Vitiligo-like rash in a patient with lung cancer caused by sintilimab: A case report

Abstract

BACKGROUND

This article discusses a case involving a 63-year-old man with non-small cell lung cancer, who was treated with a combination of chemotherapy and immunotherapy. The patient was treated with five cycles of chemotherapy (pemetrexed and carboplatin) combined with sintilimab, a programmed death 1 inhibitor.

CASE SUMMARY

After the fifth cycle of treatment, the patient developed skin itching and a vitiligo-like rash, which are known side effects of immunotherapy. Despite dermatological consultation and treatment with topical corticosteroids, the rash worsened while the itching subsided. The patient continued with the treatment, and after 15 cycles, the tumor showed a response with a reduction in size. The vitiligo-like rash increased, but the antitumor treatment remained effective.

CONCLUSION

The case highlights the use of immunotherapy in patients with non-small cell lung cancer and the potential side effect of vitiligo-like rash. The patient’s tumor responded well to the treatment, and despite the skin reaction, the treatment was not discontinued due to its effectiveness. The article suggests that further studies are needed to understand the mechanism behind vitiligo in patients with lung cancer receiving immune checkpoint inhibitors and whether the development of vitiligo-like rash after immune checkpoint inhibitor therapy is associated with improved prognosis. The case also underscores the importance of managing immune-related adverse events in the context of effective antitumor treatment.

Key Words: Lung cancer; Vitiligo; Immune checkpoint inhibitor; Sintilimab; Case report

Core Tip: The article presents a case study of a 63-year-old male with non-small cell lung cancer treated effectively with chemotherapy and immunotherapy, despite developing immune-related skin adverse events manifesting as a vitiligo-like rash. Treatment with sintilimab, a programmed death 1 inhibitor, resulted in tumor regression and highlights the need for further research into the prognostic significance and mechanisms of vitiligo-like rash in patients with lung cancer undergoing immunotherapy.

INTRODUCTION

Lung cancer remains a leading cause of cancer-related mortality worldwide, with non-small cell lung cancer (NSCLC) accounting for approximately 85% of all cases[1]. Advances in understanding the molecular landscape of NSCLC have revolutionized treatment approaches, particularly with the introduction of targeted therapies and immunotherapies. Among the latter, immune checkpoint inhibitors (ICIs) have emerged as a cornerstone in the management of various solid tumors, including NSCLC. These agents work by releasing the brakes on the immune system, allowing it to recognize and attack cancer cells[2]. However, the use of ICIs is not without its challenges, as they can also lead to immune-related adverse events (irAEs) that affect multiple organs, including the skin[3].

CASE PRESENTATION

Chief complaints

Right chest pain for 3 months and shortness of breath after activities for 1 month.

History of present illness

The patient was admitted to the hospital for chest pain and shortness of breath after activity and was diagnosed with lung adenocarcinoma. After combined chemotherapy and immunotherapy, the clinical evaluation demonstrated that the treatment was effective.

History of past illness

The patient was previously in good health.

Personal and family history

Parents died of unknown causes; siblings are healthy.

Physical examination

The patient was conscious, with thick breathing sounds in both lungs, no rales, soft abdomen, and no edema in both lower limbs.

Laboratory examinations

Medical thoracoscopy showed multiple pleural nodules in the right parietal layer, and moderate pleural effusion. Right pleural biopsy showed infiltration of lung adenocarcinoma. Immunohistochemical results showed cytokeratin 7 (CK7) (+), thyroid transcription factor 1 (+), napsin A (+), caudal type homeobox 2 (-), anaplastic lymphoma kinase (ALK) Ventana (-), CK5/6 (+), calretinin (-), and p40 (-). Gene mutation detection was negative, which included epidermal growth factor receptor, KRAS, NRAS, BRAF, human epidermal growth factor receptor 2, MET, phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha mutation and ALK, ROS1, RET fusion. Programmed death ligand 1 (PD-L1) expression by tumor proportion score was 60%. T lymphocyte classification showed CD4⁺/CD8⁺ was 4.51 (Table 1).

Table 1 Classification of T lymphocytes in different periods.

T lymphocytes	February 2021 (before the appearance of the rash)	March 2021 (after the appearance of the rash)	April 2021 (after the development of the rash)
Total absolute number of T lymphocytes (per microliter)	1860	1085	1406
Absolute number of helper/induced T lymphocytes CD4+ (per microliter)	1506	841	1012
Absolute number of suppressor/cytotoxic T lymphocytes CD8+ (per microliter)	333	242	364
Percentage of helper/induced T lymphocytes	60.93	56.07	47.36
Suppressor/cytotoxic T lymphocyte percentage	13.50	16.13	17.02
Helper/suppressor T lymphocyte ratio CD4+/CD8+	4.51	3.48	2.78

Imaging examinations

Chest computed tomography showed a 15 mm × 14 mm nodule in the upper lobe of the right lung and right pleural effusion (Figure 1).

Figure 1 Chest computed tomography. A: Chest computed tomography (CT) showed a 15 mm × 14 mm nodule in the upper lobe of the right lung and right pleural effusion (the orange arrow indicates the position of the nodule); B: Chest CT showed the nodules have shrunk and the pleural effusion has decreased significantly after 5 months of treatment; C: Chest CT showed that after more than 20 months of treatment, the nodules have not enlarged and the pleural effusion has not increased.

FINAL DIAGNOSIS

The patient was diagnosed with NSCLC.

TREATMENT

Five cycles of chemotherapy (pemetrexed and carboplatin, every 3 weeks) combined with sintilimab injection 200 mg immunotherapy were administered.

OUTCOME AND FOLLOW-UP

After the fifth cycle of treatment, the patient developed skin itching and a vitiligo-like rash, which are known side effects of immunotherapy. Despite dermatological consultation and treatment with topical corticosteroids, the rash worsened while the itching subsided. The patient continued with the treatment, and after 15 cycles, the tumor showed a response with a reduction in size. The vitiligo-like rash increased, but the antitumor treatment remained effective.

DISCUSSION

ICIs have been shown to be effective against a wide range of solid organ malignant tumors. These monoclonal antibodies lead to activation of cytotoxic T cells and subsequent elimination of cancer cells[4]. Implementation of ICIs have shown improved and sustained responses in patients with cancer[5]. With the support of a large number of clinical trials, these drugs have been approved for the treatment of melanoma, NSCLC, renal cell cancer, bladder cancer, and head and neck cancer, among others. Sintilimab injection is a monoclonal antibody against programmed death 1 (PD-1). National Medical Products Administration approves first-line treatment of sintilimab combined with pemetrexed/platinum chemotherapy in non-squamous NSCLC with negative driver gene mutation[6]. With the widespread use of immunomodulatory therapy, increased irAEs have been reported, with many manifesting in the skin[7]. Skin irAEs may vary among patients, which included maculopapular rash, pruritus, psoriasiform, lichenoid eruptions, and vitiligo-like lesions[8].

Vitiligo, an acquired pigmentary disorder of unknown origin, is the most frequent cause of depigmentation worldwide[9]. Treatment with ICIs in patients with melanoma may lead to vitiligo. The overall cumulative incidence of vitiligo was 3.4% in patients with melanoma treated with ICIs, which is higher than the normal prevalence rate of 1%[9-13]. Immunosuppression-related vitiligo is often bilateral and symmetrical in patients with melanoma, and systemic distribution is relatively common. Partial focal and segmental vitiligo is considered to be related to local skin metastasis[11,14,15]. Vitiligo-like lesions occurred after a mean of 7.5 months from the start of the therapies (range 1-42 months). There are a lack of data to support the prevalence of vitiligo-like rash in patients with non-melanoma malignant tumors, but it is considered that the prevalence rate of such patients is significantly lower than that of patients with melanoma[16].

Vitiligo is a complex disease whose pathogenesis results from the interaction of genetic components, cellular oxidative stress, and immune factors. Research has indicated that regulatory T cells (Tregs) are significantly reduced in vitiligo skin. The PD-1/PD-L1 pathway may be involved in active generalized vitiligo and may have a role in Treg exhaustion[17,18]. CD8⁺ T cells are considered the main effector cells that recognize these common melanocyte antigens[19-22]. The CD4 (+)/CD8 (+) ratio is lower in active generalized patients with vitiligo compared with stable generalized patients with vitiligo[23]. It is generally believed that vitiligo-like rashes do not subside after stopping immunotherapy[24]. There is a case report that a patient with NSCLC who had a history of vitiligo for 10 years was treated with the anti-PD-1 antibody camrelizumab. The symptoms of vitiligo worsened significantly within half a year, resulting in systemic skin depigmentation[25]. However, after 35 cycles of treatment, the patient’s vitiligo symptoms gradually decreased after discontinuation of ICIs, without any hormones or other treatment for vitiligo. The author thought the recovery of vitiligo may be related to the gradual recovery of CD8⁺ T cells after drug withdrawal[26].

In our case, this patient with lung cancer has no previous history of vitiligo. The patient was treated with anti-PD-1 antibody (sintilimab) for almost 2 years and the tumor response evaluation was “stable disease” during the treatment period. Vitiligo-like rash appeared after 5 months of lung cancer treatment. Over the next 1.5 years, the vitiligo-like rash spread over the patient’s chest, back, abdomen, and both upper and lower extremities and face (Figure 2). In our case, the ratio of CD4⁺/CD8⁺ decreased with the progression of vitiligo over time (Table 1). The patient did not receive specific treatment such as glucocorticoids for vitiligo in the follow-up, as his quality of life was not affected. We will continue to monitor the vitiligo-like rashes in the following discontinuation period.

Figure 2 The patient developed vitiligo-like rash after treatment with chemotherapy and sintilimab injection. A: The patient developed vitiligo-like rashes on the neck, chest and both upper extremities; B: The patient developed vitiligo-like skin rashes on the abdomen and perineum; C: The patient developed vitiligo-like skin rashes on both lower extremities.

Vitiligo development in patients with melanoma treated with ICIs can be seen as a good prognostic sign[27]. Favorable prognosis in a 63-year-old female with NSCLC developed vitiligo after the use of pembrolizumab was reported. This patient demonstrated “complete remission” at 16 months of follow-up. The vitiligo might be associated with increased efficacy of pembrolizumab in metastatic lung adenocarcinoma[28]. In our case, this patient with lung cancer has now survived for more than 2 years and is currently in stable primary tumor disease. It is unclear whether the presence of vitiligo is a favorable prognostic factor in patients with lung cancer. Therefore, we report a case of vitiligo like rash in a patient with lung cancer after receiving ICI treatment. Systematic analysis of vitiligo-like rash in patients with lung cancer received ICI therapy is still lacking. The mechanism of vitiligo in patients with lung cancer receiving ICI therapy remains to be explored. Whether patients with lung cancer developed vitiligo-like rash after ICI therapy have an improved prognosis needs to be studied further.

CONCLUSION

The case highlights the use of immunotherapy in patients with NSCLC and the potential side effect of vitiligo-like rash. The patient’s tumor responded well to the treatment, and despite the skin reaction, the treatment was not discontinued due to its effectiveness. The article suggests that additional studies are needed to understand the mechanism behind vitiligo in patients with lung cancer receiving ICIs and whether the development of vitiligo-like rash after ICI therapy is associated with improved prognosis. The case also underscores the importance of managing irAEs in the context of effective antitumor treatment.