What could be causing a woman's generalized tingling (paresthesia) throughout her entire body?

Generalized Tingling Throughout the Body: Diagnostic Approach

A woman presenting with generalized tingling (paresthesia) throughout her entire body most likely has a systemic metabolic, toxic, or inflammatory polyneuropathy—particularly diabetes, vitamin B12 deficiency, or thyroid dysfunction—and requires immediate laboratory evaluation including fasting glucose/HbA1c, vitamin B12, TSH, complete metabolic panel, and complete blood count before considering neuroimaging. 1, 2, 3

Critical Initial Distinction

The pattern of paresthesia fundamentally determines the diagnostic pathway:

• Generalized/diffuse tingling suggests systemic metabolic, toxic, or inflammatory causes affecting the entire nervous system 1, 2
• Distal symmetric pattern (hands and feet) indicates length-dependent polyneuropathy, most commonly diabetic neuropathy 3
• Focal or asymmetric tingling raises concern for structural CNS lesions, stroke, or focal nerve entrapment 2

This patient's "all over body" distribution is atypical for common peripheral neuropathies and warrants consideration of central causes, anxiety-induced hyperventilation, or systemic inflammatory/autoimmune conditions. 2, 4

Most Common Systemic Causes of Generalized Tingling

Metabolic Disorders

• Diabetes mellitus is the most common cause of peripheral neuropathy, typically presenting with distal symmetric sensory loss, paresthesias, numbness, and tingling 5, 3
• Vitamin B12 deficiency causes polyneuropathy and can present with widespread paresthesias 3
• Thyroid dysfunction (both hypo- and hyperthyroidism) can cause peripheral neuropathy 5
• Hypocalcemia from hyperventilation or other causes increases axonal excitability and produces widespread tingling and tetany 4

Anxiety and Hyperventilation

• Voluntary hyperventilation induces hypocapnia and hypocalcemia, leading to paraesthesiae throughout the hands, face, and trunk before progressing to tetany 4
• The mechanism involves increased excitability of cutaneous and motor axons due to reduced plasma calcium 4
• This is a common and frequently overlooked cause of generalized tingling in anxious patients 4

Inflammatory and Autoimmune Causes

• Hepatitis C virus (HCV) infection causes peripheral sensory, motor, or sensorimotor polyneuropathies in up to 50% of infected patients, with symptoms including sensory loss, paresthesias, numbness, and tingling 5
• Guillain-Barré syndrome presents with acute-onset (within days), rapidly progressive, symmetric paresthesias that can be generalized and requires urgent recognition 3
• Vasculitis can cause multifocal or generalized neuropathy 3

Immediate Diagnostic Workup

Essential Laboratory Tests (Order First)

• Fasting glucose and HbA1c to screen for diabetes 3
• Vitamin B12 level to identify deficiency 3
• TSH and free T4 to assess thyroid function 5
• Complete metabolic panel including calcium, magnesium, and renal function 4
• Complete blood count to assess for anemia 5
• Inflammatory markers (ESR, CRP) if systemic inflammatory disease suspected 5

Clinical Assessment

• Detailed neurologic examination to identify focal deficits, weakness, or dysautonomia that would suggest Guillain-Barré syndrome or CNS pathology 2, 3
• Assess for anxiety symptoms and observe respiratory pattern for hyperventilation 4
• Document distribution pattern: truly generalized versus distal-predominant versus multifocal 1, 3
• Assess for associated symptoms: weakness, pain, autonomic dysfunction, or sensory loss 5, 1

Neurophysiologic Testing

• Electromyography (EMG) with nerve conduction studies should be performed if peripheral neuropathy is suspected based on examination, but may be normal in small fiber neuropathy 5, 1
• Intraepidermal nerve fiber density testing for small fiber neuropathy if EMG is normal but clinical suspicion remains high 5

When to Consider Neuroimaging

Imaging is NOT routinely indicated for generalized symmetric tingling without focal neurologic deficits or asymmetric findings. 5, 6

Indications for MRI Brain/Spine

• New focal neurologic deficits (weakness, vision changes, coordination problems) 6, 7
• Rapidly progressive symptoms over days suggesting Guillain-Barré syndrome or CNS pathology 3
• Asymmetric distribution suggesting stroke, multiple sclerosis, or structural lesion 2
• Associated headache with vision changes in young overweight women (concern for idiopathic intracranial hypertension) 6

Treatment Approach Based on Etiology

Metabolic Causes

• Optimize glycemic control for diabetic neuropathy 5, 1
• Replace vitamin B12 if deficient 1, 3
• Correct thyroid dysfunction 5

Neuropathic Pain Management

• Duloxetine is recommended for patients with neuropathic pain, numbness, and tingling (particularly in breast cancer survivors, but applicable to other neuropathies) 5
• Physical activity is recommended for neuropathy symptoms 5
• Acetaminophen or NSAIDs for pain 5

Anxiety-Related Hyperventilation

• Reassurance and breathing retraining if hyperventilation-induced 4
• Address underlying anxiety disorder 5

Critical Red Flags Requiring Urgent Evaluation

• Acute onset (within days) with rapid progression suggests Guillain-Barré syndrome 3
• Associated weakness or dysautonomia requires immediate hospitalization 3
• Asymmetric or multifocal distribution suggests vasculitis or CNS pathology 3
• Proximal predominance is atypical for common neuropathies and warrants urgent workup 3

Common Pitfalls to Avoid

• Do not order brain MRI for symmetric generalized tingling without focal deficits—this represents low-value care with minimal diagnostic yield 6, 7
• Do not dismiss anxiety-induced hyperventilation as a purely psychological phenomenon; it has a clear physiologic mechanism via hypocalcemia and increased axonal excitability 4
• Do not delay EMG/nerve conduction studies if peripheral neuropathy is suspected, but recognize they may be normal in small fiber neuropathy 5, 1
• Do not overlook HCV infection in patients with risk factors, as it causes peripheral neuropathy in up to 50% of infected individuals 5
• Do not miss Guillain-Barré syndrome by failing to recognize acute, rapidly progressive, symmetric paresthesias with weakness 3