What to order for a patient with diffuse skin burning without a rash or fever?

Workup for Diffuse Skin Burning Without Rash or Fever

Order a comprehensive medication review, complete blood count (CBC), comprehensive metabolic panel (CMP), liver function tests (LFTs), and consider referral to dermatology for evaluation of small fiber neuropathy or other neuropathic causes. 1

Initial Laboratory Workup

Essential First-Line Tests

• Complete blood count (CBC) to evaluate for hematologic disorders including polycythemia vera, lymphoma, or iron deficiency 1
• Comprehensive metabolic panel including urea and electrolytes to assess for uremic pruritus and renal dysfunction 1
• Liver function tests (LFTs) to evaluate for hepatic causes of burning sensation 1
• Ferritin level as iron deficiency can cause generalized pruritus/burning without visible skin changes 1

Medication History Review

• Conduct thorough review of all medications to rule out drug-induced causes, particularly proton pump inhibitors (which can cause burning sensations), immunotherapy agents, and other recent cancer therapies 1, 2
• Document timing of symptom onset relative to medication initiation 1

Secondary Investigations Based on Clinical Context

If Patient Has Cancer History or Immunotherapy Exposure

• Physical examination of oral mucosa and assessment for any subtle skin changes 1
• Consider that immune checkpoint inhibitors can cause burning sensations even without visible rash (Grade 2 toxicity can present with burning and tightness) 1
• Dermatology consultation for potential skin biopsy if autoimmune skin disease is suspected 1

If Hematologic Abnormalities Suspected

• Blood film, lactate dehydrogenase, and erythrocyte sedimentation rate if suspicion of blood disorders 1
• JAK2 V617F mutation analysis if polycythemia vera suspected (raised hemoglobin or hematocrit) 1
• Referral to hematology if polycythemia vera or lymphoma suspected 1

If Neuropathic Etiology Suspected

• Consider skin biopsy to evaluate for small fiber neuropathy, which can present as burning without visible skin changes 1
• Referral to neurology or dermatology for specialized evaluation 1

Additional Targeted Testing

Do NOT Routinely Order

• Thyroid function tests unless additional clinical features suggest endocrinopathy 1
• Extensive malignancy workup unless systemic symptoms are present 1

Consider in Specific Contexts

• HIV and hepatitis A, B, C serology if risk factors present or travel history suggests infectious etiology 1
• Vitamin D level as supplementation may help some patients with generalized pruritus without rash 1
• Bile acids and antimitochondrial antibodies if LFTs are abnormal 1

Clinical Photography and Monitoring

• Serial clinical photography to document any subtle changes over time that may not be apparent on single examination 1
• Weekly monitoring if symptoms progress 1

Common Pitfalls to Avoid

• Do not dismiss burning sensations without visible rash as purely psychological without completing organic workup 1
• Do not overlook medication-induced causes, particularly in patients on chronic proton pump inhibitors or recent immunotherapy 1, 2
• Do not perform extensive endocrine or malignancy screening without specific clinical indicators, as this is low yield 1
• Do not delay dermatology referral if symptoms are severe or progressive, as conditions like small fiber neuropathy require specialized evaluation 1