Inflammatory disorders and their Mimics

Question 1

Inflammatory muscle disease definition

Answer 1

! A member of the connective tissue disease family as evidenced by autoimmune disease associations and other immunological features

! Characterised by chronic inflammation of striated muscle (polymyositis) and sometimes skin (dermatomyositis) and lung disease

! Associated with a number of different antibodies

Question 2

Inflammatory muscle disease clinical features

Answer 2

! Weakness: insidious onset of symmetrical proximal muscle weakness
! Acute Pain is not a predominant feature
! Systemic symptoms may include fever, weight loss and fatigue

! Lungs
Respiratory or pharyngeal muscle involvement
Interstitial lung disease occurs in up to 30% of patients associated with antisynthetase (Jo-1) antibodies

! Skin
Gottron’s papules (scaly, violaceous, psoriasiform plaques) over PIP and DIPs joints
heliotrope rash (violaceous discoloration of the eyelid)

Question 3

Myositis investigations

Answer 3

! Serum levels of creatine kinase- muscle breaks down, releasing CK enzyme

! MRI to find abnormal muscle- shows there is oedema

! Muscle biopsy - fibre necrosis, regeneration and inflammatory cell infiltrate

! Electromyography is very useful for highlighting non- autoimmune/non-inflammatory myopathies

! Screening for underlying malignancy (e.g. history, examination, CXR, CT of chest/abdomen/pelvis, PSA mammography~)

Question 4

Incidence of myosIitis

Answer 4

! 2 to 10 new cases per million per annum.
! Can occur at any age (childhood and adult peaks)
! Female to male = 2.5:1 overall
(10 to 1 where there is a malignancy)

With autoimmune conditions, women much more likely to have than men

Question 5

Presentation of myositis

Answer 5

Insidious (3-6 months)
Progressive
Painless (usually)
Proximal muscle weakness- hand strength stays the same
Other striated muscle (dysphonia, swallowing)

Question 6

DermatoMyositis rash

Answer 6

Upper eye lids, malar region, bridge of nose, nasolabial folds, extensor surfaces.

Erythematous or violaceous (heliotrope) and scaly.
Gottron’s papules are scaly, erythematous palpable plaques over finger joints
Gottron’s sign is erthematous, non-palpable (macule) in same sites.

Question 7

Myositis : other involvement

Answer 7

! Joints – polyarthralgia or arthritis. Can be very destructive
! Calcinosis
! Lungs – fibrosis
! Heart – rhythm disturbance
! GI tract – dysphagia and regurg

! Malignancy – Dermatomyositis may regress when malignancy is treated.

Question 8

DermatoMyositis Investigation

Answer 8

! Creatine kinase (elevated in 95%)
! Aspartate and alanine transaminases
! Lactate dehydrogenase

! EMG- don’t get asked about in exams
◦ Irritable myofibrils
◦ Complex repetitive discharges
◦ Complex potentials on muscle contraction
! Biopsy
◦ Chronic inflammatory cells in the perivascular and interstitial areas surrounding myofibrils – mostly lymphocytes

Question 9

Inclusion body myositis

Answer 9

Has inclusion bodies
Very resistant to treatment

Question 10

EULAR criteria idiopathic inflammatory myositis online tool: probability of 50%+ can be diagnosed

Don’t learn all

Answer 10

Age of onset of first symptom 0 – 17, 18 – 39, 40+

Muscles: Objective symmetric weakness, usually progressive, of the proximal upper extremities Objective symmetric weakness, usually progressive, of the proximal lower extremities Neck flexors are relatively weaker than neck extensors
In the legs proximal muscles are relatively weaker than distal muscles

Skin: Heliotrope rash, Gottron’s papules, Gottron’s sign

GI: Dysphagia or oesophageal dysmotility

Bloods: Anti-Jo-1 (anti-Histidyl-tRNA synthetase) autoantibody positivity, Elevated serum levels of creatine kinase (CK) or lactate dehydrogenase (LDH) or aspartate aminotransferase (ASAT/AST/SGOT) or, alanine aminotransferase (ALAT/ALT/SGPT)

Muscle biopsy: Endomysial infiltration of mononuclear cells surrounding, but not invading, myofibers, Perimysial and/or perivascular infiltration of mononuclear cells, Perifascicular atrophy, Rimmed vacuoles

Question 11

Antibodies associations

Don’t learn !! Just notes

Answer 11

! Mi-2 alpha antibody
! Mi-2 beta antibody
- associated with good outcomes and less lung incvolement associated with good outcomes and less lung incvolement
human transcriptional intermediary factor) children with juvenile
! TIF1 gamma antibody
dermatomyositis and adults with dermatomyositis, associated with a cancer.
! MDA5 antibody -skin and less muscle involvement
! NXP2 antibody - associated with cancer risk and calcinosis
! SAE 1 antibody - associated with cancer risk
! Ku antibody - found in various CTDs
! PM-Scl 100 antibody - overlap and lung disease
! PM Scl75 antibody - overlap and lung disease
! Positive (A)Jo-1 antibody - antisynthetase syndrome
! SRP antibody
! PL-7 antibody
! PL-12 antibody
! EJ antibody
! OJ antibody
! Ro-52 antibody
- necrotising myositis and cardiac involvement - antisynthetase syndrome
- antisynthetase syndrome - antisynthetase syndrome
- antisynthetase syndrome - commonest antibody

Question 12

Treatment of idiopathic inflammatory myositis

Answer 12

! Prednisone at an initial dose of 1mg/Kg/day. —> hit hard with high dose steroids then reduce dose
! Other possibilities described include:
◦ tacrolimus,
◦ mycophenolate mofetil,
◦ immunoglobin,
◦ azathioprine,
◦ methotrexate,
◦ cyclophosphamide, and
◦ Cyclosporine
◦ rituximab (no influence on interstitial lung disease)

Question 13

Myositis differential diagnosis:

Answer 13

! Inclusion body myositis
! PMR
! SLE
! SS
! Sjogren’s ! RA
! vasculitides

Others:
•Metabolic- endocrine •
Neurological eg MD, myasthenia gravis
•Toxic eg drugs, alcohol,
steroids, statins
•Cancer-related
•Infectious

Question 14

PMR and giant cell arthritis

Answer 14

Mimic… but Not a disease Of muscle!

PMR
! A clinical syndrome of the middle aged and elderly characterised by pain and stiffness in the neck, shoulder and pelvic girdles
! The clinical response to small doses of corticosteroids can be dramatic
! NORMAL MUSCLES

Presentation over age Of 50
Clinical diagnosis
Stiffness bad until lunch time, gets worse again in afternoon

Question 15

PMR and GCA: spectrum of disease

Answer 15

GCA
! A vasculitis commonly accompanying polymyalgia rheumatica (temporal arteritis, cranial arteritis)
! Early recognition and treatment can prevent blindness and other complications due to occlusion or rupture of arteries

Vasculitis clarified by size of blood vessel
GCA can affect any large arteries
Affects temporal arteries commonly
Can cause ischemia

Question 16

Clinical features of PMR

Answer 16

! Bilateral and symmetrical symptoms
! Stiffness is predominant
! Muscular pain is diffuse and accentuated by pain.
! Steroid therapy for 2 years
! Systemic – low grade fever, fatigue, weight loss and high inflammatory markers

! Age at onset 50 + (mean age is 70)
! Twice as many women as men
! May present as Pyrexia of unknown origin (PUO)

Question 17

Clinical features of GCA

Answer 17

! Wide range of symptoms
! Fatigue, headaches, jaw claudication (angina Of The jaw muscles. Therefore Pain on chewing), loss of vision (can be permanent), scalp tenderness, PMR.
! Temporal and occipital arteries may be thickened, tender and reduced pulsation. May be clearly visible.
! GCA is a large vessel vasculitis

Question 18

GCA ophthalmic features

Answer 18

! Visual disturbance in 25-50%
! Visual loss 6-10%
! Medical emergency – save the vision in the other eye

Question 19

GCA: other complications

Answer 19

! Cerebrovascular accident
! Myocardial infarction
! Peripheral neuropathy
! Therefore GCA is preferred to TA

Question 20

GCA testing

Answer 20

Temporal artery biopsy

However, not always positive- skip lesions. Parts of artery with no Seen inflammation

Ultrasound: able to see lumen. Halo affect allows you to see the inflammation.

Vascular ultrasound more preferred now

Question 21

PMR differential diagnosis

Answer 21

! Neoplastic disease
! Joint disease (OA, RA, CTD)
! Myeloma
! Leukaemia
! Lymphoma
! Muscle disease
! Infections (SBE)
! Bone disease
! Hypothyroidism
! Large vessel vasculitis – PET scan

Question 22

PMR Management

Answer 22

! Steroid therapy - dose depends on eye involvement. If opthalmic involvements, high dose, otherwise lower dose
! Steroid sparing agents
! Beware relapses
! Tocilizumab for refractory GCA but only commissioned for 12 months…. What to do after that?

Question 23

Polymyositis Vs PMR

Answer 23

Polymyositis
!Any age
!proximal muscle involvement ie shoulder and hip
!CPK elevated due to muscle damage
!Spectrum includes skin involvement
!Rare and needs referral

Polymyalgia rheumatica
!Over age of 50
!Shoulder and hip pain
!NO muscle involvement
!Normal CPK
!EMS and high inflammatory markers
!Spectrum includes GCA (vasculitis)
!PMR is common and often managed by GPs