Clinical TopicsDermatologyOncology

Putting Evidence Into Practice: Skin reactions


Editor’s note: One in a series of articles on managing cancer-related symptoms from the Oncology Nursing Society.

Skin reactions from chemotherapy or biotherapy can have a significant impact on the quality of life of a patient with cancer. Although rarely life threatening, skin reactions can hinder physical abilities and affect psychosocial well-being (Burtness et al., 2009). The most common forms of skin reactions are rash, palmar-plantar erythrodysesthesia (PPE), xerosis, paronychia, photosensitivity, and pruritus (Robison, 2011).

In addition, two major types of rashes are seen, acneform and maculopapular. Acneform usually appears as a diffuse erythema on the face and body and resembles acne (National Cancer Institute Cancer Therapy Evaluation Program [NCI CTEP], 2010; Polovich, Whitford, & Olsen, 2009). Maculopapular rash exhibits flat macules and elevated papules and usually affects the upper part of the body (NCI CTEP, 2010).

Various chemotherapy and biotherapy drugs may cause skin reactions in patients with cancer. The incidence of skin toxicity varies with the drug used (Robison, 2011) and, with the advancement of treatment through targeted therapies, incidence has increased (Lacouture, Basti, Patel, & Benson, 2006). Oncology nurses can use ongoing skin assessments as a tool to identify and minimize these skin reactions. By conducting physical examinations of the skin, submitting laboratory and diagnostic tests, and listening to patient-reported symptoms, an accurate diagnosis may be obtained and appropriate treatment planned (Robison, 2011).

Putting Evidence Into Practice

To promote nursing practice that is based on evidence, the Oncology Nursing Society (ONS) launched the Putting Evidence Into Practice (PEP) program in 2005. ONS PEP teams consisting of advanced practice nurses, staff nurses, and a nurse scientist were charged with reviewing the literature to determine what treatments and interventions are proven to alleviate many cancer-related problems that are sensitive to nursing interventions. Each team classified interventions under the following categories: recommended for practice, likely to be effective, benefits balanced with harms, effectiveness not established, effectiveness unlikely, not recommended for practice, and expert opinion.

Effectiveness not established

Although no treatments are listed as recommended for practice, likely to be effective, or benefits balanced with harms, a number of interventions are listed as effectiveness not established. This category includes treatments for which insufficient or conflicting data or data of inadequate quality currently exist, with no clear indication of harm.

Local and regional treatments

A series of local and regional interventions have been used to prevent and treat skin reactions (Robison et al., 2011). One case study by DeWitt, Siroy, and Stone (2007) reported on a 52-year-old Caucasian man with stage IV colon cancer who had a papulopustular rash on his face, neck, chest, back, and scalp. DeWitt et al. (2007) listed the following treatment as resulting in significant improvement to erythema and crusting: oral minocycline 100 mg twice daily, adapalene 0.1% gel twice daily, and dilute acetic acid soaks plus mupirocin cream three to four times per day applied to facial and scalp encrustations.

Regional cooling is another local treatment listed in the effectiveness not established category, however, results are mixed. According to research by Tanyi et al. (2009), patients with gynecologic cancer who received pegylated liposomal doxorubicin (PLD) had a higher incidence of PPE when they used a regional cooling mechanism compared to patients who did not. However, other studies (Mangili et al., 2008; Molpus, Anderson, Craig, & Pulee, 2004; Tedjarati, Sayer, Boulware, & Apte, 2006) have reviewed regional cooling and found a decrease in the incidence and severity of PPE when regional cooling was used.

Topical agents

A series of topical agents have been studied as well for the treatment of skin reactions. These include antiseptics, antibiotics, dimethyl sulfoxide (DMSO), steroids, retinoids, and petroleum. Most of these agents were used for the prevention and treatment of epidermal growth factor receptor (EGFR) inhibitor-induced rash, PPE, xerosis, and pruritus (Robison et al., 2011). A listing of agents and their targeted skin reactions can be found in Table 1.

Topical Agents Targeted Skin Reactions
Antiseptics EGFR inhibitor-induced rash and PPE
Antibiotics EGFR inhibitor-induced rash and paronychia
Emollients and moisturizers Xerosis, pruritus, EGFR inhibitor-induced rash, and PPE
Immune modulator EGFR inhibitor-induced rash and pruritus
Retinoids EGFR inhibitor-induced rash and photosensitivity
Steroids Rash and rash related to photosensitivity

Note. Based on information from Robison et al., 2011.

Systemic interventions

In addition to local and regional treatments and topical agents, systemic interventions also are listed in the effectiveness not established category. These interventions include amifostine, systemic antibiotics, oral steroids, cyclooxygenase-2 (COX-2) inhibitors, pregabalin, pyridoxine, and vitamin E (Robison et al., 2011). Systemic antibiotics have, perhaps, been used the most from this group—primarily to treat EGFR inhibitor-induced rashes. However, according to Tan and Chan (2009), the use of antibiotics holds promise but evidence is lacking. In many reports, this intervention was combined with multiple other treatments.

Other interventions

The effectiveness not established category lists three additional treatments that cannot be classified under the previous three headings. They are electrodessication, minimizing sun exposure, and the use of a nicotine patch. Electrodessication was reported to be successful in treating paronychia (Dainichi et al., 2003), and the nicotine patch effectively addressed dermatitis when placed on a patient’s skin during 5-FU infusions (Kingsley, 1994). However, both of these interventions were reported as case studies involving one patient. Regarding sun exposure, two case studies (Chang, Chang, Hui, & Yang, 2009; Kong et al., 2009) found that sun avoidance minimized photosensitivity secondary to vandetanib therapy. In addition, according to Burtness et al. (2009), sunscreen containing zinc oxide or titanium dioxide should be used to protect the skin from the sun.

Expert opinion

Interventions listed in the expert opinion category are consistent with sound clinical practice, are suggested by an expert in a peer-reviewed publication, but have limited evidence to support their effectiveness. Many recommendations in the expert opinion category are employed concurrently with interventions in other PEP categories (Robison et al., 2011).

  • Avoiding tissue pressure, irritation, and trauma—To minimize discomfort from PPE and to prevent paronychia, patients should avoid prolonged friction/pressure and avoid extreme temperatures (Edwards, 2003).
  • Application of warm or cool soaks—Warm water soaks may provide comfort and prevent paronychial infection in the fingers and toes (Viale, 2006). Cool soaks may relieve PPE and pruritus symptoms (Agero et al., 2006; Edwards, 2003).
  • Antihistamines—Topical or systemic antihistamines may manage pruritus from rash, photosensitivity reactions, or xerosis (Agero et al., 2006).
  • Dermatology consult—Particularly for patients with blistering and ulceration (Gerbrecht, 2003).
  • Lotions and moisturizers—These products should be applied regularly and gently. In addition, patients should apply at night and wear loose-fitting cotton clothing (Burtness et al., 2009; Edwards, 2003; Gerbrecht, 2003).
  • Patient education—Nurses should teach patients to assess for pressure-sensitive areas, report signs and symptoms of PPE, and use restorative and prophylactic strategies to minimize the likeliness of PPE (Wilkes & Doyle, 2005).
  • Topical anesthetics—If the patient has severe pruritus, topical numbing agents (e.g., pramoxine, lidocaine) may provide relief (Lacouture, 2007).
  • Techniques to prevent and manage paronychia—Use of a topical antiseptic paste (e.g., chlorhexidine) and an anti-yeast agent (e.g., nystatin) with a corticosteroid may reduce the development of severe lesions (Segaert & Van Cutsem, 2005).
  • Techniques to prevent and manage xerosis and pruritus—Patients should avoid overheating by wearing loose-fitting cotton clothing, should maintain adequate fluid intake, and use ammonium lactate 12% lotion (Pyle et al., 2008). In addition, medical-grade cyanoacrylate is often used to close fissures secondary to xerosis (Segaert & Van Cutsem, 2005).
  • Dose modification—Treatment interruption, dose reduction or delay, and lengthening the interval between drug administrations may be the most significant management for skin reactions. However, the impact on cancer treatment response and overall survival must be considered (Burtness et al., 2009).

Skin reactions, in general, may be episodic regardless of treatment interruption, and could wax and wane or spontaneously resolve (Lynch et al., 2007). Early-treatment effects oncology nurses should be aware of include sensory disturbances, erythema, edema, papulopustular rash, and crusting. Reactions such as hyperpigmentation, hair changes, paronychia/fissuring, and xerosis occur later (Lacouture et al., 2006). Healthcare providers must remain vigilant and assess for recurrent symptoms or infections related to continued use or cyclic recurrence as well as long-term effects of treatment (Anderson et al., 2009; Burtness et al., 2009).

Sean Pieszak is a staff editor in the publications department at the Oncology Nursing Society in Pittsburgh, PA. More information about the ONS PEP classification for skin reactions can be found at

Selected references

Agero, A.L.C., Dusza, S.W., Benvenuto-Andrade, C., Busam, K.J., Myskowski, P., & Halpern,
A.C. (2006). Dermatologic side effects associated with the epidermal growth factor
receptor inhibitors. Journal of the American Academy of Dermatology, 55, 657–670.

Anderson, R., Jatoi, A., Robert, C., Wood, L.S., Keating, K.N., & Lacouture, M.E. (2009). Search for evidence-based approaches for the prevention and palliation of hand-foot skin
reaction (HFSR) caused by the multikinase inhibitors (MKIs). Oncologist, 14, 291–302.

Burtness, B., Anadkat, M., Basti, S., Hughes, M., Lacouture, M.E., McClure, J.S., … Spencer, S. (2009). NCCN Task Force Report: Management of dermatologic and other toxicities
associated with EGFR inhibition in patients with cancer. Journal of the National
Comprehensive Cancer Network
, 7(Suppl. 1), S5–S21.

Chang, C.H., Chang, J.W., Hui, C.Y., & Yang, C.H. (2009). Severe photosensitivity reaction to vandetanib. Journal of Clinical Oncology, 27, e114-e115. doi:10.1200/JCO.2009.21.8479

Dainichi, T., Tanaka, M., Tsuruta, N., Furue, M., & Noda, K. (2003). Development of multiple paronychia and periungual granulation in patients treated with gefitinib, an inhibitor of epidermal growth factor receptor. Dermatology, 207, 324–325. doi:10.1159/000073100

DeWitt, C. A., Siroy, A. E., & Stone, S. P. (2007). Acneiform eruptions associated with
epidermal growth factor receptor–targeted chemotherapy. Journal of the American
Academy of Dermatology
, 56, 500–505. doi:10.1016/j.jaad.2006.06.046

Edwards, S.J. (2003). Prevention and treatment of adverse effects related to chemotherapy for recurrent ovarian cancer. Seminars in Oncology Nursing, 19(3, Suppl. 1), 19–39.

Gerbrecht, B.M. (2003). Current Canadian experience with capecitabine: Partnering with
patients to optimize therapy. Cancer Nursing, 26, 161–167.

Kingsley, E.C. (1994). 5-fluorouracil dermatitis prophylaxis with a nicotine patch [Letter]. Annals of Internal Medicine, 120, 813.

Kong, H.H., Fine, H.A., Stern, J.B., & Turner, M.L. (2009). Cutaneous pigmentation after
photosensitivity induced by vandetanib therapy. Archives of Dermatology, 145, 923–925.

Lacouture, M.E. (2007). Insights into the pathophysiology and management of dermatologic
toxicities to EGFR-targeted therapies in colorectal cancer. Cancer Nursing, 30(4 Suppl.
1), S17–S26. doi:10.1097/01.NCC.0000281758.85704.9b

Lacouture, M.E., Basti, S., Patel, J., & Benson, A., III. (2006). The series clinic: An
interdisciplinary approach to the management of toxicities of EGFR inhibitors. Journal of
Supportive Oncology
, 4, 236–238

Mangili, G., Petrone, M., Gentile, C., De Marzi, P., Vigano, R., & Rabaiotti, E. (2008). Prevention strategies in palmar-plantar erythrodysesthesia onset: The role of regional cooling. Gynecologic Oncology, 108, 332–335. doi:10.1016/j.ygyno.2007.10.021

Molpus, K.L., Anderson, L.B., Craig, C.L., & Pulee, J.G. (2004). The effect of regional cooling on toxicity associated with intravenous infusion of pegylated liposomal doxorubicin in
recurrent ovarian carcinoma. Gynecologic Oncology, 93, 513–516. doi:10.1016/j.ygyno.2004.02.019

National Cancer Institute Cancer Therapy Evaluation Program. (2010). Common terminology criteria for adverse events [v.4.03]. Retrieved from

Polovich, M., Whitford, J.M., & Olsen, M. (Eds.). (2009). Chemotherapy and biotherapy
guidelines and recommendations for practice
(3rd ed., pp. 182–197). Pittsburgh, PA:
Oncology Nursing Society.

Pyle, L., Beirne, D., Bird, J., Hoggarth, L., Jamieson, C., Lane, L., … Woods, J. (2008).
Managing the side effects of sunitinib: A guide to empowering the patient. Cancer
Nursing Practice
, 7, 42–47.

Robison, J. (2011). Skin reactions: Rash, palmar-plantar erythrodysesthesia, xerosis, paronychia, photosensitivity, and pruritus. In L.H. Eaton, J.M. Tipton, & M. Irwin (Eds.), Putting Evidence into Practice: Improving oncology patient outcomes (vol. 2, pp. 77-99). Pittsburgh, PA: Oncology Nursing Society.

Robison, J., Carpizo, T. Carlson, J., Fuhrman, A., Portz, D., Shelton, G., & Williams, L.A. (2011). Skin reactions. In L.H. Eaton, J.M. Tipton, & M. Irwin (Eds.), Putting Evidence into Practice: Improving oncology patient outcomes (vol. 2, pp. 101-121). Pittsburgh, PA: Oncology Nursing Society.

Segaert, S., & Van Cutsem, E. (2005). Clinical signs, pathophysiology and management of skin toxicity during therapy with epidermal growth factor receptor inhibitors. Annals of Oncology, 16, 1425-1433.

Tan, E.H. & Chan, A. (2009). Evidence based treatment options for the management of skin
toxicities associated with epidermal growth factor receptor inhibitors. Annals of
, 43, 1658–1666. doi:10.1345/aph.1M241

Tanyi, J.L., Smith, J.A., Ramos, L., Parker, C.L., Munsel, M.F., & Wolf, J.K. (2009).
Predisposing risk factors for palmar-plantar erythrodysesthesia when using liposomal
doxyrubicin to treat recurrent ovarian cancer. Gynecologic Oncology, 114, 219–224.

Tedjarati, S., Sayer, R., Boulware, D., & Apte, S. (2006). Regional cooling protocol (RCP) significantly reduces the incidence of pgylated liposomal doxorubicin (PLD) induced palmar-plantar erythrodysesthesia (PPE) in patients with recurrent epithelial ovarian cancer [Abstract 302]. Poster presented at the 11th Biennial International Gynecologic Cancer Society Meeting, Santa Monica, CA.

Viale, P.H. (2006). Chemotherapy and cutaneous toxicities: Implications for oncology nurses. Seminars in Oncology Nursing, 22, 144-151.

Wilkes, G.M., & Doyle, D. (2005). Palmar-plantar erythrodysesthesia. Clinical Journal of
Oncology Nursing
, 9, 103–106. doi:10.1188/05.CJON.103-106

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