Idiopathic Inflammatory Myopathies (IIM)
Tina Arkee
Background
- Heterogenous group of disorders that classically present with painless proximal muscle weakness; some subtypes may present with additional systemic features such as antisynethase syndromes (e.g. ILD, rash, inflammatory arthritis, mechanics’ hands, Raynaud phenomenon)
- Subtypes (non-exhaustive): dermatomyositis (DM), polymyositis (PM), antisynthetase syndrome, immune-mediated necrotizing myopathy (IMNM), inclusion body myositis (IBM)
- Differential diagnosis: statin-induced myopathy, metabolic (hypothyroid, electrolyte), viral/infectious myositis, diabetic myonecrosis
- Important point: PMR= painful, preserved strength vs inflammatory myopathy = painless weakness
- Consider screening patients for underlying malignancy, particularly in DM and PM – up to 15- 30% of cases are associated with malignancy (specific antibody present can further risk stratify)
Presentation
- Acute vs. Chronic
- Acute or subacute: DM, PM, IMNM
- Gradual and progressive: IBM
- Distribution of weakness
- Proximal and symmetric: DM, PM, IMNM
- Distal and asymmetric: IBM (often involves weakness of finger flexor muscles)
- Systemic signs or symptoms: fever, rash, dyspnea, dysphagia, arthritis
- DM: Gottron’s papules, heliotrope rash, shawl sign, mechanics hands
- Anti-synthetase syndrome: cough/dyspnea, arthritis, Raynaud’s or mechanics hands, and sometimes fever
- IBM: can present with dysphagia; advanced cases may present with muscle atrophy
- Consider patient’s medications including exposure to statins and steroids
Evaluation
- Diagnosis: clinical but can use 2017 EULAR/ACR Classification Criteria for Adult and Juvenile Myositis; weighted point system including age of onset, distribution, skin involvement, elevated muscle enzymes, EMG, muscle biopsy, myositis-specific antibodies
- Labs: CMP, TSH, CK level, LDH and aldolase + extended myositis panel (screens commonly associated antibodies including anti-Jo1, anti-Mi2, etc.)
- MDA5 Ab is associated with rapidly progressing ILD, which may present with AHRF
- TIF1 and NXP2 Abs are associated with underlying malignancy
- EMG: useful for ruling out neuromuscular etiologies
- MRI extremity/affected muscle group: can help guide biopsies and evaluate edema on T2 and STIR (high signal intensity on these sequences may reflect active inflammation) and fatty replacement (reflects muscle damage) on T1.
- Skin biopsy in dermatomyositis: “interface dermatitis,” notably the same findings as skin biopsy of lupus rashes
- Muscle biopsy: gold standard for diagnosis but not always necessary (especially in dermatomyositis)
- Do not do biopsy in same muscle as EMG done
- Dermatomyositis: perifascicular and perivascular inflammatory infiltrate (CD4+ T cells and dendritic cells)
- Polymyositis: endomysial inflammatory infiltrate (CD8 T cells)
- IMNM: variable stage necrotic fibers, scant inflammatory infiltrate
- IBM: endomysial infiltrate, intracellular vacuoles, protein aggregates
Management
- If suspected, consult Rheumatology !
- 1st line:
- DM/PM: high-dose steroids (1mg/kg/day prednisone) for 4-6 weeks PLUS steroidsparing agent (MTX, azathioprine, or mycophenolate mofetil)
- IMNM: high dose steroids for 4-6 weeks PLUS IVIG and rituximab
- IBM: poor response to immunotherapy; focus on supportive care and aggressive PT/OT/SLP
- 2nd line: IVIG, rituximab, abatacept, or tofacitinib
Sjögren’s syndrome
Meridith Balbach
Background
- Systemic autoimmune disorder primarily targeting exocrine glands causing sicca symptoms; may also involve musculoskeletal, pulmonary, renal, neurologic, and hematologic features
- May be primary or secondary (occurring alongside another autoimmune disease such as RA or SLE)
- Incidence: presents most often around age 40-60y; female-to-male ratio ~9:1
- Etiology: genetic predisposition (e.g. increased risk with specific HLA-DQA_DQB_ haplotypes) + environmental factors triggers aberrant autoantibody production and lymphocytic infiltration of glands (predominantly CD4+ T cells; also B cells), resulting in glandular dysfunction
Presentation
- Classic sicca: dry eyes (gritty, burning, or foreign body sensation) and dry mouth (difficulty chewing/swallowing dry foods, frequent water intake, dental caries)
- Extra-glandular features:
- MSK: arthralgias, arthritis, myalgias
- Dermatologic: eyelid dermatitis, Raynaud’s, cutaneous vasculitis
- Hematologic: cytopenias, hyper- and hypogammaglobulinemia, monoclonal gammopathy, cryoglobulinemia; non-Hodgkin lymphoma, particularly MALT lymphoma (most feared complication; higher risk if persistent parotid enlargement or hypocomplementemia)
- Pulmonary: ILD, xerotrachea, bronchiectasis
- Gastrointestinal: dysphagia, chronic diarrhea, abdominal pain
- May also include neurologic, renal, cardiovascular (but typically <5%)
Evaluation
- Serologic workup: ANA with reflex (typically + Anti-Ro/SSA or anti-La/SSB), RF (often positive, even in the absence of RA), immunoglobulins, ESR (often elevated) and CRP (usually normal or mildly elevated)
- Anti-Ro/SSA is most sensitive and specific but is not diagnostic
- Additional workup: Schirmer test, slit-lamp exam, salivary flow rate
- Gold standard: labial salivary gland biopsy
- Clinical diagnosis but 2016 ACR/EULAR classification criteria can help guide in unclear cases (score ≥4 confirms classification):
- + anti-Ro/SSA (3)
- Focal lymphocytic sialadenitis (3)
- Ocular staining score ≥5 (1)
- Schirmer’s test ≤5 mm/5 min (1)
- Unstimulated salivary flow ≤0.1 mL/min (1)
Management
- Treatment is currently targeted to organ involvement (though several biologics are being studied). Immunosuppression is not used for dryness symptoms.
- Xerophthalmia: preservative-free artificial tears, cyclosporine eye drops; punctal plugs if refractory
- Xerostomia: frequent sips, sugar-free lozenges or gum, saliva substitutes + good dental hygiene; muscarinic agonists (e.g. pilocarpine) if persistent
- MSK: hydroxychloroquine
- Organ-threatening disease: steroids +/- steroid-sparing agent (MMF, azathioprine, rituximab)
