Palmar plantar erythrodysesthesia overview
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mandana Chitsazan, M.D. [2]
Overview
Palmar plantar erythrodysesthesia (PPE), also known as hand-foot syndrome, is a dermatological side effect of a number of chemotherapeutic drugs. Estimated incidence of PPE is 6 to 64% of patients treated with chemotherapeutic drugs. Most frequently associated drugs include cytarabine, docetaxel, doxorubicin, liposome-encapsulated doxorubicin, 5-fluorouracil, and capecitabine. The exact pathogenesis of PPE is not completely understood. PPE must be differentiated from Graft-Versus-Host Disease (GVHD). Dose reduction, lengthening the interval between dose administration, and ultimately drug withdrawal are most effective strategies. Specific treatments include cooling the extremities during drug administration, vitamin B6, topical and oral corticosteroids, and topical 99% dimethyl sulfoxide. Prognosis is generally good and symptoms usually resolve within 1-2 weeks after stopping the causative chemotherapeutic agent. If left untreated, PPE can progress rapidly. Avoiding excessive manual work and walking, wound care to prevent infection, limb elevation, cold compresses, avoiding extreme temperatures, analgesics, creams and emollients are suggested to prevent, delay onset, and/or decrease the severity of PPE.
Historical Perspective
In 1974, Zuehlke was the first to describe PPE in a patient receiving mitotane for hypernephroma.
Classification
A number of different classifications have been used for grading the severity of PPE. The classifications suggested by the National Cancer Institute (NCI), and the World Health Organization are the two most commonly used.
Pathophysiology
The exact pathogenesis of PPE is not completely understood. It is thought that PPE is caused by direct toxic effect of the chemotherapeutic drugs against keratinocytes, excretion of the drugs in eccrine sweat glands, or type I allergic reaction. Unique characteristics of the palms and soles that justify their involvement in PPE. The pathological features of PPE are non-specific. However, since PPE involves a cytotoxic reaction primarily affecting keratinocytes the histopathologic findings are similar to histologic manifestation of direct toxic reactions.
Causes
Several different chemotherapeutic agents have been associated with PPE. Most frequently associated drugs include cytarabine, docetaxel, doxorubicin, liposome-encapsulated doxorubicin, 5-fluorouracil, and capecitabine.
Differentiating Palmar plantar erythrodysesthesia from Other Diseases
PPE must be differentiated from Graft-Versus-Host Disease (GVHD).
Epidemiology and Demographics
Estimated incidence of PPE is 6 to 64% of patients treated with chemotherapeutic drugs. However, the exact incidence of PPE is unknown, as most reports are isolated case reports or short case series.
Risk Factors
The most common and established risk factors are chemotherapeutic agents. The severity of the condition depends on the dose and frequency of the agent.
Natural History, Complications, and Prognosis
Prognosis is generally good and symptoms usually resolve within 1-2 weeks after stopping the causative chemotherapeutic agent. If left untreated, PPE can progress rapidly. PPE is not life-threatening, but it can be very debilitating and impair quality of life.
Diagnosis
History and Symptoms
The most common symptoms of PPE include tingling, burning pain, edema, and erythema. Less common symptoms of PPE include sensory impairment, paresthesia, and pruritus.
Physical Examination
Determination of toxicity grading of PPE requires both visual assessment and patient description of symptoms.
Laboratory Findings
There are no diagnostic laboratory findings associated with PPE.
X-ray
There are no x-ray findings associated with PPE.
CT scan
There are no CT scan findings associated with PPE.
MRI
There are no MRI findings associated with PPE.
Treatment
Medical Therapy
Dose reduction, lengthening the interval between dose administration, and ultimately drug withdrawal are most effective strategies. Specific treatments include cooling the extremities during drug administration, vitamin B6, topical and oral corticosteroids, and topical 99% dimethyl sulfoxide.
Surgery
Surgical intervention is not recommended for the management of PPE.
Primary Prevention
Avoiding excessive manual work and walking, wound care to prevent infection, limb elevation, cold compresses, avoiding extreme temperatures, analgesics, creams and emollients are suggested to prevent, delay onset, and/or decrease the severity of PPE.