What are the causes of chronic pruritus with a painful burning quality?

Causes of Chronic Pruritus with Painful Burning Quality

Chronic pruritus with a painful burning quality most commonly indicates neuropathic pruritus from small fiber neuropathy, postherpetic neuralgia, or nerve compression syndromes, though systemic causes—particularly cholestatic liver disease, uremic pruritus, and iron deficiency—must be systematically excluded before attributing symptoms to neuropathic mechanisms alone. 1, 2, 3

Primary Neuropathic Causes (Most Likely with Burning Quality)

Small fiber neuropathy is the leading cause of burning pruritus and results from damage to unmyelinated C-fibers that transmit both pain and itch signals, creating the characteristic burning-itching sensation. 1, 2, 3

• Postherpetic neuralgia following varicella-zoster infection produces localized burning pruritus in the affected dermatome, often persisting months to years after the acute infection. 4
• Notalgia paresthetica causes burning itch in the upper back (typically T2-T6 distribution) due to nerve entrapment or spinal nerve root compression. 3
• Brachioradial pruritus affects the forearms and upper arms with burning dysesthesia, typically from cervical spine pathology (C5-C8 nerve roots). 3
• Diabetic neuropathy can manifest as generalized or localized burning pruritus, particularly in the lower extremities. 1, 4

Critical Systemic Causes That Must Be Excluded

Cholestatic Liver Disease

Cholestatic pruritus characteristically affects palms and soles, worsens at night, and may have a burning quality due to bile acid accumulation activating both itch and pain receptors. 1, 2, 4

• Serum bile acids are the definitive diagnostic test and should be ordered immediately alongside liver function tests and total bilirubin. 1, 2, 4
• Primary biliary cholangitis should be suspected if antimitochondrial antibodies are positive. 2, 4
• Drug-induced cholestatic hepatitis (particularly from statins) causes pruritus in 1.1% of patients and requires immediate medication discontinuation. 2

Uremic Pruritus

Chronic kidney disease produces burning pruritus in approximately 42% of hemodialysis patients through multiple mechanisms including xerosis, metabolic disturbances, and inadequate dialysis. 2, 4

• Urea, creatinine, and electrolytes must be checked in all patients with unexplained burning pruritus. 1, 2
• Severity correlates with the stage of renal impairment. 4

Iron Deficiency

Iron deficiency causes generalized pruritus that may have a burning component and accounts for approximately 25% of systemic disease-related pruritus cases. 1, 2, 4

• Comprehensive iron studies (serum iron, ferritin, transferrin saturation) are mandatory—ferritin alone is insufficient. 2
• Iron replacement leads to complete cessation of pruritus within days to weeks of initiating therapy. 1, 2, 4

Hematologic Malignancies

Polycythemia vera characteristically presents with aquagenic pruritus (triggered by water contact) that may have a burning quality. 2, 4

• JAK2 V617F mutation testing should be ordered if aquagenic symptoms are present. 1, 2

Hodgkin lymphoma typically causes nocturnal burning pruritus, often accompanied by B symptoms (fever, night sweats, weight loss). 4

• Nocturnal pruritus with weight loss mandates immediate investigation for hematologic malignancy. 4

Mandatory Initial Laboratory Workup

Order the following tests immediately for all patients with chronic burning pruritus: 1, 2

• Complete blood count with differential (screens for polycythemia vera, lymphoma, anemia)
• Comprehensive iron studies (serum iron, ferritin, transferrin saturation)
• Liver function tests, total bilirubin, and serum bile acids
• Renal panel (urea, creatinine, electrolytes)
• Fasting glucose and hemoglobin A1c (evaluates for diabetic neuropathy)
• Thyroid-stimulating hormone (only if clinical features suggest thyroid dysfunction) 1, 2

History-Directed Additional Testing

• HIV and hepatitis A, B, C serologies if relevant travel or risk factors exist, as these infections cause generalized burning pruritus. 1, 4
• Skin biopsy for persistent unexplained cases to evaluate for cutaneous lymphoma or small fiber neuropathy (look for reduced intraepidermal nerve fiber density). 1, 2, 5
• Antimitochondrial antibodies when cholestatic liver tests suggest primary biliary cholangitis. 2, 4

Immediate Symptomatic Management (While Awaiting Results)

Begin topical neuropathic agents immediately for burning pruritus: 2, 3

• Menthol 1-3% cream or lotion applied to affected areas 2-3 times daily activates cooling receptors that inhibit itch and pain signals. 2, 3
• Pramoxine 1% lotion provides local anesthetic effect for burning dysesthesia. 2, 3
• Lidocaine 5% ointment or patch for localized burning pruritus (particularly effective for postherpetic neuralgia). 3

Combine with emollients applied liberally at least twice daily to address xerosis, which lowers the threshold for both itch and pain perception. 1, 2, 5

Avoid relying on antihistamines alone—they are generally ineffective for neuropathic or systemic causes of burning pruritus. 2, 3

Cause-Specific Treatment Algorithms

For Confirmed Neuropathic Pruritus

First-line systemic therapy: Gabapentin 300 mg at bedtime, titrate up to 300-1200 mg daily in divided doses over 1-2 weeks based on response and tolerability. 1, 2, 5, 3

• Pregabalin 75-150 mg twice daily is an alternative with faster onset but higher cost. 5, 3
• Antidepressants (sertraline 50-100 mg daily, doxepin 10-25 mg at bedtime) provide dual benefit for neuropathic pain and itch. 2, 3

For Cholestatic Pruritus

Rifampin 150 mg twice daily is first-line treatment (Strength A recommendation). 2

• Cholestyramine 9 g daily as second-line if rifampin is ineffective or contraindicated. 2
• Sertraline 75-100 mg daily as third-line option. 2

For Uremic Pruritus

Broadband UVB phototherapy is the most effective treatment (Level 1+ evidence). 2

• Gabapentin 100-300 mg post-dialysis (avoid higher doses due to renal clearance). 2
• Optimize dialysis adequacy (Kt/V ≥1.6) to relieve pruritus in approximately 40% of patients. 2

For Iron Deficiency

Oral iron replacement (ferrous sulfate 325 mg daily or equivalent elemental iron 65 mg daily) leads to complete cessation of pruritus within days to weeks. 1, 2, 4

Critical Pitfalls to Avoid

Never dismiss burning pruritus as purely psychogenic without completing the full systemic workup—approximately 15% of chronic pruritus cases have underlying systemic disease that requires specific treatment. 3, 6

Do not delay bile acid testing when cholestatic disease is suspected—this is the definitive diagnostic test and cholestatic pruritus can be severe and refractory without treating the underlying cause. 2, 4

Avoid long-term sedating antihistamines (hydroxyzine, diphenhydramine) due to increased dementia risk in older adults; use only for short-term palliative care if needed. 2, 4

Recognize that pruritus without visible rash is rarely an emergency unless accompanied by systemic signs of anaphylaxis, severe hepatic failure with altered mental status, or hemodynamic instability. 2

Referral Criteria

Refer to dermatology if pruritus persists >2-4 weeks despite first-line therapy or if diagnostic uncertainty remains. 2, 5

Refer to neurology for refractory neuropathic pruritus requiring advanced pain management techniques or when small fiber neuropathy is confirmed on biopsy. 2

Refer to hepatology for significant hepatic impairment (elevated transaminases >3× upper limit of normal, elevated bilirubin, or elevated bile acids). 2

Refer to nephrology for elevated creatinine requiring dialysis optimization or consideration of renal replacement therapy. 2