Palmar plantar erythrodysesthesia pathophysiology
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1], Associate Editor(s)-in-Chief: : Mandana Chitsazan, M.D., Zain Fatiwala M.D.
Overview
The pathophysiologic mechanism of Palmar Plantar Erythrodysesthesia is under active investigation and different mechanisms have been postulated.[1] Factors that have been implicated involve rapid cell division in palms and soles, gravitational forces, vascular anatomy peculiar to these areas and temperature 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. PPE Biopsies appear histologically nonspecific, but a consistenty toxic reaction is seen.[2]
In Palmar Plantar Erythrodysesthesia associated with Pegylated liposomal doxorubicin (PLD), it has been determined that the drug is present is deposited in sweat then smeared onto the skin surfaces. The sweat glands are present in high concentration on the palms and soles. The drug then infiltrates the stratum corneum which is a thick layer in the body. This layer acts as a reservoir for the drug leading to the symptoms of PPE.[3]
Pathophysiology
The exact pathogenesis of PPE is not completely understood. Existing theories are based on the fact that only the hands and feet are involved and posit the role of temperature differences, vascular anatomy, differences in the types of cells (rapidly dividing epidermal cells and eccrine glands).
The pathophysiologic mechanism of Palmar Plantar Erythrodysesthesia is under active investigation and different mechanisms have been postulated.[1] Factors that have been implicated involve rapid cell division in palms and soles, gravitational forces, vascular anatomy peculiar to these areas and temperature 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. PPE Biopsies appear histologically nonspecific, but a consistenty toxic reaction is seen.[2]
In Palmar Plantar Erythrodysesthesia associated with Pegylated liposomal doxorubicin (PLD), it has been determined that the drug is present is deposited in sweat then smeared onto the skin surfaces. The sweat glands are present in high concentration on the palms and soles. The drug then infiltrates the stratum corneum which is a thick layer in the body. This layer acts as a reservoir for the drug leading to the symptoms of PPE.[3]
In BMT patients, there is a 35% incidence of PPE and may be due to the use of high doses of chemotherapy with addition of total body irradiation.[4]
Associated Conditions
Palmar Plantar Erythrodysesthesia is commonly associated with chemotherapy that is used for the treatment of different cancers.
Gross Pathology
PPE commonly affects the palms more commonly than the soles. The lesion starts as just a sensation in the palms and soles, progressing to painful, tingling, symmetric, well-demarcated swelling and erythematous plaques. This is then followed by a desquamative phase that happens on resolution.[5]
Microscopic Pathology
On histopathology non-specific features seen in Palmar Plantar Erythrodysesthesia. Features include[6]:
- 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.
References
- ↑ 1.0 1.1 Baack BR, Burgdorf WH (1991). "Chemotherapy-induced acral erythema". J Am Acad Dermatol. 24 (3): 457–61. PMID 2061446.
- ↑ 2.0 2.1 Duvernoy O, Malm T, Thuomas KA, Larsson SG, Hansson HE (1991). "CT and MR evaluation of pericardial and retrosternal adhesions after cardiac surgery". J Comput Assist Tomogr. 15 (4): 555–60. PMID 2061466.
- ↑ 3.0 3.1 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.
- ↑ 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.
- ↑ "Acral Erythema - Holland-Frei Cancer Medicine - NCBI Bookshelf".
- ↑ 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.