Palmar plantar erythrodysesthesia pathophysiology: Difference between revisions
Jump to navigation
Jump to search
Mchitsazan (talk | contribs) |
No edit summary |
||
| (13 intermediate revisions by 3 users not shown) | |||
| Line 1: | Line 1: | ||
__NOTOC__ | __NOTOC__ | ||
{{Palmar plantar erythrodysesthesia}} | {{Palmar plantar erythrodysesthesia}} | ||
{{CMG}}; {{AE}} | {{CMG}}; {{AE}} {{MC}} | ||
==Overview== | ==Overview== | ||
The exact [[pathogenesis]] of palmar plantar erythrodysesthesia (PPE) is not completely understood. It is thought that PPE is caused by direct [[Toxicity|toxic]] effect of the [[Chemotherapeutic agents|chemotherapeutic drugs]] against [[Keratinocyte|keratinocytes]], [[excretion]] of the [[drugs]] in [[eccrine sweat glands]], or [[Type I hypersensitivity reaction|type I allergic reaction]]. The [[pathological]] features of PPE are non-specific. However, since PPE involves a [[Cytotoxicity|cytotoxic]] [[reaction]] primarily affecting [[Keratinocyte|keratinocytes]], the [[Histopathology|histopathologic]] findings are similar to [[Histology|histologic]] manifestation of direct [[Toxicity|toxic]] [[Reaction|reactions]]. | |||
==Pathophysiology== | ==Pathophysiology== | ||
* Direct toxic effect of the chemotherapeutic | === Pathogenesis === | ||
* The exact [[pathogenesis]] of palmar plantar erythrodysesthesia (PPE) is not completely understood. | |||
* Suggested explanations include: | |||
:* Direct [[Toxicity|toxic]] effect of the [[Chemotherapeutic agent|chemotherapeutic drugs]] against [[Keratinocyte|epidermal cells (keratinocytes)]].<ref>{{Cite journal | |||
| author = [[J. E. Fitzpatrick]] | | author = [[J. E. Fitzpatrick]] | ||
| title = The cutaneous histopathology of chemotherapeutic reactions | | title = The cutaneous histopathology of chemotherapeutic reactions | ||
| Line 15: | Line 20: | ||
}}</ref> | }}</ref> | ||
* Concentration and excretion of cytotoxic | :*[[Concentration]] and [[excretion]] of [[Cytotoxicity|cytotoxic]] [[Drug|drugs]] in [[eccrine sweat glands]] causing damage or architectural insult.<ref name="pmid2061446">{{cite journal| author=Baack BR, Burgdorf WH| title=Chemotherapy-induced acral erythema. | journal=J Am Acad Dermatol | year= 1991 | volume= 24 | issue= 3 | pages= 457-61 | pmid=2061446 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2061446 }} </ref><ref>{{Cite journal | ||
}}</ref> <ref>{{Cite journal | |||
| author = [[Hiromi Tsuboi]], [[Kohzoh Yonemoto]] & [[Kensei Katsuoka]] | | author = [[Hiromi Tsuboi]], [[Kohzoh Yonemoto]] & [[Kensei Katsuoka]] | ||
| title = A case of bleomycin-induced acral erythema (AE) with eccrine squamous syringometaplasia (ESS) and summary of reports of AE with ESS in the literature | | title = A case of bleomycin-induced acral erythema (AE) with eccrine squamous syringometaplasia (ESS) and summary of reports of AE with ESS in the literature | ||
| Line 27: | Line 27: | ||
}}</ref> | }}</ref> | ||
* A type I (immunoglobulin E [IgE]-mediated) allergic reaction <ref>{{cite book | last = Perry | first = Michael | title = Chemotherapy source book | publisher = Wolters Kluwer Health/Lippincott Williams & Wilkins | location = Philadelphia | year = 2012 | isbn = 9781451101454 }}</ref> | :* A [[Type 1 hypersensitivity|type I (immunoglobulin E [IgE]-mediated) allergic reaction]]. This explanation is based on the occasional co-occurrence of [[facial]] [[erythema]]/[[edema]], [[Papule|papular]] [[rash]], and [[fever]].<ref>{{cite book | last = Perry | first = Michael | title = Chemotherapy source book | publisher = Wolters Kluwer Health/Lippincott Williams & Wilkins | location = Philadelphia | year = 2012 | isbn = 9781451101454 }}</ref> | ||
Unique characteristics of the palms and the soles which justify their involvement as the preferred sites of involvement include <ref>{{ | * Unique characteristics of the [[Palms of the hands|palms]] and the [[Sole (foot)|soles]] which justify their involvement as the preferred sites of involvement include: <ref name="pmid2061446">{{cite journal| author=Baack BR, Burgdorf WH| title=Chemotherapy-induced acral erythema. | journal=J Am Acad Dermatol | year= 1991 | volume= 24 | issue= 3 | pages= 457-61 | pmid=2061446 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2061446 }} </ref> <ref>{{Cite journal | ||
}}</ref> <ref>{{Cite journal | |||
| author = [[W. S. Susser]], [[D. L. Whitaker-Worth]] & [[J. M. Grant-Kels]] | | author = [[W. S. Susser]], [[D. L. Whitaker-Worth]] & [[J. M. Grant-Kels]] | ||
| title = Mucocutaneous reactions to chemotherapy | | title = Mucocutaneous reactions to chemotherapy | ||
| Line 47: | Line 42: | ||
}}</ref> | }}</ref> | ||
* High density of eccrine sweat glands <ref>{{ | :* High density of [[eccrine sweat glands]]<ref name="pmid2947543">{{cite journal| author=Cox GJ, Robertson DB| title=Toxic erythema of palms and soles associated with high-dose mercaptopurine chemotherapy. | journal=Arch Dermatol | year= 1986 | volume= 122 | issue= 12 | pages= 1413-4 | pmid=2947543 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2947543 }} </ref> | ||
:* Absence of [[Hair follicle|folliculo]]-[[Sebaceous gland|sebaceous]] units ([[Hair follicle|hair follicles]] and [[Sebaceous gland|sebaceous glands]])<ref name="pmid2947543">{{cite journal| author=Cox GJ, Robertson DB| title=Toxic erythema of palms and soles associated with high-dose mercaptopurine chemotherapy. | journal=Arch Dermatol | year= 1986 | volume= 122 | issue= 12 | pages= 1413-4 | pmid=2947543 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2947543 }} </ref> | |||
:* Thick [[stratum corneum]] <ref name="pmid2947543">{{cite journal| author=Cox GJ, Robertson DB| title=Toxic erythema of palms and soles associated with high-dose mercaptopurine chemotherapy. | journal=Arch Dermatol | year= 1986 | volume= 122 | issue= 12 | pages= 1413-4 | pmid=2947543 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2947543 }} </ref> | |||
:* Wide [[dermal papillae]] <ref name="pmid2947543">{{cite journal| author=Cox GJ, Robertson DB| title=Toxic erythema of palms and soles associated with high-dose mercaptopurine chemotherapy. | journal=Arch Dermatol | year= 1986 | volume= 122 | issue= 12 | pages= 1413-4 | pmid=2947543 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2947543 }} </ref> | |||
}}</ref> | :* High [[Cell growth|proliferation]] rate of [[Epidermis (skin)|epidermal]] [[Basal cell|basal cells]] | ||
* Absence of | :* The [[temperature]] and [[pressure gradient]] | ||
:*[[Gravitation]] forces | |||
:*[[Vascular]] [[anatomy]] peculiar to these areas | |||
:* In cases caused by [[capecitabine]], higher [[expression]] of the [[capecitabine]]-activating [[enzyme]] [[thymidine phosphorylase]] in the [[skin]] of the [[Palms of the hands|palms]]<ref name="pmid3855356">{{cite journal| author=Levine LE, Medenica MM, Lorincz AL, Soltani K, Raab B, Ma A| title=Distinctive acral erythema occurring during therapy for severe myelogenous leukemia. | journal=Arch Dermatol | year= 1985 | volume= 121 | issue= 1 | pages= 102-4 | pmid=3855356 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3855356 }} </ref> | |||
}}</ref> | ==Microscopic Pathology== | ||
* Thick stratum corneum <ref>{{ | |||
* The [[pathological]] features of PPE are non-specific. | |||
* However, since PPE involves a [[Cytotoxicity|cytotoxic]] [[reaction]] primarily affecting [[Keratinocyte|keratinocytes]], the [[Histopathology|histopathologic]] findings are similar to [[Histology|histologic]] manifestation of direct [[Toxicity|toxic]] [[Reaction|reactions]]: | |||
:* Dominantly an interface [[dermatitis]] with a [[Cell (biology)|cell]]-poor infiltrate | |||
}}</ref> | :* A variable degree of [[Epidermis (skin)|epidermal]] ([[Keratinocyte|keratinocytes]]) [[necrosis]]<ref name="pmid8468414">{{cite journal| author=Fitzpatrick JE| title=The cutaneous histopathology of chemotherapeutic reactions. | journal=J Cutan Pathol | year= 1993 | volume= 20 | issue= 1 | pages= 1-14 | pmid=8468414 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8468414 }} </ref> | ||
* Wide dermal papillae<ref>{{ | |||
* Generally, in mild [[Cytotoxicity|cytotoxic]] [[Reaction|reactions]] (PPE [[World Health Organization|WHO]] [[Grading (tumors)|grades]] 1 and 2), [[necrosis]] is restricted to [[Basal cell|basal keratinocytes]]. | |||
* In severe cytotoxic reactions ([[WHO|WHO grades]] 3 and 4) destruction of the entire [[Basal lamina|basal layer]] occurs, and a [[blister]] along with complete [[epidermal]] [[necrosis]] may also be seen.<ref name="pmid9643337">{{cite journal| author=Calista D, Landi C| title=Cytarabine-induced acral erythema: a localized form of toxic epidermal necrolysis? | journal=J Eur Acad Dermatol Venereol | year= 1998 | volume= 10 | issue= 3 | pages= 274-5 | pmid=9643337 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9643337 }} </ref> | |||
* Other [[Histology|histologic]] manifestations in [[Epidermis (skin)|epidermis]] include: | |||
}}</ref> | :*[[Vacuole|Vacuolar]] degeneration of the [[Stratum basale|basal cell layer of epidermis]] | ||
* High proliferation rate of epidermal basal cells | :* Mild [[Spongiosum|spongiosis]] | ||
* The temperature and pressure gradient | :*[[Hyperkeratosis]] | ||
* Gravitation forces | :* Lymphohistiocytic infiltrates | ||
* Vascular anatomy peculiar to these areas | :*[[Apoptosis]] of [[keratinocytes]] | ||
* In cases caused by capecitabine, higher expression of the capecitabine-activating enzyme thymidine phosphorylase in the skin of the palms< | :* Partial separation of the [[epidermis]] from the [[dermis]] | ||
*[[Dermal]] changes include: | |||
:*[[Superficial]] perivascular [[Infiltration (medical)|infiltration]] of [[dermis]] by [[Lymphocyte|lymphocytes]] and [[eosinophils]] | |||
:*[[Papillary]] [[dermal]] [[edema]] | |||
:*[[Neutropenia|Neutrophilic]] [[Eccrine sweat glands|eccrine]] [[hidradenitis]] | |||
:*[[Eccrine sweat glands|Eccrine]] [[squamous]] syringometaplasia, in severe PPE ([[WHO]] grades 3 and 4) | |||
<br /> | *[[Histological|Histologic]] evidence of small-[[Nerve fiber|fiber]] [[neuropathy]], as shown by reduced [[Epidermis (skin)|epidermal]] [[nerve fiber]] [[density]], has been suggested to be responsible for occurrence of [[neuropathic pain]], [[Dysesthesia|dysesthesias]], [[Paresthesia|paresthesias]], and [[temperature]] intolerance in PPE. <ref name="pmid19078798">{{cite journal| author=Stubblefield MD, Custodio CM, Kaufmann P, Dickler MN| title=Small-Fiber Neuropathy Associated with Capecitabine (Xeloda)-induced Hand-foot Syndrome: A Case Report. | journal=J Clin Neuromuscul Dis | year= 2006 | volume= 7 | issue= 3 | pages= 128-32 | pmid=19078798 | doi=10.1097/01.cnd.0000211401.19995.a2 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19078798 }} </ref><br /> | ||
==References== | ==References== | ||
{{reflist|3}} | {{reflist|3}} | ||
[[Category:Up-To-Date]] | |||
[[Category:Oncology]] | [[Category:Oncology]] | ||
[[Category:Medicine]] | [[Category:Medicine]] | ||
Latest revision as of 19:35, 17 July 2019
|
Palmar plantar erythrodysesthesia Microchapters |
|
Differentiating Palmar plantar erythrodysesthesia from other Diseases |
|---|
|
Diagnosis |
|
Treatment |
|
Palmar plantar erythrodysesthesia pathophysiology On the Web |
|
American Roentgen Ray Society Images of Palmar plantar erythrodysesthesia pathophysiology |
|
Palmar plantar erythrodysesthesia pathophysiology in the news |
|
Directions to Hospitals Treating Palmar plantar erythrodysesthesia |
|
Risk calculators and risk factors for Palmar plantar erythrodysesthesia pathophysiology |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mandana Chitsazan, M.D. [2]
Overview
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.
Pathophysiology
Pathogenesis
- The exact pathogenesis of palmar plantar erythrodysesthesia (PPE) is not completely understood.
- Suggested explanations include:
- Direct toxic effect of the chemotherapeutic drugs against epidermal cells (keratinocytes).[1]
- Concentration and excretion of cytotoxic drugs in eccrine sweat glands causing damage or architectural insult.[2][3]
- Unique characteristics of the palms and the soles which justify their involvement as the preferred sites of involvement include: [2] [5] [6]
- High density of eccrine sweat glands[7]
- Absence of folliculo-sebaceous units (hair follicles and sebaceous glands)[7]
- Thick stratum corneum [7]
- Wide dermal papillae [7]
- High proliferation rate of epidermal basal cells
- The temperature and pressure gradient
- Gravitation forces
- Vascular anatomy peculiar to these areas
- In cases caused by capecitabine, higher expression of the capecitabine-activating enzyme thymidine phosphorylase in the skin of the palms[8]
Microscopic Pathology
- 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:
- Dominantly an interface dermatitis with a cell-poor infiltrate
- A variable degree of epidermal (keratinocytes) necrosis[9]
- Generally, in mild cytotoxic reactions (PPE WHO grades 1 and 2), necrosis is restricted to basal keratinocytes.
- In severe cytotoxic reactions (WHO grades 3 and 4) destruction of the entire basal layer occurs, and a blister along with complete epidermal necrosis may also be seen.[10]
- Other histologic manifestations in epidermis include:
- Vacuolar degeneration of the basal cell layer of epidermis
- Mild spongiosis
- Hyperkeratosis
- Lymphohistiocytic infiltrates
- Apoptosis of keratinocytes
- Partial separation of the epidermis from the dermis
- Dermal changes include:
- Superficial perivascular infiltration of dermis by lymphocytes and eosinophils
- Papillary dermal edema
- Neutrophilic eccrine hidradenitis
- Eccrine squamous syringometaplasia, in severe PPE (WHO grades 3 and 4)
- Histologic evidence of small-fiber neuropathy, as shown by reduced epidermal nerve fiber density, has been suggested to be responsible for occurrence of neuropathic pain, dysesthesias, paresthesias, and temperature intolerance in PPE. [11]
References
- ↑ J. E. Fitzpatrick. "The cutaneous histopathology of chemotherapeutic reactions". Journal of cutaneous pathology. PMID 8468414.
- ↑ 2.0 2.1 Baack BR, Burgdorf WH (1991). "Chemotherapy-induced acral erythema". J Am Acad Dermatol. 24 (3): 457–61. PMID 2061446.
- ↑ Hiromi Tsuboi, Kohzoh Yonemoto & Kensei Katsuoka. "A case of bleomycin-induced acral erythema (AE) with eccrine squamous syringometaplasia (ESS) and summary of reports of AE with ESS in the literature". The Journal of dermatology. PMID 16361756.
- ↑ Perry, Michael (2012). Chemotherapy source book. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins. ISBN 9781451101454.
- ↑ W. S. Susser, D. L. Whitaker-Worth & J. M. Grant-Kels. "Mucocutaneous reactions to chemotherapy". Journal of the American Academy of Dermatology. PMID 10071309.
- ↑ Yvonne Lassere & Paulo Hoff. "Management of hand-foot syndrome in patients treated with capecitabine (Xeloda)". European journal of oncology nursing : the official journal of European Oncology Nursing Society. doi:10.1016/j.ejon.2004.06.007. PMID 15341880.
- ↑ 7.0 7.1 7.2 7.3 Cox GJ, Robertson DB (1986). "Toxic erythema of palms and soles associated with high-dose mercaptopurine chemotherapy". Arch Dermatol. 122 (12): 1413–4. PMID 2947543.
- ↑ Levine LE, Medenica MM, Lorincz AL, Soltani K, Raab B, Ma A (1985). "Distinctive acral erythema occurring during therapy for severe myelogenous leukemia". Arch Dermatol. 121 (1): 102–4. PMID 3855356.
- ↑ Fitzpatrick JE (1993). "The cutaneous histopathology of chemotherapeutic reactions". J Cutan Pathol. 20 (1): 1–14. PMID 8468414.
- ↑ Calista D, Landi C (1998). "Cytarabine-induced acral erythema: a localized form of toxic epidermal necrolysis?". J Eur Acad Dermatol Venereol. 10 (3): 274–5. PMID 9643337.
- ↑ Stubblefield MD, Custodio CM, Kaufmann P, Dickler MN (2006). "Small-Fiber Neuropathy Associated with Capecitabine (Xeloda)-induced Hand-foot Syndrome: A Case Report". J Clin Neuromuscul Dis. 7 (3): 128–32. doi:10.1097/01.cnd.0000211401.19995.a2. PMID 19078798.