PBL: Dermatomyositis and Sjogren syndrome Flashcards
(31 cards)
Classification of dermatomyositis
- Classic dermatomyositis
- Amyopathic dermatomyositis
- Hypomyopathic dermatomyositis
- Postmyopathic dermatomyositis
What is the typical features of classic dermatomyositis?
Idiopathic inflammatory myopathy that most commonly presents with progressive, symmetric, proximal muscle weakness and a group of characteristic cutaneous findings
* Gottrons papules (hand)/ gottrons rash (if not as prominent),, gottrons sign (elbow and knee)
* Heliotrope eruption (periorbital skin)
* Intensely pruritic areas with erythema (usu scalp, face, upper body): V neck sign (if just anterior), shawl sign (extends to posterior neck)
What is amyopathic dermatomyosits?
lack muscle weakness and have no laboratory/radiologic signs of myositis despite the presence of cutaneous findings consistent with DM for at least six months
What is hypomyopathic dermatomyositis?
Absence of muscle weakness
subclinical evidence for myositis (muscle enzymes, EMG, muscle biopsy, or MRI)
CK, LDH, aldolase, AST, ALT
What is postmyopathic dermatomyositis?
persistence of cutaneous symptoms following the resolution of muscle disease
What are the lab tests for dermatomyositis?
CBC with differential
LRFT
ESR, CRP: shall be normal or only mildly elevated even in patients with active muscle disease
Marked elevation shall suspect infection, malignancy or MDA5-positive disease
CK: the most sensitive muscle enzyme; other muscle enzymes that can also be tested include LDH, AST, ALT
Aldolase: occ. tested in patients with normal CK, not routinely performed
TSH
To r/o hypo/hyper thyroid myopathy
Serology:
* ANA (non specific)
* Anti-Mi 2 antibodies (specific for DM)
ddx for proximal myopathy
What are further Ix for DM?
- DM-specific autoantibodies: used to determine phenotype
- anti-MDA5: rapidly progressive ILD, anti-NXP2, anti-SAE, anti-Mi-2, anti-ARS, anti-TIF1-gamma
- CXR & pulmonary function tests
- If abnormal, do a high resolution CT thorax to r/o interstitial lung disease
- High resolution CT thorax in ALL patients with a high risk of ILD, such as patients with antisynthetase, MDA5, and overlap antibodies
- +/- EMG, MRI muscle, muscle biopsy: If proximal muscle weakness without characteristic skin findings
- +/- skin biopsy: When ambiguous cutaneous findings / absence of clinical signs of muscle disease
What are the dermatomyositis associated cancer?
Cancer risk highest around the time of DM onset
Increased in adults but not children with DM
Associated cancers
* NPC most common
* Lung
* Breast
* Gastric
* Ovarian, pancreatic, colorectal, bladder cancer and non-Hodgkin lymphoma
What are the autoantibodies that are positive and negative risk for associated cancer?
Positive risk
* Transcription intermediary factor (TIF)-1gamma
* Nuclear matrix protein
Negative risk
* Myositis specific (antisynthetase antibodies, anti-Mi-2, anti-SRP, and anti-MDA5)
* Myositis associated antibodies (anti-RNP, anti-PM-Scl, anti-Ku)
* Associated with a decreased risk of malignancy but an increased risk of interstitial lung disease in DM
How to test for myopathy?
- To rule out other ddx e.g. motor neuron disease, neuropathy
- EMG
- low-amplitude, short-duration polyphasic motor unit action potential
- Increased insertional activity and spontaneous activity in the form of fibrillation potentials, positive sharp waves, complex repetitive discharges
- Early recruitment of motor unit potentials, in which there is an increased number of motor units firing rapidly in order to produce a low level of contraction
Types of myositis
- Inclusion body myositis: endomysial inflammatory infiltrates, rimmed vauolated muscle fibers, intracellular amyloid inclusions
- Neuropathy: angular myofibers, fiber type grouping, target and targetoid fibers
- Polymyositis: endomysial inflammatory infiltrates, muscle fiber necrosis
- Dermatomyositis: complement mediated microangiopathy, destruction of capillaries, perifascicular inflammatory infiltrates
What is the ACR/EULAR criteria for sjogren syndrome?
Score >4 when the weights from 5 criteria items are summed
Does not have any of the conditions of the exclusion criteria: history of H&N radiation treatment/active hep C infection/ AIDS/ sarcoidosis/amyloidosis/GvHD/ IgG4 related disease
Lab Ix for sjogren syndrome?
CBC with DC
* Anemia of chronic disease (10% is AIHA, 9% iron deficiency anemia)
* Leukopenia
* Thrombocytopenia (ITP associated with primary sjogrens)
Inflammatory markers: increased ESR and CRP
LFT: may have elevated liver enzymes due to viral vs autoimmune
* Viral: HCV/HBV
* Autoimmune liver disease associated with SS (type 1 case) and some have an AIH-PBC overlap
* IgG4 related disease must be investigated in patients with SS presenting with sclerosing cholangitis when autoimmune pancreatitis or retroperitoneal fibrosis are also present.
RFT: increased serum creatinine (TIN, RTA with hypoK, fanconi syndrome, DI)
What autoantibodies tested in sjogren syndrome?
General: ANA (if >1:320 it supports a dx)
SS specific antibodies
* Anti-Ro/SSA (transplacental pasasge of antibodies particularly anti-Ro52 to fetus may result in heart block)
* Anti-La/SSB
Other antibodies for ddx
* ACA: features of systemic sclerosis including Raynauds phenemonon (WBR)
* RF: occurs in some SS patients. Associated with more freqeunt extraglandular manifestation. Not a marker for concomitant RA as often anti- CCP is negative
* Anti CCP: associated with more severe articular manifestation and higher progression to RA
* AMA: PBC
Specific tests for sjogren syndrome?
Test for dry eyes
* Schirmer test: measure reflex tear production. Folded strip of filter paper placed over margin of each lower eyelid. Wetting <5mm without anesthesia is indicative of aqueous tear deficiency
* Ocular surface staining
* Tear break up time
Tests for salivary gland function
* Whole saliometry: measurement of rate of saliva production –> instimulated whole saliva flow rate <0.1ml/min
* Labial salivay gland biopsy (gold standard): focal lymphocytic sialadenitis in a minor salivary gland biopsy with >1 foci of lymphocytes per 4mm2
General features of SS?
- Dry eye (keratoconjunctivitis sicca): corneal ulcerations and scarring, eyelid infections
- Dry mouth (xerostomia): dental caries and oral infections (candidiasis), parotid gland enlargement (bilateral), gingival recession, tongue fissure, chronic esophagitis
- Vaginal dryness: dyspareunia
Respiratory features of SS?
- ILD: especially if MDA5 sero+ve (watch out for rapidly progresive ILD) –> all patients should be screened by baseline CXR, lung function test for lung volumes and spirometry and bronchodilators. High risk patients should undergo HRCT chest
- Xerotrachea: persistent dry cough. May be alleviated by secretatogogues
- Pulmonary hypertension
- Pleuropericarditis
MGUS in SS?
affects 20% of patients
Presence of plasma cell dyscrasia or lymphoma
Evaluation: serum free light chain ratio, Ig levels and cryoglobulin
Hodgkin lymphoma in SS?
Affects 5-10% of patients
Arising in the exocrine glands, LN or MALT
Most common histological subtypes include marginal zone lymphomas of MALT (parotid glands) and diffuse large B cell lymphoma
Cutaneous manifestations of SS?
Annular Erythema
* More commonly occurring in patients with anti-Ro antibodies // resembling subacute cutaneous lupus
* Clinical features: annular polycyclic lesions with wide-elevated border and central pallor
* Treatment: hydroxychloroquine, low-dose weekly Raynaud’s phenomenon
* Sequential colour changes in the digits (white > blue > red), precipitated by cold, stress and temperature changes
* Pathophysiology: vasoconstriction > ischemia (pallor) > cyanosis > vasodilatation in reperfusion hyperaemia
Cutaneous vasculitis (leukocytoclastic vasculitis) in SS presentation?
Treatment?
- Presentation: palpable purpura, erythematous macules or papules, urticarial-like lesions, cutaneous ulcers, digital necrosis
- These patients should be evaluated for other organ involvements, esp kidneys, joints and peripheral nervous system. These include cryoglobulins, complement levels and testing for hepatitis C
- Patients with mild flat, petechial // purpuric lesions on lower extremities (benign hypergammaglobulinemia purpura of Waldenstrom) can be managed with compression stockings, avoidance of prolonged standing and hydroxychloroquine +/- colchicine
- These patients are generally not at increased risk of systemic vasculitis (nephritis, nephropathy)
- Treatment-refractory vasculitis should be treated with oral DMARDs, IV rituximab or longer courses of glucocorticoids
- Severe patients should be treated with plasma exchange, high-dose oral // IV glucocorticoids, cyclophosphamide or rituximab
- These patients are also more likely to develop and die from other extra-glandular diseases including lymphoma
Renal complications of SS?
- Distal type 1 RTA with hypoK: normal anion gap metabolic acidosis
- Fanconi syndrome: proximal tubules. On top of RTA there is phosphaturia, glycosuria and aminoaciduria. Hypouricemia resulting from defective uric acid reabsorption frequently accompanies Fanconi syndrome. Hypocitraturia leads to calciuum containing stones (as citrate is a potent inhibitor of stone formation)
- Rarer acquired tubular defects: gitelman (chronic thiazide), bartter (loop diuretic ingestion)
- Nephrogenic DI
Management of SS?
80-90% symptomatic treatment
* Lifestyle changes
* Eye: eyedrop, overnight ointment. Punctal plug (Block the drainage of lacrimal duct)
* Drug: cevimeline. Hydroxychloroquine: may also improve immunological markers.
