticosteroids with methotrexate
What is scleroderma
Systemic sclerosis Caused by immune system attacking connective tissue around skin, internal organs and blood vessels Causes hardening (sclero) of the skin (derma)
What is the most common presentation of scleroderma in children
Localised is most common - can present at any age
Patches of abnormal skin
If untreated then will have active expanding disease, fibrosis and eventual softening with some remission
What can the implications of scleroderma be in children?
Cosmetic or functional if interfere with growth of a limb and SC tissues
Treatment of scleroderma in children?
Aggressive treatment regimens - corticosteroids and methotrexate - to control disease and limit severe disfigurement and disability
What type of scleroderma is rare in children
Systemic scleroderma
What organs are affected in systemic scleroderma
Lungs, GI tract, heart and kidneys
Common childhood vasculitides x2
HSP
Kawasaki disease
MSK features of vasculitides
HSP and Kawasaki often have transient arthritis affecting large joints
Features of HSP
Palpable purpura over legs and buttocks Abdominal pain Haematuria Arthritis Usually resolves completely within 4 weeks
What is Chronic recurrent multifocal osteomyelitis
Presents similarly to bacterial osteomyelitis
Often multiple sites with recurrent episodes
Bone pain, sometimes swelling too
Most often long bones but ribs, clavicle, vertebrae or mandible can be affected
Treatment of CRMO
NSAIDs
What is polymyalgia rheuamatica?
Clinical syndrome that affects older patients
Proximal muscle stiffness, especially in the shoulders and systemic features such as fatigue, weight loss and depression
What is Giant Cell arteritis?
Systemic vasculitis affects large and medium sized arteries
May involve any artery but propensity to affect branches of external carotid, particularly posterior ciliary arteries (optic nerve) and temporal artery
Why are GCA and PMR related
Clinical and pathogenetic links between the two - therefore idea is that they are manifestations on a disease spectrum that affects same disease population
Frequency of GCA and PMR occurring together?
PMR has been observed in 40-60% of cases of GCA
GCA been observed in 30-80% of patients with PMR
Environmental factors for PMR and GCA?
Acute-onset prodromal events suggest infectious trigger
Possible relationship to mycoplasma pneumoniae, chlamydia pneumoniae , parvovirus B19, respiratory syncytial virus and adenovirus
BUT no causative agent has been found
Genetic influences for PMR and GCA
Possible role for HLA-DR4
Gender ratio of PMR and GCA
Women:men = 3:1
Age of PMR and GCA patients
Rare under age 50
Ethinicity of PMR and GCA patients
Mostly northern european patients but can occur in any ethnic group
Diagnosis of PMR and GCA
Based on clinical features as there is no diagnostic test
ESR and CRP usually elevated
Can do temporal artery biopsy in GCA
Clinical features of PMR x7
Bilateral shoulder pain, stiffness NOT MUSCLE WEAKNESS Duration onset 40 Stiffness >1 hour Age >50, typically >65 Depression or weight loss Bilateral upper arm tenderness
Diagnostic criteria for PMR
Probable if 3 or more clinical features or definite if probable PMR responding to corticosteroids
Clinical features of GCA x5
Age >50 New headache Temporal artery abnormal to palpation Elevated ESR Abnormal findings on temporal artery biopsy
Muscle symptoms in PMR
Sometimes muscles of upper arms and thighs are tender to palpation
Muscle strength usually unimpaired
Patients may have difficulty turning over in bed, especially early in the morning
May be hard to lift heavy objects, walk upstairs or tender to sit on toilet
Clinical features of GCA x4
Scalp is tender to touch
May hurt to wear glasses
Jaw claudication when chewing
Artery features depends on stage, early may be bounding with full pulse but also tenderness
Later fibrosis and repair may predominate and pulse is almost absent with nodular feeling to artery
Eye involvement in GCA
Can get diplopia, partial or complete loss of vision and cranial nerve palsy if left untreated
Late complications of GCA
If large-vessel involvement occurs
Aortic aneurysms and stenosis
Histopathology of GCA - what sort of lesions are they?
Skip lesions - patchy or segmental involvement of arteries
Histopathology of GCA - what is pathology?
T-cell CD4 proliferation by unknown antigen in aventitia - CD4 lymphocytes produce interferon, attracts macrophages to arterial wall -they fuse to form multinucleated giant cells in intima-media junction - these cells produce adhesion molecules, nitric oxide and collagenases which cause tissue injury and in situ thrombosis
Histopathology of PMR
Similar to GCA
Synovitis which is a non-erosive self-limiting arthritis in 1/3 of patients
Muscles in PMR
Muscle does not seem to be considered site of pathology, muscle enzymes and biopsies are normal - although changes have been noted in ultrastructure and mitochondria
Investigations in PMR and GCA - biological
ESR and CRP are most frequently raised although both can occur with normal ESR
Both fall with effective treatment - CRP falls faster
Also normocytic normochromic anaemia
What will US and MRI in GCA show?
A “halo” around inflamed vessels and maybe even the caliber of the temporal arteries
If untreated what happens to PMR and GCA
Will burn out after a mean of 2 years (range 6 months to 10 years)
Long-term vascular complications in GCA common
Treatment of PMR
Corticosteroid - prednisolone 10-20mg daily for 1 month
Reduce dose after month by 2.5mg every 2-4weeks until 10mg daily
At 6 months reduce more
Titrate against clinical response
Most require treatment for 3 years but can be less
Treatment of GCA
Prednisolone - higher dose than for PMR and treatment for longer
eg. if risk of blindness 80mg daily
Again reduce dose steadily - maintenance at low dose likely for up to 5 years
Can also add low-dose aspirin
What is common when treating GCA and PMR
Relapses when reducing corticosteroids
What is Systemic Lupus Erythematous?
A multi-system autoimmune disease of unknown cause with a wide variety of manifestations - usually characterised by remissions and relapses
What diseases are included within the SLE spectrum? x7
Discoid Lupus Drug-induced Lupus Neonatal lupus Sjogrens syndrome Antiphospholipid antibody syndrome Dermatomyositis/polymyositis Overlap syndromes
When can antiphospholipid antibody syndrome occur?
May occur as a primary disorder or secondary to autoimmue disease such as SLE, autoimmune hypothyroidism or chronic active hepatitis
Pathology of SLE
Dendritic, B-cell and T-cell dysfunction resulting in development of autoantibodies and autoreactive T cells
Defective clearance of apoptotic cells and immune complexes
Activation of complement, cytokines, interleukins etc
Interleukins involved in SLE and role
Interleukin-6, Il-10
Their levels are increased in active disease
Cytokine involved in SLE and role
Interferon-alpha
Plays a role in activating genes involved in the disease
Who is burden of SLE disease highest in? x2
Women and non-white ethnic groups
Criteria for SLE x11
Malar rash Discoid rash Photosensitivity Mucosal ulcers Arthritis (non-erosive) Serositis = pleuritis or pericarditis Neurological disorder (psychosis, seizures) Renal disorder Haematological disorder Immunological disorder Positive antinuclear antibodies (Diagnosis with 4 out of 11)
What general features are common with SLE x2
Fatigue is common
May be associated with secondary depression or fibromyalgia (due to SLE, hypothyroidism, anaemia, pulmonary or CV symptoms)
Symptoms of active SLE disease x5
Fever Malaise Anorexia Weight loss Lymphadenopathy
What are the most common mucocutaneous features of SLE? x 4
Painful/painless mouth ulcers
Diffuse alopecia
Butterfly/malar rash
Photosensitivity
Other mucocutaneous features of SLE?
Nasal/vaginal ulcers
Subacute cutaneous lupus erythematous rash
Discoid lesions
In whom are mucocutaneous features more common with SLE?
White and Asian patients
What is subacute cutaneous lupus erythematous?
Non-scarring rash found in areas of the body exposed to sunlight (photosensitive dermatosis)
What is discoid lupus?
Discoid lesions which are chronic scarring lesions that heal with hypo or hyperpigmentation
What are the joint features of SLE? x2
Generalised non-swelling, early morning stiffness arthralgia - very common.
Non-erosive arthritis with swelling may develop
What sort of joint deformities occur with SLE?
Deformities are unusual but may occur due to ligamentous laxity rather than due to joint erosions as with RA
Muscle features of SLE
Myalgia is common
Myositis only occurs in 5% of patients
Secondary causes of myopathy eg. steroids - more common
What MSK risk is increased in SLE?
Increased risk of osteoporosis and therefore fractures due to minimal trauma
What is the most common haematological manifestation in SLE?
Leucopenia and lymphopenia caused by lymphotoxic antibodies
What is the second most common haematological manifestation of SLE? - Causes x4
Anaemia - may be multifactorial 1) Normochromic, normocytic of normal disease
2) Antibody-mediated haemolytic anaemia
3) Iron-deficiency anaemia due to dietary deficiency or blood loss (GI secondary to NSAIDs)
4) Pernicious anaemia
What is 3rd haematological manifestation of SLE?
Thrombocytopenia - may occur as immune-mediated condition.
Risk of bleeding
Incidence of renal disease in SLE?
Common - can occur in up to 50% in white patients and 75% of black patients
In whom is SLE renal disease more severe?
Non-white patients
Presentation of SLE renal disease? x3
Early nephritis picked up on urinalysis
Nephrotic syndrome
Few with devastating accelerated hypertension and renal shutdown
Most common neurological manifestations of SLE? x4
Headache, seizures, aseptic meningitis, cerebrovascular accidents
(but many more can occur)
What neurological symptom can occur secondary to SLE but also secondary to steroid treatment?
Psychosis
Common pulmonary manifestation of SLE?
Pleurisy often without physical signs
Other pulmonary manifestations of SLE? x4
Lupus pneumonitis
Pulmonary haemorrhage (sudden, acute & high mortality)
Pulmonary embolism
Pulmonary hypertension (poor prognosis)
Common cardiac manifestation of SLE?
Pericarditis but often asymptomatic
Other cardiac manifestations of SLE? x3
Myocarditis
Endocarditis
Rarely - cardiac tamponade
Common CVD in SLE?
Premature atherosclerosis is common - risk for MI due to coronary artery disease
Common GI manifestations of SLE and incidence?
50% of SLE patients experience abdominal pain, n and v and diarrhoea at some stage of disease
Cause of acute abdomen in SLE?
Mesenteric vasculitis - high risk of death
SLE and fertility?
No evidence that SLE decreases fertility
SLE and pregnancy?
If antiphospholipid syndrome then increased risk of IUGR, premature delivery, miscarriages and stillbirth
SLE treatment and pregnancy?
Doses of prednisolone >10mg/day increased risk of pre-eclampsia, isolated HTN, PROM, maternal infection
What SLE medication should be stopped in pregnancy?
ACEi or mycophenolate mofetil for renal disease
What is neonatal lupus syndrome?
Occurs in 10% of babies born to mothers with anti-Ro or anti-La antibodies
Rash induced by UV light a few days after birth - resolves if removed from sunlight or UV light
What is a more serious version of neonatal lupus syndrome?
Much rarer - congenital heart block
Usually detected in utero about 16-28 weeks into pregnancy
What is Sjogren’s syndrome?
Clinical syndrome characterised by sicca (dryness) symptoms: dry eyes and dry mouth due to failure of salivary and mucosal glands
Often preceded by salivary gland swelling
When does Sjogrens occur as secondary disease?
May occur secondary in SLE, RA, systemic sclerosis, primary biliary cirrhosis
What is primary Sjogrens syndrome?
Occurs with features that resemble mild SLE (mild symmetrical arthritis, photosensitivity, fatigue and diffuse alopecia) Also dry upper airways (uncommon - dry vagina and dry skin/hair)
Biological features of primary Sjogrens syndrome?
Associated with hypergammaglobulinaemia ( IgG levels high)
Positive antinuclear antibodies, rheumatoid factor, anti-Ro and anti-La
Raised amylase if salivary glands are involved
Diagnostic criteria for polymyositis? x4
Proximal muscle weakness, elevated muscle enzymes, myopathic changes on electromyography, inflammatory changes on muscle biopsy
Diagnostic criteria for dermatomyositis?
Features of polymyositis (proximal muscle weakness, elevated muscle enzymes, myopathic changes on electromyography, inflammatory changes on biopsy) + characteristic rash
What does antiphospholipid syndrome cause? x3
Recurrent arterial and venous thrombosis and miscarriages
Most common presentation of anti-phospholipid syndrome?
Venous thrombosis in arms or legs
Recurrent, multiple and bilateral
Propensity for PE
Most common site of arterial thrombosis in anti-phospholipid syndrome?
Brain - therefore as stroke or TIA
Antiphospholipid syndrome and pregnancy?
IUGR due to placental insufficiency and pre-eclampsia
Recurrent losses in 2nd or 3rd trimester
Premature birth therefore plan early delivery
Prognosis of SLE and antiphospholipid syndrome?
Survival has improved but patients still succumb to late complications of disease or its therapy
Contributors to mortality in SLE and antiphospholipid syndrome x5
Hyperlipidaemia, hypertension, premature IHD, DM and osteoporotic fractures
Investigations for diagnosis and monitoring in SLE
FBC with WCC, urinalysis and serum creatinine (detect renal disease - also GFR)
Diagnostic tests for SLE
ANA
anti-extractable nuclear antigen tests
Test to predict risk of developing of renal disease in SLE?
Anti-ds DNA antibodies
Test which falls with SLE disease activity
C3 and C4 - because of complement consumption
SLE tests which should be done in women planning pregnancy
Anti-Ro, Anti-La and Antiphospholipid antibodies
Investigations in antiphospholipid syndrome?
80-90% of patients are positive for ab’s to a complex of anticardiolipin antibodies and B2-glycoprotein
Management of SLE patients with sun-reactive dermatological problems?
Wear sunblock for >6 months of the year
What contraception should be used in SLE?
Contraceptive pills that contain oestrogen can exacerbate disease therefore barrier methods or progesteron only methods are preferred
Treatment of mild SLE
Steroid creams, short NSAIDs courses and hydroxycholoroquine
Treatment of severe SLE
Oral corticosteroids + hydroxycholoroquine
What might be needed in very severe SLE
IF need >10mg a day of pred + hydroxycholoroquine
Might need azathioprine, cyclosporin, methotrexate or cyclophosphamide
Lupus nephritis treatment
Mycophenolate mofetil
Treatment of SLE in pregnancy? x3
Prednisolone
Hydroxycholoroquine
Azathioprine
Treatment of SLE during lactation?
Pred and hydroxycholoquine
Aza at low doses
Contraindication SLE treatment in pregnancy and breast feeding? x4
Methotrexate
Mycophenolate
Lefluonamide
Cyclophosphamide
Treatment of immunosuppressant resistant SLE x4
Cyclosporin A
Tacrolimus
Lefluonamide
Preferred anti-hypertensives in SLE x3 and why?
Calcium-channel blockers
ACE inhibitors
ARBs
Helpful in management of Raynauds whereas B-blockers make it worse
Treatment in antiphospholipid syndrome
Aspirin
Avoid oestrogen-containing contraceptives and HRT
Heparin to treat thrombosis, then warfarin (INR aim 2-3 for venous and 3-4 for arterial)
Treatment of antiphospholipid syndrome in pregnancy
LMWH and low-dose aspirin
Pathology behind gland failure in Sjogrens
Inflammation and subsequent destruction
HLA linked to Sjogrens
HLA-B8 and DR3
Gender of Sjogrens
More common in women than men 9:1
Investigations in Sjogrens
Raised ESR and amylase
What is Shirmers test
Test for lacrimal gland dysfunction in sjogrens - filter paper under eyelid and +ve test if less than 10mm wet after 5mins
Treatment of sjogrens
steroids or immunosuppresants
Rituximab shown to be effective
Complications of sjogrens
Vasculitis, interstitial nephritis
Lymphoma (usually non-hodgkin b-cell type)
Prognosis of SLE
10 years is 80-90%
Mortality due to infection or renal failure
