What causes itching and pain in the limbs?

Itching and Pain in Limbs: Differential Diagnosis and Management

Itching and pain in the limbs are not primarily psychiatric symptoms but rather indicate underlying neurological, systemic, or dermatological pathology that requires systematic medical evaluation. 1

Primary Diagnostic Considerations

Neuropathic Causes (Most Common)

Neuropathic itch and pain develop from peripheral nerve dysfunction or central nervous system disorders, presenting in normal-appearing skin without primary dermatological lesions. 2

• Peripheral neuropathy is the most frequent cause, presenting as "cold burning pain" in a glove-and-stocking distribution starting distally, with lower extremities more affected than upper limbs. 1
• Restless legs syndrome (RLS) manifests as compelling urges to move the lower extremities with creepy-crawly, burning, itching, or painful sensations that worsen at night and improve with movement. 1
• Complex regional pain syndrome (CRPS) can present atypically with neuropathic itching as the primary symptom rather than pain, accompanied by swelling, sweating, and skin flushing. 3
• Neuropathic symptoms result from sensory polyneuropathy, radiculopathy, herpes zoster, stroke, multiple sclerosis, or diabetes mellitus. 2

Systemic Disease Manifestations

• Iron deficiency causes generalized pruritus that may affect the limbs, and iron replacement leads to complete cessation in some cases. 1
• Renal disease (uremia) produces pruritus through unclear mechanisms related to metabolic derangements. 1
• Hepatobiliary disease, particularly cholestasis, causes generalized itching including the extremities. 1
• Hematological disorders including polycythemia vera and lymphoma present with pruritus that can involve the limbs. 1

Infectious and Parasitic Etiologies

• Helminth infections (strongyloidiasis, schistosomiasis, onchocerciasis) cause pruritic dermatitis predominantly over legs and buttocks during migratory stages. 1
• Larva currens from Strongyloides presents as itchy, linear urticarial rash moving several millimeters per second, most common around trunk, upper legs, and buttocks. 1

Essential Clinical Evaluation

History Components

• Onset and timing: Determine when symptoms began, diurnal variation (RLS worsens at night), and relationship to rest versus activity. 1, 4
• Symptom characteristics: Distinguish between burning, crawling, itching, or frank pain; assess whether movement provides relief. 1
• Distribution pattern: Note if symptoms follow glove-and-stocking distribution (neuropathy), are unilateral (CRPS), or bilateral and symmetric. 1, 3
• Associated features: Document fever, weight loss, travel history, medication use, diabetes, alcohol use, vitamin deficiencies, or recent infections. 1
• Aggravating factors: Identify worsening with rest, heat, cold, or specific times of day. 1

Physical Examination

• Skin inspection: Look for primary lesions versus secondary changes from scratching; examine for rash patterns, color changes, hair loss, or tissue alterations suggesting CRPS. 1, 4
• Neurological assessment: Test sensation in glove-and-stocking distribution, assess reflexes, and evaluate for focal deficits. 1
• Vascular examination: Check for edema, temperature differences, or sweating asymmetry indicating autonomic dysfunction. 3

Diagnostic Algorithm

Initial Laboratory Workup

Order complete blood count with differential, comprehensive metabolic panel (renal and hepatic function), thyroid function tests, fasting glucose/HbA1c, and ferritin/iron studies as first-line investigations. 1, 5

• Elevated eosinophils suggest helminth infection or T-helper-2 polarization. 5
• Abnormal renal function indicates uremic pruritus. 1
• Elevated liver enzymes or bilirubin suggest cholestatic disease. 1
• Low ferritin confirms iron deficiency as potential cause. 1

Condition-Specific Testing

• For suspected neuropathy: Obtain vitamin B12, B6, folate levels; consider hemoglobin A1c, thyroid function, and syphilis serology. 1
• For RLS diagnosis: Clinical diagnosis based on four criteria: (1) urge to move legs with uncomfortable sensations, (2) symptoms begin/worsen with rest, (3) relief with movement, (4) circadian pattern with evening/night worsening. 1
• For travel-related symptoms: Send stool for ova and parasites (three samples), blood microscopy within 2 hours of midnight for microfilaria, and serology for schistosomiasis or strongyloides. 1
• For CRPS: Diagnosis is clinical based on characteristic presentation following injury with autonomic changes. 1, 3

Management Approach

Neuropathic Itch and Pain

Treat neuropathic symptoms with medications that calm excess neuronal firing, including gabapentin, pregabalin, or tricyclic antidepressants as first-line agents. 1, 2

• Gabapentin or carbamazepine provide relief for neuropathic pruritus associated with various conditions. 1
• Topical capsaicin or lidocaine may help localized neuropathic symptoms. 2
• Address underlying causes: optimize diabetes control, supplement vitamin deficiencies, treat thyroid dysfunction. 1

Restless Legs Syndrome

• Dopaminergic agents are standard treatment for moderate-to-severe RLS. 1
• Check and correct iron deficiency (ferritin <75 μg/L warrants supplementation). 1
• Discontinue exacerbating medications: tricyclic antidepressants, SSRIs, lithium, dopamine antagonists. 1
• Reduce caffeine intake, increase physical activity, and maintain regular sleep schedule. 1

Complex Regional Pain Syndrome

Initiate multimodal therapy including physical therapy, neuropathic pain medications (gabapentin, pregabalin), and topical agents for CRPS with neuropathic itching. 3

• Treatment according to neuropathic pain protocols improves pruritus symptoms. 3
• Early mobilization and physical therapy prevent progression. 1

Systemic Disease-Related Pruritus

• Iron deficiency: Supplement with oral iron until ferritin normalizes. 1
• Uremic pruritus: Consider UV light therapy, activated charcoal, or adjustment of dialysis parameters. 6
• Cholestatic pruritus: Treat underlying liver disease; consider cholestyramine or rifampin. 1

Parasitic Infections

• Strongyloidiasis: Ivermectin 200 mcg/kg as single dose or albendazole 400 mg daily for 3 days. 1
• Schistosomiasis: Praziquantel at appropriate dosing for species. 1
• Onchocerciasis: Ivermectin with specialist guidance due to potential severe reactions. 1

Critical Pitfalls to Avoid

• Do not dismiss limb itching and pain as purely psychological without completing systematic medical evaluation, as this delays diagnosis of treatable neurological and systemic conditions. 2, 5
• Do not overlook iron deficiency as a reversible cause of generalized pruritus affecting the limbs. 1
• Do not miss CRPS when itching rather than pain predominates following limb injury or surgery. 3
• Do not forget travel history, as helminth infections cause characteristic limb pruritus patterns months after exposure. 1
• Consider malignancy in patients over 60 years with new-onset diffuse pruritus lasting less than 12 months, especially with liver disease history. 5

When Psychiatric Evaluation Is Appropriate

Psychogenic pruritus should be a diagnosis of exclusion only after thorough medical workup excludes organic causes. 1, 4

• Psychiatric referral is appropriate when: (1) comprehensive medical evaluation is negative, (2) symptoms have clear temporal relationship to psychological stressors, (3) patient has established psychiatric diagnosis, or (4) excessive scratching behavior appears compulsive. 1
• Even with psychiatric comorbidity, always rule out concurrent medical causes, as conditions frequently coexist. 4