Palmar plantar erythrodysesthesia overview: Difference between revisions

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{{CMG}}; {{AE}} {{MC}}
{{CMG}}; {{AE}} {{MC}}
==Overview==
==Overview==
Palmar plantar erythrodysesthesia (PPE), also known as hand-foot syndrome, is a [[dermatological]] [[Side effects|side effect]] of a number of [[Chemotherapeutic agent|chemotherapeutic drugs]]. Estimated [[incidence]] of PPE is 6 to 64% of patients treated with [[Chemotherapeutic agent|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|Graft-Versus-Host Disease]] ([[GVHD]]). [[Dose]] reduction, lengthening the interval between dose administration, and ultimately [[drug withdrawal]] are most effective strategies. Specific treatments include [[Cold compression therapy|cooling]] the [[extremities]] during drug administration, [[vitamin B6]], [[topical]] and [[oral]] [[Corticosteroid|corticosteroids]], and [[topical]] 99% [[dimethyl sulfoxide]]. [[Prognosis]] is generally good and [[Symptom|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 compression therapy|cold compresses]], avoiding extreme [[temperatures]], [[Analgesic|analgesics]], creams and [[Emollient|emollients]] are suggested to [[Prevention|prevent]], delay onset, and/or decrease the severity of PPE.
Palmar plantar erythrodysesthesia (PPE), also known as hand-foot syndrome, is a [[dermatological]] [[Side effects|side effect]] of a number of [[Chemotherapeutic agent|chemotherapeutic drugs]]. Estimated [[incidence]] of PPE is 6 to 64% of patients treated with [[Chemotherapeutic agent|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|Graft-Versus-Host Disease]] ([[GVHD]]). [[Dose]] reduction, lengthening the interval between [[dose]] administration, and ultimately [[drug withdrawal]] are most effective strategies. Specific treatments include [[Cold compression therapy|cooling]] the [[extremities]] during drug administration, [[vitamin B6]], [[topical]] and [[oral]] [[Corticosteroid|corticosteroids]], and [[topical]] 99% [[dimethyl sulfoxide]]. [[Prognosis]] is generally good and [[Symptom|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 compression therapy|cold compresses]], avoiding extreme [[temperatures]], [[Analgesic|analgesics]], creams and [[Emollient|emollients]] are suggested to [[Prevention|prevent]], delay onset, and/or decrease the severity of PPE.


==Historical Perspective==
==Historical Perspective==
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==Classification==
==Classification==
A number of different [[Classification|classifications]] have been used for [[Grading (tumors)|grading]] the severity of Palmar plantar erythrodysesthesia. The [[Classification|classifications]] suggested by the [[National Cancer Institute]] (NCI), and the [[World Health Organization]] are the two most commonly used.
A number of different [[Classification|classifications]] have been used for [[Grading (tumors)|grading]] the severity of PPE. The [[Classification|classifications]] suggested by the [[National Cancer Institute]] (NCI), and the [[World Health Organization]] are the two most commonly used.


==Pathophysiology==
==Pathophysiology==
The exact [[pathogenesis]] of palmar plantar erythrodysesthesia is not completely understood. It is thought that PPE is caused by direct [[toxic]] effect of the [[Chemotherapeutic agent|chemotherapeutic drugs]] against [[Keratinocyte|keratinocytes]], excretion of the drugs in [[eccrine sweat glands]], or [[Type I hypersensitivity reaction|type I allergic reaction]]. Unique characteristics of the [[Palms of the hands|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 [[Keratinocyte|keratinocytes]] the [[histopathologic]] findings are similar to [[histologic]] manifestation of direct [[toxic]] [[Reaction|reactions]].
The exact [[pathogenesis]] of PPE is not completely understood. It is thought that PPE is caused by direct [[toxic]] effect of the [[Chemotherapeutic agent|chemotherapeutic drugs]] against [[Keratinocyte|keratinocytes]], excretion of the drugs in [[eccrine sweat glands]], or [[Type I hypersensitivity reaction|type I allergic reaction]]. Unique characteristics of the [[Palms of the hands|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 [[Keratinocyte|keratinocytes]] the [[histopathologic]] findings are similar to [[histologic]] manifestation of direct [[toxic]] [[Reaction|reactions]].


==Causes==
==Causes==
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==Risk Factors==
==Risk Factors==
The most common and established [[Risk factor|risk factors]] are [[chemotherapeutic agents]]. The severity of the condition depends on the [[dose]] and [[frequency]] of the agent.
The most common and established [[Risk factor|risk factors]] are [[chemotherapeutic agents]]. The severity of the [[condition]] depends on the [[dose]] and [[frequency]] of the agent.


==Natural History, Complications, and Prognosis==
==Natural History, Complications, and Prognosis==
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===Laboratory Findings===
===Laboratory Findings===
There are no diagnostic laboratory findings associated with PPE.
There are no diagnostic [[laboratory]] findings associated with PPE.


===X-ray===
===X-ray===

Revision as of 19:55, 16 July 2019

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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.