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. In 1974, Zuehlke was the first to describe palmar plantar erythrodysesthesia (PPE) in a patient receiving mitotane for hypernephroma. A number of different classifications have been used for grading the severity of palmar plantar erythrodysesthesia (PPE). The classifications suggested by the National Cancer Institute (NCI), and the World Health Organization (WHO) are the two most commonly used. The exact pathogenesis of palmar plantar erythrodysesthesia (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. 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. Several different chemotherapeutic agents have been associated with palmar plantar erythrodysesthesia (PPE). Most frequently associated drugs include cytarabine, docetaxel, doxorubicin, liposomal-encapsulated doxorubicin, 5-fluorouracil, and capecitabine. Palmar plantar erythrodysesthesia (PPE) must be differentiated from other skin disorders that involve palms and/or soles, such as Graft-versus-host disease, contact dermatitis, palmoplantar plaque psoriasis, dyshidrotic eczema, and palmoplantar pustulosis. Palmar plantar erythrodysesthesia (PPE) has been reported to occur in 6 - 64% of patients treated with different chemotherapy regimens. However, the exact incidence of PPE is unknown, as most reports are isolated case reports or short case series. The most common and established risk factors are chemotherapeutic agents. The severity of the condition depends on the dose and frequency of the agent. There is insufficient evidence to recommend routine screening for palmar plantar erythrodysesthesia. Prognosis is generally good and symptoms usually resolve within 1 - 2 weeks after stopping the causative chemotherapeutic agent. If left untreated, palmar plantar erythrodysesthesia (PPE) can progress rapidly. PPE is not life-threatening, but it can be very debilitating and can significantly impair quality of life. There is no single diagnostic study of choice for the diagnosis of palmar plantar erythrodysesthesia (PPE). PPE is primarily diagnosed based on the history and clinical presentation. 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 of patients with PPE depends on the grade of the disease. Determination of toxicity grading of PPE requires both visual assessment and patient description of symptoms. Skin findings include erythema, edema, hyperkeratosis, peeling, blisters, bleeding, and fissures. There are no diagnostic laboratory findings associated with palmar plantar erythrodysesthesia. There are no ECG findings associated with palmar plantar erythrodysesthesia. There are no x-ray findings associated with palmar plantar erythrodysesthesia. There are no echocardiography/ultrasound findings associated with palmar plantar erythrodysesthesia. There are no CT scan findings associated with palmar plantar erythrodysesthesia. There are no MRI findings associated with palmar plantar erythrodysesthesia. There are no other imaging findings associated with palmar plantar erythrodysesthesia. There are no other diagnostic studies associated with palmar plantar erythrodysesthesia. Dose reduction, lengthening the interval between dose administration, and ultimately drug withdrawal are the most effective strategies. Specific treatment strategies include cooling the extremities during drug administration, vitamin B6, topical and oral corticosteroids, and topical 99% dimethyl sulfoxide. Surgical intervention is not recommended for the management of palmar plantar erythrodysesthesia. Avoiding excessive manual work and walking, wound care to prevent infection, limb elevation, cold compresses, avoiding extreme temperatures, analgesics, and creams/emollients are suggested to prevent, delay onset, and/or decrease the severity of palmar plantar erythrodysesthesia (PPE). There are no established measures for the secondary prevention of palmar plantar erythrodysesthesia.
Historical Perspective
In 1974, Zuehlke was the first to describe palmar plantar erythrodysesthesia (PPE) in a patient receiving mitotane for hypernephroma.
Classification
A number of different classifications have been used for grading the severity of palmar plantar erythrodysesthesia (PPE). The classifications suggested by the National Cancer Institute (NCI), and the World Health Organization (WHO) are the two most commonly used.
Pathophysiology
The exact pathogenesis of palmar plantar erythrodysesthesia (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. 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 palmar plantar erythrodysesthesia (PPE). Most frequently associated drugs include cytarabine, docetaxel, doxorubicin, liposomal-encapsulated doxorubicin, 5-fluorouracil, and capecitabine.
Differentiating Palmar plantar erythrodysesthesia from Other Diseases
Palmar plantar erythrodysesthesia (PPE) must be differentiated from other skin disorders that involve palms and/or soles, such as Graft-versus-host disease, contact dermatitis, palmoplantar plaque psoriasis, dyshidrotic eczema, and palmoplantar pustulosis.
Epidemiology and Demographics
Palmar plantar erythrodysesthesia (PPE) has been reported to occur in 6 - 64% of patients treated with different chemotherapy regimens. 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.
Screening
There is insufficient evidence to recommend routine screening for palmar plantar erythrodysesthesia.
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, palmar plantar erythrodysesthesia (PPE) can progress rapidly. PPE is not life-threatening, but it can be very debilitating and can significantly impair quality of life.
Diagnosis
Diagnostic Study of Choice
There is no single diagnostic study of choice for the diagnosis of palmar plantar erythrodysesthesia (PPE). PPE is primarily diagnosed based on the history and clinical presentation.
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
Physical examination of patients with PPE depends on the grade of the disease. Determination of toxicity grading of PPE requires both visual assessment and patient description of symptoms. Skin findings include erythema, edema, hyperkeratosis, peeling, blisters, bleeding, and fissures.
Laboratory Findings
There are no diagnostic laboratory findings associated with palmar plantar erythrodysesthesia.
Electrocardiogram
There are no ECG findings associated with palmar plantar erythrodysesthesia.
X-ray
There are no x-ray findings associated with palmar plantar erythrodysesthesia.
Echocardiography/Ultrasound
There are no echocardiography/ultrasound findings associated with palmar plantar erythrodysesthesia.
CT scan
There are no CT scan findings associated with palmar plantar erythrodysesthesia.
MRI
There are no MRI findings associated with palmar plantar erythrodysesthesia.
Other Imaging Findings
There are no other imaging findings associated with palmar plantar erythrodysesthesia.
Other Diagnostic Studies
There are no other diagnostic studies associated with palmar plantar erythrodysesthesia.
Treatment
Medical Therapy
Dose reduction, lengthening the interval between dose administration, and ultimately drug withdrawal are the most effective strategies. Specific treatment strategies 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 palmar plantar erythrodysesthesia.
Primary Prevention
Avoiding excessive manual work and walking, wound care to prevent infection, limb elevation, cold compresses, avoiding extreme temperatures, analgesics, and creams/emollients are suggested to prevent, delay onset, and/or decrease the severity of palmar plantar erythrodysesthesia (PPE).
Secondary Prevention
There are no established measures for the secondary prevention of palmar plantar erythrodysesthesia.