HAND-FOOT SYNDROME DUE TO CAPECITABINE

Hand-foot syndrome, also known as Palmar-Plantar Erythrodysesthesia is a side-effect which mostly occurs with chemotherapy or biologic therapy. In mild to moderate cases, there may be painful erythema and edema, various degrees of dysesthesia, which may be followed by dry or moist desquamation of the palms and the soles. In more severe cases, there may be cracking, flaking, peeling of skin, blisters, ulcers and severe pain. These may interfere with the daily activities.¹

It was first reported by Lokich and Moore in 1984 with 5-flurouracil.² Drugs that have been associated include 5-FU, capecitabine, cytarabine, doxorubicin, epirubicin, high-dose Interleukin-2, fluorodeoxyuridine (FUDR), hydroxyurea, mercaptopurine, cyclophosphamide and docetaxel.

We document a case of hand-foot syndrome caused by capecitabine. A 50-year-old female patient was operated for moderately differentiated adenocarcinoma of the common bile duct (cholangiocarcinoma). Post-procedural ultrasound of the abdomen was suggestive of a space occupying lesion (SOL) of altered echotexture measuring 2.3 cm in the left lobe of the liver and a mixed echogenic mass of size 4 cm in the right ovary. Positron Emission Tomography scan and MRI-Fluorodeoxyglucose scan was suggestive of metastasis. Multiple nodal metastases were seen in the peripancreatic, gastrosplenic, cardiophrenic, celiac, aortocaval, supraclavicular, right axillary nodes and in the abdominal wall on both sides.

In view of metastasis, the patient was started on Tab. Capecitabine (500 mg) 4 bid for two cycles. After the second cycle, patient was referred to us for blackish discoloration of the palms and soles, painful shedding of nails, erosions and ulcerations on the medial aspect and ball of the great toes. On examination, patient had hyperpigmentation and dryness of skin with fissuring of palms and soles. There was loss of nails and ulcerations over the great toes (Fig. 1).

Fig. 1.

Dry, hyperpigmented palms and soles with ulceration over great toes with capecitabine therapy

Patient was diagnosed as a case of hand-foot syndrome. Patient was treated with topical and systemic antibiotics. She was advised to put her hand in lukewarm water daily for 5-10 min and liquid paraffin for local application. The dosage of Tab. capecitabine (500 mg) was reduced to 3 bid for two cycles followed by 3-0-2 for four cycles since the metastatic lesions had reduced. After stopping the drugs, the pigmentation and dryness decreased with resolution of ulceration in three months (Fig. 2).

Fig. 2.

Resolution of dryness, pigmentation and ulceration after three months of stopping capecitabine

Capecitabine is a systemic prodrug of 5-fluorouracil (5-FU). Hand-foot syndrome has proven to be a dose limiting toxicity of capecitabine, leading to significant morbidity. The pathophysiology of the hand-foot syndrome is largely unknown. Histopathological changes include vacuolar degeneration of basal keratinocytes, dermal perivascular lymphocytic infiltration, apoptotic keratinocytes and dermal edema.³ Treatment includes topical emollient, antibiotics to prevent secondary infection, topical steroid, Vitamin B₆⁴ and discontinuation of the offending drug in severe cases. In case of relapse on withdrawal, the offending drug may be cautiously re-introduced in a lower dose, which may gradually be stepped up.