Gutzmer, R., Becker, J.C., Enk, A., Garbe, C., Hauschild, A., Leverkus, M., . . . Homey, B. (2011). Management of cutaneous side effects of EGFR inhibitors: Recommendations from a German expert panel for the primary treating physician. Journal der Deutschen Dermatologischen Gesellschaft, 9, 195–203.

To describe the underlying mechanisms, clinical presentation, severity grading (according to National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE], version 4.0), and strategies to prevent and manage epidermal growth factor receptor inhibitor (EGFRI)-associated skin side effects, emphasizing evidence-based practice.

The type of patients addressed was adults receiving an EGFRI, including monoclonal antibodies (e.g., cetuximab, panitumumab) and tyrosine kinase inhibitors (e.g., erlotinib, gefitinib, lapatinib).

In this expert opinion article, a panel of German dermatologists met in June 2009 in Frankfurt am Main, Germany, to generate mutual recommendations on the management of cutaneous side effects of EGFRIs. Those recommendations were passed after an internal revision in July 2010. The authors stated the basis of the recommendations was the physicians’ long-term personal experiences with affected patients.

Databases searched were not reported.

Search keywords were EGFR, cutaneous side effects, and papulopustular exanthema.

Studies were included in the review if they were published up to April 2010.

Exclusion criteria were not reported.

Patients were undergoing the active treatment phase of care.

General and Preventive Measures for All Patients Receiving EGFRI Therapy:

• Give patient education regarding various cutaneous side effects, usual time points for manifestation, and positive correlation between early occurring papulopustular exanthems and therapy success and general measures. 
• The following advice was recommended for preventive skin care procedures for all patients receiving therapy with EGFRIs:
  • Avoid frequent hand washing; daily, long showers; or frequent, long baths.
  • Use mild bath or shower oils or syndets (no soap).
  • Use moisturizers or urea-containing skin care products (e.g., ointment, cream) without fragrances or other skin irritants (no lotion or gel).
  • Avoid sun-tanning parlors, and consistently use sun protection products (light exposure factor > 20) or clothing protection from ultraviolet radiation.
  • Avoid skin contact with irritants such as solvents, disinfectants, and polishes.
  • Avoid activities that mechanically stress the skin (e.g., garden work, carrying heavy objects, hot hair drying).
  • For adequate treatment of preexisting skin diseases, refer to a dermatologist.

Medicinal Prophylaxis of EGFRI Cutaneous Lesions:

• A few studies on medicinal prophylaxis of papulopustular exanthema have been performed, and their results do not allow for reliable recommendations.
• Prophylactic treatments included oral tetracycline, minocycline, and doxycycline; topical pimecrolimus; skin moisturizer; and topical sunscreen, glucocorticosteroids, and vitamin K3.

Therapy of the Papulopustular Exanthems on the Face and Trunk:

• Initiate combined therapy with a topical metronidazole or nadifloxacin-containing ointment and a systemic tetracycline (doxycycline: 50 or 100 mg BID;  minocycline: 50 mg BID; tetracycline: 2–4 x 250 mg daily).
• Treatment of rash with wound gel containing collagen or lidocaine and topical vitamin K3 is being studied.

Advanced Diagnostics and Therapy for Rash (Usually With a Dermatologist):

• Obtain microbial diagnostics in papulopustular exanthema.
• If Demodex mites are detected in the lesions, employ topical metronidazole, a short course of an azelaic acid cream, or a cream containing permethrin.
• If Pityrosporum yeasts are identified, ciclopirox olamine, clotrimazole, or ketoconazole is recommended.
• In bacterial superinfection, depending on the antibiogram (usually identification of Staphylococcus aureus), topical therapy with an antiseptic agent (e.g., octenidine) and targeted systemic antibiotic therapy are recommended.
• For eczematous skin lesions with scaling and pruritus on the trunk, mild-to-moderate potency topical glucocorticosteroids (e.g., hydrocortisone butyrate, methylprednisolone aceponate) are recommended.
• When clinical features of seborrheic dermatitis or perioral dermatitis are present in the face, pimecrolimus or tacrolimus and a topical antifungal agent (e.g., ciclopirox) may be used.

Therapy of Papulopustular Exanthems on the Scalp:

• Early treatment with a systemic antibiotic usually offers effective protection from the development of a severe papulopustular rash on the scalp.
• In patients who develop a superinfection despite administration of a systemic antibiotic, microbiological diagnostics should be performed and therapy based on the antibiogram should be changed to an antibiotic effective against S. aureus (e.g., flucloxacillin).
• Antimicrobial shampoos may be used.

Treatment Recommendations: Dry Skin and Pruritus:

• Use of emollients (e.g., urea-containing products), perhaps with the addition of an antiseptic (e.g., triclosan) can be used for dry, sensitive skin.  
• If marked inflammation exists, a short course of glucocorticosteroid ointment is recommended.
• If severe inflammation exists, a short course of glucocorticosteroid ointment and an antiseptic is recommended.
• Topical products containing polidocanol and oral antihistamines can be used on a supplemental basis for dry skin and pruritus.
• If inflamed skin fissures exist, obtain a referral to a dermatologist.

Treatment Recommendations: Paronychia:

• In early stages of paronychia, treatment with a topical antifungal agent (e.g., ciclopirox olamine) and a topical antibiotic (fusidic acid) is recommended.
• In the event of damage to the cuticle, a nail lacquer containing ciclopirox should be applied every two days.
• Combination of a topical glucocorticosteroid and a disinfectant can be considered.
• Systemic therapy can include one of the oral tetracyclines, or an oral cephalosporin or quinolone.
• In advanced or persistent inflammation, the patient should be referred to a dermatologist for further treatment.
• For severe inflammation, microbiological tests and targeted antibiotic therapy are recommended.
• Excessive granulation tissue should be removed surgically or with silver nitrate.
   

Effective management of frequent cutaneous side effects is important for tumor therapy. The present recommendations developed by a German expert panel are based on a three-step concept.

• Patient education and general preventive measures
• Measures that should be initiated as early as possible by the primary treating physician at the first sign of skin lesions
• Advanced diagnostics and therapy by a specialized dermatologist

Although the article had 36 references, several interventions (especially in rash—advanced diagnostics and therapy, rash—therapy on scalp, measures for dry skin and pruritus, and therapy of paronychias) do not have a specific reference.

Adequate management of cutaneous side effects is necessary for optimal therapeutic benefit and enhanced quality of life. Because of their visibility, cutaneous side effects are experienced by many patients as a psychological burden that can impair quality of life and often endangers compliance with therapy, or leads to a dose reduction or discontinuation. This article provided nurses with practical recommendations for the prevention and management of cutaneous side effects of EGFRIs.