Palmar Plantar Erythrodysesthesia: Difference between revisions
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==Causes== | ==Causes== | ||
===Risk Factors=== | ===Risk Factors=== | ||
The occurrence of this condition has been linked to dose and prolonged chemotherapeutic drug exposure especially with more continuous IV infusion, daily ingestion and liposomal encapsulationg of PLD which prolong half-life of drug. The use of cooling mechanism, higher number of PLD cycles, and occurrence of mucositis, neutropenia and peripheral neuropathy are possible predictors of PPE. <ref name="pmid194468682">{{cite journal| author=Tanyi JL, Smith JA, Ramos L, Parker CL, Munsell MF, Wolf JK| title=Predisposing risk factors for palmar-plantar erythrodysesthesia when using liposomal doxorubicin to treat recurrent ovarian cancer. | journal=Gynecol Oncol | year= 2009 | volume= 114 | issue= 2 | pages= 219-24 | pmid=19446868 | doi=10.1016/j.ygyno.2009.04.007 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19446868 }}</ref> | |||
===Genetics=== | ===Genetics=== | ||
===Common Causes=== | ===Common Causes=== | ||
Revision as of 20:36, 3 September 2018
For patient information, click Insert page name here
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Synonyms and keywords:Palmar plantar erythrodysesthesia, Palmar-Plantar Erythrodysesthesia; Palmoplantar Erythrodysesthesia; Hand-Foot Syndrome, peculiar AE, chemotherapy-induced AE, toxic erythema of the palms and soles, palmar-plantar erythema, and Burgdorf’s reaction.
Overview
Palmar Plantar Erythrodysesthesia or Hand-Foot syndrome is a skin-related reaction to chemotherapy and other drugs used to treat patients with cancer.
Historical Perspective
In 1975, Zuehlke[1] reported the first case of Palmar Plantar Erythrodysesthesia due to chemotherapy.
Classification
Palmar Plantar Erythrodysesthesia may be classified according to toxicity or severity of symptoms into 4 grades.
| GRADES | |
|---|---|
| 1 | Mild erythema, edema, or desquamation that doesn't interfere with daily activities |
| 2 | Blisters or ulcers <2 cm diameter; Erythema edema or desquamation complication but not precluding daily activities. |
| 3 | Blisters, ulcers or edema that interfere with daily activities; Person cannot wear regular clothing. |
| 4 | Lesions complicated with infection; hospitalized or bed ridden |
Pathophysiology
The pathophysiologic mechanism of Palmar Plantar Erythrodysesthesia is under active investivation. Factors that have been implicated involve rapid cell diision in palms and soles, gravitational forces, vascular anatomy peculiar to these areas and tempereature gradients that may be present in distal end of extremities. The higher drug concentration in the eccrine glands of palms and soles also play a role in this condition.
Associated Conditions
Palmar Plantar Erythrodysesthesia is commonly associated with chemotherapy that is used for the treatment of different cancers.
Gross Pathology
The hands are more commonly affected than the feet. The lesion starts of as an abnormal sensation in the palms and soles. Then it matures into painful, tingling, symmetric, well-demarcated swelling and erythematous plaques. This is then followed by a desquamative phase that happens on resolution. [3]
Microscopic Pathology
On histopathology non-specific features seen in Palmar Plantar Erythrodysesthesia. Features include[2]:
- Vacuolar degenration of the basal cell layer
- Mild spongiosis, keratinocytes necrosis
- Papillary dermal edema
- Lymphocytic infiltrates
- Partial separation of epidermis from the dermis
- Dermis shows perivascular infiltrates made up of eosinphils and lymphocytes
- May have presence of eccrine squamous syringometaplasia or netruophilic eccrine hidradenitis.
- Some data suggests that small-fibre neuropathy may cause the pain and dysesthesia.
Causes
Risk Factors
The occurrence of this condition has been linked to dose and prolonged chemotherapeutic drug exposure especially with more continuous IV infusion, daily ingestion and liposomal encapsulationg of PLD which prolong half-life of drug. The use of cooling mechanism, higher number of PLD cycles, and occurrence of mucositis, neutropenia and peripheral neuropathy are possible predictors of PPE. [4]
Genetics
Common Causes
- Several different Chemotherapeutic agents have been associated with acral erythema[5]. Common ones are listed below.
Less Common Causes
| Cardiovascular | No underlying causes |
| Chemical / poisoning | No underlying causes |
| Dermatologic | No underlying causes |
| Drug Side Effect | No underlying causes |
| Ear Nose Throat | No underlying causes |
| Endocrine | No underlying causes |
| Environmental | No underlying causes |
| Gastroenterologic | No underlying causes |
| Genetic | No underlying causes |
| Hematologic | No underlying causes |
| Iatrogenic | No underlying causes |
| Infectious Disease | No underlying causes |
| Musculoskeletal / Ortho | No underlying causes |
| Neurologic | No underlying causes |
| Nutritional / Metabolic | No underlying causes |
| Obstetric/Gynecologic | No underlying causes |
| Oncologic | No underlying causes |
| Opthalmologic | No underlying causes |
| Overdose / Toxicity | No underlying causes |
| Psychiatric | No underlying causes |
| Pulmonary | No underlying causes |
| Renal / Electrolyte | No underlying causes |
| Rheum / Immune / Allergy | No underlying causes |
| Sexual | No underlying causes |
| Trauma | No underlying causes |
| Urologic | No underlying causes |
| Dental | No underlying causes |
| Miscellaneous | No underlying causes |
Causes in Alphabetical Order
- 5-Flurouracil[6]
- Capecitabine[8]
- Capacitabine-based chemotherapy[9]
- Cytarabine[6]
- Docetaxel[8]
- Doxorubicin (Pegylated liposomal Doxorubicin)[6]
- Gemcitabine[8]
- Methotrexate - even low dose used to treat ALL[7]
- Mitotane[1]
- PLD[8]
- Sorafenib[8]
- Vinorelbine[8]
Differentiating Palmar Plantar Erythrosysesthesia from other Diseases
- Palmar Plantar Erythrosysesthesia must be differentiated from Tinea manuum which can also present in patients being treated with chemotherapy. Tinea Manuum infection responds to antifungal therapy.
- It should be differentiated from Acute Graft Versus Host Response commonly seen in bone marrow transplanted patients who are on chemotherapy such as in leukemia.[11] In graft-versus-host disease the condition progresses to involve other regions of the body. Palmar Plantar Erythrosysesthesia, on the the other hand is limited to hands and feet. Differentiating the two disorders is possible with serial biopsies every 3 - 5 days.[12]
Epidemiology and Demographics
Age
Gender
Race
Developed Countries
Developing Countries
Risk Factors
The occurrence of this condition has been linked to dose and prolonged chemotherapeutic drug exposure especially with more continuous IV infusion, daily ingestion and liposomal encapsulationg of PLD which prolong half-life of drug. The use of cooling mechanism, higher number of PLD cycles, and occurrence of mucositis, neutropenia and peripheral neuropathy are possible predictors of PPE.[13]
Screening
Natural History, Complications and Prognosis
Initially, the patient of Palmar Plantar Erythrosysesthesia experiences a sensation of numbness/tingling in the palms and soles. This progresses into a painful, tingling, symmetric, well-demarcated swelling with an erythematous plaques. It is followed by a phase of desquamation upon resolution.[14]
Diagnosis
Diagnostic Criteria
In cancer patients receiving chemotherapy, swelling of hands and feet that is painful is enough to make the diagnosis. The differentials stated above should also be considered.
History
A directed history should be obtained to ascertain
Symptoms
"Type symptom here" is pathognomonic of the "type disease name here".
Erythematous changes of the palms with associated oedema, blistering and desquamation[15].
Past Medical History
Family History
Social History
Occupational
Alcohol
The frequency and amount of alcohol consumption should be characterized.
Drug Use
Smoking
Allergies
Physical Examination
Appearance of the Patient
Vital Signs
Skin
Head
Eyes
Ear
Nose
Mouth
Throat
Heart
Lungs
Abdomen
Extremities
Neurologic
Genitals
Other
Laboratory Findings
Electrolyte and Biomarker Studies
Electrocardiogram
Chest X Ray
CT
MRI
Echocardiography or Ultrasound
Other Imaging Findings
Other Diagnostic Studies
Treatment
Pharmacotherapy
Acute Pharmacotherapies
Chronic Pharmacotherapies
Surgery and Device Based Therapy
Indications for Surgery
Pre-Operative Assessment
Post-Operative Management
Transplantation
Primary Prevention
Secondary Prevention
- Dr Kuznecovs with his colleagues came to the conclusion that atorvastatin and polyprenol combination can prevent PPE due to capecitabine. https://www.medscape.com/viewarticle/848530
- Application of ointment containing antioxidants with high radical protection factors can effectively prevent the development of PPE.[16]
Cost-Effectiveness of Therapy
Future or Investigational Therapies
References
- ↑ 1.0 1.1 1.2 Zuehlke RL (1974). "Erythematous eruption of the palms and soles associated with mitotane therapy". Dermatologica. 148 (2): 90–2. PMID 4276191.
- ↑ 2.0 2.1 Farr KP, Safwat A (2011). "Palmar-plantar erythrodysesthesia associated with chemotherapy and its treatment". Case Rep Oncol. 4 (1): 229–35. doi:10.1159/000327767. PMC 3085037. PMID 21537373.
- ↑ "Acral Erythema - Holland-Frei Cancer Medicine - NCBI Bookshelf".
- ↑ Tanyi JL, Smith JA, Ramos L, Parker CL, Munsell MF, Wolf JK (2009). "Predisposing risk factors for palmar-plantar erythrodysesthesia when using liposomal doxorubicin to treat recurrent ovarian cancer". Gynecol Oncol. 114 (2): 219–24. doi:10.1016/j.ygyno.2009.04.007. PMID 19446868.
- ↑ Baack BR, Burgdorf WH (1991). "Chemotherapy-induced acral erythema". J Am Acad Dermatol. 24 (3): 457–61. PMID 2061446.
- ↑ 6.0 6.1 6.2 6.3 Webster-Gandy JD, How C, Harrold K (2007). "Palmar-plantar erythrodysesthesia (PPE): a literature review with commentary on experience in a cancer centre". Eur J Oncol Nurs. 11 (3): 238–46. doi:10.1016/j.ejon.2006.10.004. PMID 17350337.
- ↑ 7.0 7.1 Wysocki M, Nowaczyk-Michalak A, Pilecki O, Kurylak A, Balcar-Boroń A, Trybuś L (1992). "[Burgdorf's reaction (painful acral erythema) in patients with acute lymphoblastic leukemia following medium-dose methotrexate therapy]". Wiad Lek. 45 (11–12): 462–4. PMID 1441532.
- ↑ 8.0 8.1 8.2 8.3 8.4 8.5 8.6 Farr KP, Safwat A (2011). "Palmar-plantar erythrodysesthesia associated with chemotherapy and its treatment". Case Rep Oncol. 4 (1): 229–35. doi:10.1159/000327767. PMC 3085037. PMID 21537373.
- ↑ 9.0 9.1 Krikorian A, Rahmani R, Bromet M, Bore P, Cano JP (1989). "Pharmacokinetics and metabolism of Navelbine". Semin Oncol. 16 (2 Suppl 4): 21–5. PMID 2652317.
- ↑ Harris CS, Wang D, Carulli A (2014). "Docetaxel-associated palmar-plantar erythrodysesthesia: a case report and review of the literature". J Oncol Pharm Pract. 20 (1): 73–80. doi:10.1177/1078155213475466. PMID 23478198.
- ↑ Demirçay Z, Gürbüz O, Alpdoğan TB, Yücelten D, Alpdoğan O, Kurtkaya O; et al. (1997). "Chemotherapy-induced acral erythema in leukemic patients: a report of 15 cases". Int J Dermatol. 36 (8): 593–8. PMID 9329890.
- ↑ Crider MK, Jansen J, Norins AL, McHale MS (1986). "Chemotherapy-induced acral erythema in patients receiving bone marrow transplantation". Arch Dermatol. 122 (9): 1023–7. PMID 3527075.
- ↑ Tanyi JL, Smith JA, Ramos L, Parker CL, Munsell MF, Wolf JK (2009). "Predisposing risk factors for palmar-plantar erythrodysesthesia when using liposomal doxorubicin to treat recurrent ovarian cancer". Gynecol Oncol. 114 (2): 219–24. doi:10.1016/j.ygyno.2009.04.007. PMID 19446868.
- ↑ "Acral Erythema - Holland-Frei Cancer Medicine - NCBI Bookshelf".
- ↑ Wysocki M, Nowaczyk-Michalak A, Pilecki O, Kurylak A, Balcar-Boroń A, Trybuś L (1992). "[Burgdorf's reaction (painful acral erythema) in patients with acute lymphoblastic leukemia following medium-dose methotrexate therapy]". Wiad Lek. 45 (11–12): 462–4. PMID 1441532.
- ↑ Lademann J, Martschick A, Kluschke F, Richter H, Fluhr JW, Patzelt A; et al. (2014). "Efficient prevention strategy against the development of a palmar-plantar erythrodysesthesia during chemotherapy". Skin Pharmacol Physiol. 27 (2): 66–70. doi:10.1159/000351801. PMID 23969763.