What is the diagnosis for a 47-year-old woman presenting with progressive muscle weakness, particularly in her shoulders, hips, and thighs, with symptoms including difficulty combing her hair, getting up from a chair, and walking up stairs, and experiencing generalized fatigue, with no recent trauma or infections, and an unremarkable past medical history?

From the Guidelines

For this 47-year-old woman with progressive proximal muscle weakness, I would prioritize obtaining a comprehensive history and conducting first-line diagnostic tests, including creatine kinase (CK) levels, electromyography (EMG), and muscle biopsy, to establish a definitive diagnosis and guide treatment. The patient's symptoms of progressive muscle weakness, particularly in her shoulders, hips, and thighs, suggest a myopathic process. To further evaluate this, I would obtain additional history regarding any skin changes, dysphagia, shortness of breath, Raynaud's phenomenon, family history of neuromuscular disorders, and exposure to medications or toxins that could cause myopathy 1.

The differential diagnosis for this patient's presentation includes muscular dystrophy, mitochondrial myopathies, and inflammatory myopathies, among others 1. Given the patient's symptoms and the potential for irreversible muscle damage, it is crucial to establish a definitive diagnosis promptly. First-line diagnostic tests should include CK levels, comprehensive metabolic panel, complete blood count, inflammatory markers (ESR, CRP), thyroid function tests, and EMG with nerve conduction studies 1. These tests help establish the presence of muscle inflammation and rule out metabolic, endocrine, or neurogenic causes.

If inflammatory myopathy is suspected, additional testing should include autoimmune serologies (ANA, anti-Jo-1, anti-Mi-2, anti-SRP antibodies) to identify specific inflammatory myopathies like dermatomyositis or polymyositis 1. Muscle MRI can help identify affected muscle groups and guide biopsy, which remains the gold standard for diagnosis 1. A muscle biopsy can help distinguish among various neuromuscular diseases and genetic testing can confirm specific diagnoses, such as muscular dystrophy or mitochondrial myopathies 1.

Key elements of the patient's history that should be obtained include:

• Skin changes, such as rash, particularly on the face, knuckles, or chest
• Dysphagia or shortness of breath
• Raynaud's phenomenon
• Family history of neuromuscular disorders
• Exposure to medications or toxins that could cause myopathy
• History of trauma or infections

First-line diagnostic tests should include:

• Creatine kinase (CK) levels
• Comprehensive metabolic panel
• Complete blood count
• Inflammatory markers (ESR, CRP)
• Thyroid function tests
• Electromyography (EMG) with nerve conduction studies
• Muscle biopsy, if warranted by initial test results.

From the Research

Additional Key Elements of History

To further understand the patient's condition, the following key elements of her history should be obtained:

• Family history of muscle weakness or neuromuscular disorders, as some muscular dystrophies have a genetic basis 2
• Detailed description of the progression of her symptoms, including the rate of progression and any factors that exacerbate or relieve her symptoms
• History of medication use, as some medications can cause muscle weakness 3
• Presence of any other symptoms, such as pain, numbness, or tingling, which could indicate a neuropathic or inflammatory component

First-Line Diagnostic Tests

The first-line diagnostic tests for this patient would include:

• Serum creatine kinase level, as an elevated level would be a strong pointer to a muscle disease 2, 4
• Electromyography (EMG) to evaluate for a myopathy or neuropathy 3
• Thyroid-stimulating hormone (TSH) assay to evaluate for endocrine causes of muscle weakness 3
• Blood chemistries to evaluate for electrolyte imbalances that could contribute to muscle weakness 3
• A thorough physical examination, including a neurologic survey, to objectively document the patient's loss of strength and search for patterns of weakness and extramuscular involvement 3

Rationale for Diagnostic Tests

These diagnostic tests are chosen because they can help to distinguish between different causes of muscle weakness, such as muscular dystrophy, inflammatory myopathy, and endocrine disorders. The serum creatine kinase level and EMG can help to identify muscle disease, while the TSH assay and blood chemistries can help to identify endocrine and electrolyte causes of muscle weakness. A muscle biopsy may also be considered if the diagnosis remains unclear after initial testing 5.