Acral erythema in Adult
See also in: Cellulitis DDxAlerts and Notices
Important News & Links
Synopsis

Acral erythema, also known as palmoplantar erythrodysesthesia and hand-foot syndrome, has been described following treatment with several systemic chemotherapeutic agents. The exact pathogenic mechanisms of this disorder are still unknown. Typically, the eruption involves the hands and feet and often occurs within the first week of treatment. Common provoking agents include BRAF inhibitors (eg, vemurafenib, dabrafenib), imatinib, multikinase inhibitors (MKIs), epidermal growth factor receptor (EGFR) inhibitors (eg, canertinib, lapatinib, vandetanib, sorafenib, sunitinib), cytarabine (cytosine arabinoside), 5-fluorouracil, doxorubicin (particularly pegylated liposomal doxorubicin), hydroxyurea, capecitabine, and mercaptopurine.
Reactions may occur sooner (24 hours to 3 weeks) and more severely with bolus chemotherapy than with low-dose continuous infusion and are usually reproducible with challenge.
Acral erythema may occur as part of a broader eruption, known as toxic erythema of chemotherapy, in which acral and intertriginous areas are involved. It is characterized by a painful erythematous rash, often with associated edema located on the palms, fingers, and soles preceded by dysesthesia.
A similar condition, hand-foot skin reaction (HFSR), occurs with MKI therapy; it has been reported in both children and adults. It can affect up to 60%-70% of patients being treated with MKIs, particularly those treated with regorafenib, sorafenib, sunitinib, and cabozantinib, with the incidence being reported to decrease with each subsequent cycle of MKI therapy.
Patients may experience prodromal symptoms such as tingling, burning, and pain in their palms and soles within 1-6 weeks of starting treatment with MKIs. There are 3 clinical stages of HFSR: the inflammatory phase, the hyperkeratotic phase, and the resolution phase. The National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.0 criteria can be used to grade HFSR severity. (See Management Pearls.)
Reactions may occur sooner (24 hours to 3 weeks) and more severely with bolus chemotherapy than with low-dose continuous infusion and are usually reproducible with challenge.
Acral erythema may occur as part of a broader eruption, known as toxic erythema of chemotherapy, in which acral and intertriginous areas are involved. It is characterized by a painful erythematous rash, often with associated edema located on the palms, fingers, and soles preceded by dysesthesia.
A similar condition, hand-foot skin reaction (HFSR), occurs with MKI therapy; it has been reported in both children and adults. It can affect up to 60%-70% of patients being treated with MKIs, particularly those treated with regorafenib, sorafenib, sunitinib, and cabozantinib, with the incidence being reported to decrease with each subsequent cycle of MKI therapy.
Patients may experience prodromal symptoms such as tingling, burning, and pain in their palms and soles within 1-6 weeks of starting treatment with MKIs. There are 3 clinical stages of HFSR: the inflammatory phase, the hyperkeratotic phase, and the resolution phase. The National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.0 criteria can be used to grade HFSR severity. (See Management Pearls.)
Codes
ICD10CM:
L27.1 – Localized skin eruption due to drugs and medicaments taken internally
SNOMEDCT:
238993006 – Acral erythema
L27.1 – Localized skin eruption due to drugs and medicaments taken internally
SNOMEDCT:
238993006 – Acral erythema
Look For
Subscription Required
Diagnostic Pearls
Subscription Required
Differential Diagnosis & Pitfalls
- Raynaud phenomenon
- Cellulitis
- Acute contact dermatitis / contact dermatitis (pediatric)
- Burn (see thermal or electrical burn; chemical burns are covered separately, by chemical agent)
- Frostbite
- Erythromelalgia
- Early serum sickness
- Angioedema
- Periungual erythema may be seen with dermatomyositis / juvenile dermatomyositis, systemic lupus erythematosus, HIV, and hepatitis C.
- Papular-purpuric gloves and socks syndrome has been reported with parvovirus B19 and cytomegalovirus infection.
- Acute graft-versus-host disease
- PATEO syndrome (periarticular thenar erythema with onycholysis)
- Acquired palmoplantar keratoderma
- Keratoderma climactericum
- Neutrophilic eccrine hidradenitis
- Hypertrophic lichen planus
- Crusted scabies
Best Tests
Subscription Required
Management Pearls
Subscription Required
Therapy
Subscription Required
Drug Reaction Data
Below is a list of drugs with literature evidence indicating an adverse association with this diagnosis. The list is continually updated through ongoing research and new medication approvals. Click on Citations to sort by number of citations or click on Medication to sort the medications alphabetically.
Subscription Required
References
Subscription Required
Last Reviewed:10/16/2022
Last Updated:11/09/2022
Last Updated:11/09/2022
Acral erythema in Adult
See also in: Cellulitis DDx