Skin hyperpigmentation: a rare presenting symptom of nitrous oxide abuse.

Context: Recreational nitrogen oxide (N ₂ O) abuse can cause nervous system damage. There was a sharp increase in the number of patients with neurological disorders associated with recreational N ₂ O use in China, as recreational N ₂ O use became popular in young people nationwide. Among cases with neurological disorders caused by N ₂ O abuse, a few showed skin hyperpigmentation, which has rarely been reported. We explored the characteristics of hyperpigmentation in N ₂ O abusers to draw the attention of clinicians to this rare cutaneous symptom related to N ₂ O abuse. Methods: We retrospectively collected data of patients with neurological disorders related to recreational N ₂ O abuse in Shengjing Hospital of China Medical University from January 2014 to June 2019. Detailed clinical data were gathered from patients who manifested skin pigmentation, including the history of N ₂ O abuse and characteristics of neurological lesions and skin pigmentation. Results: In total, 66 patients (average age: 22.7 ± 4.5 years, 36 males) with neurological disorders due to N ₂ O abuse were included; four of them (17-23 years old, 1 male) manifested skin hyperpigmentation. The duration of N ₂ O abuse of the four patients ranged from 2 to 24 months, and they all had peripheral neuropathy; the two patients also had subacute combined degeneration of the spinal cord. One patient exhibited significant hyperpigmentation throughout the body (trunk, limbs, and face), with no abnormalities in cortisol and other biochemical tests. One patient presented with punctuate pigmentation throughout the trunk. Two patients presented with finger skin pigmentation, especially in the distal phalanxes. Pigmentation after N ₂ O use remitted slowly with vitamin B12 supplementation. Conclusion: Skin hyperpigmentation is a rare symptom in N ₂ O abusers, which can distribute locally in hands or diffusely throughout the body. Therefore, attention should be paid to a history of N ₂ O abuse and serum vitamin B12 level should be tested.