Rheumatology Flashcards
What are the main considerations re treatment of dermatomyositis?
acute vs chronic
skin disease vs combined skin and muscle disease
What is the ongoing/chronic treatment for dermatomyositis with skin and muscle disease?
1) high dose oral steroids eg prednisolone 0.75-1.5mg/kg/d for 2-4 weeks then taper (use lowest possible dose)
- steroids reduce morbidity, improve muscle strength and motor function
2) Photoprotection - high protection sunscreen
3) topical steroids - even if treated with systemic corticosteroids
- often help control erythema and pruritis
- otherwise consider topical antipruritics and oral antihistamines OR topical tacrolimus
4) simple moisturisers and emollients
IF underlying malignancy - treat underlying malignancy - improvement or complete resolution of DM has been reported in some cases after successful treatment of underlying malignancy
Consider
Antimalarials eg hydroxycholoroquine
2nd line =
Methotrexate (both muscle and skin)
- steroid-sparing
- more rapid onset of effect than azathioprine
Azathioprine (more muscle disease than skin)
- takes longer than MTX to have effect eg >6mths
3rd line =
Mycophenolate
Ciclosporin - skin and early ILD
4th line =
IVIG
How do you treat patients with dermatomyositis with skin manifestations unresponsive to topical treatments?
Add Hydroxychloroquine
2nd
Methotrexate
Azathioprine
3rd
Mycophenolate
Ciclosporine
recalcitrant disease
IVIG, dapsone, thalidomide
How do you treat acute dermatomyositis?
If severe muscle weakness (e.g., quadriplegia), interstitial lung disease, myocarditis, respiratory failure, severe dysphagia, or other life-threatening complications.
- IV methylpred1g daily for 3-5 days then PO steroids
+
IVIG
What features may predict treatment-resistance to steroid therapy for dermatomyositis and necessitate early adjunctive treatment?
Anti-signal recognition particle (SRP) antibodies in patients with DM are associated with acute severe, treatment-resistant necrotising myositis - IVIG is often required at an early disease stage in these patients; alternative = Rituximab
Patients diagnosed with anti-synthetase syndrome may be corticosteroid-resistant and concomitant use of immunosuppressive drugs (e.g. methotrexate, azathioprine) is required
Presence of anti-melanoma differentiation-associated gene 5 (MDA5) is specific to clinically amyopathic DM, and is strongly associated with rapidly progressive interstitial lung disease. Patients often require treatment with immunosuppressive drugs as well as high-dose systemic corticosteroids from an early disease stage
What are the specific risks of IVIG in dermatomyositis treatment?
acute renal failure
skin rashes
aseptic meningitis
stroke
What is the most sensitive muscle enzyme test for the diagnosis of dermatomyositis?
CK
Other than CK, what other serum markers can elevated in dermatomyositis (incl if CK is normal)?
Serum aldolase
ANA - not specific
Myositis specific antibodies (MSAs) and myositis associated antibodies (MAAs)
- Anti-Mi-2 antibodies
- Anti‐U1 ribonucleoprotein (RNP)
- anti‐Ku
- Anti-Jo-1 and other anti-aminoacyl-tRNA synthetase antibodies (anti-ARS antibodies; including anti‐PL‐7, anti‐PL‐12, anti‐EJ, anti‐OJ, and anti‐KS
What is the significance of finding Anti-transcription intermediary factor 1 gamma in a patient with dermatomyositis?
Strongly assoc with malignancy therefore need extensive search for underlying malignancy
What is the significance and association of Anti-signal recognition particle (SRP) antibodies in dermatomyositis?
Found almost exclusively in polymyositis and assoc with acute severe, treatment-resistant necrotising myositis - need early IVIG +/- Rituximab
What are the key clinical features and antibodies assoc with anti-synthetase syndrome?
ILD, fever, myostitis, polyarthritis, mechanic’s hands, raynaud’s phenomenon
Anti-Jo-1 and other anti-aminoacyl-tRNA synthetase antibodies (anti-ARS antibodies; including anti‐PL‐7, anti‐PL‐12, anti‐EJ, anti‐OJ, and anti‐KS
What is Anti-melanoma differentiation-associated gene 5 (MDA5; also known as CADM‐140) specific for in dermatomyositis?
Clinically amyopathic dermatomyositis (CADM)
It is strongly associated with a rapidly progressive ILD with poor prognosis (need early immunosuppressive tx)
Tender palm papules and diffuse alopecia may be present
Anti-NXP2 is strongly associated with what form of dermatomyositis?
Juvenile DM with a high proportion suffering from cutaneous calcinosis due to dystrophic calcification
Anti-PM-Scl antibodies are often found in patients with?
Overlapping myositis and scleroderma
Describe the ideal muscle biopsy in patients with suspected dermatomyositis?
In symptomatic patients the biopsy should be taken from a weak but not severely atrophied muscle. Quadriceps and deltoid are common sites
Greater yield with open surgical biopsy cf needle biopsy
Greater yield if pre-biopsy EMG or MRI to target biopsy (given possible patchy muscle involvement)
What pattern of atrophy on muscle biopsy is diagnostic of dermatomyositis?
Perifascicular atrophy is seen due to phagocytosis and necrosis of muscle fibres
How are patients with dermatomyositis commonly classified according to severity?
Severe disease - those with severe muscle weakness (e.g., quadriplegia), interstitial lung disease, myocarditis, respiratory failure, severe dysphagia, or other life-threatening complications
Non-severe disease - 4/5 muscle power + none of life threatening complications
How do you diagnose dermatomyositis?
By using the European League Against Rheumatism and American College of Rheumatology (EULAR/ACR) classification criteria for adult and juvenile idiopathic inflammatory myopathies (IIMs)
- based on scoring system results in definite’, ‘probable’, and ‘possible’ IIM
- patients can be further subclassified based on classification tree
What is the mode of inheritance of Marfan syndrome?
Autosomal dominant
What is the most typical genetic abnormality in Marfan Syndrome?
FBN1 - encodes the connective tissue protein fibrillin-1
What is the most typical genetic abnormality in Marfan Syndrome?
FBN1 - encodes the connective tissue protein fibrillin-1
What is the clinical hallmark of ankylosing spondylitis?
Inflammatory back pain
What is the clinical hallmark of ankylosing spondylitis?
Inflammatory back pain
90% of patients with ankylosing spondylitis have what gene?
HLA-B27
90% of patients with ankylosing spondylitis have what gene?
HLA-B27
Ankylosing spondylitis is more common in which gender?
Males
There is a strong genetic risk to developing Ankylosing spondylitis and the disease severity - what genes are implicated?
HLA B27 (but unclear role)
ERAP1
ARTS1
What is HLA-B27?
A heterotrimeric complex with beta-2-microglobulin that presents intracellular pathogens for recognition by the T-cell receptor of CD8 T cells. HLA-B27 can also be expressed as cell surface beta2-microglobulin (beta2m)-free homodimers (B27[2])
What is the role of antibodies to Klebsiella pneumoniae in Ankylosing spondylitis?
Unclear - Antibodies directed against an epitope of a Klebsiella pneumoniae-derived protein are present in the majority of patients with AS but studies have yet to elucidate role in pathogenesis of AS
How does the pathophysiology of ank spond differ from RA?
Both involve inflammation and cartilage erosion but ankylosing spondylitis involves an additional process - repair or ossification
What is the Calin criteria for Inflammatory Back pain?
Age <40
Back pain > 3 months
Insidious onset
Improves with exercise
Early morning stiffness
In addition to inflammatory back pain, what other disease associations/manifestations may be present in patients with Ank Spond?
Uveitis
Iritis
Enthesitis
Psoriasis
Inflammatory bowel disease
Dyspnoea
Fatigue
Family history of spondyloarthropathy
Sleep disturbance
What are some of the key physical examination findings in patients with ankylosing spondylitis?
Loss of lumbar lordosis and flexion
Tenderness at sacroiliac joints
Kyphosis
Peripheral joint involvement
Tragus-to-wall distance
Lumbar flexion
Cervical rotation
Lumbar side flexion
Intermalleolar distance
- these measurements taken together to form Bath Ankylosing Spondylitis Metrology Index
What test is diagnostic of Ankylosing spondylitis?
None
What is the first test you should order in a patient suspected of having ankylosing spondylitis?
Pelvic XRAY
Does a negative pelvic X-RAY exclude Ankylosing spondylitis?
No!
If suspicious need to obtain MRI + often helpful to check if HLA-B27 positive
What is the risk of developing AS among HLA-B27-positive first-degree relatives of HLA-B27-positive probands with AS, compared with HLA-B27-positive individuals in the population
16-fold increased risk
What is the risk of developing AS among HLA-B27-positive first-degree relatives of HLA-B27-positive probands with AS, compared with HLA-B27-positive individuals in the population
16-fold increased risk
What is the classic MRI pelvis finding in a patient with ankylosing spondylitis?
Bone marrow oedema on a T2-weighted sagittal short-tau inversion recovery (STIR) image
What are some distinguishing features between Ankylosing spondylitis and Inflammatory-bowel related arthritis?
IBD-related arthritis tend to:
Have a hx of UC or Crohns
Have no sex bias (males and females equally affected)
Less likely to be HLA-B27 positive (only 30%)
More likely to have peripheral joint involvement
May have asymmetric sacroillitis
May have pyoderma gangrenosum or erythema nodosum
What are some distinguishing features between Ankylosing spondylitis and psoriatic arthritis?
Patients with psoriatic arthritis tend to:
Develop disease at slightly older age (30-40s as opposed to 20s)
Have asymmetric/unilateral sacroillitis
Have a history of psoriasis
Have dactylitis
Have erosive disease on X-ray
What are some distinguishing features between Ankylosing spondylitis and psoriatic arthritis?
Patients with psoriatic arthritis tend to:
Develop disease at slightly older age (30-40s as opposed to 20s)
Have asymmetric/unilateral sacroillitis
Have a history of psoriasis
Have dactylitis
Have erosive disease on X-ray
What are some distinguishing features between Ankylosing spondylitis and psoriatic arthritis?
Patients with psoriatic arthritis tend to:
Develop disease at slightly older age (30-40s as opposed to 20s)
Have asymmetric/unilateral sacroillitis
Have a history of psoriasis
Have dactylitis
Have erosive disease on X-ray
What are the known
What are the known
What are the known predictors of radiographic progression of Ankylosing spondylitis?
Syndesmophytes on initial X-RAY
Elevated CRP/ESR
Smoking
What are the known predictors of radiographic progression of Ankylosing spondylitis?
Syndesmophytes on initial X-RAY
Elevated CRP/ESR
Smoking
What non-pharmacological measures are appropriate for Ankylosing spondylitis?
1) Smoking cessation
2) active physio therapy
3) patient education
4) cardiovascular disease risk calculation and modification
- as px with AS have increased CVD related mortality
What is the first line therapy for pain and stiffness in Ankylosing spondylitis?
NSAIDs
- conflicting evidence whether reduced disease progression but helpful for symptoms
- should trial at least 2 at highest tolerated dose before moving on to other treatments
What is the role of steroids in Ankylosing spondylitis?
No role for systemic steroids
Can consider intra-articulate or local-site specific steroid injections as required
What therapies are indicated for peripheral joint involvement in Ankylosing spondylitis?
Sulfasalazine or methotrexate
- note these do not treat axial disease and evidence is weak
For Ankylosing spondylitis patients with axial disease refractory to NSAIDs and physiotherapy +/- steroid injections and sulfasalazine what treatment is indicated?
TNF-alpha inhibitors
Eg Adalimumab, certolizumab pegol, etanercept, golimumab, and infliximab
Should you continue NSAIDs in patients with ankylosing spondylitis commenced on TNF-alpha inhibitors?
Yes - recommended to continue continuous NSAIDs whilst active disease / established on TNF-alpha inhibitor then can reduce to PRN use
Should you attempt to wean TNF-alpha inhibitor therapy for Ankylosing spondylitis once patients achieve remission/disease control?
You can but high risk of disease flare - individual decision
What do you give a patient with ankylosing spondylitis who relapses after initial remission on TNF-alpha inhibitor therapy?
Try another TNF-alpha inhibitor before trying an alternative bDMARD therapy
What do you give a patient with ankylosing spondylitis who relapses after initial remission on TNF-alpha inhibitor therapy?
Try another TNF-alpha inhibitor before trying an alternative bDMARD therapy
If TNF-alpha inhibitor fails in Ankylosing spondylitis, what should you give?
1) can try another TNF-alpha inhibitor
OR
2) IL-17 inhibitor (eg Secukinumab, Ixekizumab)
- these are more effective in TNF-alpha naive patients and in patients with psoriasis
After TNF-alpha inhibitors and IL-17 inhibitors, what is the third line bDMARD therapy for refractory Ankylosing spondylitis?
JAK inhibitors eg tofacitinib, upadacitinib)
After TNF-alpha inhibitors and IL-17 inhibitors, what is the third line bDMARD therapy for refractory Ankylosing spondylitis?
JAK inhibitors eg tofacitinib, upadacitinib)
What is the mechanism of action of Hydroxychloroquine?
It is an antimalarial drug with anti-inflammatory (and possibly immunosuppressive effects)
Also appears to:
- have lipid lowering properties
- improves glycaemic control
- have antithrombotic/anticoagulant affects by inhibiting platelet aggregation and adhesion (but not increasing bleeding time/risk)
Anti-inflammatory effect:
- blocks constimulation of B cell antigen receptor and Toll-like receptor (TLR)-9 pathways + inhibits TLR signalling
- interferes with normal function of subcellular compartments that depend on an acidic milieu as it is a weak base - so called “lysosomotrophic action” - this may interfere with various processes incl secretion of cytokines/inflammatory mediators
Which patients with SLE should receive hydroxychloroquine?
ALL patients unless contraindicated
What is the typical/initial dose of hydroxychloroquine in SLE?
5mg/kg up to max 400mg daily
What are the 2 most significant side effects of hydroxycholoroquine therapy?
Vision-threatening toxic retinopathy
QTc prolongation
What monitoring is required when on hydroxychloroquine therapy?
Baseline ocular assessment/opthal review then annual opthalmology review starting after 5 years of therapy
What are the risk factors for vision threatening toxic retinopathy secondary to hydroxychloroquine (HCQ)?
Daily HCQ dose >5mg/kg
Long duration HCQ therapy > 5 years
CKD3+
Tamoxifen use
Female gender
Macular disease
What are the benefits of hydroxychloroquine therapy in SLE?
Reduces mortality
Reduces risk of disease flare
Reduces fatigue
Reduces skin and musculoskeletal symptoms
Reduces thrombotic events
Reduces end-organ damage accrual
Reduces cancer
What must you do if a patient on HCQ therapy for SLE presents with vision impairment?
Stop HCQ and obtain opthal review
What are the symptoms/signs of retinopathy secondary to HCQ therapy?
Early - asymptomatic; only detected by spectral domain optical coherence tomography
Later - symptoms incl dropout of letters when reading, photophobia, blurred distance vision, reduced night vision, visual field defects, flashing lights; o/e - central patchy area of depigmentation of macula surrounded by concentric ring of pigmentation (“bull’s eye”)
Do you need to adjust HCQ dosing in renal impairment?
Renally cleared and tend to reduce dose to 200mg (ie half dose) in ESKD
Note HCQ decreases creatinine clearance by ~10% by competitively inhibiting creatinine secretion (not a true change in kidney function)
Is it safe to take hydroxychloroquine in pregnancy?
Yes
What are some less significant side effects of HCQ therapy?
Nausea and vomiting
Pruritic maculopapular rash/skin reaction
Headaches
Myopathy
What rheumatological drugs are considered relatively safe to take in pregnancy?
Hydroxychloroquine
Sulfasalazine
Low dose aspirin
Azathiopurine
6-mercaptopurine
Colchicine
