Effectiveness of hyaluronic acid gel (Jalosome soothing gel) for the treatment of radiodermatitis in a patient receiving head and neck radiotherapy associated with cetuximab: A case report and review

Abstract

One of the principal side effects in patients that receive radiotherapy is radiodermatitis. Radiodermatitis can be highly invalidating for patients, causing pain, ulceration, swelling, and increased infection risk, with a negative effect on the quality of life, requiring dressings and medications. Therapeutic approaches reported so far in the literature have not proved to be effective in treating radiodermatitis. Therefore, new approaches are needed to deal with these side effects more effectively. The aim of the study was to evaluate the effectiveness of hyaluronic acid gel (HAG) (Jalosome soothing gel) for the treatment of a case of radiodermatitis. This is a case study of a patient affected by squamous cell carcinoma at the tongue base, who was treated with head and neck radiotherapy associated with the administration of cetuximab. About 1 month after this therapy was started the patient developed radiodermatitis, which did not regress with standard treatment. Therefore, HAG was applied once a day for about 20 days. The regression of radiodermatitis was measured using the Radiation Toxicity/Oncology Grading scale, pain relief was measured with a numerical scale, and patient satisfaction was done through a semi‐structured interview. The patient presented a dramatic reduction of skin toxicity, which had been resistant to all previous therapeutic approaches. Pain, which was severe at the beginning, gradually disappeared. The patient showed great satisfaction for the reduction of pain and the regression of the radiodermatitis. The effectiveness of HAG appears to be promising for the treatment of radiodermatitis.

1. INTRODUCTION

Radiodermatitis is one of the principal complications in individuals receiving radiotherapy, with a frequency of 95%, especially in patients affected by breast cancer, head and neck cancer, lung cancer, or sarcoma. This high incidence is due to the high doses of radiation on the skin of these patients. In most cases, the dermatitis is mild or moderate, but in 20–25% of the cases, it can degenerate into moist desquamation and ulceration.1, 2, 3, 4, 5, 6, 7 Radiodermatitis has a negative effect on the patient's quality of life because of pain, itch, and discomfort. If it becomes particularly invalidating, it may lead individuals to abandon the treatment and consequently nullify its effectiveness.8, 9

Other factors that increase the risk of developing radiodermatitis in the irradiated area, mostly in the anterior region of the neck, are female gender, older age, constant exposure to sunrays, smoking, obesity, scleroderma, ataxia, and taking specific drugs, such as antibiotics and anti‐tuberculosis medications.1, 2 In the literature, it is reported that radiotherapy associated with the administration of cetuximab exacerbates the severity of dermatitis after its onset. This interaction favours a more marked xerosis, a stronger inflammatory reaction, the reduction of skin thickness, and the formation of crusts caused by the increased exudation process. The crusts often cause pain, bleed, and slow down the healing process.7, 10, 11

Dermatitis usually manifests after 90 days of treatment. Skin alterations may include loss of hairs, pigment changes, oedema, and dry or moist desquamation.4, 12 Erythema usually onsets and resolves within hours and becomes evident with doses ≥2 Gy, whereas doses of 12‐20 Gy cause dry desquamation, doses of ≥20 Gy induce moist desquamation, and doses of ≥35 Gy cause skin necrosis.12 For the measurement of the severity of dermatitis, there are various tools. The scientific community has agreed on a four‐level grading tool.11, 13 Dermatitis usually resolves in about 10 days after radiations are interrupted, but grade of ≥3 dermatitis may require more time to heal and can lead to fibrosis and functional impairment of the irradiated area.14 In subjects with severe reactions, unpredictable inflammatory curves may also occur after weeks or even years after radiation exposure.15 Radiations also lead to reduced immune defences of the skin, thus increasing the risk of infections.16

The prevention of radiodermatitis mainly consists in keeping the irradiated area clean and dry, washing it with warm water and mild soap, using aqueous creams, with no perfumes nor Lanolin, avoiding skin irritants, such as perfumes and alcohol‐based lotions, wearing loose clothes to avoid friction, avoiding sun exposure, and avoid putting corn starch or baby powder in the skinfolds.17 In severe radiodermatitis, corticosteroids have been found to play a role in reducing complications, even though they did not reduce the number of events nor the level of seriousness.17 Other treatments, such as Aloe vera, trolamine, sucralfate, and other hyaluronic acid formulations have not proved to be effective in treating radiodermatitis, and in some cases, they have even been counterproductive.18, 19, 20, 21, 22, 23, 24, 25, 26, 27

As radiodermatitis is a highly disabling condition and worsens the quality of life in cancer patients undergoing radiotherapy, and given that in the literature a particularly effective therapeutic approach has not been reported yet, it is essential to test new methods for the treatment of this bad complication. The application of products made with new formulations, which, as in this case report, offer promising results in terms of healing of the lesion and patient well‐being, can lay the ground for more powerful studies, such as randomised controlled trials, to test their real effectiveness. For this reason, it is very important to inform the scientific community about this case study.

The objective of this study is to report our experience with using hyaluronic acid gel (HAG) (Jalosome soothing gel) to heal a severe skin erythema and its efficacy.

2. METHODOLOGICAL ASPECTS

The case reporting guidelines (CARE) guidelines for the reporting of case studies were followed for the present case study.28 The Radiation Oncology/Toxicity Grading (RTOG) scale was used to assess the grade of dermatitis. A numeric scale from 0 to 10 was used to assess pain. A semi‐structured interview was used to assess patient's satisfaction. The patient provided a written informed consent for the processing of personal data and a waiver for the use of photographs. Data are presented without revealing the patient's identity. We complied with the Helsinki Declaration guidelines on clinical research and with legislation on the protection of privacy in force in the country where this study was conducted. During patient treatment, the scientific association of swiss radiation oncology (SASRO) guidelines were followed to treat the skin of cancer patients receiving radiotherapy (http://sasro.ch/sasro/publications).

2.1. Description of the standard medications

At the beginning of radiotherapy treatment, all patients receive a therapeutic education intervention from the nurses, which has the purpose to (a) inform patients about possible side effects of the treatment and (b) educate patients on what to do to prevent possible side effects.

The internal protocol refers to practical indications on skin toxicity and oral mucositis of the Oncology Nursing Society (https://www.ons.org/practice-resources/pep/radiodermatitis) and to the SASRO guidelines (http://sasro.ch/sasro/publications).

After radiotherapy, the skin is moistened with Pliazon cream twice a day.

2.2. Description of medications with Jalosome

1. Application of a Protosan solution compresses the skin cleansed with saline solution and is slightly debrided.

2. A vial of HAG is applied with a large sterile cotton tipped applicator.

3. Dried with cold air.

4. 10 × 20 sterile gauzes are applied to prevent the skin from rubbing against the neck.

HAG was applied once a day and at the end of each radiotherapy session. The patient had received specific education and self‐managed the treatment at home when not receiving radiotherapy.

3. CASE REPORT

The patient is a 77‐year‐old man, married, and had smoked for 30 years. On 17 October 2016, a squamous‐cell carcinoma was diagnosed at the base of the left side of his tongue with a left laterocervical metastasis (stage cT2 cN2b M0). Comorbidities included diabetes mellitus, not insulin dependent, and the patient was receiving treatment for arterial hypertension. On the basis of the patient's clinical status, physicians recommended radiotherapy of the area involved with the concomitant administration of cetuximab. As no improvement was observed with standard treatment, Jalosome soothing gel was applied. Unlike other products that include hyaluronic acid, this product was more effective because it was absorbed more easily into the deeper layers of the cornea. Jalosome soothing gel is usually employed as a preventive medication; therefore, in the present case, an off‐label use of it was made.

4. TIMELINE

Table 1 shows the timeline and the patient's clinical course. The details of the radiotherapy treatment are reported in Table 2. Radiotherapy employed the V‐MAT technique and was performed bilaterally at the level of the oral cavity and neck.

Table 1.

The clinical course of a patient affected by radiodermatitis

Event	Timeline, short note on what happened
Diagnosis of squamous cell carcinoma of the left tongue base, with left laterocervical metastasis. Stage cT2 cN2b M0	17 November 2016 Magnetic resonance shows a voluminous adenopathy
Chemotherapy is started with cetuximab 400 mg/m2, using Lubex cleansing emulsion as soap and Pliazon cream	14 December 2016
Radiotherapy is started at the level of the oral cavity and of the neck bilaterally, using the V‐Mat technique (RapidArc)	21 December 2016
Therapeutic education session regarding skin care preventive interventions during radiotherapy in ENT patients	21 December 2016 Continues using Lubex cleansing emulsion as soap and Pliazon cream
Administration of chemotherapy with cetuximab 250 mg/m2	22 December 2016
Widespread folliculitis due to cetuximab at the torso, neck, and starting on the face	27 December 2016
Folliculitis extends also to thorax, back, arms, and scalp, grade G3	29 December 2016
Introduction of doxycycline for a total of 10 days and cetirizine as necessary	29 December 2016
Significant acneiform eruption on face and chest. Back and arms bilaterally. Persistence of G3 toxicity	5 January 2017
Administration of chemotherapy with cetuximab 250 mg/m2	5, 12, and 19 January 2017
Erythematous, dry, and desquamated skin	19 January 2017 Bepanthen Cream is applied on the skin
Introduction of Minocin acne 50 mg	19 January 2017
Sees dermatologist; continues with Minocin acne	24 January 2017
Administration of chemotherapy with cetuximab and Minocin acne is interrupted	26 January 2017
Administration of chemotherapy with cetuximab	2 February 2017
Onset of skin erythemaInitially treated with standard therapy	3 February 2017 Grade 2 acute skin toxicity on the neck and grade 2 toxicity on the oral cavity mucosa. Radiotherapy is interrupted
Worsening of skin erythema. Treatment with hyaluronic acid gel (HAG) (Jalosome soothing gel) is started	3 February 2017 Upon follow up, skin erythema is found to be worse G3. Treatment with HAG is started
Regression of skin erythema	6 February 2017 Initial improvement of the skin. Patient reports the beneficial effect and relief after applying HAG. Radiotherapy is resumed 7 February. Treatment with cortisone is gradually started
Boost radiotherapy started in the macroscopic area of the disease using V‐Mat (RapidArc)	8 February 2017
Skin erythema continues to improve	9 February 2017 Further regression of dermatitis, with prevalence of lesions covered with crusts. Cetuximab is interrupted
Constant improvement of neck skin and mucositis	From 13 to 20 February 2017
Neck erythema regresses up to G1	24 February 2017 Bepanthen cream is continued up to next follow‐up
Complete regression of skin erythema to G0	21 March 2017

Table 2.

Scheme of the radiotherapy

Dates	Beam	Energy	Fractionation	Total dose	Notes
21 December 2016 to 7 February 2017	Photons	6 MV	1.8 Gy	54 Gy
8 February 2017 to 17 February 2017	Photons	6 MV	2 Gy	16 Gy	Interrupted from 3 February 2017 to 7 February 2017
Total dose				70 Gy

Figures 1, 2, 3, 4 show how the application of HAG gradually improved the patient's erythema until its complete remission. Pain gradually diminished as the lesion healed. In fact, the patient felt the benefit of HAG immediately after the first application. Therefore, the patient was very satisfied with the successful course of the clinical condition of his skin. Previously, owing to pain and discomfort caused by radiodermatitis, his quality of life had worsened significantly.

Figure 1.

Condition of the skin on second week of February before the application of HAG (with standard medication). HAG, hyaluronic acid gel

Figure 2.

Condition of the skin on third week of February before application of HAG (with standard medication). HAG, hyaluronic acid gel

Figure 3.

Condition of the skin on sixth week of February after 3 days application of HAG. HAG, hyaluronic acid gel

Figure 4.

Condition of the skin at the end of treatment with HAG. HAG, hyaluronic acid gel

Table 3 includes the questions of the interview and the answers the patient gave regarding his treatment with HAG, which confirmed the results reported above. Therefore, the patient judged the treatment with HAG excellent.

Table 3.

The patient's interview regarding his experience with HAG

Questions	Patient's answers
What do you think about the treatment with HAG that you were offered? Did you have any benefits? If yes, could you describe them?	Exceptional, because it was refreshing, it softened the crusts of the lesions, thus avoiding them from cracking and speeding up their healing process
Did you notice any difference in the amount of pain before and after treatment with HAG?	Before treatment with HAG I had too much pain, and the lesions could not heal because the crusts were hard and when they cracked, the skin was still red and caused new lesions. Afterwards, apart from feeling refreshed by the product, pain diminished, and the lesions healed
Was there any aspect that did not satisfy you during treatment with HAG? If yes, which?	No, none

Abbreviation: HAG, hyaluronic acid gel.

5. DISCUSSION

Radiodermatitis is an invalidating complication for patients receiving radiotherapy and has a negative impact on their quality of life. In particular, the combined administration of radiotherapy and chemotherapy drugs, such as cetuximab can exacerbate the lesions caused by the radiations, thus increasing the risk of negative effects.7, 10, 11 The most recent systematic reviews highlight that there is no enough evidence about interventions for the prevention and treatment of radiodermatitis17, 29 in subjects receiving radiotherapy, although the positive effects of hyaluronic acid had been confirmed by another systematic review with other types of lesions.30 Other treatments, such as Aloe vera, trolamine, sucralfate, and other formulations of hyaluronic acid did not prove to be effective in the treatment of radiodermatitis, and some studies even found that they were counterproductive.18, 19, 20, 21, 22, 23, 24, 25, 26, 27

In the present study, treatment with HAG led to a rapid improvement of the lesion, and the patient perceived immediate benefit with the reduction of pain and discomfort caused by the crusts.

The specific formulation of HAG, which ensures a deeper absorption of the active ingredient into the skin, could be the main reason of the major efficacy of this product compared to other hyaluronic acid products in enhancing the healing process. Therefore, the present study could be the starting point for designing randomised controlled trials including an appropriate sample size, to test the actual efficacy of HAG in preventing and/or treating radiodermatitis caused by chemotherapy with cetuximab.

CONFLICT OF INTEREST

The authors declare that they have no conflicts of interest and no relationship whatsoever with the company that produces Jalosome soothing gel.

AUTHOR CONTRIBUTIONS

G.P., A.P., L.B., A.T., D.S., and D.V. made substantial contributions to the conception and design of the case report. P.G. and A.P. were also involved in data collection. All the authors were involved in drafting the manuscript and revising it critically for important intellectual content. All the authors approved the version to be published.

Presta G, Puliatti A, Bonetti L, Tolotti A, Sari D, Valcarenghi D. Effectiveness of hyaluronic acid gel (Jalosome soothing gel) for the treatment of radiodermatitis in a patient receiving head and neck radiotherapy associated with cetuximab: A case report and review. Int Wound J. 2019;16:1433–1439. 10.1111/iwj.13210