Changes in the Skin Microbiome of a Patient with Head and Neck Cancer with Severe Radiodermatitis: A Case Report

Abstract

Introduction

Identifying the skin microbiome associated with severe radiodermatitis could lead to the development of preventive care strategies and early healing interventions, which are currently lacking. In this study, we investigated changes in the skin microbiome of a patient with head and neck cancer who developed severe radiodermatitis from the initiation of radiation therapy to the resolution of dermatitis.

Case Presentation

An 82-year-old male underwent chemoradiotherapy with cisplatin (69.96 Gy/33 fractions) for recurrent laryngeal cancer after a total laryngectomy. At baseline, Cutibacterium accounted for 64.3% of the skin microbiome and Staphylococcus for 23.2%. During the occurrence of moist desquamation associated with severe radiodermatitis, Cutibacterium decreased sharply to 0.2%, whereas Staphylococcus increased to 91.0%. Species-level analysis revealed that Staphylococcus aureus was dominant at 50.6%, whereas Staphylococcus hominis and Staphylococcus epidermidis were identified at 0.4% and 1.7%, respectively.

Conclusion

These findings demonstrated that changes in the skin microbiome occur during the progression of severe radiodermatitis. The reduction in Cutibacterium and overgrowth of Staphylococcus, particularly Staphylococcus aureus, suggest their involvement in the development of severe radiodermatitis in patients with head and neck cancer.

Introduction

In addition to surgery, definitive radiotherapy is an essential treatment option for head and neck cancer that is administered to many patients. Radiation induces DNA damage in basal epidermal and hair follicle stem cells, triggering inflammatory responses. Consequently, most patients with head and neck cancers develop radiodermatitis that manifests as dry skin and erythema, and approximately 25% experience severe radiodermatitis with moist desquamation [1]. Severe radiodermatitis significantly reduces patients’ quality of life as it causes intense pain, making its prevention a critical aspect of care. Numerous studies on its prevention using recommended cleansing and moisturizing agents have been conducted; however, effective preventive care strategies remain unclear.

Recent studies have revealed an association between inflammatory skin diseases and the skin microbiome, leading to the development of new treatment approaches targeting Staphylococcus aureus in atopic dermatitis [2]. As radiodermatitis is also caused by radiation-induced inflammation, it is plausible that the skin microbiome is involved. Previous studies have demonstrated an increase in S. aureus on skin affected by severe radiodermatitis [3], and a lower relative abundance of Staphylococcus epidermidis, Staphylococcus hominis, and Cutibacterium acnes is associated with the development of severe radiodermatitis in patients with breast cancer [4]. However, no studies have investigated the longitudinal changes in the skin microbiome throughout the course of severe radiodermatitis in patients with head and neck cancer, making it unclear which bacterial species could serve as potential targets for preventive interventions.

In this study, we examined the longitudinal changes in the skin microbiome at the irradiated site in a patient with head and neck cancer who developed radiodermatitis with moist desquamation from before the initiation of radiotherapy until radiodermatitis resolved.

Case Presentation

The patient was an 82-year-old male who underwent chemoradiotherapy (cisplatin combined with 69.96 in Gy/33 fractions using volumetric modulated arc therapy with 6 MV X-ray) for recurrent stage IV laryngeal cancer in January 2023. Radiotherapy was administered once daily in five fractions per week without discontinuation. The prescribed dose of radiotherapy was 70 Gy for gross tumor volume, 59.4 Gy for high-risk clinical target volume, and 54 Gy for low-risk clinical target volume in 33 fractions. The patient underwent a total laryngectomy, resulting in a tracheostoma. Before radiotherapy (baseline), skin barrier function assessment indicated corneometer hydration at 56.0, transepidermal water loss at 13.57 g/h/m², skin pH at 4.90, and sebum secretion at 6 µg.

Faint erythema appeared during the first week of treatment (10.6 Gy) and intensified to moderate erythema by the 6th week (63.3 Gy). By the 7th week (1 day after completion of radiotherapy), extensive moist desquamation was observed. However, dermatitis healed with scab formation by the 10th week (22 days after radiotherapy completion) (Fig. 1). Starting from the 5th week, the patient was administered heparin lotion and azulene ointment on the irradiated area. From the 7th week, when moist desquamation occurred, corticosteroids and nonadherent gauze were applied until healing was achieved. Due to the presence of a tracheostoma, the patient had difficulty performing self-care, so nurses performed skin cleansing and treatment.

Fig. 1.

The course of radiodermatitis in this case. Radiodermatitis progressed from faint erythema during the first week/10.6 Gy (a) to moderate erythema at 6 weeks/63.30 Gy (b), extensive moist desquamation at 7 weeks/1st day post-radiotherapy (c), and dermatitis healed with scab formation by the 10th week (22 days after radiotherapy completion) (d).

Skin samples were collected weekly from baseline until the resolution of radiodermatitis from the side of the neck (within the irradiated field) using swabs. The skin microbiome composition was analyzed with 16S rRNA gene sequencing using a next-generation sequencer based on the relative abundance of bacterial species. At baseline, the microbiome consisted of Cutibacterium (64.3%) and Staphylococcus (23.2%). During radiotherapy, Cutibacterium remained predominant; however, by the 7th week (1 day after radiotherapy completion), Staphylococcus accounted for 91.0%, whereas Cutibacterium dropped to 0.2% and did not recover even after radiodermatitis healed (Fig. 2). At the species level (Fig. 3), S. aureus accounted for 50.6%, S. hominis for 0.4%, and S. epidermidis for 1.7% during the 7th week when Staphylococcus had increased. DNA amplification failed in skin microbiome samples from the 3rd, 6th, and 8th weeks, making analysis impossible.

Fig. 2.

Changes in the skin microbiome. Cutibacterium replaced Staphylococcus when severe radiodermatitis occurred and did not rebound, even after the radiodermatitis healed. Blank spaces indicate samples where analysis was impossible.

Fig. 3.

Changes in the skin microbiome at the species level of Staphylococcus. After severe radiodermatitis, the prevalence of Staphylococcus aureus increased. Blank spaces indicate samples where analysis was impossible.

Discussion

In a patient with head and neck cancer treated with radiotherapy, the onset of severe radiodermatitis coincided with changes in skin microbiome composition: a marked decrease in Cutibacterium and an increase in Staphylococcus. These findings suggest a possible association between skin microbiome dysbiosis and severe radiodermatitis. The skin microbiome is predominantly composed of Cutibacterium, Staphylococcus, and Corynebacterium, the relative abundances of which are influenced by physical, chemical, and biological factors, including skin moisture [5]. During head and neck radiotherapy, high doses (approximately 70 Gy) are delivered, exacerbating skin inflammation and dryness when radiodermatitis becomes severe. The baseline skin barrier function of the patient was intact; however, changes in the skin condition due to radiodermatitis appear to have led to alterations in the composition of the skin microbiome, characterized by a decrease in Cutibacterium and an increase in Staphylococcus.

Moist desquamation leads to exudate production and alters skin pH owing to the application of ointments, which may also promote changes in the composition of the skin microbiome. As Staphylococcus thrives in moist environments, such as the axillae [5], the moist conditions caused by exudate and ointment application during severe radiodermatitis likely facilitated its proliferation. Conversely, Cutibacterium was predominant in sebum-rich areas. Radiation-induced impairment of sebaceous gland function and a subsequent decrease in sebum levels likely contributed to the reduction in Cutibacterium. Similar trends have been reported in patients with atopic dermatitis, where reduced Cutibacterium and increased Staphylococcus counts were associated with impaired skin barrier function, elevated skin pH, and decreased sebum levels [6]. In the present case, even after radiodermatitis healed, the skin microbiome did not return to its baseline composition. This may be due to persistent skin barrier dysfunction, as skin temperature elevation [7] and increased transepidermal water loss levels [8] reportedly persist even after the resolution of radiodermatitis.

The skin microbiome plays a vital role in maintaining skin health owing to its diversity and balance. A previous study has reported a significant reduction in skin microbiome diversity in areas affected by radiodermatitis [9]. At the microbial species level, an increased S. aureus density promotes inflammation [5]. S. aureus colonization is common in severe atopic dermatitis, in which skin barrier dysfunction allows it to penetrate the dermis and trigger inflammatory cytokines [10]. In contrast, S. hominis and S. epidermidis inhibit S. aureus colonization [11]. The low abundances of S. hominis and S. epidermidis in this case may have contributed to the proliferation of S. aureus. Previous studies have reported an association between reduced S. hominis and S. epidermidis levels and the onset of radiodermatitis [4], as well as increased S. aureus levels in radiation-damaged skin [3]. Additionally, because the stratum corneum becomes thinner during radiodermatitis and the skin barrier is compromised, increased inflammation caused by S. aureus proliferation may exacerbate the severity of radiodermatitis. S. hominis, S. epidermidis, and S. aureus may serve as key bacterial targets for preventing severe radiodermatitis in patients with head and neck cancer.

The findings of this study suggest that dysbiosis of the skin microbiome may contribute to the development of severe radiodermatitis, with particular involvement of Cutibacterium and Staphylococcus, especially S. aureus. Recent work has demonstrated a gut-skin microbial axis, suggesting that interventions to maintain gut microbial balance could help prevent skin-microbiome dysbiosis [12]. Additionally, a report shows topical prebiotics can restore skin microbial diversity and reduce S. aureus abundance [13]. However, further case reports and studies are needed to develop preventive care strategies based on microbiome alterations. Study limitations include the inability to analyze certain samples due to radiation-induced DNA degradation and the challenge of collecting microbiome samples from fragile, radiation-damaged skin. To overcome these limitations, future studies should explore alternative skin microbiome sampling methods and incorporate additional biomarkers, such as skin blotting, a technique that collects molecules non-invasively.

Conclusions

This case reveals that changes in the skin microbiome occur during the progression of severe radiodermatitis, suggesting that Cutibacterium and Staphylococcus, particularly S. aureus, are involved in the development of severe radiodermatitis in patients with head and neck cancer.

The CARE Checklist has been completed by the authors for this case report, attached as online supplementary material (for all online suppl. material, see https://doi.org/10.1159/000546634).

Statement of Ethics

The study was conducted in accordance with the principles of the Declaration of Helsinki and its amendments. Approval was granted by the Ethics Committee of Kanazawa University (February 15, 2022/No. 711039), Hyogo Medical University (May 25, 2022/No. 202205-176), and Ishikawa Prefectural Nursing University (November 2, 2023/No. 2023-339). Written informed consent was obtained from the patient for the publication of this case report and the accompanying images.

Conflict of Interest Statement

The authors have no conflicts of interest to declare.

Funding Sources

This study was supported by the JSPS KAKENHI (Grant No. JP23K09996). The funder played no role in the design, data collection, data analysis, or reporting of this study.

Author Contributions

Nao Miyamae: conceptualization, methodology, data collection, formal analysis, data curation, writing – original draft, writing – review and editing, funding acquisition. Kazuhiro Ogai: investigation, resources, writing, review and editing. Mao Kunimitsu: formal analysis, writing, review and editing. Shigefumi Okamoto: writing – review and editing, and supervision. Masayuki Fujiwara: validation, writing, review and editing. Makoto Nagai: validation, writing, review, and editing. Maandarin Okuwa: writing – review and editing and supervision. Makoto Oe: conceptualization, methodology, formal analysis, writing, review and editing, supervision, and project administration. All authors had full access to all data in the study, and the corresponding author had the final responsibility for the decision to submit the manuscript for publication. The corresponding authors attest that all listed authors meet the authorship criteria and that no others meeting the criteria have been omitted.

Funding Statement

This study was supported by the JSPS KAKENHI (Grant No. JP23K09996). The funder played no role in the design, data collection, data analysis, or reporting of this study.

Data Availability Statement

All data generated or analyzed during this study are included in this article and its online supplementary material. Further inquiries can be directed to the corresponding authors.