Definition and research guide
This page combines a MeSH definition, publication statistics and selected research abstracts. It is a starting point for reading the literature, not a medical textbook or a systematic evidence review.
Content available: 4 complete abstracts (835 words), 10 references. Full article text is not stored or reproduced here; follow the PMID, DOI or PMC links to read the original sources and their access terms.
Definition
Chemotherapy-induced dermal side effects that are associated with the use of various cytostatic agents. Symptoms range from mild erythema and/or paresthesia to severe ulcerative dermatitis with debilitating pain involving typically palmoplantar and intertriginous areas. These cutaneous manifestations are sometimes accompanied by nail anomalies.
Definition: NLM Medical Subject Headings (MeSH) scope note (Public domain (U.S. National Library of Medicine); attribution requested). View the MeSH record.
Also known as: Hand Foot Syndrome; Hand-Foot Syndromes; Syndrome, Hand-Foot; Syndromes, Hand-Foot; Chemotherapy-Induced Acral Erythema; Acral Erythema, Chemotherapy-Induced; Acral Erythemas, Chemotherapy-Induced; Chemotherapy Induced Acral Erythema.
Where it fits in the MeSH classification
- Broader topics
- Drug Eruptions
- See also
- Hand, Foot and Mouth Disease
Related concepts
- Cytostatic Agents
- Erythema
- Paresthesia
Research landscape
PubMed indexes 545 records tagged with the MeSH heading “Hand-Foot Syndrome” (counts retrieved 2026-11-04). 185 of them (33.9%) were published from 2020 onward, and the busiest period so far is 2010-2019 with 368 records.
Reviews account for 75 records (13.8%) and meta-analyses for 33. Randomized controlled trials number 80 (14.7%) as a share of all records on the topic. Randomized trials make up a comparatively large share of this literature, which means many treatment questions have been tested directly.
Show the data
| Period | Records |
|---|---|
| through 1999 | 0 |
| 2000-2009 | 0 |
| 2010-2019 | 368 |
| 2020 onward | 185 |
Publication-type chart data
| Type | Records | Share |
|---|---|---|
| Reviews | 75 | 13.8% |
| Meta-analyses | 33 | 6.1% |
| Randomized controlled trials | 80 | 14.7% |
Method: PubMed query "Hand-Foot Syndrome"[MeSH Terms] with publication-type and date filters, retrieved 2026-11-04.
Reading the evidence in bones, joints, muscles and skin
Joint, bone, muscle and skin conditions are often judged by pain scores, function questionnaires, imaging or photographs, and symptoms can fluctuate, so placebo response and natural improvement matter. Imaging changes are common in people without symptoms. Nothing on this page is advice about treatment. Check how outcomes were measured, whether the comparison group received a placebo or usual care, and how long the benefit lasted.
Evidence from open-access studies
These open-access studies come from PubMed’s best-match results for this heading (papers whose main topic it is), ranked here by citation count, with one recent addition. Each abstract is reproduced in full under its recorded open licence so that you can read the authors’ own words. They illustrate the literature; they are not a systematic summary of it. Citation counts measure attention, not reliability or clinical benefit.
| Study / authors | Year | Source label / design | Europe PMC citations | Licence / source |
|---|---|---|---|---|
| Pathogenesis of Hand-Foot Syndrome induced by PEG-modified liposomal Doxorubicin | 2013 | Research article Design not recorded in structured metadata | 67 | cc by PMID 23386177 · DOI · PMC3595474 |
| Pyridoxine for prevention of hand-foot syndrome caused by chemotherapy: a systematic review | 2013 | Meta-analysis Design not recorded in structured metadata | 27 | cc by PMID 23977264 · DOI · PMC3748123 |
| Use of omeprazole, the proton pump inhibitor, as a potential therapy for the capecitabine-induced hand-foot syndrome | 2021 | Research article Design not recorded in structured metadata | 16 | cc by PMID 33903667 · DOI · PMC8076322 |
| Evaluation of the efficacy of topical cosmetic products in patients with hand-and-foot syndrome undergoing oncological treatments | 2026 | Research article Design not recorded in structured metadata | 1 | cc by PMID 42286807 · DOI · PMC13351728 |
Pathogenesis of Hand-Foot Syndrome induced by PEG-modified liposomal Doxorubicin [1]
Abstract reading summary — source excerpts
- Opening excerpt
- PEGL-DOX is an excellent treatment for recurrent ovarian cancer that rarely causes side-effects like cardiotoxicity or hair loss, but frequently results in Hand-Foot Syndrome (HFS).
- Closing excerpt
- In the future, we plan to develop preventative as well as therapeutic treatments by trapping the ROS.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (219 words)
PEGL-DOX is an excellent treatment for recurrent ovarian cancer that rarely causes side-effects like cardiotoxicity or hair loss, but frequently results in Hand-Foot Syndrome (HFS). In severe cases, it can become necessary to reduce the PEGL-DOX concentration or the duration of the drug therapy, sometimes making it difficult to continue treatment. In this study, we prepared an animal model to compare the effects of DOX versus PEGL-DOX, and we noticed that only treatment with PEGL-DOX resulted in HFS, which led us to conclude that extravasation due to long-term circulation was one of the causes of HFS. In addition, we were able to show that the primary factor leading to the skin-specific outbreaks in the extremities was the appearance of reactive oxygen species (ROS) due to interactions between DOX and the metallic Cu(II) ions abundant in skin tissue. ROS directly disturb the surrounding tissue and simultaneously induce keratinocyte-specific apoptosis. Keratinocytes express the thermoreceptor TRPM2, which is thought to be able to detect ROS and stimulate the release of chemokines (IL-8, GRO, Fractalkine), which induce directed chemotaxis in neutrophils and other blood cells. Those cells and the keratinocytes then undergo apoptosis and simultaneously release IL-1β, IL-1α, and IL-6, which brings about an inflammatory state. In the future, we plan to develop preventative as well as therapeutic treatments by trapping the ROS.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 23386177 · DOI · PMC3595474
Pyridoxine for prevention of hand-foot syndrome caused by chemotherapy: a systematic review [2]
Abstract reading summary — source excerpts
- Opening excerpt
- BackgroundHand-foot syndrome (HFS) is a relatively frequent dermatologic toxic reaction to certain anti-cancer chemotherapies.
- Closing excerpt
- Further studies of large sample sizes are needed to evaluate the efficacy and safety of pyridoxine, especially at high dose, in comparison with placebo.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (237 words)
BackgroundHand-foot syndrome (HFS) is a relatively frequent dermatologic toxic reaction to certain anti-cancer chemotherapies. The syndrome can evolve into a distressing condition that limits function and affects quality of life. Pyridoxine (vitamin B6) has been used empirically for the prevention of HFS caused by anti-cancer therapy. However, evidence of its efficacy remains controversial.Methodology//principal findingsSystematic literature searches were conducted on the Cochrane Library, PUBMED, EMBASE, LILACS, CBM, CNKI, VIP, WANFANG and the U.S. ClinicalTrials.gov website. We included all related randomized controlled trials (RCTs) irrespective of language. Reviewers from different professions independently assessed all potential studies and extracted data. Subgroup analysis was planned according to dose of pyridoxine. 5 RCTs involving 607 patients were contributed to the meta-analysis. No significant differences were found between patients receiving pyridoxine and placebo for prevention of incidence of HFS and grade 2 or worse HFS (relative risk (RR) 0.96, 95%confidence interval (CI) 0.86-1.06; RR0.95, 95%CI 0.73-1.24, respectively). Similarly, no significant improvement in quality of life was detected among patients. However, significant difference was found for prevention of grade 2 or worse HFS with pyridoxine 400 mg daily compared to 200 mg (RR0.55, 95%CI 0.33-0.92).Conclusions/significanceThere is inadequate evidence to make any recommendation about using pyridoxine for prevention of HFS caused by chemotherapy. However, pyridoxine 400 mg may have some efficacy. Further studies of large sample sizes are needed to evaluate the efficacy and safety of pyridoxine, especially at high dose, in comparison with placebo.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 23977264 · DOI · PMC3748123
Use of omeprazole, the proton pump inhibitor, as a potential therapy for the capecitabine-induced hand-foot syndrome [3]
Abstract reading summary — source excerpts
- Opening excerpt
- Hand-foot syndrome (HFS), also known as palmar-plantar erythrodysesthesia (PPE), is a major side effect of capecitabine.
- Closing excerpt
- Our results suggest that omeprazole may be a potential prophylactic agent for capecitabine-induced HFS.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (184 words)
Hand-foot syndrome (HFS), also known as palmar-plantar erythrodysesthesia (PPE), is a major side effect of capecitabine. Although the pathogenesis of HFS remains unknown, some studies suggested a potential involvement of inflammation in its pathogenesis. Proton pump inhibitors (PPIs) have been reported to have anti-inflammatory effects. In this study, we investigated the ameliorative effects of omeprazole, a PPI on capecitabine-related HFS in mice model, and a real-world database. Repeated administration of capecitabine (200 mg/kg, p.o., five times a week for 3 weeks) increased fluid content, redness, and tumor necrosis factor (TNF)-α substance of the mice hind paw. Co-administration of omeprazole (20 mg/kg, p.o., at the same schedule) significantly inhibited these changes induced by capecitabine. Moreover, based on the clinical database analysis of the Food and Drug Administration Adverse Event Reporting System, the group that has used any PPIs had a lower reporting rate of capecitabine-related PPE than the group that has not used any PPIs. (6.25% vs. 8.31%, p < 0.0001, reporting odds ratio (ROR) 0.74, 95% confidence interval (CI) 0.65-0.83). Our results suggest that omeprazole may be a potential prophylactic agent for capecitabine-induced HFS.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 33903667 · DOI · PMC8076322
Evaluation of the efficacy of topical cosmetic products in patients with hand-and-foot syndrome undergoing oncological treatments [4]
Abstract reading summary — source excerpts
- Opening excerpt
- BackgroundHand-foot syndrome (HFS) is a complication of many anticancer therapies and negatively affects patients' quality of life (QoL).
- Closing excerpt
- After 45 days, the application of the cosmetic set increased skin hydration by 33% (P ConclusionThese results show that a set of cosmetic products specific for cancer skin care can effectively manage HFS-related symptoms, resulting in improved QoL for patients, regardless of the anticancer treatment received.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (195 words)
BackgroundHand-foot syndrome (HFS) is a complication of many anticancer therapies and negatively affects patients' quality of life (QoL). Currently, little data are available on using non-pharmacological skin products as standard therapy for HFS.AimThis study aims to investigate whether a specific set of cosmetic products is effective for managing HFS skin side effects in cancer patients.Materials and methodsThis single-arm study involved 53 cancer patients with grade 1 HFS undergoing chemotherapy, targeted, or hormonal treatments at the European Institute of Oncology. The study included a baseline visit and a follow-up visit 45 days later. All enrolled patients were prescribed a set of four cosmetic products for skin treatment. Patients underwent instrumental measurement to evaluate skin hydration and erythema, while their QoL was assessed using the Skindex-16 self-questionnaire. Additionally, physicians clinically evaluated the HFS severity, using the CTCAE (Common Terminology Criteria for Adverse Events) scale and by comparing patient photographs.ResultsNo patients worsened. After 45 days, the application of the cosmetic set increased skin hydration by 33% (P ConclusionThese results show that a set of cosmetic products specific for cancer skin care can effectively manage HFS-related symptoms, resulting in improved QoL for patients, regardless of the anticancer treatment received.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 42286807 · DOI · PMC13351728
Key reviews and meta-analyses
The most cited review-type papers among PubMed’s best-match results for this heading, listed with bibliographic details only. Follow the links for the full text and access terms.
- Research article Chemotherapy-induced hand-foot syndrome and nail changes: a review of clinical presentation, etiology, pathogenesis, and management [5]
- Research article Regorafenib-associated hand-foot skin reaction: practical advice on diagnosis, prevention, and management [6]
- Research article Incidence and implications of chemotherapy related hand-foot syndrome [7]
- Research article Risk of hand-foot skin reaction with the novel multikinase inhibitor regorafenib: a meta-analysis [8]
- Research article Possible Pathways of Capecitabine-Induced Hand-Foot Syndrome [9]
- Research article Prevention strategies for chemotherapy-induced hand-foot syndrome: a systematic review and meta-analysis of prospective randomised trials [10]
References
- Yokomichi N, Nagasawa T, Coler-Reilly A, Suzuki H, Kubota Y, Yoshioka R, et al.. Pathogenesis of Hand-Foot Syndrome induced by PEG-modified liposomal Doxorubicin. . 2013. PMID 23386177 · DOI · PMC3595474
- Chen M, Zhang L, Wang Q, Shen J. Pyridoxine for prevention of hand-foot syndrome caused by chemotherapy: a systematic review. . 2013. PMID 23977264 · DOI · PMC3748123
- Hiromoto S, Kawashiri T, Yamanaka N, Kobayashi D, Mine K, Inoue M, et al.. Use of omeprazole, the proton pump inhibitor, as a potential therapy for the capecitabine-induced hand-foot syndrome. . 2021. PMID 33903667 · DOI · PMC8076322
- Martuscelli A, Tosti G, Maisonneuve P, Redaelli C, Indino M, Cereda M, et al.. Evaluation of the efficacy of topical cosmetic products in patients with hand-and-foot syndrome undergoing oncological treatments. . 2026. PMID 42286807 · DOI · PMC13351728
- Miller KK, Gorcey L, McLellan BN. Chemotherapy-induced hand-foot syndrome and nail changes: a review of clinical presentation, etiology, pathogenesis, and management. J Am Acad Dermatol. 2014. PMID 24795111 · DOI
- McLellan B, Ciardiello F, Lacouture ME, Segaert S, Van Cutsem E. Regorafenib-associated hand-foot skin reaction: practical advice on diagnosis, prevention, and management. Ann Oncol. 2015. PMID 26034039 · DOI · PMC4576906
- Nikolaou V, Syrigos K, Saif MW. Incidence and implications of chemotherapy related hand-foot syndrome. Expert Opin Drug Saf. 2016. PMID 27718746 · DOI
- Belum VR, Wu S, Lacouture ME. Risk of hand-foot skin reaction with the novel multikinase inhibitor regorafenib: a meta-analysis. Invest New Drugs. 2013. PMID 23700287 · DOI
- Lou Y, Wang Q, Zheng J, Hu H, Liu L, Hong D, et al.. Possible Pathways of Capecitabine-Induced Hand-Foot Syndrome. Chem Res Toxicol. 2016. PMID 27631426 · DOI
- Macedo LT, Lima JP, dos Santos LV, Sasse AD. Prevention strategies for chemotherapy-induced hand-foot syndrome: a systematic review and meta-analysis of prospective randomised trials. Support Care Cancer. 2014. PMID 24463616 · DOI
About this article
- Sources
- NLM Medical Subject Headings (definition, synonyms); NCBI PubMed (counts, identifiers); Europe PMC (open-access abstracts and citation counts).
- Verification
- Every reference was resolved against PubMed on 2026-11-04; title, year and DOI matched.
- Review state
- automated source verified; no human expert review has been recorded yet.
- Version
- 1, last updated 2026-11-04.
See how EvidenceLib is built. Spotted an error? Email support@evidencehelix.com.
Evidence strength
EvidenceHelix's computed view of the study designs behind this topic: how common meta-analyses, randomized trials and reviews are, how recent the literature is, and a plain-language reading. It describes the design mix of the literature. It is not a quality appraisal of any study, and it is not medical advice.