Single and multiple kinase inhibitors are now targeted therapeutic strategies for the treatment of human malignancies, producing variable outcomes compared with conventional cytotoxic therapy. However, 45-100% of patients treated with an EFGR inhibitor present with cutaneous toxicities [2]. This is due to the key role of EGFR signalling in skin [2]. As Dr Salena described, EGFR is centrally involved in the maintenance of normal skin architecture, in growth and repair processes, and in the regulation of the inflammatory response of the epithelia. EGFR is most prominently expressed in proliferating basal keratinocytes.
EGFR inhibition results in numerous adverse effects on the skin, such as apoptosis, atrophy, telangiectasia, and a reduced photoprotection. Skin toxicities are due to damage of the epithelial barrier, loss of antimicrobial mechanisms (especially protective mechanisms against Staphylococcus aureus), and the extensive release of inflammatory chemokines and cytokines [2]. Adverse events after therapy with an EGFR inhibitor follow a typical time course: acneiform rash is common in the first 4 weeks of therapy, followed by post-inflammatory effects. Xerosis starts after more than 5 weeks, and fissures typically emerge after 7 weeks. The last manifestation is paronychia. Cutaneous rash caused by EGFR inhibitors is characterised by follicular and perifollicular papules and pustules, pruritus, and/or burning sensations. It typically occurs in a seborrhoeic distribution, primarily on the face, scalp, neck, and upper torso.
In a trial, a pre-emptive skin treatment regimen to avoid skin toxicities that included the use of skin moisturisers, sunscreen, topical steroid, and doxycycline was able to reduce the incidence of grade 2 skin toxicities by more than 50% [3]. This skin reaction had an early onset, but the severity of EGFR inhibitor-induced papulopustular eruptions often decreases with continued use of the drug. “Usually, the eruptions are sterile. Therefore, perform systematic bacterial swabs only in case of persistent, atypical, or late form of acneiform eruptions,” recommended Dr Sollena. Late papulopustular rash is a distinct clinical entity [4]. It occurs after several months, usually on the limbs, sparing the face, and with pruritus and S. aureus superinfection. Xerosis and pruritus usually start more than 5 weeks after treatment and have a major negative impact on quality of life. Fissures are also complications appearing in later treatment phases [6]. Nail changes such as paronychia are less common and generally seen after a longer period of treatment [6]. This disorder is characterised by an inflammatory process involving the soft tissues around the nail. It can lead to infection and the consequent swelling and tenderness often affect daily activities. According to a meta-analysis, the overall incidence of all-grade nail toxicity was 17.2% in patients [7].
When undergoing treatment with EFGR inhibitors it is further important “to avoid skin irritants and soaking of hands and feet for a prolonged time period in soapy water,” stated Dr Sollena. Patients are advised to make sure that their feet are dry before putting on shoes. The EGFR is also expressed on eye surfaces as well as in the tear and sebaceous glands. Up to 15% of patients receiving anti-EGFR therapy can experience ocular toxicity [8]. “Treating a skin reaction only once it occurs may not be the most effective management approach. Prophylactic strategies for cleansing, skincare, and sun protection are more successful in reducing the incidence of skin adverse events”, concluded Dr Sollena.
- Sollena P. 24th World Congress of Dermatology, 10-15 June 2019, Milan, Italy.
- Lacouture ME. Nat Rev Cancer 2006:6:803-12.
- Lacouture ME, et al. J Clin Oncol 2010:28:1351-7.
- Sibaud V, et al. Clin Exp Dermatol 2016;41:34-7.
- Clabbers JMK, et al. Support Care Cancer 2016:24:513-521.
- Ehmann LM, et al. Skin Therapy Lett 2011:16:1-3.
- Garden BC, et al. J Am Acad Dermatol 2012;67:400-8.
- Lacouture ME, et al. Clin Colorectal Cancer 2018;17:85-96.
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Table of Contents: WCD 2019
Featured articles
Letter from the Editor
Insights into pathogenesis of AD define novel therapeutic targets
Treating Psoriasis in 2019
Choosing the right biologic in psoriasis
Registries – an important research tool in biologics
Atopic Dermatitis – What is New
Insights into pathogenesis of AD define novel therapeutic targets
Combinations are hot in AD treatment
Dermal Reactions to Systemic Drugs
Cutaneous adverse events due to EGFR inhibitors
Management strategies for drug-induced mucositis
Skin toxicity of immune checkpoint inhibitors
Lupus Erythematosus Today
New targets and biologics for cutaneous lupus erythematosus
Novel lupus classification will aid future research
Hidradenitis Suppurativa
Various guidelines with much overlap
Antibiotics in hidradenitis suppurativa
Biologicals beyond TNF blockade
Small Molecules – What to Expect
Novel treatment options for many dermatologic indications
Long awaited oral therapy for moderate-to-severe AD
Novel treatment options in alopecia areata and vitiligo
Optimising the Management of Keloids
Keloids: a faulty switch in wound healing?
What the future of keloid treatment could hold
Malignant Melanoma – Advances in Management
Will malignant melanoma become a curable disease?
Best of the Posters
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