Luciano Schiazza M.D.
c/o InMedica - Centro Medico Polispecialistico
Largo XII Ottobre 62
cell 335.655.97.70 - office 010 5701818



Hand-foot syndrome (HFS) is a dose-limiting cutaneous reaction localized on the palms of the hands and/or the soles of the feet as a toxic side effect of some types of chemotherapy or biologic therapy drugs used to treat cancer. It is never life threatening but can interfere with patient’s daily activity.

It may also be referred to as:

hand foot syndromeHand foot syndrome

(erythodysestesia=tingling sensation  progressing to severe pain and tenderness with erythema and edema)

It was first described by Zuehlke in 1974 associated with mitotane (Lysodren) therapy for the hypernephroma and definied by Burdgorf in 1982.

It has been estimated that HFS occurs in 6-64% of patient treated with different chemotherapy regimens, in nearly 80% of cases with less severe grades and 5% severe grade condition.

The HFS appears to be predominantly drug and dose dependent (peak plasma drug concentration, total cumulative dose, administration schedule) in its onset and severity.

Patients with HFS usually first note a prodrome of dysesthesia (impairment of sensitivity, especially to touch) or paresthesia (skin sensation such as burning, pricking, itching or tingling), characterized by a tingling sensation on the palms and soles, which progress over several days to a burning pain and well-definied symmetric erythema (sometimes particularly on the pads of the distal phalanges) and edema (swelling), sometimes with a fine desquamation.

The hands are usually more severally affected than the feet, or may be the only area involved.


HFS can progress from mild to moderate symptoms:

to severe symptoms

Usually two systems have been used for the classification of HFS: the NCI grading criteria and WHO grading criteria.
The NCI (National Cancer Institute) has a 3-grade classification system. The WHO (World Health Organisation) classification system is based on 4 grades.

National Cancer Institute classification system


Histologically, HFS has not specific findings: mild spongiosis, scattered necrotic and dysckeratotic keratinocytes, vacualar degeneration of the basal layer, papillary edema. A sparse superficial perivascular lymphohistiocytic infiltrate can be found in varying degrees in the epidermis. Basement membrane is intact and there is no damage to sweat gland or duct.

Some chemotherapy is more likely to cause HFS than others. The drugs known to cause HFS include:


But not everyone who is treated with these medications develops HFS, and the severity of HFS can vary from person to person, even among people taking the same medication for the same form of cancer.

HFS ususally first appear within days treatment (sorafenib, sunitinib, pazopanib) or after two-three months with other chemotherapies.

HFA occurs when small amounts of drug leak out of capillaries (small blood vessels) in the palms of the hands and soles of the feet: it can damage the sorrounding tissues and cause a range of symptoms.

There are ways to manage symptoms of HFS and prevent it from worsening.

For a period of time following treatment (approximately one week after IV medication, much as possible during the time taking oral medication) it is important to avoid activities that rub the skin of palms and soles, put pressure on the palms and soles and/or expose to heat, modifying some of  normal daily activity, because of the  increase of the amount of drug in the capillaries and the amount of drug linkage.


The following tips may help, first of all reducing friction and heat:


Because HFS can worsen  and have a considerable impact on the patient’s quality of life (QOL), disrupting patient’s ability to pursue normal daily activities, it is important to instruct patients regarding the possibility of HFS: they should be made aware of the first signs and symptoms.

HFS is manageable but if it is not recognized early and left untreated it can progress  rapidly from a mild cutaneous reactions to a painful, debilitating condition.

Early their communication to the doctor or  a member of the nursing staff help them to identify and grading of HFS, allowing care interventions to manage symptoms. In fact sooner implemented, there is a rapid reversal of signs and symptoms without conseguences.

In addition doctor can modify dose changing treatment schedule  with dose reduction, less frequent dosing or ultimately drug withdrawal until resolved or permanently if necessary to prevent worsening.

About treatment of HFS:

Pyridoxine (vit B6) may be beneficial as preventing measure when drugs with a strong association with HFS are going to be administred.