Dermatological Side Effects of Cancer Treatment: Psychosocial Implications—A Systematic Review of the Literature

Cancer is a leading cause of mortality and morbidity all over the world and the second major cause of death in Portugal. Dermatological side effects resulting from cancer treatment have a psychosocial impact on patients’ lives, such as quality of life (QoL), body image, cognitive fusion and social inhibition. This systematic review aimed to explore and synthesize the psychosocial impact of dermatological side effects of cancer treatment, answering the following research objectives: (i) Do the dermatological side effects of the cancer treatment present any psychosocial impact for the patients? (ii) How does the psychosocial impact of the dermatological toxicities of the cancer treatment manifest in patients’ lives? Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed and guided a systematic search through the PubMed, Cochrane Library and PyscNet databases. The considered studies correlate dermatological side effects of cancer treatments and their psychological/psychosocial outcomes. The studies found were all published in peer-reviewed journals. The results obtained established that cancer treatment causes the most varied skin changes, consequently reducing self-esteem and QoL; disturbing body image; and contributing to cases of stress, depression and anxiety. There is still limited literature that profoundly investigates the experience of living with these skin toxicities. The development of research lines to improve knowledge in this field will allow for significant improvements in healthcare for patients undergoing cancer treatment who need to focus more on the psychosocial implications of skin toxicities. The novelty of this review lies in adding knowledge summarizing the psychosocial implications of dermatological side effects of cancer treatment to support healthcare providers in the development of integrative therapeutic strategies for these patients in their clinical practice.


Introduction
Cancer continues to be a leading cause of mortality and morbidity worldwide [1].Most of the existing oncological diseases are treated based on chemotherapy or radiotherapy alone or in combination with other treatments, with the side effects of these treatments being a clinical limitation of their administration.Health-related side effects induced by the cancer treatment may appear during or a long time after the treatment ends and often rely on the patient's radiosensitivity [2].The patient receiving cancer treatment usually has severe side effects such as pain, nausea, diarrhea, cardiotoxicity, depression of the immune system, hair loss, disruption of the cutaneous barrier, and changes in skin color and dryness [3][4][5][6].This cutaneous toxicity could change the body image of the patient with significant psychosocial impact.Likewise, individuals suffering from skin diseases frequently encounter a situation characterized by physical disfigurement, psychological distress and societal stigma [7].Dose reduction and discontinuation of treatment are not suitable options to avoid dermatological side effects since they can adversely affect cancer treatment outcomes [8].
The present review aims to synthesize and discuss the evidence from studies examining the psychosocial impact of dermatological effects resulting from cancer treatment and assess whether the psychological and emotional impact is integrated into the therapeutic strategies of the treatment of cancer patients.Thus, this review intends to answer the two following main research questions: RQ1. Do the dermatological side effects of the cancer treatment present any psychosocial impact on the patients?RQ2.How does the psychosocial impact of the dermatological toxicities of cancer treatment manifest in patients' lives?

Background
Dermatological toxicity is assumed to be a common side effect caused by cancer treatment [9], which, if not properly managed, can become uncomfortable and disfiguring [6,[10][11][12][13][14].The symptoms usually appear around the second to the third week of cancer treatment [15], and although they are mild at first, they can become severe over time [16].The impact of cancer on patients is multifaceted and has been documented in some studies [17,18].The emotional consequences observed in people with cancer are depression, worry, fear, anger and guilt [19,20].Furthermore, emotional distress is often referred to as the "sixth vital sign" for cancer patients, and healthcare professionals routinely evaluate it in conjunction with other vital signs like pulse, breathing, blood pressure, temperature and pain [21].Besides the direct impacts, the connections between cancer and psychosocial consequences can also be influenced by the physical symptoms of cancer or the adverse effects of its treatment [22], such as nausea, vomiting and pain.This premise is supported by some studies that show that higher degrees of pain from cancer are related to a decrease in social activities, support and functioning [23].Simultaneously, fatigue, which is a prevalent symptom among cancer patients, has been identified as a predictor of depression and anxiety [24].Therefore, the impact of body image change due to the cutaneous toxicity of cancer treatment on the emotional and psychological components of the patient remains to be studied.Accordingly, this review could serve to identify gaps regarding the psychosocial impact of dermatological side effects resulting from cancer treatment and propose future studies and clinical practices to minimize this impact through clinical and psychological therapeutic management strategies.The authors present a discussion of the state of the art and reflections on future research needs.

Search Strategy
The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guided a systematic search through the PubMed, Cochrane Library and PyscNet databases.The keywords used combined: "cancer" with "chemotherapy" or "treatment", or "derma-tological side effects" or "skin side effects" or "alopecia" or "body image" and "quality of life" or "psychosocial impact" or "social inhibition" or "cognitive fusion".Some additional records were assessed through these articles' references.The resulting studies were filtered.However, no time limit was imposed.All authors have been actively involved in all the other phases of the review process.

Inclusion Criteria
The studies' titles and abstracts were assessed and screened for inclusion following specific criteria: (a) complete studies (no protocols); (b) studies correlating cancer and its psychological and psychosocial outcomes; (c) studies involving specific cancer treatments and their psychological and psychosocial outcomes; (d) studies assessing the psychological and psychosocial consequences of skin toxicities; and (e) studies published in peer-reviewed journals.The articles considered are in the English and French languages.

Exclusion Criteria
Studies were excluded if they only focused on cancer and its physical outcomes and not on its psychological or psychosocial impacts or if they focused only on the dermatological literature, not establishing an association with psychology.Studies that focused only on the impact of the family/loved ones/caregivers (as their perspective could be biased) were also excluded.Works that only mentioned pharmacological therapies and with a small sample size (<10 participants) were also excluded.

Screening
The title/abstract of the studies was selected independently by each of the authors, always based on the inclusion and exclusion criteria.

Results
The initial searches through the databases considered resulted in a total of 725 articles, of which 213 (29.38%) were removed because they were duplicates.The abstracts of the remaining 512 (70.62%) studies were screened, and 397 (54.76%) were excluded.From the remaining 115 (15.86%) full-text articles, 98 (13.10%) were ruled out, resulting in 17 (2.76%)articles for review (Figure 1).
The presence of a skin rash did not appear to influence the psychological well-being or social interactions of the patients.This observation can be attributed to two plausible reasons: firstly, individuals with advanced cancer may view a skin rash as an inherent component of the multifaceted challenges posed by the disease itself; secondly, oncologists often motivate patients to persevere with their treatment regimens since a skin rash typically signifies a positive response to the therapy.Such expectations can instill hope and assist patients in coping with the side effects associated with the medication.

Cutaneous side-effects in patients on long-term treatment with epidermal growth factor receptor inhibitors
Osio et al. [27] Assess the influence of 5HT3 antagonists on how patients perceive the adverse effects of chemotherapy.

Exploratory study
Patients ranked nausea, hair loss and vomiting as the most distressing side effects, as they can impact QoL and compliance with treatment.
The ranking of the four most distressing side effects was quite consistent for gender, age and marital status.In comparison to men, women gave greater importance to hair loss over vomiting, and they also rated emotional distress (depression), anxiety or tension as more significant concerns than men did.On the other hand, men expressed more apprehension regarding treatment attendance, the duration of clinic visits and infertility issues.Notably, infertility was a source of greater distress among younger patients.As patients grew older, the importance of factors like the impact on family and partners and feelings of anxiety or tension diminished, while concerns about constipation and the need for injections became more prominent.Additionally, the anticipation of undergoing treatment had a lesser effect on older patients.
The findings from the study emphasize the need to stay attuned to how patients perceive the side effects of chemotherapy, which might not align with the perspectives of healthcare professionals.While acknowledging the significance of introducing new and effective supportive care measures like 5HT3 antagonists, the study also urges caution against overly optimistic interpretations of their impact.However, the subjective evaluation of physical well-being among patients who received perioperative chemotherapy did not significantly diverge from that of the control group.Moreover, there were no discernible disparities in psychological well-being, concerns and fears, daily activity performance or the overall assessment of life between the two groups.
Prior to this research, the prevailing assumption was that chemotherapy-induced alopecia would inevitably have a detrimental impact on the QoL.However, the findings revealed that the interconnections between these factors were more intricate than previously believed.The question that remains unresolved is how breast cancer and/or its surgical interventions shape the perception of alopecia as a side effect of adjuvant chemotherapy.The CIA approach should be tailored to each patient's specific requirements, with a particular emphasis on addressing the precise timing of hair loss.Both support groups and self-care strategies constitute essential elements of any comprehensive management approach.

Changes in self-concept and body image during alopecia induced cancer chemotherapy
Münstedt et al. [36]; Q2 (medium) Investigate how chemotherapy-induced hair loss affects different aspects of body image perception.

Longitudinal study
Upon histological confirmation predominantly indicating ovarian cancer, a group of 29 patients who received a chemotherapy regimen known to induce complete alopecia (loss of hair) was analyzed.
The assessment was conducted prior to the initiation of treatment, then repeated once hair loss was complete, and finally after the completion of therapy when patients had already undergone hair regrowth.Across all scales, the results demonstrated a deterioration during chemotherapy, but they did not return to baseline or improve when patients experienced hair regrowth.The findings indicated that 73.3% of the patients did not feel as self-confident as they did before undergoing treatment, and for 46.6%, alopecia represented the most distressing side effect of chemotherapy.
Given the absence of any chemotherapeutic regimen or alternative treatment capable of averting alopecia, one of the following conclusions can be drawn: The observed differences may not solely be attributed to alopecia but could also result from coping mechanisms triggered by chemotherapy, potentially exacerbated by the presence of alopecia.Alternatively, these changes persist even after chemotherapy has ceased.
The regrowth of hair and other adaptive processes do not lead to the restoration or enhancement of the compromised body image and self-concept.Longitudinal study.
Among the 40 patients who underwent management, assessments were conducted before, after radiotherapy (at 4 weeks), and during follow-up (6 months post-radiotherapy).During these evaluations, symptoms of fatigue, skin erythema and levels of circulating proinflammatory cytokines were recorded.Among these patients, 17.5% experienced fatigue without concurrent depression or anxiety, and grade ≥2 erythema was observed in 5 out of these 7 patients.The blood markers demonstrated a notable impact on fatigue.Interestingly, there appeared to be an apparent rise in fatigue, erythema and proinflammatory markers between the fourth and fifth weeks of treatment, followed by a subsequent decrease after radiotherapy.
The research findings imply that fatigue is linked to the presence of severe breast skin erythema during radiotherapy, likely due to elevated cytokine levels.These increased cytokine levels were found to be associated with concurrent high-grade breast skin erythema, potentially contributing to the biological mechanisms underlying fatigue.This suggests the possibility of developing radiation therapy modifications or novel medications specifically targeting erythema, which could reduce the intensity of skin erythema and fatigue.Such interventions could lead to improved therapy adherence and enhanced QoL for patients.

Descriptive design
In the group of elderly women under investigation, 40% experienced an extremely profound impact on their QoL due to skin symptoms.Furthermore, 64% of them reported an extremely severe effect on their emotions and functioning, resulting in a total mean QoL score of 103.72 ± 11.6.Additionally, statistically significant associations were identified between the QoL and factors such as age, lack of formal education, insufficient monthly income, the presence of chronic diseases, the stage at which breast cancer was diagnosed, and the receipt of ten or more chemotherapy cycles.
Regarding the overall aspects of QoL, the research findings indicated that approximately two-thirds of the elderly women included in the study reported an extremely significant impact of their skin symptoms on their emotional well-being and daily functioning.Furthermore, nearly half of these individuals stated that their skin symptoms had an extremely profound effect on their overall QoL.Cytotoxic chemotherapy treatments have the potential to cause lasting harm or depletion of epithelial hair follicle stem cells, which are essential for the regeneration of hair follicles.This harm may elucidate the notably higher prevalence of diffuse alopecia observed in patients with pCIA compared to those with EIAC.In addition to the scalp, it was observed that eyebrow and eyelash alopecia were present in 37% of patients with pCIA, contributing to an adverse psychosocial impact, as indicated in the QoL analyses.Studies have shown that scalp cooling can prevent severe alopecia in 51% of breast cancer patients.Moreover, among patients with pCIA, there was a generally moderate to significant clinical improvement observed in 36 out of 54 individuals (67%) who received treatment with topical minoxidil, 5% and/or oral spironolactone.Multivariate analysis demonstrated a negative emotional impact in both groups when compared to other domains, such as symptoms and functioning.Furthermore, specific dermatological symptoms such as itching, dry skin, easy bruising, pigmentation issues, papulopustules on the face, periungual inflammation, nail abnormalities and palmoplantar lesions were linked to significantly higher scores on the Dermatology Life Quality Index (DLQI).Among these symptoms, periungual inflammation and palmoplantar lesions were associated with the highest DLQI scores.
The findings of this study indicated that factors such as being female, having breast cancer, using targeted agents and undergoing extended periods of anticancer therapy were linked to increased disruption in dermatology-specific QoL.All of the skin issues examined, with the exception of hair loss, had a notable impact on dermatology-specific QoL.Notably, periungual inflammation and palmoplantar lesions were associated with the highest DLQI scores.These results could serve as valuable insights for clinicians when counseling and managing patients undergoing anticancer therapy.

Studies' Results Summary
The analysis of Tables 1-3 allows for the understanding that while the methodology and instruments may differ (Tables 2 and 3), most studies are highly qualified in terms of metrics (Table 1), mostly Q1 and Q2, which demonstrate how valued studies on this topic are.The most studied variables were sociodemographic and clinical characteristics, such as age, sex, type of cancer and treatment (Table 2).QoL is clearly the focus of most articles, underlining aspects related to the psychological well-being or social interactions of the patients.The side effects of cancer treatment and medication are extensively addressed in the reviewed studies, demonstrating the importance given to this specific factor in the well-being of patients.Treatment with EGFRI seems to result in significant physical and psychosocial discomfort of patients and was associated with more dermatological side effects, therefore highlighting the need to further invest in the well-being of patients during the treatment phase.The sense of hope and despair during the illness has been described in some studies, once more within the contest of QoL.While dealing with chemotherapy, there is a perceived need to move away from the disease symptoms and focus on the QoL.These connections need to be better explored, tailored to each patient beyond the improved aspects of health and also specifically address the psychological aspects involved in the QoL.
Thus, skin changes are frequently perceived as secondary issues in the context of cancer, often overshadowed by more evident symptoms of the disease.Nevertheless, these dermatological changes can exert a substantial and sometimes underestimated impact on a patient's QoL, primarily due to their unpredictable nature.It is well established that healthcare practitioners frequently possess limited knowledge regarding these dermatological effects, thereby impeding their ability to provide comprehensive support not only to patients but also to their families.Consequently, it becomes imperative for healthcare professionals to proactively engage in self-education concerning the potential side effects of cancer treatments, particularly those related to changes in physical appearance that may evolve gradually over time.Furthermore, healthcare providers should endeavor to facilitate the holistic management of patients, addressing both the physical and psychological repercussions of these dermatological side effects.This not only empowers patients with a deeper understanding of what they might encounter during their cancer journey but also equips healthcare professionals with the necessary tools to offer more comprehensive and empathetic care.In doing so, the aim is to enhance the overall well-being and QoL of cancer patients and their families, acknowledging the significant role that skin changes can play in their cancer experience.
Clearly, through this systematic review, the two research questions being addressed in this study were answered: The dermatological side effects of the cancer treatment result in psychosocially impacting the patients (RQ1).The psychosocial impact of the dermatological toxicities of the cancer treatment manifest in patients' lives is demonstrated in the reviewed studies (RQ2).

Discussion and Conclusions
Patients with the most varied types of cancer survive longer and mention an improvement in the level of QoL as a consequence of new cancer therapies.Dermatological changes are a common side effect of this treatment [12,42].They can range from mild to severe and can affect a patient's physical appearance, comfort and QoL.Some of the most common skin alterations in cancer patients include dryness, itching, rashes, changes in skin color, hair loss or nail changes.These skin effects can be caused by a variety of factors, including chemotherapy, radiation therapy, immunotherapy and surgery.The severity of skin changes can vary depending on the type of cancer treatment, the patient's individual response to treatment and the patient's skin type.In some cases, skin changes can be temporary and improve after treatment is finished [43,44].However, in other cases, these cutaneous alterations can be permanent.It is important for cancer patients to be aware of the potential skin changes that can occur during treatment and the effect they may have on their QoL.Skin toxicities are often understood as minor concerns when compared to cancer symptoms, but they can seriously affect patients' QoL due to their unforeseen nature.They can impact a patient's self-esteem, body image and sense of well-being.Skin changes can also make it difficult for patients to perform everyday activities, such as bathing, dressing and sleeping [25,26].Few studies have addressed the psychosocial impact of the side effects of cancer treatment, as demonstrated in this review.However, the psychological and social impact of dermatoses is well documented, and so it is expected that this impact will be high, similar to what happens with these diseases [45][46][47][48].Health professionals often have limited knowledge about these effects, which limits their ability to effectively support not only patients but also their families.Therefore, this impact is not considered in therapeutic strategies, and if it were, it would greatly benefit the patient [49].It is important for healthcare providers to be aware of the potential skin alterations that can occur in cancer patients.They should also be able to provide patients with information and support to help them manage these effects.It is important that these professionals educate themselves and the patients about the possible side effects of cancer treatment, such as modifications in the appearance that may manifest over time, and also seek to help the management of patients' physical and psychological dimensions.
Following the PRISMA guidelines, this article aimed to address the psychosocial impacts of cancer treatment-related dermatological side effects and how they can be synthesized through a systematic review.While there is a recognition of the adverse impact of dermatological side effects caused by cancer treatments on patients, there remains a dearth of understanding regarding how coping with these effects influences the psychological and social dimensions of cancer patients' daily lives.This review highlights that the majority of the studies developed have focused on the physical aspects of cancer, and no additional relevance was given to the dermatological aspects associated with the side effects of the treatment.Additionally, research studies concentrating on the consequences of dermatological alterations as their primary focus did not establish a direct connection to cancer itself.This review aimed to contribute to further clarification in relation to the aspects contributing to clarify the key points in the treatment of skin cancer diseases, adding knowledge in this respect.The development of further research studies that are able to assess the psychosocial impact of the dermatological side effects of cancer treatment and psychological interventions to minimize this impact will allow a significant improvement in healthcare for patients undergoing cancer treatment.

Figure 1 .
Figure 1.PRISMA flow diagram comprising the different phases of this systematic review.

Figure 1 .
Figure 1.PRISMA flow diagram comprising the different phases of this systematic review.

Table 1 .
Resume of the studies reviewed for this literature review.

Table 2 .
[41]ables, analysis and statistical methods used in the studies reviewed for this literature review.The articles where references are Hesketh et al.[35], Helms et al.[39], Agero et al.[31], and Silva, D. et al.[41]are literature reviews or systematic reviews; therefore, they do not have the information required in this table. Note:

Table 3
details the instruments used in the analyzed studies.

Table 3 .
[41]ruments used in the studies reviewed for this review.The articles where references are Hesketh et al.[35], Helms et al.[39], Agero et al.[31], and Silva, D. et al.[41]are literature reviews or systematic reviews; therefore, they do not have the information required in this table. Note: