Cutaneous Effects: Skin Rash Associated With Targeted Therapy
Background
Backround: Skin rash is a common cutaneous side effect associated with targeted therapies, affecting up to two thirds of patients receiving epidermal growth factor receptor (EGFR) inhibitors (cetuximab, erlotinib, gefitinib). It is often characterized by interfollicular and follicular-based erythematous papules and pustules and is seen during the first 2 weeks of therapy.1,2 The cutaneous eruptions appear primarily on the face, neck, and upper torso and are mild to moderate in severity as seen in Figure 1. Several studies have demonstrated a positive correlation between rash and tumor response and/or survival with cetuximab and erlotinib; findings are less consistent with gefitinib. Although it is frequently referred to as acnelike or acneiform, this rash is not associated with acne; therefore, acne medications are not appropriate for use and should be avoided to prevent their drying effects. Paronychia (painful inflammation of tissue around fingernails and toenails more commonly seen in the big toe and thumbs) also may occur as a delayed event in a smaller subpopulation. Figures 2 and 3 show papulopustular eruptions in lateral nailbeds and granulation tissue. There are no evidenced-based treatment recommendations, and rash management is based solely on anecdotal information.1-3
Figure 1.
A) Mild, B) moderate, and C) severe rash associated with HER1/EGFR inhibitor treatment.
From Pérez-Soler et al3, with permission.
Figures 2 (Left) and 3 (Right).
Figure 2 – Papulopustular eruption due to HER1/EGFR inhibitor therapy, characterized by erythematous and edematous lateral nail folds. From Dick and Crawford1, with permission.
Figure 3 – Papulopustular eruption due to HER1/EGFR inhibitor therapy, characterized by prominent granulation tissue. From Dick and Crawford1, with permission.
Assessment Tools
Adverse Event |
Grade |
||||
1 |
2 |
3 |
4 |
5 |
|
Nail changes |
Discoloration; ridging (koilonychias); pitting |
Partial or complete loss of nail(s); pain in nailbed(s) |
Interfering with ADL |
— |
— |
Rash/ desquamation |
Macular or papular eruption or erythema without associated symptoms |
Macular or papular eruption or erythema with pruritus or other associated symptoms; localized desquamation or other lesions covering < 50% of BSA |
Severe, generalized erythrodema or macular, popular, or vesicular eruption; desquamation covering ≥ 50% BSA |
Generalized exfoliative, ulcerative, or bullous dermatitis
|
Death |
ADL = activities of daily living; BSA = body surface area.
Clinical Practice Guidelines
No evidence-based guidelines are currently available.
Patient Care Management Protocols or Algorithms
Measures for Managing Skin Rash3-6
Management principle: consider the interaction of the agent with EGFR inhibitors
- Adequate fluid intake for hydration; bath and shower oils (not gels) and bathing in tepid water are recommended
- Sun exposure should be limited; wear a hat; sun barriers reduce risk of hyperpigmentation
- Xerosis (abnormally dry skin) can be alleviated by using oil-in-water creams or ointments; a suggested emollient is Vaseline Intensive Care Advanced Healing Lotion®; if eczema develops, weak topical steroids are recommended short-term. A dermatologist-approved make-up can be used along with a liquid cleanser to remove the make-up; retinoids (creams that contain vitamin A) should be avoided, because they can aggravate skin rashes
- Paronychia can be prevented by wearing shoes that are not too tight; avoid friction; use topical antiseptic or antibiotic soaks and/or creams; soaking and cushioning brings comfort. Does not diminish as therapy continues and may take several months to heal after therapy has stopped
- Telangiectasia (chronic dilation of groups of capillaries leading to elevated dark red blotches on the skin)
- Trichomegaly (increased hair growth of eyelashes and eyebrows) is rare
- Infected rash can be treated with a short course of oral antibiotics such as tetracyclines because of their effectiveness against Staphylococcus. If S. aureus is confirmed, consider topical mupirocin (Bactroban)
Suggested management of skin rash per grade* |
|||
1 |
2 |
3 |
4 |
Rash is usually inflammatory, not infectious; not dose limiting; no therapy or anti-inflammatory agents may be needed; avoid alcohol-based agents to prevent drying of the skin and any topical or systemic steroids, because they may aggravate the acne
|
Creams that may be used for grade 1 rash could be added to topical menthol cream or an oral antihistamine for pruritus. Oral isotretinoin (Accutane) is not recommended
|
Dose limits are likely. Physiologic solution compresses may help with inflammation. Oral antihistamines and tetracyclines are recommended
|
Rashes rarely progress to this grade. If so, hospitalization is necessary and EGFR inhibitors should never be given again
|
*Conflicting studies have shown that any grade of rash is associated with increased survival compared with patients without a rash.5 Others have stated the absence of an acneiform rash does not mean the therapy is ineffective.6 Management per grade should be incorporated into general management suggestions.
EGFR = epidermal growth factor receptor.
References
- Dick S, Crawford G. Managing cutaneous side effects of epidermal growth factor receptor (HER1/EGFR) inhibitors. Community Oncol. 2005;2:492-496.
- Pérez-Soler R, Saltz L. Cutaneous adverse effects with HER1/EGFR-targeted agents: is there a silver lining? J Clin Oncol. 2005;23:5235-5246. [ Pub Med ]
- Pérez-Soler R, Delord J, Halpern A, et al. EGFR inhibitor-associated HER1/EGFR inhibitor rash: future directions for management and investigation outcomes from the Management Forum. Oncologist. 2005;10:345-356.
- Segaert S, Van Cutsem E. Clinical signs, pathophysiology and management of skin toxicity during therapy with epidermal growth factor inhibitors. Ann Oncol. 2005;16:1425-1433.
- Yamamoto DS, Viale PH, Zhao G. Severe acneiform rash. Clin J Oncol Nurs. 2004;8:654-656.
- Thomas M. Cetuximab: adverse event profile and recommendations for toxicity management. Clin J Oncol Nurs. 2005;9:332-338.
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