What are the differential diagnoses for a patient presenting with tingling and burning sensations on the lips, initially affecting the bottom left lip and later involving the top and bottom lips on the right, with no visible lesions, redness, or rash, and a history of lip licking when dry?

Differential Diagnoses for Tingling and Burning Lips Without Visible Lesions

The most likely diagnosis is primary burning mouth syndrome (BMS) affecting the lips, given the bilateral burning and tingling sensations, absence of visible lesions, and the characteristic migratory pattern of symptoms. 1, 2

Primary Differential Considerations

Primary Burning Mouth/Lip Syndrome

• This is the leading diagnosis when burning and tingling sensations affect the lips bilaterally with normal-appearing mucosa on examination 1, 2
• The migratory pattern described (starting left lower lip, then involving upper and lower right, occasionally extending or involving multiple areas simultaneously) is consistent with the neuropathic nature of primary BMS 1
• Primary BMS represents a disorder of peripheral nerve fibers with central nervous system changes, characterized by continuous burning, stinging, or itchy sensations 2
• The condition predominantly affects peri- and post-menopausal women, though a distinct "burning lips syndrome" entity has been described that affects men equally and typically occurs between ages 50-70 3
• Associated symptoms often include dry mouth and abnormal taste, with significantly lower density of epithelial nerve fibers in affected tissues 2, 4

Contact Cheilitis (Allergic or Irritant)

• Must be considered despite patient denying new products, as chronic low-grade exposure to existing contactants can cause delayed hypersensitivity reactions 5
• The lip licking behavior when lips are dry creates both mechanical irritation and potential for saliva-induced irritant contact cheilitis 5
• Contact cheilitis may present with burning sensations before visible erythema or scaling develops 5
• Patch testing should be considered if this diagnosis is suspected 6

Post-Traumatic Trigeminal Neuropathic Pain

• Consider if there is any history of dental procedures, facial trauma, or injections within the past 3-6 months 1, 7
• Presents as continuous burning or tingling in the trigeminal distribution, which includes the lips 1, 7
• The unilateral onset (left lower lip initially) followed by contralateral spread could represent evolving neuropathic pain 7
• Typically develops within 3-6 months following the inciting event 1

Herpes Labialis Prodrome (HSV-1)

• The prodrome of herpes labialis is associated with itching, burning, and/or paresthesia prior to visible lesion appearance 8
• However, the one-week duration without progression to visible vesicles, erythema, or ulceration makes active HSV infection unlikely 8
• Reactivation stimuli include UV light exposure, fever, psychological stress, and menstruation 8
• Peak viral titers occur within the first 24 hours after lesion onset, so the absence of lesions after one week argues against this diagnosis 8

Secondary Causes Requiring Exclusion

Nutritional Deficiencies

• Vitamin B12 deficiency is a well-established cause of secondary burning mouth syndrome 2
• Iron deficiency anemia frequently presents with burning tongue and lips 2
• These deficiencies can cause burning sensations before other clinical signs become apparent 2

Oral Candidiasis

• Can cause burning mouth symptoms even without visible thrush 2
• Diagnosis requires scraping and KOH preparation or culture 2
• Must be excluded before diagnosing primary BMS 2

Medication-Related Causes

• Various medications can cause oral burning as a side effect 1, 2
• A thorough medication review is essential, even if the patient denies medication allergies 1

Autoimmune Conditions

• Sjögren's syndrome and sicca syndrome can manifest with oral burning 2
• The dry lips prompting lip licking could indicate underlying salivary gland dysfunction 2

Thyroid Disorders

• Hyperthyroidism can cause tongue and lip erythema with burning sensations 2
• Thyroid function testing (TSH, free T4) should be performed 1

Recommended Diagnostic Workup

Initial Laboratory Testing

• Complete blood count with differential to identify anemia 1, 2
• Vitamin B12 level 1, 2
• Iron studies (ferritin, serum iron, TIBC) 1, 2
• Fasting glucose and HbA1c 1
• Thyroid function tests (TSH, free T4) 1, 2
• Vitamin D 25(OH) level 1

Clinical Assessment

• Thorough oral examination to identify any mucosal lesions, candidiasis, or traumatic factors (sharp tooth edges, ill-fitting dental work) 1, 2
• Document the specific distribution, timing, and character of symptoms 1
• Assess for xerostomia and salivary gland function 2
• Review all current medications for potential causative agents 1, 2

Additional Testing if Initial Workup Negative

• Consider patch testing if contact cheilitis is suspected 6
• Qualitative sensory testing (QST) if neuropathic etiology is suspected 1, 7
• Tongue/lip biopsy only if suspicious lesions develop or diagnosis remains uncertain 1, 2

Critical Clinical Pearls

• The absence of visible lesions after one week strongly favors a neuropathic process (primary BMS) over infectious or inflammatory causes 1, 2
• The migratory and bilateral nature of symptoms is characteristic of primary BMS rather than focal pathology 1, 6
• Lip licking behavior can perpetuate symptoms through mechanical irritation and should be addressed 5
• If antihistamines are tried and ineffective, this further supports a neuropathic rather than allergic etiology 1
• Most cases will ultimately be diagnosed as primary BMS after excluding secondary causes 1, 2