Thanks to Cameron and Adam for presenting the case of a middle aged man with no significant PMH who presented with diffuse myalgias and chronic progressive proximal muscle weakness, found to have a CK >12k and EMG findings concerning for an inflammatory myopathy, awaiting muscle bx for diagnosis.

Clinical Pearls

• Rhabdomyolysis literally means dissolution of skeletal muscle and has a broad differential outside of the typical traumatic or exertional processes associated with it see below).
• The four main inflammatory myopathies are dermatomyositis, polymyositis, inclusion body myositis, and necrotizing autoimmune myositis.
• Polymyositis is rare and a diagnosis of exclusion after the other three main inflammatory myopathies have been investigated.
• Overall, the prognosis of inflammatory myopathies is good with appropriate treatment.  The exception is inclusion body myositis which is a progressive disorder without any effective therapy.
• Pigment nephropathy can occur with rhabdo regardless of the underlying etiology especially in patients with CK >5000.  Aggressive IV hydration to lower CK levels is important to reduce the risk of kidney injury.

Rhabdomyolysis:

DDx:

• Traumatic
  • Crush injuries, surgery, prolonged compression from immobility or coma
• Non-traumatic
  • Exertional:
    • Normal muscle: strenuous exercise, heat stroke, seizures, hyperkinetic states
    • Abnormal muscle: metabolic myopathies, mitochondrial myopathies, malignant hyperthermia, NMS
  • Non-exertional
    • Alcoholism
    • Drugs and toxins: lipid-lowering drugs (fibrates, statins), alcohol, heroin, cocaine, meth, colchicine
    • Infections: influenza, coxsackie, EBV, HIV, legionella
    • Electrolyte abnormalities: hypokalemia, hypophosphatemia, hypocalcemia
    • Endocrinopathies: DKA, HHS, hypothyroidism, vitamin D deficiency
    • Inflammatory myopathies (rare)
    • Paraneoplastic
    • Miscellaneous

Inflammatory myopathies

Largest group of potentially treatable myopathies in children and adults.

• Four subtypes: distinguishing which process is important because each subtype has a different prognosis and response to therapy
  • DM
    • Anti-Mi-2, anti-MDA-5, anti-TIF-1, anti-NXP-2
  • PM
    • Rare, often misdiagnosed
    • Dx of exclusion
  • Necrotizing autoimmune myositis
    • More common than PM
    • Occurs alone or after viral infections or in association with cancer, CTD, or post-statin
    • Anti-SRP or anti-HMGCR
    • Highest CK level
  • Inclusion body myositis
    • Most common in people >50
    • 7.9 cases/million in the US
    • Distal muscles impacted first
    • Facial muscles impacted
    • Muscle atrophy occurs earlier than in others
    • Extramuscular manifestations are uncommon
    • Dysphagia occurs in >50%
    • Muscle atrophy is common
    • Lowest CK level
• Up to 30% of patients with DM or PM have a constellation of clinical findings termed “antisynthetase syndrome”
  • Acute disease onset
  • Constitutional symptoms (fever, weight loss)
  • Myositis
  • Raynaud’s
  • Mechanic’s hands
  • Non-erosive arthritis
  • ILD
  • Labs show antibodies to tRNA synthetase enzymes (anti-Jo-1)
• Extramuscular manifestations
  • systemic symptoms
  • cardiac arrhythmias or ventricular dysfunction
  • pulmonary complications (ILD)

Table above adapted from this and this review article by NEJM.

Thanks to Becky Lee yet again for presenting an interesting case of a young woman presenting with acute onset of fever and polyarthritis, found to have a history of similar episodes in the past together with a rash concerning for Still’s disease!

Clinical Pearls

• Still’s disease is a diagnosis of exclusion!  Yamaguchi criteria can help with ruling in the diagnosis.
• Still’s remains a multi-systemic disorder of unknown etiology because it’s difficult to diagnose and rare (0.16 cases per 100,000).
• RF and ANA are generally negative but can be positive in <10% of patients with Still’s in low titers.
• ~66% of patients present with sore throat secondary to cricothyroid perichondritis or aseptic nonexudative pharyngitis.
• The disease is often recurrent.  Predictors of poor outcome include erosive polyarthritis on presentation and shoulder/hip involvement.

Acute polyarthritis (>5 joints involved):

Remember that for rheumatologic disorders, timing, symmetry, and number of joints involved is crucial to coming up with a differential diagnosis.  So for our patient with acute polyarthritis, consider the following:

• Infection
  • Viral: hepatitis, HIV, parvovirus B19
  • Spontaneous bacterial endocarditis
• Rheumatologic:
  • Rheumatoid arthritis
  • Reactive arthritis
  • SLE
  • Dermatomyositis
• Vasculitis
  • PAN
• Drug reactions
• Auto-inflammatory or disease of the innate immune system (as opposed to autoimmune or diseases of the adaptive immune system):
  • Periodic fever syndromes (TRAPS, PFAPA, hyper-IgD syndrome)
  • Still’s disease
• Schnitzler’s syndrome – chronic urticaria associated with a monoclonal gammopathy (usually IgM kappa)
• Sweet syndrome – painful skin lesions
• Sarcoid
• Kikuchi disease – cervical LAD and fever (necrotizing lymphadenitis)
• HLH/Macrophage activation syndrome – leukopenia and thrombocytopenia, elevated triglycerides, low fibrinogen and haptoglobin

Still’s disease:

• Some clarifications on nomenclature:
  • Systemic juvenile idiopathic arthritis (sJIA): first presentation <17 years old, previously referred to as Still’s disease
  • Adult onset Still’s disease (AOSD): first presentation  > 17 years old
• Epidemiology of AOSD:
  • 0.16 cases per 100,000
  • No sex predominance (F=M)
  • Bimodal age distribution with peak between 15-25 and another 36-46 years of age.  New diagnosis in patients >60 have been reported.
• Clinical features ⇒ Yamaguchi criteria (need 5 total with  > 2 major)
  • Major criteria:
    • Daily fevers to 39
    • Arthritis >2 weeks
    • Non-pruritic salmon-colored macular/maculopapular rash on trunk or extremities (though cases of pruritic rash have also been reported)
    • ↑ WBC >10k, >80% neutrophils
  • Minor
    • Sore throat
    • LAD and/or splenomegaly
    • ↑ AST, ALT, or LDH
    • Negative ANA/RF
• Treatment
  • Mild: NSAIDs
  • Moderate: NSAIDs + DMARDs
  • Severe: NSAIDs + DMARDs (IL1 receptor antagonists like anakinra appear to be more helpful than TNF inhibitors especially in sJIA)
• Prognosis:
  • Overall good prognosis
  • Disease can be limited to one episode or recurrent over time
  • Poor prognostic indicators:
    • Hip and shoulder involvement
    • Erosive polyarthritis at initial diagnosis
• Complications
  • Macrophage activation syndrome (ie HLH) can occur in 15% of cases
  • DIC
  • TTP
  • Diffuse alveolar hemorrhage
  • Pulmonary HTN
  • Aseptic meningitis

References: 

Great recent review article on Still’s disease (AOSD Review) and this prior post on our blog!