Palmar plantar erythrodysesthesia pathophysiology: Difference between revisions
Jump to navigation
Jump to search
No edit summary |
No edit summary |
||
| Line 57: | Line 57: | ||
* The [[pathological]] features of PPE are non-specific. | * 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]]: | * 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 | :* 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> | :* 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> | ||
| Line 63: | Line 64: | ||
* 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> | * 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 include: | * Other [[Histology|histologic]] manifestations in [[Epidermis (skin)|epidermis]] include: | ||
:*[[Vacuole|Vacuolar]] degeneration of the [[Stratum basale|basal cell layer of epidermis]] | :*[[Vacuole|Vacuolar]] degeneration of the [[Stratum basale|basal cell layer of epidermis]] | ||
:* Mild [[Spongiosum|spongiosis]] | :* Mild [[Spongiosum|spongiosis]] | ||
| Line 72: | Line 73: | ||
*[[Dermal]] changes include: | *[[Dermal]] changes include: | ||
:*[[Superficial]] perivascular [[Infiltration (medical)|infiltration]] of [[dermis]] | |||
:*[[Superficial]] perivascular [[Infiltration (medical)|infiltration]] of [[dermis]] by [[Lymphocyte|lymphocytes]] and [[eosinophils]] | |||
:*[[Papillary]] [[dermal]] [[edema]] | :*[[Papillary]] [[dermal]] [[edema]] | ||
:*[[Neutropenia|Neutrophilic]] [[Eccrine sweat glands|eccrine]] [[hidradenitis]] | :*[[Neutropenia|Neutrophilic]] [[Eccrine sweat glands|eccrine]] [[hidradenitis]] | ||
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.