Hand-foot syndrome in cancer patients

Nadia Dembskey, a podiatrist, explains the development of hand-foot syndrome in cancer patients and the current management strategies.

In the last two decades, considerable advances have been made in cancer treatment. With more patients surviving for prolonged periods of time, treatment-related toxicities have become more relevant.

What is hand-foot syndrome?

A commonly observed toxicity is hand-foot syndrome (HFS) and is a relatively common skin reaction to chemotherapy. It’s characterised by palmoplantar numbness, tingling, or burning pain. These symptoms usually correspond with sharply defined red patches with or without swelling, cracking, or peeling.

In advanced stages, blistering and ulceration may occur. The fat pads of the palms tend to be affected before the soles of the feet. In individuals with skin of colour (Fitzpatrick skin types V-VI), HFS may present as macular hyperpigmentation instead of red patches.

It’s also important to differentiate HFS from hand-foot skin reaction (HFSR) – a skin reaction to treatment that occurs in about 30% of patients. HFSR is characterised by painful, yellowish, thick skin patches in high-pressure or high-friction areas such as the heels, fingertips, areas over the joints, and in the interdigital web spaces.

HFSR plaques are often accompanied by numbness, tingling, and burning sensations. Unlike HFS, HFSR appears on the feet before the palms of the hands.

Although HFS isn’t considered life-threatening, it can be painful and interfere with daily activities, thereby seriously compromising quality of life.

How does HFS develop?

The reason why HFS occurs is poorly understood and it’s theorised to be different for each class of drug. HFS shows a range of toxic skin damage varying from non-specific scattered cell death to full gangrene of the top layer of skin and blistering in the skin layer beneath it.

The unique make-up of the palms and soles may provide some insight into why the effects of these drugs are focused on these areas. The palms and soles are highly vascular and have higher rates of division of skin cells than other skin areas, high concentrations of sweat glands, and unique temperature modulation. Chemotherapeutic drugs have been shown to infiltrate these sweat glands and the superficial layer of skin of the palms and soles upon infusion. This causes an accumulation of drug in the sweat ducts in these areas, leading to eventual cell death of the superficial layer of skin, leading to red patches, blistering, cracks, thickened skin, etc.

Management

Management of HFS in cancer treatment involves a combination of prevention, patient education, symptom improvement, and dose intensity management.

Patient education and prevention

The implementation of a structured patient education programme prior to treatment may increase the ability of patients to identify and manage HFS on their own.

Prior to cancer treatment, pre-existing skin conditions of the hands and feet should be treated, and patients should be educated about preventive measures to reduce stress on skin areas. These measures include reducing skin friction, avoidance of heat, the use of emollients and creams, and rapid attention to any wearing away of the skin that may predispose to infection.

Regional cooling using ice packs, ice water immersion, or frozen gloves or socks to cool hands and feet during treatment administration has shown success in reducing rates of HFS.

The use of pyridoxine (vitamin B6) has been recommended for prevention of HFS due to the similarity of HFS symptoms to those of pyridoxine deficiency (acrodynia).

Preventative use of urea-based cream has shown to reduce the incidence of any grade HFSR.

Taking preventative anti-inflammatory medication, specifically COX-2 inhibitors, was shown to be effective for the prevention of HFS. However, with these medications, potential side effects including cardiovascular risks and upper gastrointestinal bleeding should be considered.

Preventive and symptomatic treatment options

Avoid mechanical stress/trauma (friction, pressure, tight footwear).
Avoid exposure to high temperatures around administration (bathing with hot water, vigorous exercise, wearing tight clothing and shoes).
Maintenance of good hygiene with regular visits to a podiatrist in case of corns and calluses.
Referral to a podiatrist for treatment of pre-existing dermatologic conditions on the feet.
Moisturising with urea-based cream three times per day (avoid excessive rubbing).
Local hypothermia (regional cooling) at time of administration (only for short-term infusions).
Pain: analgesics or topical anaesthetics (lidocaine patches).
Inflammation: topical high-potency corticosteroids.
Hyperkeratosis: removal of hard skin by a podiatrist and the use of topical keratolytics regularly at home.
Erosions: petroleum/lanolin-based ointments.

Conclusion

HFS occurs often, though sometimes only after repeated courses of treatment, and should be anticipated with specific chemotherapeutic drugs. HFS can have a serious impact on quality of life and thus a patient’s ability to continue or complete treatment.

Awareness and early recognition are important to ensure timely treatment and avoidance of dose reductions or treatment discontinuation. Effective measures exist for prevention and treatment of HFS including routine podiatry visits, systemic and topical treatments, dose reductions, and switching to other drugs in the same class that have lower rates of HFS. These approaches allow patients to continue cancer treatment while reducing negative impacts on quality of life.