Photodynamic Therapy Mediated by Curcumin and Blue Light for Recurrent Herpes Labialis: A Case Report

ABSTRACT

This study is the first to use photodynamic therapy (PDT) mediated by curcumin and blue light for the treatment of recurrent herpes labialis. According to our study, PDT effectively accelerated lesion healing and reduced its recurrence. PDT may represent a promising, safe, and cost‐effective treatment option for this challenging disease.

1. Introduction

Herpes simplex virus type 1 (HSV‐1) is a common orofacial infection, affecting 60%–90% of the global population, with approximately 500,000 new cases reported each year. Herpes simplex recurs in 20%–40% of infected individuals [1, 2]. The majority of initial herpes simplex virus (HSV) infections in children are either unnoticed or so mild that neither the children nor the parents recognize the symptoms. Some research suggests that specific clinical manifestations occur in 25%–30% of those infected. After an incubation period of 2–20 days, general symptoms like malaise or myalgia may appear, followed by mucocutaneous vesicular eruptions 1–3 days later. The oral mucosal and gingival symptoms are typically associated with fever, fatigue, decreased appetite, irritability, and excessive saliva production. At times, there may be symptoms like irritability, headaches, and bilateral cervical lymphadenopathy [3].

The virus remains latent in the trigeminal ganglion and can reactivate due to factors like psychological stress, mechanical trauma, immune stress, UV radiation, hormonal changes, or other viral infections, leading to recurrent outbreaks with stages, including prodrome, vesicle, ulcer, crust, and healing [4]. Antiviral medications such as acyclovir are the standard treatment for HSV‐1 but can lead to high viral resistance due to mutations in viral genes. Although the prevalence rate of HSV resistance to acyclovir is low (0.2%–0.7%) in immunocompetent patients, the prevalence rate of acyclovir‐resistant isolates in immunocompromised patients can be up to 46.5% [5]. These drugs are most effective in the prodromal phase and do not prevent recurrence [6]. Hence, special attention should be given to alternative therapies. For many centuries, light has been acknowledged as a possible therapeutic tool. It has primarily been utilized alongside reactive chemicals to treat several conditions, including vitiligo, psoriasis, and various types of cancer, such as skin cancer [7]. Photodynamic therapy (PDT) is a combination of a light source and a suitable photosensitizer that produces reactive oxygen species (ROS) [8]. ROS can damage proteins, nucleic acids, and lipids, potentially resulting in cell death. The phototoxic mechanism of photosensitizers includes the formation of an excited triplet state when light is absorbed, which can participate in electron (Type 1) or energy (Type 2) transfer processes. Type 1 electron transfer reactions usually result in the formation of radical species like superoxide or hydroxyl radicals, whereas Type 2 energy transfer generates cytotoxic singlet oxygen. A photosensitizer can trigger both Type 1 and Type 2 photoprocesses at the same time, influenced by the specific chemistry of the photosensitizing agent and its environment. Due to the high reactivities and short lifetimes of oxidizing molecules, it is anticipated that only viral structures nearby activated photosensitizing agents will be impacted [9].

At present, PDT is part of the clinical management of skin lesions resulting from HSV, human papillomavirus (HPV), and varicella zoster virus (VZV), and more recently, in the treatment of COVID‐19 [7].

Curcumin is a natural, inexpensive, and side‐effect–free compound known for its wide range of biological effects, including antioxidant, anti‐inflammatory, and anticancer properties. It can also disrupt viral infections by targeting viral entry, essential viral components for replication, and other cellular or molecular processes involved in the viral life cycle [10]. Additionally, extensive research has demonstrated that curcumin, when used as a photosensitizer in combination with blue light irradiation, exhibits effective photoreactivity against cancer cells and microorganisms even at low concentrations [11]. With optimal light absorption at 420–430 nm, curcumin's cytotoxicity can be enhanced, enabling it and blue light to effectively inactivate the HSV and better control the disease.

2. Case History/Examination

A 56‐year‐old female patient presented with recurrent herpes simplex labialis of the upper lip, currently in the ulceration stage, with some vesicles present. The overall dimensions of the lesion were 1.8 × 0.8 cm (Figure 1). The patient reported a pain score of 5 on the visual analog scale at the site of the lesion. During the history taking, the patient mentioned experiencing this lesion's disturbing recurrence on a monthly basis and reported no other systemic diseases or skin conditions, such as eczema or atopic dermatitis. She noted her frequent use of topical acyclovir at the onset of tingling in the lip, but without any benefit. On this occasion, the patient did not apply any medication to the lesions before seeking treatment. We assessed her quality of life using the Oral Health Impact Profile, which resulted in a score of 11 in Domain 2, representing physical pain [12].

FIGURE 1.

Stages of applying photodynamic therapy.

3. Methods

The curcumin solution was freshly prepared before use by dissolving 7.5 mg of pure curcumin in 100 μL of Tween 80 in a sterile glass container. After dissolution, 9.9 mL of sterile distilled water was added, and the solution was stirred in a dark environment to ensure complete homogenization.

PDT was performed as follows:

• Skin cleaning: The patient's skin and affected lips were cleaned with a pH‐neutral liquid soap using a cotton ball to remove any remnants of cosmetics, creams, or sunscreens.

• Photosensitizer application: The curcumin solution was applied to the lesions using an opaque syringe with a blunt tip. In all, 0.1 mL of curcumin solution was applied.

• Preirradiation time: The photosensitizer was left on the lesions for 10 min before applying the LED light.

• Irradiation: PDT was administered using the Woodpecker LED C with a wavelength of 420–480 nm, a light intensity of 800–1000 mW/cm², and an irradiation time of 2 min.

• Final cleaning: Any remaining photosensitizer was removed with a sterile cotton swab soaked in sterile saline.

4. Discussion

The photodynamic approach has been identified as a promising technique for the diagnosis (photodynamic diagnosis [PDD]) and treatment (PDT) of numerous conditions, such as cancer as well as bacterial, viral, fungal, and parasitic infections. PDT involves three crucial steps: (1) the administration of a photosensitizer that enhances the sensitivity of the targeted tissue; (2) exposure to a light source, which activates the photosensitizers; and (3) the photochemical reaction, with oxygen dissolved, leading to the selective destruction of the affected tissues. The substances most frequently employed for PDT are porphyrins along with their derivatives chlorins and phthalocyanines. Other nonporphyrin photosensitizers are frequently utilized, such as 5‐aminolevulinic acid (ALA), phenothiazines (like methylene blue), xanthenes, triarylmethanes, curcumin, and hypericin. In a previous review by Lotufo et al. assessing the effectiveness of PDT for herpes labialis patients, it was discovered that the majority of studies utilized methylene blue as a photosensitizer, whereas only one study employed ALA [13]. All studies featured in that review demonstrated positive outcomes with both photosensitizers (ALA and methylene blue); however, Osiecka et al. noted that patients receiving ALA PDT experienced moderate to severe pain during the treatment [14]. Nonetheless, the authors believe that this resulted from the high dose of light the patients encountered.

In a randomized controlled clinical trial conducted by Ajmal et al., topical antiviral therapy in combination with PDT (using 0.005% methylene blue and diode laser) was found to significantly reduce pain and pro‐inflammatory biomarkers in adolescent patients with herpes labialis [15].

Curcumin has demonstrated multiple health benefits, including potential therapeutic effects against various viral infections such as HIV, hepatitis B and C viruses, influenza A virus, and HPV. This biomolecule exhibits antioxidant, anti‐inflammatory, and anticancer properties. Its antiviral activity involves inactivating viruses by targeting viral entry and essential components for viral replication and transcription. Extensive in vitro and in vivo studies have explored how curcumin combats HSV, focusing on its ability to inhibit key cellular and molecular processes crucial for viral gene expression, transcription, and pathogenicity [10]. In the quest for effective antiviral immune modulators, curcumin is a notable natural product that is inexpensive, has no side effects, and effectively stimulates key components of the immune system. It influences intracellular signaling pathways and affects the expression of antioxidant and immune‐regulating genes. Research shows that curcumin modulates enzymes, reduces oxidative stress, enhances antioxidant capacity, and decreases lipid peroxidation [16]. The use of curcumin as a photosensitizer is currently under extensive investigation. Curcumin absorbs light in the blue wavelength range (300–500 nm). Studies have demonstrated that even low concentrations of curcumin can effectively protect against cancer cells and microorganisms when combined with blue light irradiation. The primary antimicrobial mechanism of curcumin‐based PDT involves the generation of ROS, which causes lethal damage to target cells and tissues [17]. Several studies have assessed the effectiveness of PDT using curcumin against oral bacteria, fungi, and drug‐resistant strains. Overall, curcumin‐mediated PDT significantly reduced various oral pathogens [11]. Additionally, blue light (wavelength 400–470 nm) not only excites curcumin but also serves as an effective “drug‐free” method for microbial killing by photoexciting endogenous porphyrins, which generate ROS that damages membranes, DNA, and lipids [18].

Our case report indicates that PDT using curcumin and blue light accelerates the healing of herpes simplex, attributed to the combined antiviral effects of curcumin and blue light, as well as curcumin's immunomodulatory properties. Notably, PDT also reduced the frequency of lesion recurrence, with no recurrences reported over 8 months. This may be due to PDT's impact on the immune system, which activates the adaptive arm of the innate immune response, stimulating cytotoxic T lymphocytes to identify and eliminate altered cells and enhance mediator release. This adaptive immune response underscores the value of PDT in achieving long‐term control and preventing recurrence through immune memory [16].

5. Conclusion and Results

Crusts formed immediately after PDT, and the pain score was 1 on the visual analog scale. The lesion healed within 3 days, with the crusts completely disappearing. The patient was followed up monthly for 8 months, during which no herpetic lesions recurred, and the oral health impact score was 0 throughout the follow‐up period.

Author Contributions

Marwa Khalil: conceptualization, data curation, formal analysis, funding acquisition, investigation, methodology, project administration. Omar Hamadah: resources, software, supervision, validation, visualization, writing – original draft, writing – review and editing.

Ethics Statement

Ethical Approval was obtained from the Scientific Research Council at Damascus University (Damascus University, Damascus, 00963, Syria; +963 11 33923000; president@damasuniv.edu.sy), ref.: 2025 on January 18, 2023.

Consent

The patient has given her consent for their images and other clinical information to be published in the journal.

Conflicts of Interest

The authors declare no conflicts of interest.

Data Availability Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.