Dermatomyositis Flashcards
What other connective tissue diseases can dermatomyositis overlap with?
Scleroderma/systemic sclerosis (most common)>>SLE, Sjogren’s, RA
Epidemiology of dermatomyositis?
Bimodal age distribution (i) Juvenile DM: no increased risk of internal disease, Does have calcinosis cutis and small vessel vasculitis II Adult DM: a/w occult malignancy (~25% of time.
Most commonly associated tumors with DM in adults?
ovarian and colon, nasopharyngeal in SE asians
Pathogenesis of DM?
Environmental factors (malignancy, UV radiation, viral infection) trigger an immune response in susceptible people
Muscle inflammation –> cell-mediated immunity (CD8+ T-cells attack muscles)
Cutaneous eruption –> humoral immunity
In what % of patients are ANA + in DM?
60% of pts
- Some target DM antigens are in the cytoplasm (Synthetase and MDA5)
Clinical features of DM?
Gottron’s papules Violaceous hue of upper eyelids w/ periorbital edema - heliotrope sign Naifold telangiectasias –> ragged cuticles, proximal nail fold with dilated capillary loops alternate with vessel dropout.
Is DM pruritic?
Yes! unlike LE and other papulosquamous diseases, DM is very pruritic and can cause pt’s severe distress with this.
Common DM cutaneous manifestations?
Heliotrope sign, eyelid edema, gottron papules, gottron sign, photo distributed poikiloderma, scalp poikiloderma and scaling, non-scarring alopecia, nail-fold changes (ragged cuticles, cuticular hypertrophy, nail-fold telangiectasias), Holster sign (poikiloderma of the lateral thighs), psoriasiform lesions, calcinosis cutis
Myositis workup for DM?
-Proximal extensor muscle weakness (shoulder/hips) -Serum CK and aldolase, repeat q2-3 months -U/s or MRI of proximal muscle -Electromyography -Muscle bx
What is the definition of amyopathic DM?
Amyopathic DM is when muscle enzymes are normal w/ no muscle weakness for >2 years
Systemic workup for DM?
-Check for overlapping syndromes (i.e. scleroderma) -Check for interstitial lung dz (PFTs - DLCO or high-resolution CT) - affect 15-30% of pts -ECG
Evaluation for new DM/Amyopathic DM?
-Check at baseline and repeat annually x 2-3 years -Malignancy screen: breast and pelvic (W), testicular and prostate (M), rectal/colon (M/W)
Histology of DM?
- Epidermal atrophy - vacuolar interface dermatitis [sparse lymphocytic infiltrate] - Dermal mucin deposition - Gottron’s papules show a lichenoid infiltrate but have acanthosis rather than epidermal atrophy
What are the Anti-aminoacyl-tRNA synthetase autoantibodies and what is their significance?
Anti-Jo-1 (histidyl) and anti-PL-7 (threonyl) These are associated with antisynthetase syndrome (fever, polyarthritis, ‘mechanic’s hands,’ Raynaud’s phenomenon, interstitial lung disease) -Present in up to 20% of adult patients
Significance of the Anti-Mi-2 antibody in DM?
Most specific for classic DM, milder muscle disease, good response to treatment, present in up to 10-15% of patients
What is the most specific antibody for classic DM?
Anti-Mi-2
What is the signifcance of the Anti-TIF1-gamma (ANTI-155/140) antibody?
Severe cutaneous DM; malignancy-associated; amyopathic
What antibody is a/w rapidly progressive interstitial lung disease?
Anti-MDA5 (CADM-140)
What is the clinical significance of the Anti-MDA5 antibody?
Clinically amyopathic CM -Characteristic mucocutaneous findings, including tender palmar papules, ulcerations on the knuckles/elbows, oral/gum pain, diffuse alopecia -Rapidly progressing interstitial lung disease
What is the significance of the Anti-NXP-2 (anti-p140) antibody?
Juvenile -onset classic DM w/ calcinosis cutis
What antibody is a/w juvenile-onset classic DM?
Anti-NXP-2 (anti-p140) antibody
What is the significance of the Anti-SAE antibody
Clinically amyopathic DM that may progress to myositis and dysphagia. -ILD is uncommon
How do you treat the myositis of DM?
Initiate steroids at 1mg/kg/day + steroid-sparing agent (i.e. MMF, weekly MTX) the taper steroids by 1/2 stargin dose by 6 months –> long taper over 2 years.
How do you treat the cutaneous eruption of DM?
Topical CS + anitmalarias + sun protenction
Risk of Hydroxychloroquine in patients with DM?
Still the first line but there is an increased risk of a cutaneous drug reaction to HCQ in DM patis, may tolerate chloroquine -2nd line is MTX, MMF, IVIG for refractory cutaneous DM –> maybe rituximab as an emerging treatment option.
What drugs should be avoided in DM?
TNF-a because of drug-induced or drug-exacerbated DM
How do you treat the calcinosis cutis in DM?
CCB +/- surgical excision
What is the genetic predisposition in juvenile DM?
TNF-a308A –> capillary occlusion (increased thrombospondin-1)
What is the Brundsting variant of DM?
This is the classic juvenile DM (calcinosis cutis, less ulceration, less vasculopathy, steroid-responsive)
What is the Banker variant of DM?
<10%, rare, ulcerative/vasculopathic, severe myositis, recalcitrant to steroids, poor prognosis
Most common cause of drug-induced DM?
Hydroxyurea >> statins
What is the difference between Hydroxyurea-induced vs non-hydroxyurea-induced DM?
- Hydroxyurea-induced: long latency period (60 months, no myositis)
- Non-hydroxyurea induced: short latency (2 months, 80% with myositis, more ANA positivity).
Significance of vasculitis in DM?
Bad prognostic indicator. Ulcerations, widespread calcinosis, poor response to tx
What is the character of the risk of malignancy in DM?
Ovarian and GI (Colon>>others) most common.
- Risk of cancer returns to normal after 5 years of DM onset EXCEPT pancreatic and colorectal CA
For which cancers does the risk of occurrence not return to baseline after 5 years?
Pancreatic and colorectal
What are the most common causes of death in adults with DM?
Malignancy, ischemic heart dz, pulmonary dz.
What percentage of adults diagnosed with dermatomyositis have simultaneous neoplasm?
25%
What percentage of patients with dermatomyositis have the amyopathic form?
20%
Why is the ANA often negative in dermatomyositis?
Because the anti-synthetase and MDA5 antibodies are targeted against cytoplasmic proteins
What causes the shape of the shawl sign and the v-neck sign?
These are relatively sun-exposed areas and the sun exposure makes it worse
What type of UV exposure triggers dermatomyositis more?
UVA
Can visible light affect dermatomyositis?
There is some evidence that even visible light spectrum radiation can worsen the rash in dermatomyositis.
What muscles are most commonly affected?
Proximal extensor muscles: quadriceps and triceps
In NXP-2 related DM, distal muscles can be affected
What is the target of Mi-2 autoantibody in dermatomyositis?
Nuclear DNA helicase involved in DNA transcription
What is the clinical significance of the anti Mi-2 autoantibody?
Often a classic appearing DM, heliotrope rash, shawl sign, myositis of proximal muscles, gottran’s papules etc. Often responds well to treatment
What is the target of TIF-1 autoantibody in dermatomyositis?
TIF-1 is a tumor suppressor/transcriptional corepressor. Three subtypes alpha, beta, gamma, which have their own autoantibodies.
Clinical significance of TIF-1 autoantibodies?
The biggest thing is a strong association with underlying malignancy. Positive predictive value is estimated at 58% and negative at 95%. The autoantibody is thought to be generated from the anti-tumor immune response
- Also associated with severe photosensitive disease, heliotrope rash, v sign, gottron papules, palmar hyperkeratosis, psoriasiform plaques, ovoid palatal patches and atrophic hypopigmented patches w/ overlying telangiectasias, hypomyopathic disease, GI involvement, and lack of ILD, Raynaud, and arthritis
What is the most common cause of drug-induced DM?
Hydroxyurea (>50%)
What is the target of MDA5 autoantibody in dermatomyositis?
RNA-specific helicase involved in antiviral immune responses
Clinical associations with anti MDA5 dermatomyositis?
- Clinically amyopathic disease
- More common in Asian populations
- Increased risk of ILD and rapidly evolving ILD
- Associated w/ cutaneous ulceration (often at Gottran’s papules, nail folds), painful palmar papules (inverse Gottran’s papules), and panniculitis. All signs of vasculopathy
Most common autoantibodies associated with juvenile dermatomyositis?
Anti-NXP2, Anti-MDA5, Anti-TIF1
What is the target of NXP-2 autoantibody in dermatomyositis?
NXP-2 is a protein that regulates transcription and RNA metabolism.
Clinical associations with NXP-2?
- Common antibody in juvenile dermatomyositis
- Classic cutaneous findings + calcinosis (children>adults)
- Can be associated with severe myopathy leading to contractures (Juvenile form)
- GI bleeding (juvenile form, 2/2 bad vascular disease)
- Juvenile form w/ this autoantibody does not portend to increased cancer risk
What is the target of SAE autoantibody in dermatomyositis?
SAE, small nuclear enzyme involved in posttranslational modification of proteins
Clinical associations of SAE autoantibody?
Starts w/ severe cutaneous dz and minimal myopathy and then progressives to more severe myopathy. Can lead to severe dysphagia.
- Systemic sx’s like fever, weight loss
- Predictive of hydroxychloroquine triggered rash
What are the different anti-synthetase autoantibodies?
Includes: Anti Jo-1 (histidyl), anti-PL7 (alanyl), Anti-PL-12 (glycyl), Anti-EJ (isoleucyl), anti-OJ (isoluecyl), anti-KS (asparginyl), anti-Zo (phenylalnyl), and anti -YRS/HA(tyrosyl)
What is the clinical implications of positive anti-synthetase autoantibodies?
Myositis with ILD, Raynaud’s, Gottran’s papules, “mechanics hands”, more severe ILD and poorer prognosis
“Anti-synthetase syndrome”
Clinical associations of Anti-SRP antibodies?
Sudden, severe, progressive muscle weakness that can include the cardiac muscle and esophagus/pharynx (dysphagia). tends to be treatment-resistant and carries no increased risk of malignancy
“Necrotizing myopathy”
What components tend to be more prevalent in the DIF in DM?
Less intense lupus band area positivity
- Tends to have more C5-9 complement > C3 more IgM
Clinical associations of anti-HMGCR dermatomyositis?
Increased risk of malignancy, statin-induced myopathy
Clinical associations with Anti-CN1A dermatomyositis?
Progressive weakness and functional impairment in older patients (>50 y/o)
What gene mutation can be associated with juvenile DM?
TNF-alpha308A
- Leads to increased thrombospondin-1 (potent anti-angiogenic factor) –> increased occlusion of capillaries
What are the main drugs associated with drug-induced DM?
Hydroxyurea (>50%), statins, D-penicillamine, cyclophosphamide, BCG vaccine, TNF-alpha inhibitors
What is the clinical presentation of muscle involvement in DM?
Usually symmetric, slowly progressive weakness of the (extensors>flexors)
- Not painful ask about difficulty walking up stairs, standing up from sitting position, or brushing hair
Why is checking neck flexor strength important?
Can signal more advanced dz, wil potentially impending head drop, dysphagia, or diaphragm involvement
What is the significance of the Anti-Ku antibody/
Tend to be associated with polymyositis overlapping with either SLE, Sjogren syndrome, or scleroderma
What is the significance of anti-PM-1 (PM/Scl)?
Associated with DM/PM + scleroderma overlap dz
What is the difference in the clinical presentation of hydroxyurea-induced vs non-hydroxyurea-induced DM?
Hydroxyurea-induced DM: Longer latency (avg =60 months) after drug initiation. NO MYOSITIS, 16% w/ + ANA
Non-hydroxyurea-induced DM: Occurs within 2 months of drug initiation; 80% have myositis; ANA usually + in 54%
Both have classic skin findings and resolve 1-2 months after stopping drug
What treatment should be avoided if a patient is found to have cancer and needs a lymph node biopsy?
Don’t start prednisone/steroids! This alters the architecture of the nodes
