Trichomegaly of the eyelashes following treatment with cetuximab

We report on a 74-year-old female patient who was diagnosed with metastatic rectal cancer in July 2002. She was treated initially by preoperative pelvic radiotherapy (25 Gy) followed by proctectomy and liver resection. After metastatic relapse, she received three lines of polychemotherapy (LV5FU2, FOLFOX6 then FOLFIRI) with best response as stabilization of disease. In April of 2004, the radiological assessment confirmed progressive disease in lung and liver after 20 courses of chemotherapy with the FOLFIRI regimen. The tumor was expressing epidermal growth factor receptor (EGFR); therefore, cetuximab (Erbitux®; Merck KgaA, Darmstadt, Germany) was administered at an initial dose of 400 mg/m2 followed by weekly infusions (250 mg/m2) in combination with irinotecan (180 mg/m2 biweekly).

After 3 months of treatment, the patient developed mild typical acneiform lesions commonly described in patients receiving EGFR inhibitors. She also observed a marked increase in the length of her eyelashes after 5 months of treatment (Figure 1) without associated hypertrichosis. This trichomegaly induced visual discomfort and obligated the patient to cut her eyelashes. She received 36 courses of cetuximab during 9 months with stabilization of metastatic lesions, but the last assessment, performed in December 2004, showed progressive disease. Our patient did not receive other trichomegaly-inducing drugs. One month after the stopping of cetuximab the eyelashes were normal.



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Figure 1. Trichomegaly of the eyelashes in a patient treated with cetuximab.

 
Trichomegaly or lengthening of the eyelashes has been found to be familial, paraneoplastic [1Go], associated with immunodeficiency syndrome (AIDS) or dermatomyositis [2Go], and to be induced by many drugs (interferon-{alpha}-2b, cyclosporin, bimatoprost [3Go], gefitinib [4Go]).

Cetuximab is the first monoclonal antibody (IgG1) that has demonstrated activity in metastatic colorectal cancer patients with EGFR expression [5Go]. Cetuximab binds specifically to the EGFR preventing dimerization, and blocks signal transduction pathways implicated in the proliferation and survival of cancer cells and improve apoptosis [5Go]. EGFR is expressed in the epidermis, the sweat gland apparatus and hair follicle epithelium, especially the outer root sheath of the hair follicles. Experimental studies have demonstrated a central role of the EGFR in the normal differentiation and development of the hair follicle [6Go]. Acneiform eruptions, paronychial swellings, are more specific skin toxicity observed with cetuximab. Busam et al. [6Go] suggested that alteration of p27kip1 (negative growth regulator) may be the mechanism by which cetuximab can affect follicular and epidermal homeostasis.

This upregulation of p27kip1 has also been reported with gefitinib (Iressa®; AstraZeneca, Wilmington, DE, USA), which increase apoptosis and maturation. This maturation can explain trichomegaly induced by gefitinib [4Go]. Two cases of trichomegaly associated with cetuximab were reported by Dueland et al. [7Go], who suggested that the mechanism regulating the growth of hair may differ in different parts of the body, with stimulation of the growth of the eyelashes at the same time as hair loss induced by irinotecan.

In our case, trichomegaly of the eyelashes was reported after the beginning of cetuximab with completely regression of this symptom 1 month after stopping administration of cetuximab, and the patient did not receive other trichomegaly-inducing drugs. These arguments can confirm the relationship between cetuximab and trichomegaly. Cetuximab can be added to the list of drugs responsible for trichomegaly of the eyelashes.

O. Bouché1,*, H. Brixi-Benmansour1, A. Bertin1, G. Perceau2 and S. Lagarde1

Departments of 1 Gastroenterology and 2 Dermatology, University Hospital of Reims, Reims, France

* E-mail: obouche{at}chu-reims.fr

References

1. Farina MC, Tarin N, Grilli R et al. Acquired hypertrichosis lanuginosa: case report and review of the literature. J Surg Oncol 1998; 68: 199–203.[CrossRef][ISI][Medline]

2. Sharma RC, Mahajan VK, Sharma NL, Sharma A. Trichomegaly of the eyelashes in dermatomyositis. Dermatology 2002; 205: 305.[CrossRef][ISI][Medline]

3. Tosti A, Pazzaglia M, Voudouris S, Tosti G. Hypertrichosis of the eyelashes caused by bimatoprost. J Am Acad Dermatol 2004; 51: S77–S78.[CrossRef][Medline]

4. Pascual JC, Banuls J, Belinchon I et al. Trichomegaly following treatment with gefitinib (ZD1839). Br J Dermatol 2004; 151: 1111–1112.[CrossRef][ISI][Medline]

5. Cunningham D, Humblet Y, Siena S et al. Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med 2004; 351: 337–345.[Abstract/Free Full Text]

6. Busam KJ, Capodieci P, Motzer R et al. Cutaneous side-effects in cancer patients treated with the antiepidermal growth factor receptor antibody C225. Br J Dermatol 2001; 144: 1169–1176.[CrossRef][ISI][Medline]

7. Dueland S, Sauer T, Lund-Johansen F et al. Epidermal growth factor receptor inhibition induces trichomegaly. Acta Oncol 2003; 42: 345–346.[CrossRef][ISI][Medline]





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