PMC9424493_01
(A) Timeline for the diagnosis, treatment, and changes of the vitiligo condition. (B) Chest computed tomography scans revealed the clinical response during the treatment. The efficacy evaluation was stable disease after the two cycles of 'SHR-1210 combined with pemetrexed and carboplatin, but as the treatment time was prolonged, the tumor density gradually decreased, suggesting that the tumor has been effectively controlled.
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She underwent chest computed tomography examination and found space-occupying lesions and large pleural effusion in the right lung in November 2017( Figure 1B ). SHR-1210 (anti-PD-1 antibody) combined with pemetrexed and carboplatin as the first-line treatment for patients with the advanced or metastatic non-squamous NSCLC. She was randomly assigned to an experimental group in December 2017 and received 6 cycles of "SHR-1210 combined with pemetrexed and carboplatin" regimens, followed by 29 cycles of "SHR-1210 in combination with pemetrexed" as subsequent therapy ( Figure 1A ). After the first two cycles of treatment in February 2018 (6 weeks), lung cancer was effectively controlled, and the efficacy evaluation was stable disease( Figure 1B ). According to the provisions of this clinical study, the immunotherapy was discontinued after 2 years (total of 35 cycles) in December 2019 and single agent pemetrexed was started as maintenance therapy until now ( Figure 1A ). With the extension of the treatment time, the tumor density gradually decreased, suggesting that the patient reached a durable stabilization of her tumor ( Figure 1B ).
The images of the patient's facial and limbs changes under the natural light and wood's light during and after the treatment of the anti-PD-1 antibody. (A) During the treatment of immunotherapy, the vitiligo areas on the face were gradually enlarged, even involving the hair (including hair on the head/eyelashes/eyebrows), which showed depigmentation. (B-D) With the prolongation of immunotherapy withdrawal, the vitiligo areas on the face were gradually narrowed and the hair was gradually turned black. (E) Wood's light examination showed that the vitiligo areas were bright bluish-white, and the hypopigmentation area was also found at the junction of the normal and depigmented skin. The hypopigmentation areas around the mouth under wood's light examination presented a bright bluish-white signal. (F-H) With the prolongation of the immunotherapy withdrawal, the bright bluish-white areas on the mouth-around were gradually narrowed and faded. (I, L) Scattered pigmented spots began to emerge on the patient's right forearm and lower legs under the wood's light examination 9 months after stopping the immunotherapy. (J, M) The pigment macules of the right forearm and the lower legs became lighter than before under the natural light 18 months after stopping the immunotherapy, which may be related to the lack of sunlight during the winter in northern China. Under the wood's light, the amount and range of pigmentation of the right forearm were increased than before, while the macules on lower legs were stable 18 months after the immunotherapy withdrawal. (K, N) With the prolongation of the immunotherapy withdrawal, the amount and range of pigmentation of the right forearm and lower legs were further increased and expanded than before.
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Additionally, her hair (on the head, eyelashes, and eyebrows) also gradually turned white ( Figures 2A, E ). Figures 2B, F ). Furthermore, we found that the patient began to have marked pigmentation on the forearms and lower legs ( Figures 2I, L ). The specific manifestation was that the patient's hair was darker than half a year before, and the facial depigmentation areas were also gradually narrowed and faded( Figures 2C, G ). Moreover, the number and extent of pigmentation of the right forearm have increased than before, while the macules on the lower legs were stable under the wood's light ( Figures 2J, M ). About 31 months after the immunotherapy withdrawal (July 2022), we found that the vitiligo areas on the face were narrower and lighter, and the hair became darker than before ( Figures 2D, H ). The amount and range of pigmentation of the right forearm and lower legs were also increased and expanded compared to before ( Figures 2K, N ).
Differences in the reflectance confocal microscopy (RCM) images during and after the treatment of the anti-PD-1 antibody. (A-D) During the treatment of immunotherapy, the RCM images displayed the absence of pigment rings in the basal cell layer of the mouth-around, right inguinal region, right forearm, and left lower leg (yellow arrow). (E-H) Nine months after immunotherapy was discontinued, there was still no pigment ring on the mouth-around and right inguinal region (yellow arrow). Pigment rings gradually appeared on the right forearm and the left lower leg (red arrow). (I-L) Eighteen months after the immunotherapy withdrawal, there were no pigment rings in the mouth-around and right inguinal region (yellow arrow). But on the right forearm and left lower leg, the pigment rings became brighter (red arrow).
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The RCM images of the patient showed almost the absence of pigmented cells and pigmented rings on the whole skin( Figures 3A-D ). The RCM images of the patient also showed that the pigment rings were gradually appeared in the forearms and left lower legs but there were no significant changes on the mouth-around and inguinal region( Figures 3E-H ). Moreover, there were more and brighter pigment rings and pigment cells on the forearms and lower legs than before( Figures 3I-L ).