An observational prospective study of mucocutaneous adverse effects of chemotherapeutic drugs and radiotherapy

Introduction

Our understanding of cancer and treatment approaches has advanced significantly over the years. The management of cancer has become more difficult as cancer prevalence rises, making it a challenge for modern clinical care. Cancer patients are currently being treated using a variety of methods, including radiotherapy, chemotherapy, combination therapy, immunotherapy, and hormone therapy.¹ Modernized equipment and increasingly sophisticated restorative regimens have revolutionized functionality and greatly reduced, but not eliminated, the negative effects they produce on the body. The negative effects of chemotherapy on the skin, nails, and hair can significantly lower the quality of life and cause therapy to be discontinued. significant advancements. The creation of anticancer agents has seen significant advancements. The importance of genetic changes is particularly highlighted by the development of targeted treatments for the treatment of solid cancers. Through this advancement, cancer patient’s chances of survival and quality of life have increased, and hematological and non-specific toxicities have decreased in tandem. A new and broad spectrum of dermatologic adverse effects have, however, also emerged as a result of the introduction of newer drugs.²

Hyperpigmentation, alopecia, radiation recall, hand-foot syndrome, hypersensitivity, extravasation injuries, and nail dystrophies are among the most common cutaneous reactions. Although most post-chemotherapy side effects are not life-threatening, they can nonetheless be stressful for the patient, especially if they result in baldness. In rapidly growing cells like skin, adnexa, and mucous membranes, chemotherapeutic drugs’ toxicities, and unfavorable effects can be noticed. While other adverse effects including erythema, hyperpigmentation, rash, and hypersensitivity happen less frequently, the side effects that occur in these rapidly reproducing cells are typically dose-dependent. The administration of chemotherapy medications needs to be done cautiously since extravasation of intravenous chemotherapy medications might result in serious skin irritation and necrosis.³

Phototoxicity, the recall phenomenon, and radiation enhancement are three examples of cutaneous adverse effects that are linked to the interaction between chemotherapy and radiation. Other, less common side effects such as sclerodermiform dermatitis, Raynaud’s phenomenon, and hypersensitivity syndrome are also discussed. Sometimes cutaneous side effects are rather exclusive to a particular class of medication. Taxanes are most frequently connected to capillary leak syndrome. Perhaps as a result of the drug’s prolonged use, hydroxyurea causes certain odd cutaneous side effects (ulcerations, pseudodermatomyositis). Despite the frequent and occasionally severe mucocutaneous adverse effects of chemotherapy, stopping the offending medication is rarely necessary. However, dose adjustments or measures to prevent some of these adverse effects are still required.⁴

Alopecia is one of the most frequent dermatologic adverse effects of chemotherapy. Drugs frequently target the rapidly producing hair cells. As a result, the production of hair shafts is lost, resulting in weak, frizzy hair. The scalp’s terminal hair follicles, which produce hair more quickly than axillary, pubic, or slower-growing brow, eyelash, or axillary hair, are more affected. Chemotherapy-induced alopecia is reversible, and hair regrowth occurs with a change in texture and color (switching from straight to curly).²

The Palmar-plantar erythrodysesthesia, also called the hand-foot condition, is characterized by erythematous, painful lesions on the skin that affect the palms and soles. and was first noticed in patients receiving high doses of cytarabine medication.² After 2 to 12 days of medication exposure, the patient often has a burning feeling on their hands and feet, which is followed by a severe erythema that is symmetrical and well-defined. The dorsal and lateral fingers, as well as the periungual skin, are frequently affected after the lesions are initially noticed on the thenar and hypothenar eminences of the palms.⁵ Eventually, the entire hand or foot may be affected, causing swelling and potentially the appearance of vesicles or bullae. After weeks to years of radiation, doxorubicin, in particular, causes the development of radiation dermatitis. Dermatologic symptoms can be desquamation, vesicle development, and maculopapular eruptions with erythema. From a minor rash to a serious case of skin necrosis, reactions can vary in severity. Nail alterations for chemotherapy patients happen regularly. The presence of transverse ridges is indicative of cyclic damage to the nail matrix.²

Ionizing radiation is a crucial therapeutic option for cancer patients. Tissues can undergo a variety of functional and structural changes as a result of radiation. The overall radiation dose, the amount of tissue exposed, and the duration between radiation doses are just a few of the variables that affect how much radiation damage there is. The highly oxygenated cells and proliferative cells are the most vulnerable to radiation damage. The most radiosensitive cells in the integumentary system are basal keratinocytes, hair follicle stem cells, and melanocytes.⁶

Hypersensitivity responses, contact dermatitis, vasculitis, and fixed drug eruptions are frequent misdiagnoses for the skin symptoms brought on by chemotherapy and radiotherapy. Patients receiving chemotherapy and radiotherapy frequently experienced changes in skin, nails, hair, and mucosa as serious side effects. To increase patient compliance, it is crucial to understand the range and presentation of mucocutaneous symptoms in those undergoing chemotherapeutic medicines and radiation therapy.

With the introduction of newer modalities and upgradation in the treatment of cancer there is an increase in the survival rate of cancer patients but at the same time, there is an increase in adverse effects of chemotherapeutic drugs and radiotherapy. The administration of chemotherapeutic drugs can lead to a host of mucocutaneous manifestations ranging from adverse effects that are specific to drugs like flagellate dermatitis caused by bleomycin to non-specific toxic reactions like painful erythema involving hands and feet, intertriginous areas by a variety of drugs like Cytarabine, Doxorubicin, Capecitabine, Paclitaxel. The skin manifestations caused by chemotherapy and radiotherapy are often misdiagnosed as hypersensitivity reactions, contact dermatitis, vasculitis, and fixed drug eruptions. Therefore, it is important to identify the various presentations of mucocutaneous manifestations in patients receiving chemotherapeutic drugs and radiotherapy to improve the compliance of the patient.

Objectives

Methods

Discussion

It is highly common for patients following chemotherapy and radiation therapy to present with a variety of mucocutaneous symptoms. If these symptoms occur frequently, it can lower the patient’s quality of life. The adverse effects might be asymptomatic observations, incapacitating symptoms, or a combination of these.

In a descriptive study of 226 patients, Naveed S et al.² found that the most common symptom was nail changes (194; 5.84%). Discoloration of nails was more common in patients receiving combination therapy than chemotherapy alone. The second most common manifestation was skin changes (191; 84.51%), followed by hair changes (159; 70.35%), mucosal involvement (34; 15.04%), and other non-specific presentations. The most frequent negative impact on the skin was skin pigmentation. Other skin abnormalities included hirsutism, hypertrichosis, and alopecia.²

Susser et al.⁷ in a study has found that the most common adverse effect of cancer chemotherapy was Alopecia. Anagen effluvium was most commonly produced by Anticancer agents. Oral mucositis although was a dose-limiting side effect, affects almost 40% of individuals. The drugs most commonly associated with oral mucositis were bleomycin, docetaxel, and daunorubicin.⁷

Biswal SG et al.⁸ conducted an observational study of 1000 receiving chemotherapy. Out of 1000 patients, 384 presented with any one of the dermatological manifestations. Anagen Effluvium was the most common affecting 78.6% of patients. The other less common manifestations were Sweet syndrome and Bullous Photodermatitis.⁸

Lalla RV et al.⁹ conducted a study and reported the oral complication in patients receiving chemotherapy and radiotherapy was Oral mucositis affecting 20 to 40% of patients. The pain associated with oral mucositis has led to a reduction in chemotherapy and radiotherapy doses.⁹

Gabriella et al.¹⁰ in their study of 100 patients receiving chemotherapeutic drugs. The patients on EGFR inhibitor developed papulopustular reaction [55.8%], dry skin [41.17%], nail alterations [29.41%], and alopecia [17.64%].¹⁰

In their descriptive analysis of 53 chemotherapy patients, Pavey et al.¹¹found that the most prevalent mucocutaneous adverse effects were changes to the nails (33; 62.2%), then changes to the hair (20; 37.7%), skin (19; 33.9%), and mucosa (2; 3.7%).¹¹

In a study conducted by Zeynep Utlu et al.¹² total of 128 patients were enllored and divided into two groups one receiving classic chemotherapeutic agents and the other receiving targeted agents The majority of the adverse effects, xerosis, were observed in 93 (72.7%) of the 128 individuals. Alopecia, mucositis, pruritus, pigmentation of skin, and hand-foot erythema were other common adverse effects. In the traditional chemotherapeutic group, xerosis, pruritus, alopecia, and nail alterations were the most frequently reported adverse effects, occurring in 71 (75.5%) individuals, 50 (53.2%), 49 (52.1%), and 43 (45.7%) of the patients. In the targeted chemotherapeutic group, xerosis (22/64.7%), nail alterations (17/50%), alopecia (15/44.1%), and pruritus (13/38.2%) were the most frequently reported adverse effects.¹²

Hospital-based observational research was carried out by Menon A et al.¹³ with the participation of 100 patients, including 37 female and 63 male patients. Hair was the most often seen adverse impact among the cutaneous side effects, followed by changes in the skin, changes in nails, and mucosal involvement. The most often noted negative effects on the skin were hyperpigmentation and xerosis.¹³

Thapa DP et al.¹⁴ performed hospital-based research in which 62 patients in all were included. Eczema accounted for 39% of all dermatoses, with infection coming in at 25%, pruritus at 14%, insect bite hypersensitivity at 3.2%, pilosebaceous unit disorder at 3.2%, urticaria at 3.2%, pigmentary alterations at 3.2%, nail involvement at 3.2%, drug rash at 2%, vesiculo-blistering disorder at 2%, and cutaneous metastases at 2%.¹⁴