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Hand-foot skin reaction. Hyperkeratotic lesions on the flexor surfaces of the fingers, with the formation of calluses and, in some cases, of superficial blisters on an erythematous base. The characteristic peripheral erythematous halo can be seen. Figure courtesy of Dr Tuneu and Dr López Pestaña of Hospital Donostia, San Sebastian, Spain.
Source publication
As new antiangiogenic therapies have been introduced and added to the therapeutic arsenal against various types of cancer, previously unknown adverse effects have been detected. These effects negatively impact patients' quality of life and can even make it necessary to suspend treatment. Adverse skin reactions occur in 90% of patients treated with...
Context in source publication
Context 1
... Clinically, HFSR develops within the first 2 to 6 weeks of treatment as hyperkeratotic lesions, with the formation of calluses and, in some cases, superficial blisters on an erythematous base, mainly affecting the palms and soles bilaterally, though calluses can also appear on the flexor surfaces of the fingers. The lesions usually have a characteristic peripheral erythematous halo (Figs. 2 and 3). 14 This clinical presentation contrasts with the acute appearance of erythema, edema, paresthesia, pain, and subsequent diffuse peeling typical of classic HFS. ...
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Bevacizumab is one of the most widely used anti-angiogenic drugs in oncology, but the overall beneficial effects of this VEGF-A targeting agent are relatively modest, in part due to the lack of a biomarker to select patients most likely to respond favorably. Several molecular aberrations in cancer influence angiogenesis, including mutations in the...
Background: Angiogenesis inhibitors have become an important therapeutic approach in the treatment of hepatocellular carcinoma (HCC) patients. The therapeutic inhibition of angiogenesis of Sorafenib in increasing overall survival of patients with HCC is a fundamental element of the treatment of this disease. Considering the heterogeneous aspects of...
Citations
... Sorafenib is a multitargeted protein kinase inhibitor that suppresses tumor proliferation (Raf serine/threonine kinases, Fms-like tyrosine kinase-3 or FLT-3, c-Kit, rearranged during transfection or RET blocker) and angiogenesis (vascular endothelial growth factor receptor or VEGFR-2, VEGFR-3, plateletderived growth factor receptor or PGDF-R-β blocker). 1,3,6,7 In addition to its approved indications, that is, advanced renal cell carcinoma, unresectable hepatocellular carcinoma, and recurrent or metastatic differentiated thyroid carcinoma, it is used off-label in various malignancies. 6,[8][9][10] Approximately 70 to 90% of these patients manifest mucocutaneous AE with hair and nail changes, within 6 weeks of receiving treatment. ...
... 1,3,6,7 In addition to its approved indications, that is, advanced renal cell carcinoma, unresectable hepatocellular carcinoma, and recurrent or metastatic differentiated thyroid carcinoma, it is used off-label in various malignancies. 6,[8][9][10] Approximately 70 to 90% of these patients manifest mucocutaneous AE with hair and nail changes, within 6 weeks of receiving treatment. 1,2,6,7,10,11 HFSR, rash and desquamation, alopecia, facial erythema, subungual splinter hemorrhages, scalp dysesthesias, xerosis, and pruritus are frequently reported; whereas, stomatitis and cheilitis, hyperkeratosis of nipples, eruptive cysts, eruptive nevi, squamoproliferative lesions like actinic keratoses, keratoacanthomas, and squamous cell carcinomas are rarely seen. ...
... 1,2,6,7,10,11 HFSR, rash and desquamation, alopecia, facial erythema, subungual splinter hemorrhages, scalp dysesthesias, xerosis, and pruritus are frequently reported; whereas, stomatitis and cheilitis, hyperkeratosis of nipples, eruptive cysts, eruptive nevi, squamoproliferative lesions like actinic keratoses, keratoacanthomas, and squamous cell carcinomas are rarely seen. 1,[6][7][8]11 They may be self-limiting or can persist during treatment. Depending on its type and severity, the AE is managed symptomatically, by dose reduction, treatment interruption, or discontinuation. ...
Sorafenib is a multikinase inhibitor used in the treatment of various solid tumors. Mucocutaneous adverse events are experienced by 70 to 90% of the patients receiving sorafenib, underscoring the importance of awareness among oncologists and dermatologists. Spiny follicular hyperkeratosis (SFH) is a benign and rarely reported skin reaction linked to sorafenib. It is characterized by flesh-colored or white, follicular hyperkeratotic spicules, preferentially involving the face, scalp, upper trunk, and upper arms. Besides being acknowledged as a paraneoplastic cutaneous manifestation of multiple myeloma, SFH has also been linked to a few diseases and drugs, other than sorafenib. However, the precise etiopathogenesis remains to be elucidated. We report an interesting case of SFH in a 14-year-old child, 1 week following the initiation of sorafenib. Trichodysplasia spinulosa, multiple minute digitate hyperkeratosis, keratosis pilaris, filiform warts, and pityriasis rubra pilaris are morphologically similar conditions that were excluded by clinicopathological correlation. A complete resolution of skin rash following sorafenib dose reduction further reinforced our diagnosis. Our patient also developed hand-foot skin reaction, facial erythema, and eruptive nevi during treatment. The regrowth of curly hair following chemotherapy-induced anagen effluvium was an interesting development in our case. We report this case to familiarize clinicians with this rare entity.
... The package insert for Avastin 2005 for intravenous infusion states that skin desquamation of BV is less than 1%. When used in combination with chemotherapy, skin disorders such as exfoliative dermatitis and rash have been reported to occur in 19-46% of patients and delayed wound healing in 13% of patients [6,7]. All of the skin disorders in this report resolved spontaneously after treatment was completed [7]. ...
... When used in combination with chemotherapy, skin disorders such as exfoliative dermatitis and rash have been reported to occur in 19-46% of patients and delayed wound healing in 13% of patients [6,7]. All of the skin disorders in this report resolved spontaneously after treatment was completed [7]. This is similar to the course of the present case. ...
The standard of care for ovarian cancer chemotherapy is paclitaxel-carboplatin. In Stage III and Stage IV patients, the addition of bevacizumab has been reported to be effective, and bevacizumab combined with paclitaxel-carboplatin and bevacizumab combined with docetaxel-carboplatin are used. Patients who received bevacizumab combined with docetaxel-carboplatin experienced a high incidence of skin hardening followed by peeling. In patients treated with bevacizumab combined with docetaxel-carboplatin, we experienced a high incidence of post-sclerotic peeling of the skin, a symptom that is rarely seen with paclitaxel-carboplatin (TC), docetaxel-carboplatin (DC), or bevacizumab combined with paclitaxel-carboplatin, and has been reported in a few cases. Therefore, we investigated the actual situation of skin desquamation caused by bevacizumab combined with docetaxel-carboplatin. Thirty-one patients were included in the study, and their age (mean ± SD) was 62.9 ± 9.0. The breakdown of treatment was as follows: TC in nine patients, bevacizumab combined with paclitaxel-carboplatin in ten patients, DC in six patients, and bevacizumab combined with docetaxel-carboplatin in six patients. No number of patients with TC or bevacizumab combined with paclitaxel-carboplatin showed skin desquamation. One for DC, and five for bevacizumab combined with docetaxel-carboplatin. The five patients treated with bevacizumab combined with docetaxel-carboplatin improved with topical steroids and moisturizers, but symptoms repeatedly appeared after each course. Skin desquamation was more frequent in bevacizumab combined with docetaxel-carboplatin.
... The most frequent adverse cutaneous reaction is a hand-foot-skin reaction, which has been reported in different series to occur in 21%-93% of patients on sorafenib [2,4]. Other cutaneous reactions include the development of an erythematous rash on the scalp and face occurring in 63% of patients, subungual splinter hemorrhages (70%), scalp dysesthesia (49%), alopecia (4%-57%), pruritus (4%-32%), xerosis (6%-27%), and skin follicular hyperkeratosis (21%), [2,4]. ...
... The most frequent adverse cutaneous reaction is a hand-foot-skin reaction, which has been reported in different series to occur in 21%-93% of patients on sorafenib [2,4]. Other cutaneous reactions include the development of an erythematous rash on the scalp and face occurring in 63% of patients, subungual splinter hemorrhages (70%), scalp dysesthesia (49%), alopecia (4%-57%), pruritus (4%-32%), xerosis (6%-27%), and skin follicular hyperkeratosis (21%), [2,4]. Reports of less common cutaneous reactions have included skin neoplasms, areolar hyperkeratosis, eruptive nevi, and psoriasiform rashes [4]. ...
... Other cutaneous reactions include the development of an erythematous rash on the scalp and face occurring in 63% of patients, subungual splinter hemorrhages (70%), scalp dysesthesia (49%), alopecia (4%-57%), pruritus (4%-32%), xerosis (6%-27%), and skin follicular hyperkeratosis (21%), [2,4]. Reports of less common cutaneous reactions have included skin neoplasms, areolar hyperkeratosis, eruptive nevi, and psoriasiform rashes [4]. Herein, we present a patient that developed hidradenitis suppurativa (HS) after initiation of sorafenib. ...
Sorafenib is a multi-kinase inhibitor approved for the treatment of renal cell and hepatocellular carcinoma. Adverse cutaneous reactions are a very common side effect of the medication. We report the development of hidradenitis suppurativa (HS) in a patient after initiation of treatment with sorafenib. HS is marked by recurrent deep painful nodules, fluctuant abscesses, and draining sinus tracts most frequently occurring in the groin and axilla. To our knowledge, sorafenib-induced HS in the axillary and inguinal skin folds has not been previously reported.
... 6,7 Dermatologists might be more familiar with the cutaneous adverse effects that occur in 90% of patients treated with antiangiogenic agents for other neoplastic disease. 8 Another target of potential anti-angiogenesis therapy, although less known are the angiopoietins (Ang-1 and Ang-2) and its receptor. Both Ang-2 and Ang-1 bind to the same endothelial cell membrane tyrosine kinase receptor Tie-2 (also known as TEK) and stimulate similar signaling cascades. ...
Angiogenesis is the growth of new blood vessels from pre-existing vessels. It is a biological process essential in physiological wound healing or pathological inflammation and tumor growth, which underlies a complex interplay of stimulating and inhibiting signals. Extracellular matrix, cells of innate and adaptive immunity and endothelial cells itself are a major source of angiogenic factors that activate or inhibit specific receptors and consequently influence intracellular signaling pathways.
Most inflammatory and neoplastic diseases in dermatology are characterized by excessive angiogenesis, such as psoriasis, atopic dermatitis, as well as melanoma, non-melanoma skin cancer, but also benign vascular neoplasia. In this article we describe current knowledge of angiogenesis and its most relevant mechanisms in different dermatological disorders with particular emphasis on the angiogenic factors (vascular endothelial growth factor) and angiopoietins as a target of current and future directions of anti-angiogenic therapy.
... There has also been report of lichenoid keratosis with ranibizumab use [22]. Although ranibizumab has not been specifically linked to precancerous and cancerous skin lesions, other antiangiogenesis agents have been [20,23]. Sorafenib, a multikinase inhibitor (including VEGF receptors), has been associated with actinic keratosis, focal squamous atypia, keratoacanthoma, and squamous cell carcinoma [23][24][25]. ...
... Although ranibizumab has not been specifically linked to precancerous and cancerous skin lesions, other antiangiogenesis agents have been [20,23]. Sorafenib, a multikinase inhibitor (including VEGF receptors), has been associated with actinic keratosis, focal squamous atypia, keratoacanthoma, and squamous cell carcinoma [23][24][25]. The mechanism is thought to be inhibition of the RAF kinase signaling pathway which results in keratinocyte differentiation and proliferation. ...
... Interestingly, these lesions have mostly been seen in men and have occurred in non-sunexposed regions. Typically, skin lesions will arise between 2 weeks and 3 years after starting sorafenib [23]. The patient presented in the case report indicated that he began taking ranibizumab approximately several weeks to months prior to him noticing the lesion. ...
Keratoacanthoma (KA) is a benign epithelial tumor that typically presents as a firm, cone-shaped, flesh-colored nodule with a central horn-filled crater. KA is considered to be a low-grade variant of squamous cell carcinoma (SCC). We report a rare case of a 72-year-old male who presented with a KA involving the nasal septum, possibly related to ranibizumab use. A flesh-colored lesion on the right anterior nasal septum lesion was visualized on examination. Histologic examination revealed a well-circumscribed, dome-shaped central crater filled with keratin, well-differentiated squamous epithelium with ground-glass cytoplasm with pushing margins, and intraepithelial microabscesses establishing the diagnosis of KA. KA of the nasal septum has only been reported once in the literature. This case is unusual because it normally presents on sun-exposed areas. Additionally, this patient was taking ranibizumab, a vascular endothelial growth factor (VEGF) inhibitor for macular degeneration. Despite ranibizumab not being directly linked to precancerous and cancerous skin lesions, agents in this medication class have been. Although it is difficult to prove associations in this isolated case, the role of ranibizumab causing cutaneous lesions should be further investigated.
... Although various dermatological side-effects have been seen in patients using Sunitinib maleate, prevalence of its skin toxicity has been reported as nearly <15% in previous studies. Moreover, Sunitinib maleate-related scrotal skin toxicity is extremely rare [1][2][3][4]. ...
Abstract
With the current treatment modalities like molecular targeted therapy, general survival rates have increased in patients with advanced-stage renal cell carcinoma. Sunitinib maleate is one of these drugs and its most frequently side effects are fatigue, diarrhea, hypertension, stomatitis, and hair hypo-pigmentation. Additionally, various dermatological side-effects may also be seen such as hand-foot syndrome, a yellowish color change to the face, splinter hemorrhage, erythematous reactions on the trunk, facial edema, facial erythematous changes, alopecia, acneiform rash on the face and dysesthesia in the scalp. Although Sunitinib maleate-related scrotal skin toxicity is extremely rarely seen, it should not be forgotten that this side-effect can be easily managed. Herein, we report two cases with Sunitinib maleate-related scrotal skin toxicity, which were diagnosed with advanced-stage renal cell carcinoma in this case report.
... 8 About 90% of the patients treated with sorafenib may suffer from its cutaneous side effects including handefoot skin reaction, erythematous rash on the face and scalp, subungual splinter hemorrhages, scalp dysesthesia, alopecia, pruritus, xerosis, spiny follicular hyperkeratosis, and skin neoplasmas. 9 Less commonly described are areolar hyperkeratosis or pain, eruptive nevi, eruptive facial cyst, and psoriasiform rash. 9 To our knowledge, only seven cases of sorafenib-associated psoriasiform eruption have been reported, but pathogenesis remained undetermined. ...
... 9 Less commonly described are areolar hyperkeratosis or pain, eruptive nevi, eruptive facial cyst, and psoriasiform rash. 9 To our knowledge, only seven cases of sorafenib-associated psoriasiform eruption have been reported, but pathogenesis remained undetermined. 1e7 Dysfunctional CD4 þ CD25 þ immunosuppressive regulatory T cells leading to an imbalance between regulatory and effector T-cell functions may play a crucial role. ...
Sorafenib is a multikinase inhibitor that blocks tumor cell proliferation and angiogenesis. While adverse skin reactions occur in 90% of patients treated with angiogenesis inhibitors, only a few cases of psoriasiform eruption associated with sorafenib therapy have been reported. We report a rare case of sorafenib-related psoriasis that responded well to topical treatment and narrow-band UV-B phototherapy after discontinuation of sorafenib. Copyright (C) 2016, Taiwanese Dermatological Association. Published by Elsevier Taiwan LLC.
... Skin toxicities of sorafenib are mainly mild or moderate as they usually do not require drug withdrawal [5][6][7][8][9][10]. Sometimes they require dose modifications and/or treatment interruptions [11]. Increased awareness by dermatologists who work with oncologists, of the diversity, frequency, and treatment of sorafenib-induced cutaneous adverse reactions will be helpful for patients who require long-term therapy with this medication for their cancers. ...
Drug reactions are a known risk in combined anti-cancer therapy. Less commonly recognized risks of chemotherapies and targeted immunotherapies include toxic erythema of chemotherapy reactions. With the immunosuppressive quality of cancer combined with anti-cancer treatments, patients are also susceptible to increased infection. We report a rare case of combined targeted anti-cancer treatment with bevacizumab and lorlatinib, and an associated transformation of an eczematous process into a toxic erythema of chemotherapy vasculitic eruption, with combined malignant intertrigo characteristics and superimposed infection following the initiation of bevacizumab.
Purpose
Bevacizumab is a recombinant humanized monoclonal antibody that specifically binds to vascular endothelial growth factor (VEGF). Cutaneous side effects of bevacizumab are seen with substantial frequency and may require the interruption of the treatment. The aim of the study was to conduct a biochemical and histopathological investigation of the effects of carvacrol against the possible oxidative skin damage caused by bevacizumab in rats.
Materials and methods
A total of 18 adult male Wistar albino rats were randomly assigned to three groups as healthy (H group; n = 6), bevacizumab alone (B group; n = 6), and carvacrol + bevacizumab (CB group; n = 6). Carvacrol was injected intraperitoneally (IP) at a dose of 50 mg/kg in the CB group. Sterile salt solution (0.9% NaCl) was used as a solvent for the H and B groups. One hour after the administration of carvacrol and solvent, bevacizumab at a dose of 10 mg/kg IP was administered to the CB and B groups. Bevacizumab was given once daily for a total of two doses, 15 days apart. Carvacrol was administered once daily for one month. After that period, all animals were sacrificed and their skin tissues removed. Malondialdehyde (MDA), glutathione (GSH), glutathione peroxidase (GPO), catalase (CAT), superoxide dismutase (SOD), total oxidant status (TOS), total antioxidant status (TAS) levels in rats' skin tissues were biochemically evaluated. The parameters were measured with spectrophotometric method by using a microplate reader (BioTek, Winooski, Vermont, USA). The skin tissues were also examined histopathologically by the pathologist (blind) for the study groups.
Results
The MDA and TOS levels of the H and CB groups were significantly lower than the B group (p < 0.05). The mean scores of the other biochemical levels (GSH, GPO, CAT, SOD, TAS) in the H group were significantly higher than in the B and CB groups. Pathological examination of H group was normal. In B group epidermal atrophy, abnormal keratin accumulation, degenerated hair follicles, edema and inflammatory cells accumulation in the dermis were observed. In the CB group, these findings were significantly improved.
Conclusion
The positive effect of carvacrol against possible local oxidative skin damage due to bevacizumab in rats was demonstrated. In addition, more detailed studies are required to clarify the mechanism of the protective effect of carvacrol against bevacizumab-induced skin toxicity. The effect should be evaluated through further human studies, as well as studies using different doses of carvacrol.
