Palifermin-Associated Cutaneous Papular Rash of the Head and Neck
Practice Points
- Palifermin is a recombinant keratinocyte growth factor that is US Food and Drug Administration approved to prevent oral mucositis in patients undergoing chemotherapy or radiation therapy.
- Histologically, the rash can resemble verrucae with evidence of hypergranulosis, hyperorthokeratosis, and papillomatosis.
- Cutaneous reactions have been reported with use of palifermin and generally are benign and self-limited with removal of the offending agent.
The proliferative effect of palifermin on the oral mucosa is beneficial to patients but likely is the driving force behind its cutaneous adverse effects. A nonspecific rash is the most commonly cited treatment-related adverse event associated with palifermin, occurring in approximately 62% of patients.5,7,9
Our case is a rare report of a palifermin-associated cutaneous reaction. Previous cases have cited the occurrence of palmoplantar erythrodysesthesias, papulopustular eruptions involving the face and chest, and a papular rash involving the dorsal hands and intertriginous areas.1-4 Another report documented a “mild rash” but failed to further characterize the morphology or the body site involved.5
In 2009, King et al6 reported the occurrence of a lichen planus–like eruption involving the intertriginous regions and of white oral plaques in a patient treated with palifermin. Hematoxylin and eosin staining of a representative lesion in that patient demonstrated an appearance similar to that of verrucae, including papillomatosis, hypergranulosis, and hyperorthokeratosis.
King et al6 expanded analysis of the reaction to include immunohistochemical study, using targeted antibody stains for cytokeratin 5/6 and Ki-67 protein. Staining with Ki-67 showed dramatically increased activity within basilar and suprabasilar keratinocytes in a biopsy taken at the height of the reaction. Biopsy specimens obtained when the eruption was clinically resolving—2 days after the first biopsy—showed decreased Ki-67 staining. These findings taken together suggest a direct causal effect of palifermin inducing hyperkeratotic changes appreciated on examination of treated patients.6
We present this case to add to current data regarding palifermin-induced cutaneous changes. Unique to our patient was a strikingly well-demarcated rash confined to the head and neck. Although a photosensitive eruption due to trimethoprim-sulfamethoxazole is conceivable, the fixed time course of the eruption—corresponding to (1) initiation and discontinuation of palifermin and (2) histologic findings—led us to conclude that this self-limited eruption likely was due to palifermin.
