Rosaceiform eruption induced by cetuximab

ARTICLE

Auteur(s) : Rose Fernández-Torres¹, Walter Martínez Gomez¹, Jesús Cuevas Santos², Sabela Paradela¹, Eduardo Fonseca Capdevila¹

¹Dermatology Department, Complejo Hospitalario Universitario A Coruña, Spain
²Pathology Department, Hospital Universitario de Guadalajara, Spain

Epidermal growth factor receptor inhibitors (EGFRI) are often associated with cutaneous side effects, mainly papulopustular eruptions. We report a rosaceiform eruption which started one year and a half after beginning cetuximab treatment and caused reversible scalp and eyebrow alopecia.

A 72-year-old male presented with a grade IV colorectal cancer (T₃N₃M₁) in September 2005, for which he received radiotherapy and chemotherapy. In June 2006, because of disease progression, a combined therapy with cetuximab, 400 mg/m² for the first administration, followed by 250 mg/m², and irinotecan (180 mg/m²), both given intravenously every week, was initiated. Three weeks after the first infusion, he developed erythematous papules and pustules without comedones on his face and upper trunk. The patient was diagnosed as having an acneiform eruption induced by cetuximab and was treated with topical clindamycin and prednicarbate, with improvement.

Eighteen months later, he developed erythematous plaques with telangiectasia and follicular scales on the cheeks, temporal regions of the scalp and eyebrows, which caused hair loss resembling scarring alopecia (figures 1A, 1B). A papulopustular eruption on the chest, abdominal wall and upper back was newly noticed. A skin biopsy from an erythematous plaque revealed an almost unaltered epidermis with mild keratin plugs. In the dermis, dilated blood vessels and a perifollicular and perivascular inflammatory infiltrate of lymphocytes, plasma cells and multinucleated giant cells were seen. Vascular damage and mucin deposition were not observed. Based on the physical and histological examinations, a diagnosis of rosaceiform eruption induced by cetuximab was made.

Topical 0.75% metronidazole gel and oral minocycline 100 mg daily for 4 months were prescribed, while cetuximab and irinotecan therapy were continued. A gradual regrowth of scalp hair and a marked improvement of the rosaceiform lesions and papulopustular eruption were observed one month later (figure 1C). Three months later, the patient had recovered the hair and the facial lesions had faded, with only a mild papulopustular eruption on the trunk remaining (figure 1D). Treatment with cetuximab and irinotecan has continued without recurrence of cutaneous lesions after a 4-month follow-up.

Acneiform eruptions affect almost all patients treated with cetuximab [1]. They consist of erythematous papules and pustules without comedones involving seborrheic areas of the face and trunk, starting 7-10 days after initiation of treatment [2-4]. Our patient presented with a typical acneiform eruption. However, one and a half years later, he developed facial lesions with striking telangiectasia and follicular scales leading to hair loss and accompanied by moderate papulopustular eruptions in the usual locations. Although a diffuse erythema and telangiectasia may sometimes be seen in patients treated with cetuximab, making the differential diagnosis with rosacea difficult, we have not found similar cases in the literature. Patrizi et al. reported a rosaceiform eruption with erlotinib [5]. Unlike our case, this eruption started earlier after erlotinib administration and was more similar to a typical papulopustular eruption.

Hair modifications are less frequent. A diffuse, non-scarring alopecia with pruritus may be seen in up 50% of patients. Conversely, facial hair, eyelashes and eyebrows may become more abundant and rigid [6].

Our patient developed patchy scalp alopecia and eyebrow loss with erythema and scale, which resembled scarring alopecia. However, it resolved with minocycline without discontinuation of cetuximab therapy.

Taking into account the clinical appearance, histological features and response to minocycline therapy, we believe that rosaceiform eruption is the most accurate diagnosis. Since EGFR inhibitors have become a mainstay of therapy for several cancers, it is expected that rosaceiform eruptions and other skin toxicities are likely to be seen with increasing frequency.

Acknowledgements

References

2 Robert C, Soria JC, Spatz A, et al. Cutaneous side-effects of kinase inhibitors and blocking antibodies. Lancet Oncol 2005; 6: 491-500.

3 Katzer K, Tietze J, Klein E, Heinemann V, Ruzicka T, Wollenberg A. Topical therapy with nadifloxacin cream and prednicarbate cream improves acneiform eruptions caused by EGFR-inhibitor cetuximab- A report of 29 patients. Eur J Dermatol 2009; 20: 82-4.

4 De Noronha E, Menezes NM, Lima R, et al. Descriptionand management of cutaneous side effecrts during erlotinib and cetuximab treatment in lung and colorectal cancer patients: A prospective and descriptive study of 19 patients. Eur J Dermatol 2009; 19: 248-51.

5 Patrizi A, Bianchi F, Neri I. Rosaceiform eruption induced by erlotinib. Dermatol Ther 2008; 21 (Suppl 2): S43-S45.

6 Galimont-Collen AFS, Vos LE, Lavrijsen APM, Ouwerkerk J, Gelderblom H. Clasification and management of skin, hair, nail and mucosal side-effects of epidermal growth factor receptor (EGFR) inhibitors. Eur J Cancer 2007; 43: 845-51.