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Histopathologic findings in mild palmar plantar erythrodysesthesia (WHO grades 1 and 2): interface dermatitis, isolated necrotic keratinocytes, vascular dilatation, and dermal edema can be seen.
Source publication
Palmar plantar erythrodysesthesia (PPE) is a distinctive and relatively frequent toxic reaction related to some chemotherapeutic agents. Doxorubicin, cytarabine, docetaxel, and fluorouracil are the most frequently implicated agents. PPE seems to be dose dependent and both peak drug concentration and total cumulative dose determine its occurrence. P...
Context in source publication
Context 1
... epidermal necrolysis or generalized epider- mal necrolysis. All these adverse skin reactions demonstrate the same basic histologic pattern of an interface dermatitis with a cell-poor infiltrate and a variable degree of epidermal necrosis. [92] Early or mild cytotoxic reactions (PPE WHO grades 1 and 2) show isolated necrotic basal keratinocytes ( fig. 4). In severe cytotoxic reactions (WHO grades 3 and 4) the entire basal layer is destroyed, and a blister may form together with complete epi- dermal necrosis ( fig. 5). [15] Dermal changes in most cases include dilated blood vessels, papillary edema, and a sparse superficial perivascular lympho- histiocytic infiltrate. Eccrine glands may ...
Citations
... The involvement of hands and soles only could be due to the anatomy and greater number of blood capillaries in these areas, temperature gradient, leaking of the drug from the capillaries of the hands and feet; secretion of chemotherapy drugs from the eccrine glands, and higher turnover of the epidermal basal cells. 2 The clinical presentation could manifest within 24 hours of dosage or from the first cycle and reports of late development of symptoms are seen during subsequent cycles or almost 10 months post discontinuation. 3 In a case by Payne et al. patient developed severe grade 4 symptoms 8 days after the bolus dose which is the earliest 4 Here, the exaggeration after a single dose was postulated to the hypoabuminemia due to hepatic dysfunction in the patient. ...
Hand-foot syndrome (HFS) is a common complication of several chemotherapy agents. But the incidence of paclitaxel-associated HFS is rare. Here, we present such a rare case of paclitaxel induced HFS in a 70-year-old female with advanced metastatic squamous cell carcinoma of the buccal mucosa. Clinical presentation was of grade 3 severity with blisters formation and ulceration requiring discontinuation of paclitaxel. The intent to present such a rare case is to create awareness about such occurrences while administering paclitaxel and for prompt action; as delay can lead to severe limitations of daily activities of the patient therein hampering the quality of life.
... Hand-Foot syndrome which is known as palmar-plantar erythrodysesthesia syndrome (PPE) or chemotherapy-induced peripheral neurotoxicity (CIPN) is the major side effect caused by chemotherapy (Nagore et al., 2000). Common symptoms of Hand-Foot syndrome are numbness, dysesthesia, tingling sensations, and even severe pain in the hands and feet, and rarely on the trunk, neck, chest and scalp (Baack & Burgdorf, 1991;Nagore et al., 2000). ...
... Hand-Foot syndrome which is known as palmar-plantar erythrodysesthesia syndrome (PPE) or chemotherapy-induced peripheral neurotoxicity (CIPN) is the major side effect caused by chemotherapy (Nagore et al., 2000). Common symptoms of Hand-Foot syndrome are numbness, dysesthesia, tingling sensations, and even severe pain in the hands and feet, and rarely on the trunk, neck, chest and scalp (Baack & Burgdorf, 1991;Nagore et al., 2000). Although these side effects are not critical or life-threatening, they may cause inconveniences in daily life because the hands and feet are the most frequently used body parts. ...
We investigated the effects of peripheral cooling using chemotherapy gloves and socks at three cooling temperatures on subjective perceptions. The hands and feet were cooled with 8, 11, and 14°C by water-perfused gloves or socks. Nine females participated in six experimental conditions: hands or feet cooling at 8, 11, and 14°C. The heat was extracted at 3.8, 5.4, and 7.7 kJ·min ¹ via the gloves and at 4.1, 6.0, and 9.0 kJ·min ⁻¹ via the socks. While the results showed that overall subjective perceptions did not differ among the three temperatures (~ 9.0 kJ·min ⁻¹ ), there were significant differences in local thermal comfort, pain sensation, and pain discomfort among the three cooling temperatures ( P < 0.05). When cooling the hands or feet at 8, 11 or 14°C, subjects felt ‘cold’ or ‘cool’, on average, at the end of 60-min cooling with no significant differences among the three temperatures, whereas subjects felt more uncomfortable at 8°C than 14°C for cooling either the hands or feet ( P < 0.05). Subjects felt more pain at 8°C than 14°C cooling for both hands and feet. These results indicate that the 8°C cooling for 60 min might cause uncomfortable pain sensation, especially for cold-vulnerable individuals. We recommend 1) a cooling bout of less than 60 min, 2) a cooling temperature higher than 8oC when cooling the hands or feet, and 3) a higher temperature for the feet when the hands are simultaneously cooled. However, the present results on subjective perceptions should be interpreted with peripheral vasoconstriction of fingers and toes while cooling.
... Similarly, the associations of the genetic predictors with hand-foot syndrome, namely the TLR4 (rs4986790) SNP with decreased probability, and the IL10 (rs1800871) SNP with increased probability remains unclear with no previous reports in the literature. Whilst the mixed (increased and decreased) probability of association of chemotherapy regimen types with this adverse effect mostly likely is explained by the differing potential of chemotherapeutics to cause this adverse effect (for review see Ref. [41]). With regards to validating our pilot study findings that identified TLR2 and TNF genetic and colorectal and gastric cancer type non-genetic predictors of overall GI toxicity [11], a combined model in the current study only improved the % AUC of ROC curves from the genetic predictors model by 6% and observed different genetic (TGFB1) and non-genetic predictors. ...
Purpose
Adverse effects following fluoropyrimidine-based chemotherapy regimens are common. However, there are no current accepted diagnostic markers for prediction prior to treatment, and the underlying mechanisms remain unclear. This study aimed to determine genetic and non-genetic predictors of adverse effects.
Methods
Genomic DNA was analyzed for 25 single nucleotide polymorphisms (SNPs). Demographics, comorbidities, cancer and fluoropyrimidine-based chemotherapy regimen types, and adverse effect data were obtained from clinical records for 155 Australian White participants. Associations were determined by bivariate analysis, logistic regression modeling and Bayesian network analysis.
Results
Twelve different adverse effects were observed in the participants, the most common severe adverse effect was diarrhea (12.9%). Bivariate analysis revealed associations between all adverse effects except neutropenia, between genetic and non-genetic predictors, and between 8 genetic and 12 non-genetic predictors with more than 1 adverse effect. Logistic regression modeling of adverse effects revealed a greater/sole role for six genetic predictors in overall gastrointestinal toxicity, nausea and/or vomiting, constipation, and neutropenia, and for nine non-genetic predictors in diarrhea, mucositis, neuropathy, generalized pain, hand–foot syndrome, skin toxicity, cardiotoxicity and fatigue. The Bayesian network analysis revealed less directly associated predictors (one genetic and six non-genetic) with adverse effects and confirmed associations between six adverse effects, eight genetic predictors and nine non-genetic predictors.
Conclusion
This study is the first to link both genetic and non-genetic predictors with adverse effects following fluoropyrimidine-based chemotherapy. Collectively, we report a wealth of information that warrants further investigation to elucidate the clinical significance, especially associations with genetic predictors and adverse effects.
... At the end of the experiment, the rats were anesthetized and skin samples from the soles of the left hind paw were dissected, about 1 cm 2 , fixed in 10% formalin, paraffin sections (4 μm) were prepared and stained with hematoxylin and eosin, and processed for examination of histopathological changes by light microscope. Histopathological scoring of the skin samples was made according to the histopathological findings correlation to clinical severity established by Nagore et al. (2000) and given a score of 0, 1, 2, 3, or 4 (Table 1). ...
Hand–foot syndrome (HFS) is a common adverse effect of capecitabine affecting the quality of life of cancer patients. To enhance the tolerability of capecitabine, this work evaluated the incorporation of quercetin into topical collagen matrix formula to target thymidine phosphorylase enzyme, oxidative stress, and apoptosis underlying HFS. Forty Sprague Dawley rats were allocated to four equal groups. The control group received distilled water orally. HFS was induced by oral capecitabine (200 mg/kg/day) for 21 days. The untreated HFS group received no treatment. In the treated groups, topical collagen and quercetin-incorporated collagen matrix formula were administered concomitantly with the HFS induction protocol. Treatment with quercetin-incorporated collagen matrix showed a significant decrease in thymidine phosphorylase level compared with the untreated and collagen-treated groups. Treatment with quercetin-incorporated collagen matrix showed a significant decrease in malondialdehyde and caspase-3 levels, and a significant increase in the total antioxidant capacity of the skin and B cell lymphoma/leukemia 2 levels compared with the untreated group. Additionally, a significant improvement in the gross picture and histopathological score of HFS was observed. In conclusion, the quercetin-incorporated collagen matrix is a promising formula for the prevention of HFS, due to the targeted effect on thymidine phosphorylase and subsequent antioxidant and antiapoptotic effects.
... Traditional cytotoxic chemotherapy-induced HFS, also known as palmar-plantar erythrodysesthesia syndrome, acral erythema, or toxic erythema, is a skin disorder characterized by local redness, swelling, marked discomfort, and tingling in the palms of the hands or the soles of the feet [8]. HFS is associated with various cytotoxic chemotherapy regimens, such as 5-fluorouracil, capecitabine, doxorubicin, and docetaxel [9,10]. ...
Hand-foot skin reaction (HFSR) is a common skin-related adverse event induced by multikinase inhibitors targeting both platelet-derived growth factor receptor and vascular endothelial growth factor receptor, possibly due to inadequate repair following frictional trauma. Zinc is a trace element and essential nutrient in humans that plays critical roles in the development and differentiation of skin cells. Zinc transporters (Zrt- and Irt-like proteins and Zn transporters) and metallothioneins are involved in zinc efflux, uptake, and homeostasis and have been reported to be involved in skin differentiation. The underlying mechanism of HFSR remains unclear, and the association between HFSR and zinc has not been previously studied. However, some case reports and case series provide potential evidence to suggest that zinc deficiency may be involved in HFSR development and zinc supplementation may relieve HFSR symptoms. However, no large-scale clinical studies have been conducted to examine this role. Therefore, this review summarizes the evidence supporting a possible link between HFSR development and zinc and proposes potential mechanisms underlying this association based on current evidence.
... Patients on capecitabine may experience impaired quality of life as a result of these symptoms [5,6]. Apoptotic keratinocytes, vacuolar degeneration of basal keratinocytes, dermal edema, and dermal perivascular lymphocytic infiltration are pathological changes of HFS [7]. Capecitabine is a more selective alternative to 5-fluorouracil (5FU) since it is transformed into the active form only in tumor cells, reducing the side effects of 5FU, such as neutropenia and stomatitis [1]. ...
... According to the grade of toxic and side effects of chemotherapeutic drugs, her symptoms were considered as grade 3 or 4 ( Table 3) Adverse Event (AE) [8]. Due to the efficacy of the current chemotherapy regimen was evaluated as stable disease (shrinkage), so according to AE treatment strategies ( Figure 2), we withdrew albumin-paclitaxel and selected tegafur as her maintenance treatment [7,9]. ...
Dorsal hand-foot syndrome (dorsal HFS), also known as an atypical presentation of hand-foot syndrome (HFS) on the dorsum of hands and feet. Only taxanes have been reported to develop dorsal HFS according to the current literature reviews.
... Some studies suggest that patients with hematological malignancies have a reduced risk of HFS. 16 MM patients who were treated with PLD were all given dexamethasone. However, steroid use was an exclusion criterion in other studies, which could factor into the occurrence of HFS. 17 Since dexamethasone is an integral part of the chemotherapy regimen for MM patients, in our study, we could not exclude the influence of steroids. ...
Purpose
Pegylated liposomal doxorubicin (PLD) is highly effective for treating multiple myeloma (MM). Hand-foot syndrome (HFS) is a dose-limiting adverse event of PLD that may reduce a patient’s quality of life or prevent certain patients from receiving PLD. Several researchers have discovered that pyridoxine, an activated form of vitamin B6, may prevent PLD-associated HFS. We designed a prospective randomized trial to examine whether prophylactic pyridoxine might prevent the incidence or delay the occurrence of PLD-induced HFS in patients with MM.
Methods
Patients who met the trial’s eligibility requirements were randomized and then administered either pyridoxine 100 mg twice daily or no pyridoxine, in both cases accompanied by their PLD-containing chemotherapeutic agent. Follow-up of patients was performed until the completion of induction therapy, the development of HFS or disease progression.
Results
Between January 1, 2017, and January 1, 2019, 105 patients were randomly assigned to the pyridoxine group (n = 52) or the no pyridoxine group (n = 53). In the pyridoxine and no pyridoxine groups, HFS developed after a median of 4 (range, 1-8 cycles) and 3 (range, 1-7 cycles) chemotherapeutic cycles, respectively. There were no grade 3 incidents recorded. Overall, 13.3% of patients experienced HFS. A 11 of 53 (20.8%) patients in the no pyridoxine group experienced HFS, compared to 3 of 52 (5.8%) patients in the pyridoxine group ( P = .042); there was no difference in HFS grades ( P = .725).
Conclusions
The findings of benefit from prophylactic pyridoxine in this open-label trial have suggested its promise as a treatment for reducing HFS in MM patients. Further research with a placebo-controlled design is recommended.
Clinical Trial Registration
ChiCTR2100050294.
... При применении капецитабина существуют дополнительные проявления токсичности препарата в виде ладонно-подошвенной дизестезии, покраснения, чрезмерной чувствительности и шелушения кожи ладоней и стоп. Однако в доступной нам научной литературе не описаны случаи кожной токсичности капецитабина [5][6][7], в отличие от таргетной терапии, для которой весьма характерны кожные проявления [3,5]. Эти побочные явления могут снижать приверженность терапии: пациенты могут откладывать начало цикла химиотерапии, обдумывают возможность отказа от дальнейшего лечения из-за страха повторного возникновения токсичности. ...
When using capecitabine, manifestations of toxicity in the form of palmar-plantar dysesthesia, redness, excessive sensitivity and peeling of the skin of the palms and feet are well known. However, in the scientific literature available to us, we did not find a single case of skin toxicity with capecitabine, in contrast to targeted therapy, for which skin manifestations are very characteristic. The dermal toxicity described in this paper developed as a result of patient noncompliance. These side effects reduced the adherence to therapy: the next courses of chemotherapy were postponed.
... 4 The severity of HFS is usually assessed according to the National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI-CTCAE) 5 or the World Health Organization (WHO) HFS grading scale. 6 Several drugs are known to cause HFS, such as PEGylated liposomal doxorubicin (PLD), capecitabine, 5-fluorouracil (5-FU), cytarabine, docetaxel, and tyrosine kinase inhibitors. Among them, capecitabine causes a higher incidence of HFS (about 50%-60%). ...
Capecitabine‐induced hand‐foot syndrome is common in clinical practice. There are many regimens used to prevent hand‐foot syndrome. However, the most effective preventive regimen has not yet been identified. Thus, we conducted a network meta‐analysis to investigate the best preventive regimen for hand‐foot syndrome. The PRISMA‐NMA guidelines were used in this study. The PubMed, Cochrane, and Embase databases were searched. The main endpoint was set as hand‐foot syndrome of NCI grade 2 or more. We included only randomized control trials. The P‐score was used to rank the regimens. Among all the regimens, topical silymarin had the best preventive ability compared with the placebo (OR: 0.08; 95% CI: 0.01‐0.71). The other identified effective regimen included pyridoxine (400 mg) and celecoxib; compared with the placebo, the odds ratio was 0.27 (95% CI: 0.08‐0.91) and 0.41 (95% CI: 0.18‐0.95), respectively. Topical silymarin is the most useful regimen for preventing capecitabine‐induced hand‐foot syndrome. This article is protected by copyright. All rights reserved.
