Can skin disease cause neuropathic pain? A study in pachyonychia congenita

Pachyonychia congenita (PC) is a rare skin disorder caused by an autosomal dominant mutation in one of five genes encoding keratin (K6a, K6b, K6c, K16 or K17; each defining one PC subtype). Pain is a prominent symptom, but its severity and type are poorly characterized.

In total, 35 genotyped US patients with PC consented to clinical assessment including the quality of life (QoL) questionnaire EQ-5D-3L, the Brief Pain Inventory (BPI) and painDETECT. Abbreviated quantitative sensory testing (QST) was also performed, and included mechanical detection threshold (MDT), mechanical pain threshold (MPT), wind-up pain ratio (WUR) and vibration detection threshold (VDT).

Significant pain in patients with PC was confirmed, as indicated by mean BPI severity and interference of 4.2 ± 1.7 and 4.4 ± 2.2, respectively, as well as QoL impairment, as indicated by mean EQ-5D index of 0.69 ± 0.18. PD identified neuropathic pain in 62% of patients, the remainder being nociceptive. The painDETECT score was most significantly related to EQ-5D index (R(2)  = 0.26, P = 0.02). The K17 and K6a subtypes exhibited significantly worse QoL (0.584 and 0.613 respectively) than the K16 and K6b subtypes (P = 0.02). In QST analysis, abnormal pressure pain (assessed as MPT) was frequently observed, with more than half of patients with PC affected (54%), and 57% of patients with K17 also exhibiting abnormality in minimum touch threshold (assessed as MDT, P < 0.05). Very few patients were receiving analgesic therapy appropriate for neuropathic pain.

Significant neuropathic pain was observed in PC, which warrants appropriate treatment. The health states observed in this sample are at a level that the average US citizen would forfeit one-third of their remaining lifespan to avoid.