Papular eruption associated with palifermin
Authors: Loren Gorcey, Jesse M. Lewin, Joshua Trufant, Shane A. Meehan, Beth N. McLellan
Journal: Journal of the American Academy of Dermatology (2014)

To the Editor: A 52-year-old man with nasal-type extranodal natural killer T-cell lymphoma presented with a 2-day history of scattered faintly erythematous and skin-colored papules on the back of the neck and bilateral upper extremities. He noted mild pruritus associated with these lesions. Three days before the eruption, the patient began treatment as an inpatient with palifermin as mucositis prophylaxis for chemotherapy and autologous stem cell transplantation. Physical examination was notable for scattered flat-topped erythematous papules on the back of the neck, back of the hands, and forearms (Fig 1). Examination of the oral mucosa was unremarkable. A shave biopsy specimen obtained from the back of the left hand (Fig 2) revealed a slightly mamillated epidermis with acanthosis, hypergranulosis, and mild keratinocytic atypia of the basal and lower spinous layers. The patient was given the diagnosis of a palifermin-associated papular eruption and was given triamcinolone acetonide for relief of pruritus.Fig 2Palifermin-associated papules. Slightly mamillated epidermis with acanthosis, hypergranulosis, and mild keratinocytic atypia of the basal and lower spinous layers. (Hematoxylin-eosin stain; original magnification: ×100.)View Large Image Figure ViewerDownload Hi-res image Download (PPT) Palifermin is a recombinant, N-truncated version of human keratinocyte growth factor with similar binding properties but increased stability. It is Food and Drug Administration approved for reducing the incidence and duration of severe oral mucositis in patients with hematologic malignancies receiving chemotherapy, radiotherapy, and hematopoietic stem cell transplantation.1McDonnell A.M. Lenz K.L. Palifermin: role in the prevention of chemotherapy- and radiation-induced mucositis.Ann Pharmacother. 2007; 41: 86-94Crossref PubMed Scopus (38) Google Scholar Palifermin is administered intravenously at a dose of 60 μg/kg/d for 3 consecutive days before radiation therapy and 3 consecutive days after stem cell transplantation.1McDonnell A.M. Lenz K.L. Palifermin: role in the prevention of chemotherapy- and radiation-induced mucositis.Ann Pharmacother. 2007; 41: 86-94Crossref PubMed Scopus (38) Google Scholar The average cost of palifermin for a 70-kg patient is approximately $10,000.1McDonnell A.M. Lenz K.L. Palifermin: role in the prevention of chemotherapy- and radiation-induced mucositis.Ann Pharmacother. 2007; 41: 86-94Crossref PubMed Scopus (38) Google Scholar Adverse cutaneous reactions to palifermin in early clinical trials were described as “rash,” “erythema,” or “pruritus” and were noted in 55%, 44%, and 50% of treated patients, respectively.1McDonnell A.M. Lenz K.L. Palifermin: role in the prevention of chemotherapy- and radiation-induced mucositis.Ann Pharmacother. 2007; 41: 86-94Crossref PubMed Scopus (38) Google Scholar, 2King B. Knopp E. Galan A. Nuovo G. Tigelaar R. McNiff J. Palifermin-associated papular eruption.Arch Dermatol. 2009; 145: 179-182Crossref PubMed Scopus (7) Google Scholar Other mucocutaneous reactions, including thickening and whitening of the tongue, oral and flexural hyperpigmentation or erythema, acanthosis nigricans–like eruptions, palmoplantar erythrodysesthesia, and intertriginous papular eruptions have since been described in the literature.2King B. Knopp E. Galan A. Nuovo G. Tigelaar R. McNiff J. Palifermin-associated papular eruption.Arch Dermatol. 2009; 145: 179-182Crossref PubMed Scopus (7) Google Scholar, 3Grzegorczyk-Jazwinska A. Kozak I. Karakulska-Prystupiuk E. Rokicka M. Ganowicz E. Dwilewicz-Trojaczek J. et al.Transient oral cavity and skin complications after mucositis preventing therapy (palifermin) in a patient after allogeneic PBSCT: case history.Adv Med Sci. 2006; 51: 66-68PubMed Google Scholar, 4Kaloyannidis P. Papalexandri A. Papaemanouil E. Papaioannou M. Sakellari I. Reversible painful oral mucosal hyperpigmentation following palifermin administration.Acta Haematol. 2010; 124: 185-187Crossref PubMed Scopus (3) Google Scholar, 5Lane S.W. Manoharan S. Mollee P.N. Palifermin-induced acanthosis nigricans.Intern Med J. 2007; 37: 417-418Crossref PubMed Scopus (15) Google Scholar, 6Sibelt L.A. Aboosy N. van der Velden W.J. Blijlevens N.M. Blokx W.A. Seyger M.M. Palifermin-induced flexural hyperpigmentation: a clinical and histological study of five cases.Br J Dermatol. 2008; 159: 1200-1203PubMed Google Scholar Our patient's presentation most closely resembles cases of flexural lichenoid or verruca plana–like papular eruptions associated with palifermin. One report describes a patient with multiple myeloma who developed intertriginous erythema and a papular eruption of the neck, trunk, and extremities 1 day after completing a 3-day course of palifermin.2King B. Knopp E. Galan A. Nuovo G. Tigelaar R. McNiff J. Palifermin-associated papular eruption.Arch Dermatol. 2009; 145: 179-182Crossref PubMed Scopus (7) Google Scholar In situ hybridization to test for human papillomavirus types was negative in that case, whereas staining with the proliferation markers Ki-67 and cytokeratin 5/6 showed dramatically increased labeling of basilar and suprabasilar keratinocytes. Another report described 5 patients with intertriginous erythema and hyperpigmented papules that began 7 to 30 days after the first palifermin dose. Pathology revealed a prominent granular layer with coarse granules in biopsy samples, features also seen in our case. In addition, they demonstrate up-regulation of filaggrin, a well-described effect of keratinocyte growth factor.6Sibelt L.A. Aboosy N. van der Velden W.J. Blijlevens N.M. Blokx W.A. Seyger M.M. Palifermin-induced flexural hyperpigmentation: a clinical and histological study of five cases.Br J Dermatol. 2008; 159: 1200-1203PubMed Google Scholar Although our patient's eruption was not predominantly intertriginous, the timing, clinical morphology, and histopathologic findings are consistent with palifermin-associated papules. Based on immunohistochemical studies performed in the aforementioned cases, it seems reasonable to conclude with those investigators that the papular eruption is likely a result of palifermin's proliferative effect on epithelial tissues.2King B. Knopp E. Galan A. Nuovo G. Tigelaar R. McNiff J. Palifermin-associated papular eruption.Arch Dermatol. 2009; 145: 179-182Crossref PubMed Scopus (7) Google Scholar, 6Sibelt L.A. Aboosy N. van der Velden W.J. Blijlevens N.M. Blokx W.A. Seyger M.M. Palifermin-induced flexural hyperpigmentation: a clinical and histological study of five cases.Br J Dermatol. 2008; 159: 1200-1203PubMed Google Scholar The vast majority of cutaneous reactions caused by palifermin have been benign, minimally symptomatic, and self-limited, with resolution of lesions soon after stopping the medication. Three days after completion of palifermin, our patient already demonstrated partial regression of the lesions, although we did recommend a mid-potency topical corticosteroid for relief of pruritus that improved his symptoms.