Drs. Chung and McMahan reply

To the Editor:

We appreciate the interest of Yin et al¹ in our article² on perifollicular hypopigmentation (also known as salt-and-pepper pigmentation) in systemic sclerosis (SSc) and for sharing 2 case presentations that potentially shed light on the pathogenesis of this interesting phenomenon.

In our cross-sectional study, we found that perifollicular hypopigmentation is observed in a distinct subset of patients with SSc and independently associates with diffuse cutaneous disease and higher modified Rodnan skin scores, but can occur on nonsclerotic skin. However, the pathogenesis of perifollicular hypopigmentation remains poorly understood. It has been hypothesized that the activation of cellular and humoral immune factors in combination with external factors, such as trauma or inflammation, may result in the destruction of melanocytes.

Yin et al report 2 unique cases of Asian women with new-onset salt-and-pepper skin changes shortly after influenza vaccination or trauma, with a subsequent SSc diagnosis.¹ Although difficult to prove causation, the temporal and spatial associations are certainly suggestive that a specific insult (ie, immunogenic components of the vaccine or tissue injury from vaccination or trauma) may trigger an abnormal immune response resulting in destruction of melanocytes. Both cases are compelling, as salt-and-pepper skin developed directly at the sites of vaccination or trauma; thus, these are unlikely to be coincidental findings. Notably, the second case developed an arc-shaped pigmentary change that clearly corresponded to the source of trauma (ie, edge of cylindrical moxa sticks). However, as the authors mentioned, not all patients with pigmentation changes have a history of significant trauma; thus, microtrauma from friction and pressure should be investigated in future studies.

Yin et al¹ discussed a recent case series in which treatment with mycophenolate mofetil (MMF) resulted in greater than 75% improvement of salt-and-pepper pigmentation.³ At our institution, we implement MMF as the first-line treatment for patients with SSc with active skin and lung disease. Although we did not formally evaluate medication effects on perifollicular hypopigmentation in our study, from our clinical experience we have not observed direct improvement of salt-and-pepper pigmentation changes with MMF. However, our study did not specifically evaluate the natural course of salt-and-pepper pigmentation over time or study treatment effects on patients.²

We applaud the efforts of Yin et al¹ in describing 2 fascinating cases of salt-and-pepper pigmentation occurring shortly after trauma and vaccination. It will be worthwhile for the authors to longitudinally follow these patients to observe whether these pigmentation changes evolve, if new sites of pigmentary changes arise either spontaneously or in response to trauma, and whether immunosuppressant medications (if applicable) change the appearance of lesions. Their cases add to the growing literature that salt-and-pepper pigmentation can be an early cutaneous finding in a subset of patients with SSc, thereby serving as a harbinger to the diagnosis, as well as highlight the potential role of external factors triggering aberrant immune responses resulting in salt-and-pepper pigmentation.

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