Exudative, Nonhealing Scalp: A Complication of Systemic Chemotherapy With Capecitabine and Bevacizumab

Capecitabine, a prodrug of fluorouracil, is a pyrimidine analogue that can inflame actinic keratoses.¹ The inflammation manifests primarily as simple erythema in areas of actinic keratoses, although acral erythema and other cutaneous adverse effects have been reported.^{1 - 2} Bevacizumab inhibits angiogenesis by blocking vascular endothelial growth factor and can produce cutaneous adverse effects such as exfoliative dermatitis, skin ulceration, and acneiform eruptons.³ We describe a severe complication resulting from the combination of capecitabine and bevacizumab.

A 70-year-old man with a history of nonmelanoma skin cancers of the face and scalp was diagnosed as having metastatic colon cancer and treated with systemic capecitabine for 1 year and bevacizumab for 6 months. Thereafter, he developed mild erosions of the scalp, which quickly progressed into exudative, yellow-brown, crusted plaque (Figure 1). In addition, a tender, erythematous papule grew within the plaque. Biopsy specimens demonstrated the papule to be a squamous cell carcinoma requiring removal with Mohs surgery.

Afterward, the patient elected to undergo therapeutic debridement of the plaque, which was limited by the exquisitely tender nature of the lesion. Topical antibiotics, topical steroids, and topical calcineurin inhibitors also failed to improve the lesion. Biopsy specimens from the area demonstrated a thick, neutrophilic serum crust overlying mild fibrosis of the dermis (Figure 2). Serial cultures grew Serratia marcescens, Klebsiella pneumoniae, Pseudomonas aeruginosa, and yeast. The patient was treated with oral ciprofloxacin and fluconazole as indicated by culture sensitivities without substantial improvement.

A year later, a second squamous cell carcinoma developed within the plaque, and the patient was prescribed oral acitretin, 25 mg/d, for its antiproliferative effects. With no improvement after 6 weeks, the patient elected to stop acitretin treatment and pursue radiation therapy. He received a total dose of 70 Gy to a 10-cm cone surrounding the squamous cell carcinoma (to convert grays to rads, multiply by 100). The squamous cell carcinoma resolved, but the remaining plaque within the radiation field was unchanged. At last follow-up, the patient had severely tender, exudative crusting over his entire scalp and continued systemic chemotherapy for treatment of metastatic disease.

Some clinical features of the patient's complication are consistent with erosive pustular dermatosis of the scalp (EPDS), a rare, sterile condition manifesting as extensive pustular lesions, erosions, and crusting of the scalp in elderly individuals.⁴ Local trauma of actinically damaged skin, which results from topical treatment of actinic keratosis with fluorouracil, has been suggested as a trigger.⁴ However, EPDS may not best classify this complication because of the extensive nature of the plaque, its bacterial colonization, and failure to respond to steroids.⁴ Perhaps the term toxic erythema of chemotherapy would better characterize this patient's condition.⁵

We theorize that several months of microvascular inhibition caused by bevacizumab therapy exaggerated the inflammation initiated by capecitabine leading to severely impaired wound healing. The subsequent necrotic environment promoted the development of chronic infections. Why a similar complication did not progress in other actinically damaged areas of the body is unclear, although the extent of damage on the scalp may have been a factor.

Correspondence: Dr Black, Tulane University School of Medicine, 1430 Tulane Ave, TB36, New Orleans, LA 70112 (jblack2@tulane.edu).

Financial Disclosure: None reported.