Palmar plantar erythrodysesthesia pathophysiology: Difference between revisions

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{{Palmar plantar erythrodysesthesia}}
{{Palmar plantar erythrodysesthesia}}
{{CMG}}; {{AE}}  
{{CMG}}; {{AE}} {{MC}}
 
==Overview==
==Overview==
The exact pathogenesis of [disease name] is not fully understood.
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]].
 
OR
 
It is thought that [disease name] is the result of / is mediated by / is produced by / is caused by either [hypothesis 1], [hypothesis 2], or [hypothesis 3].
 
OR
 
[Pathogen name] is usually transmitted via the [transmission route] route to the human host.
 
OR
 
Following transmission/ingestion, the [pathogen] uses the [entry site] to invade the [cell name] cell.
 
OR
 
 
[Disease or malignancy name] arises from [cell name]s, which are [cell type] cells that are normally involved in [function of cells].
 
OR
 
The progression to [disease name] usually involves the [molecular pathway].
 
OR
 
The pathophysiology of [disease/malignancy] depends on the histological subtype.


==Pathophysiology==
==Pathophysiology==
The exact pathogenesis of palmar plantar dysesthesia is not completely understood. Suggested explanations include:


* Direct toxic effect of the chemotherapeutic drug against epidermal cells (keratinocytes) <sup>2,3</sup>
=== Pathogenesis ===


* Concentration and excretion of cytotoxic drug in eccrine sweat glands causing damage or alteration in these structures <sup>4,5</sup>
* The exact [[pathogenesis]] of palmar plantar erythrodysesthesia (PPE) is not completely understood.
* Suggested explanations include:


* A type I (immunoglobulin E [IgE]-mediated) allergic reaction<sup>6</sup>, suggested based on the occasional co-occurrence of facial erythema/edema, papular rash, and fever.
:* Direct [[Toxicity|toxic]] effect of the [[Chemotherapeutic agent|chemotherapeutic drugs]] against [[Keratinocyte|epidermal cells (keratinocytes)]].<ref>{{Cite journal
| author = [[J. E. Fitzpatrick]]
| title = The cutaneous histopathology of chemotherapeutic reactions
| journal = [[Journal of cutaneous pathology]]
| pmid = 8468414
}}</ref>


:*[[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
| 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
| journal = [[The Journal of dermatology]]
| pmid = 16361756
}}</ref>


Unique characteristics of the palms and the soles which justify their involvement as the preferred sites of involvement include<sup>4,7,8</sup>: 
:* 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>


·       High density of eccrine sweat glands<sup>9</sup>  
* 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
| author = [[W. S. Susser]], [[D. L. Whitaker-Worth]] & [[J. M. Grant-Kels]]
| title = Mucocutaneous reactions to chemotherapy
| journal = [[Journal of the American Academy of Dermatology]]
| pmid = 10071309
}}</ref> <ref>{{Cite journal
| author = [[Yvonne Lassere]] & [[Paulo Hoff]]
| title = Management of hand-foot syndrome in patients treated with capecitabine (Xeloda)
| journal = [[European journal of oncology nursing : the official journal of European Oncology Nursing Society]]
| doi = 10.1016/j.ejon.2004.06.007
| pmid = 15341880
}}</ref>


·       Absence of folliculosebaceous units (hair follicles and sebaceous glands)<sup>9</sup>
:* 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>


·       Thick stratum corneum<sup>9</sup>  
:* 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>
:* High [[Cell growth|proliferation]] rate of [[Epidermis (skin)|epidermal]] [[Basal cell|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 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>


·       Wide dermal papillae<sup>9</sup>
==Microscopic Pathology==
 
·       High proliferative 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<sup>10</sup>
 
===Pathogenesis===
*The exact pathogenesis of [disease name] is not completely understood.
OR
*It is understood that [disease name] is the result of / is mediated by / is produced by / is caused by either [hypothesis 1], [hypothesis 2], or [hypothesis 3].
*[Pathogen name] is usually transmitted via the [transmission route] route to the human host.
*Following transmission/ingestion, the [pathogen] uses the [entry site] to invade the [cell name] cell.
*[Disease or malignancy name] arises from [cell name]s, which are [cell type] cells that are normally involved in [function of cells].
*The progression to [disease name] usually involves the [molecular pathway].
*The pathophysiology of [disease/malignancy] depends on the histological subtype.
 
==Genetics==
[Disease name] is transmitted in [mode of genetic transmission] pattern.
 
OR


Genes involved in the pathogenesis of [disease name] include:
* The [[pathological]] features of PPE are non-specific.
*[Gene1]
* 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]]:
*[Gene2]
*[Gene3]


OR
:* Dominantly an interface [[dermatitis]] with a [[Cell (biology)|cell]]-poor infiltrate
:* 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>


The development of [disease name] is the result of multiple genetic mutations such as:
* 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>


*[Mutation 1]
* Other [[Histology|histologic]] manifestations in [[Epidermis (skin)|epidermis]] include:
*[Mutation 2]
:*[[Vacuole|Vacuolar]] degeneration of the [[Stratum basale|basal cell layer of epidermis]]
*[Mutation 3]
:* Mild [[Spongiosum|spongiosis]]
:*[[Hyperkeratosis]]
:* Lymphohistiocytic infiltrates
:*[[Apoptosis]] of [[keratinocytes]]
:* Partial separation of the [[epidermis]] from the [[dermis]]


==Associated Conditions==
*[[Dermal]] changes include:
Conditions associated with [disease name] include:


*[Condition 1]
:*[[Superficial]] perivascular [[Infiltration (medical)|infiltration]] of [[dermis]] by [[Lymphocyte|lymphocytes]] and [[eosinophils]]
*[Condition 2]
:*[[Papillary]] [[dermal]] [[edema]]
*[Condition 3]
:*[[Neutropenia|Neutrophilic]] [[Eccrine sweat glands|eccrine]] [[hidradenitis]]
:*[[Eccrine sweat glands|Eccrine]] [[squamous]] syringometaplasia, in severe PPE ([[WHO]] grades 3 and 4)


==Gross Pathology==
*[[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 />
On gross pathology, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].
 
==Microscopic Pathology==
On microscopic histopathological analysis, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].


==References==
==References==
{{reflist|3}}
{{reflist|3}}
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Latest revision as of 19:35, 17 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

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:
  • Unique characteristics of the palms and the soles which justify their involvement as the preferred sites of involvement include: [2] [5] [6]

Microscopic Pathology

References

  1. ↑ J. E. Fitzpatrick. "The cutaneous histopathology of chemotherapeutic reactions". Journal of cutaneous pathology. PMID 8468414.
  2. ↑ 2.0 2.1 Baack BR, Burgdorf WH (1991). "Chemotherapy-induced acral erythema". J Am Acad Dermatol. 24 (3): 457–61. PMID 2061446.
  3. ↑ 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.
  4. ↑ Perry, Michael (2012). Chemotherapy source book. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins. ISBN 9781451101454.
  5. ↑ W. S. Susser, D. L. Whitaker-Worth & J. M. Grant-Kels. "Mucocutaneous reactions to chemotherapy". Journal of the American Academy of Dermatology. PMID 10071309.
  6. ↑ 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. ↑ 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.
  8. ↑ 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.
  9. ↑ Fitzpatrick JE (1993). "The cutaneous histopathology of chemotherapeutic reactions". J Cutan Pathol. 20 (1): 1–14. PMID 8468414.
  10. ↑ 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.
  11. ↑ 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.
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