Is the recent pins‑and‑needles sensation in the feet of a patient with pachyonychia congenita related to his underlying condition?

Pachyonychia Congenita and Neuropathic Symptoms

The pins-and-needles sensation in your patient's feet is likely directly related to his pachyonychia congenita, as this condition is associated with neuropathic changes including mechanical hyperalgesia, thermal hypoaesthesia, and altered sensory innervation that can manifest as paresthesias. 1

Understanding the Neuropathic Component of Pachyonychia Congenita

Pachyonychia congenita (PC) is not simply a skin disorder—it involves significant neuropathic changes that explain sensory symptoms like pins-and-needles:

• Neuropathic pain is highly prevalent in PC, with 62% of patients scoring ≥4 on the DN4 (Douleur Neuropathique-4) questionnaire, which is diagnostic for neuropathic pain. 1

• Tingling and paresthesias are common, reported in 53% of PC patients, particularly in the feet. 1

• Histological studies demonstrate alterations in sensory innervation in PC-affected skin, providing a structural basis for neuropathic symptoms. 1

• Patients exhibit both thermal and mechanical hypoaesthesia (reduced sensation) alongside mechanical hyperalgesia (increased pain sensitivity), a pattern consistent with small-fiber neuropathy. 1

Clinical Features Supporting Neuropathic Origin

The sensory profile in PC differs from simple mechanical pain:

• Static allodynia (pain from normally non-painful stimuli) occurs in 55% of PC patients. 1

• Pain quality is neuropathic in character—described as throbbing and stabbing rather than purely pressure-related. 1

• Conditioned pain modulation is reduced in PC patients, indicating central sensitization and altered pain processing. 1

Distinguishing PC-Related Neuropathy from Other Causes

While the symptoms may mimic diabetic or other peripheral neuropathies, several features are distinctive:

• The specific gene mutation (KRT6A, KRT6B, KRT6C, KRT16, or KRT17) does not affect the sensory features, suggesting a common neuropathic pathway across PC genotypes. 1

• Symptoms are typically focal to areas of keratoderma rather than the length-dependent stocking-glove distribution seen in metabolic neuropathies. 1, 2

• Worsening over the past month could reflect progression of plantar keratoderma, increased mechanical trauma, or seasonal factors (increased sweating in warmer weather exacerbates symptoms). 3

Recommended Evaluation Approach

Confirm the diagnosis is PC-related rather than a superimposed neuropathy:

• Examine the feet for focal palmoplantar keratoderma, hypertrophic nail dystrophy, and areas of callus formation that correlate with symptom location. 2

• Assess whether paresthesias are localized to areas of keratoderma or follow a more generalized distribution. 1

• Screen for diabetes (fasting glucose or HbA1c) and vitamin B12 deficiency to exclude common treatable causes of peripheral neuropathy, even though PC itself is the likely culprit. 4, 5

• Consider whether the patient has started any new medications, particularly nitrofurantoin, which markedly increases neuropathy risk. 4

Management Strategy for PC-Related Neuropathic Symptoms

Because PC pain has a neuropathic origin, neuropathic pain medications are appropriate:

• Initiate pregabalin, duloxetine, or gabapentin as first-line therapy for neuropathic symptoms, following the same approach used for diabetic peripheral neuropathy. 5, 1

• Duloxetine 60 mg daily may be preferred if the patient has comorbid depression or anxiety related to chronic pain. 5

• Gabapentin titrated to 1200 mg daily (divided three times daily) is the most cost-effective option. 5

• Pregabalin 150-300 mg daily (divided twice daily) is FDA-approved for neuropathic pain and may provide faster symptom relief. 5

Addressing the Underlying Keratoderma

Reducing plantar keratoderma may decrease mechanical triggers for neuropathic symptoms:

• Regular mechanical debridement by a podiatrist experienced in PC management reduces callus thickness and associated pain. 2, 6

• Topical keratolytic agents (urea-based creams) applied daily help soften hyperkeratotic areas. 7, 2

• Proper footwear with cushioning and pressure redistribution is essential to minimize trauma. 7, 2

• For severe cases with hyperhidrosis exacerbating symptoms, botulinum toxin type A injections into plantar skin have shown remarkable pain relief lasting 6 weeks to 6 months. 3

Emerging Therapies

Rosuvastatin has shown promise in case reports:

• One patient with a KRT6A mutation experienced 3.6-mm reduction in plantar callosity thickness and significant pain relief on rosuvastatin. 8

• This represents a potential disease-modifying approach rather than purely symptomatic treatment. 8

Common Pitfalls to Avoid

• Do not dismiss paresthesias as unrelated to PC—the neuropathic component is well-documented and requires specific treatment. 1

• Do not rely solely on mechanical debridement and footwear modifications for neuropathic symptoms; pharmacologic management of neuropathic pain is indicated. 1, 6

• Do not overlook infection risk—PC patients are prone to secondary bacterial or fungal superinfection of keratotic areas, which can worsen pain. 7, 2

• Do not prescribe nitrofurantoin for urinary tract infections in this patient, as it significantly increases neuropathy risk. 4

Follow-Up Monitoring

• Reassess symptom severity and functional impact at 2-4 weeks after initiating neuropathic pain medication. 5

• Monitor for progression of keratoderma and ensure regular podiatry follow-up for debridement. 2, 6

• Consider referral to a dermatologist with PC expertise if symptoms remain refractory to standard neuropathic pain management. 2