Hand-foot syndrome (HFS) and cancer
Hand-foot syndrome (HFS) is a skin reaction commonly experienced by cancer patients undergoing chemotherapy, particularly with certain high-dosage agents like 5-fluorouracil and capecitabine. Symptoms of HFS include swelling, redness, tenderness, and pain in the palms and soles, which can progress to blistering if not addressed. This condition can significantly affect a patient’s quality of life, as it may lead to a reduction or interruption of chemotherapy doses due to the discomfort and potential complications. Although the precise cause of HFS remains unclear, it is believed to involve damage to capillaries in the hands and feet, possibly exacerbated by factors like pressure and temperature.
Diagnosis is often challenging, as histological examinations do not provide definitive markers for HFS. Management strategies focus on symptomatic relief through cold compresses, moisturizing creams, and pain relievers, with a strong emphasis on early patient education to prevent severe outcomes. Patients are advised to avoid tight clothing, excessive heat, and strenuous activities. While the symptoms typically resolve with a decrease or cessation of chemotherapy, proactive measures can help mitigate the impact of HFS during treatment.
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Hand-foot syndrome (HFS) and cancer
ALSO KNOWN AS: Palmar-plantar erythrodysesthesia (PPE), hand-to-foot syndrome, Burgdorf’s reaction, chemotherapy-induced acral erythema
RELATED CONDITIONS: Hand-foot skin reaction (HSFR)
DEFINITION: Hand-foot syndrome (HFS) is a chemotherapy-induced skin reaction characterized by swelling, tingling, redness, tenderness, pain, and possibly peeling and blistering of the palms of the hands and soles of the feet. Occurrence of HFS in patients receiving chemotherapy may result in a lowering of dosage levels and interruption or discontinuation of treatment.
Risk factors: HFS is a common side effect of high-dosage treatment of certain traditional cancer chemotherapeutic agents, including 5-fluorouracil (5-FU), capecitabine, liposomal doxorubicin, and cytarabine. HFS typically occurs within the first few weeks of chemotherapy, but it may also occur after several weeks or months of treatment.
Etiology and the disease process: The cause of HFS is not completely understood. The most widely accepted theory is that capillaries in the palms and soles break because of several factors, including overuse, pressure, or increased temperature. Breakage of the blood vessels may release small amounts of the chemotherapeutic agent into the surrounding tissue, resulting in an inflammatory reaction in the affected areas. Another theory is that the drugs pass from the body through sweat secretion, and the hands and feet are more susceptible to HFS due to the large number of sweat glands present in those areas. The hands are more commonly affected than the feet; in some patients, they may be the only areas affected. HFS may also occur elsewhere on the skin, such as the neck and chest, but it is much less common. HFS is distinct from hand-foot skin reaction (HSFR), a condition reported with various targeted kinase inhibitors (such as sunitinib) characterized by more localized, thicker, callus-like lesions.
Incidence: The occurrence of HFS is known to depend on the agent, dose, and administration of the chemotherapeutic drug responsible. For example, in early phase II studies of capecitabine monotherapy for metastatic colorectal and breast cancer patients, HFS occurred in approximately 50 percent of patients; severe HFS was noted in approximately 10 percent of these patients.
Symptoms: HFS typically begins with numbness or tingling in the palms or soles. These symptoms may rapidly progress to swelling, redness, tenderness, and burning pain in the affected areas in three to four days. If treatment with the chemotherapeutic agent is not promptly interrupted or the dose of the agent reduced, blisters may develop, causing increased pain and interfering with general activities of daily living such as walking and handling objects.
Screening and diagnosis: Histological examination of affected tissue does not discern from normal inflammation processes, preventing an accurate diagnostic marker for HFS. The National Cancer Institute has a general system for classifying HFS and HFSR based on three grade levels of severity:
- Grade 1: Skin changes or dermatitis without pain, for example, erythema, peeling
- Grade 2: Skin changes with pain, not interfering with function
- Grade 3: Skin changes with pain, interfering with function
Treatment and therapy: Control of symptomatic pain may occur through the use of cold compresses, particularly those that conform to the shape of the hands and feet (such as ice packs or bags of frozen corn or peas). Frequent but gentle application of highly moisturizing lotions and creams is also recommended. Urea cream and mapisal ointment, which contains antioxidants and oil extracts, may relieve symptoms. Elevation of the hands and feet may reduce swelling, and pain may be controlled by using pain relievers such as acetaminophen. Avoiding sources of heat is also recommended. Systemic corticosteroids, vitamin B6 (pyridoxine), and dimethyl-sulfoxide (DMSO) have been proposed to reduce or relieve symptoms, but conclusive evidence for these treatments has yet to be demonstrated. In 2023, the American Society of Clinical Oncology suggested diclofenac, a topical medication for the treatment of HFS, held promise, along with medications containing vitamin E. The only proven means to reverse the signs and symptoms of HFS is through interruption or dose reduction of chemotherapeutic therapy.
Prognosis, prevention, and outcomes: Patient education in the early phases of treatment is vital to prevent complications HFS brings. Patients should be instructed to contact their doctor immediately if symptoms develop, as a quick reaction can often prevent more severe effects. Patients receiving agents known to cause HFS are instructed to avoid wearing tight-fitting clothes (gloves, socks, stockings) and shoes and to avoid excessive sun exposure, hot baths and showers, steam rooms, and excessive rubbing of the soles and palms. Comfortable slippers, sandals, or shock-absorbing shoe liners should be worn to relieve painful pressure points. Moisturizing creams and lotions should be applied liberally but gently to the hands and feet. However, creams or lotions containing alcohol, perfumes, or glycerin should be avoided. Sunscreen (SPF 30 or higher) and long-sleeved shirts and pants should be worn during prolonged exposure to the sun. Strenuous physical activity and long-term alcohol use should be avoided. Once actions to interrupt or reduce the dose of chemotherapy are undertaken, reversal of symptoms is typically rapid and without long-term consequences. Chemotherapeutic treatment can typically resume at a lower dose once symptoms improve.
Bibliography
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