Alopecia is one of the most well-known dermatologic alterations due to cancer therapies (Figure 7A), and although it does not have a significant impact on physical health, it does lead to decreased quality of life. Hair loss is usually reversible, although the hair may grow with different texture.
Figure 3 lists the most common chemotherapeutic agents that cause hair abnormalities including alopecia. These agents include but are not limited to doxorubicin(Drug information on doxorubicin), dactinomycin(Drug information on dactinomycin), cytarabine(Drug information on cytarabine), and etoposide(Drug information on etoposide) (60% of patients experience hair alterations). For instance, cytarabine is associated with alopecia within 2 to 4 weeks of the initiation of therapy.
Cooling the scalp before, during, and after chemotherapy decreases the incidence of alopecia.[47-49] Other modalities used to decrease scalp alopecia include scalp tourniquets and minoxidil(Drug information on minoxidil). Tourniquet pressure is thought to decrease scalp blood flow.[49-51] Longer and thicker eyelashes (trichomegaly) develop in up to 33% of patients receiving EGFR inhibitors (Figure 7B).
Nail and Periungual Reactions
Periungual inflammation is one side effect that causes significant pain. It is characterized by paronychial edema, erythema, and tenderness as well as onycholysis on the affected fingers or toes (Figure 8). Although not usually responsive to antistaphylococcal therapy, minocycline(Drug information on minocycline), doxycycline(Drug information on doxycycline), and topical steroids have been used to treat paronychial inflammation.[13,52]
The EGFR inhibitors have been implicated in paronychial inflammation. Cetuximab(Drug information on cetuximab) (Erbitux), a chimeric immunoglobulin (Ig)G1 monoclonal antibody to the EGFR receptor, has been reported to induce—in addition to the papulopustular eruption on the face, chest, and upper back—follicular plugging, neutrophilic folliculitis, and tender paronychial inflammation of toes and fingers.
Onycholysis and onychomadesis have both been reported as cutaneous side effects of capecitabine(Drug information on capecitabine), bleomycin(Drug information on bleomycin), and hydroxyurea. With hydroxyurea, nail changes are less common and include brittle nails, onychodystrophy, onycholysis, and melanonychia (longitudinal more than transverse).
Docetaxel, a taxane, induces onycholysis, and dyschromia of the nails, subungual hematoma and suppuration, acute paronychia, and Beau's lines. The incidence of such nail changes ranges from 0% to 44%. A frozen glove was demonstrated to prevent such nail changes, when worn by patients 15 minutes before the administration of docetaxel(Drug information on docetaxel), during the 1-hour docetaxel infusion, and 15 minutes after the end of infusion.
Dermatologic entities in cancer survivors after completion of scheduled regimens range from therapy-induced sequelae to signs indicating recurrent disease. Although this category of dermatoses remains the most underreported and underrecognized, it is anticipated that increased survival times with newer agents, and consequent attention on survivorship issues will bring about further interest in this topic.
Scarring associated with oncologic surgical procedures has been associated with psychological problems in 15% to 16% of survivors of childhood cancer. Both short- and long-term psychological repercussions have been found in breast cancer survivors who received mastectomies, especially in younger women. Not surprisingly, patients with disfiguring skin conditions with a prior diagnosis of head and neck squamous cell carcinoma had significant psychosocial difficulties, with high levels of anxiety, depression, and social anxiety and avoidance, and decreased quality of life.
Chronic Radiation Dermatitis
Chronic radiation dermatitis changes develop months to years after radiation exposure. These changes can include hyper- or hypopigmentation, scaling, xerosis, and thickened or hyperkeratotic skin. In addition, irradiated areas are devoid of hair follicles or sebaceous glands, yet have prominent blood vessels manifested as telangiectasias. Treatment is symptomatic and includes different modalities such as pulsed dye laser for telangiectasia, hyperbaric oxygen therapy to alleviate the pain caused by edema, erythema, or lymphedema, as well as keratolytic agents for the scaling and xerosis.
Increased Secondary Cancers
Therapy-related skin cancers, especially basal cell carcinoma, have been described in survivors of childhood and adolescent cancer. Such cancers are known as second primary cancers, and they could be the result of factors that caused the primary cancer in the first place, such as smoking, drinking alcohol(Drug information on alcohol), alterations in hormonal and immunologic status, and environmental factors. Other factors also include the carcinogenic effects of cytotoxic drugs and radiation therapy.
It is well established that ionizing radiation increases the likelihood of precancerous and cancerous skin lesions such as basal and squamous cell carcinomas. This is attributed to the fact that irradiated cells are genetically unstable, therefore more prone to mutations. In addition, cancer patients may have mutations in their tumor-suppressor genes; hence, they might have an increased risk of other malignancies. Although other skin malignancies such as melanomas and angiosarcomas are thought to be radiation-related, this conclusion cannot be drawn with certainty due to the lack of definitive data.
Cutaneous metastases are a frequent sign of recurrence but may be overlooked, as their appearance tends to be unimpressive.[58-60] Although uncommon, cutaneous metastases are often a sign of advanced grade and poor prognosis. The most common malignancies associated with metastases to the skin are breast and lung cancer, and the most common site of cutaneous metastasis is the chest.[58-61] Therefore, clinicians should have a high level of suspicion when cancer survivors present with the sudden onset of nodules or firm papules that are persistent, specifically if they are located on the chest.
Other cancers that have been reported to metastasize to the skin include colorectal, stomach, ovarian, bladder, and renal cancers.[58-62] A rare form of cutaneous metastasis from breast cancer is a form of scarring alopecia, known as alopecia neoplastica.[63,64] Lung cancer, especially adenocarcinoma, has been known to metastasize to the skin, which correlates with a poor prognosis.
The most common sites for metastases include the chest and abdominal walls. However, other areas such as the lip, scrotum, and perianal skin have been described.[58-60] Renal cell carcinoma has been reported to metastasize to the skin, presenting as nodules to the scalp (cutaneous horn or pyoderma gangrenosum–like) or to the subungual unit.[58-60] In ovarian cancer, the most common cutaneous metastasis is known as Sister Joseph's nodule, a rare cutaneous metastasis to the umbilicus. Clinically, it is a painful, sometimes ulcerated nodule with irregular borders that is firmly attached to the anterior abdominal wall. A bloody, mucinous, or purulent discharge may be present. The size of this nodule is as variable as its morphology, and it has been reported to be as large as 10 cm.
Stem cell transplantation has proven to be lifesaving in many malignancies. The triad of dermatitis, hepatitis, and enteritis arising within 100 days after transplantation is described as acute graft-vs-host disease (GVHD).[65,66] Classically, acute cutaneous GVHD occurs 2 to 3 weeks after transplants, and it manifests as a pruritic or painful rash. The rash is initially localized to the palms and soles, and gradually involves the entire body, occasionally with bullae and vesicle formation and erythroderma. In both acute and chronic GVHD (that which appears after 100 days), xerosis is an extremely common complaint, and proper management with hydrating agents and soft gentle soaps is essential for patient comfort.
Other cutaneous manifestations of GVHD include diffuse alopecia, and sclerodermoid skin changes. Mucosal changes include oral mucosa atrophy, erosions, and ulceration, pyogenic granulomas, xerostomia, oral lichen planus–like changes, and submucosal fibrosis. Nail changes are also common, presenting as longitudinal streaks and roughness of the nail plates. It is essential to be vigilant and detect these skin changes, as progression to other organs could be fatal.[65,66]
The success of improved detection and therapeutic strategies has led to a remarkable 65% survival rate at 5 years for all cancers.[1-3] As such, issues relating to the emotional and physical well-being of cancer survivors have gained increased attention. Importantly, unintended dermatologic consequences of surgery, chemotherapy, or radiation are common in treated individuals, all of which may have a significant impact on quality of life and physical status.
Although dermatologic care for cancer patients through the establishment of specialized dermatology clinics will contribute to better knowledge and treatment options, it still remains a damage control exercise that focuses on directly addressing urgent issues so that patients may continue on antineoplastic therapy. Progress in dermatologic care for cancer patients commands increased attention to the skin and appendages as part of everyday patient care and during clinical trials. Moving forward, careful observation and insightful analysis between dermatologists and oncologists will generate recommendations for new and improved dermatologic care in oncology.
Financial Disclosure: Drs. Agha and Bennettand Ms. Kinahan have no significant financial interest or other relationship with the manufacturers of any products or providers of any service mentioned in this article. Dr. Lacouture is a speaker for ImClone and Onyx and a consultant for Bristol-Myers Squibb and Bayer.