Clinical and histopathologic characteristics of rash in cancer patients treated with mammalian target of rapamycin inhibitors

Yevgeniy Balagula, Alyx Rosen, Belinda H. Tan, Klaus J. Busam, Melissa P. Pulitzer, Robert J. Motzer, Darren R. Feldman, Jason A. Konner, Diane Reidy-Lagunes, Patricia L. Myskowski, Mario E. Lacouture

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

BACKGROUND: Dermatologic adverse events stemming from anticancer therapies have become an increasingly frequent clinical problem. Inhibitors of mammalian target of rapamycin (mTOR), such as temsirolimus and everolimus, have been associated with a high rate of skin eruptions, but their clinical and histopathologic characteristics have not been explored. METHODS: A retrospective analysis of patients who were referred to the Dermatology Service for diagnosis and management of rash in the setting of therapy with the mTOR inhibitors everolimus and temsirolimus was performed. The parameters that were studied included the time to onset, clinical presentation at the time of dermatologic evaluation, associated symptoms, evolution, results of microbiologic studies, concomitant medications, the need for dose reduction and/or treatment interruption because of rash, and routine histopathology. RESULTS: In total, 13 patients were analyzed. Most rashes were mild (grade 1; 31%) and moderate (grade 2; 54%) in severity, and grade 3 rashes were observed only in 2 patients (15%). The trunk was the most frequently affected region (77%), with the scalp (23%), face (38%), neck (54%), and extremities (69%) also commonly involved. Erythematous papules and pustules constituted the predominant primary lesion morphology (62%). No unique or uniform histopathologic reaction pattern was observed. The most common reaction pattern was that of a mixed, spongiotic interface and perivascular dermatitis, which was observed in 7 of 11 patients (63%). CONCLUSIONS: Although mTOR inhibitors may commonly induce erythematous papules and pustules, they are associated with a spectrum of lesion morphologies and a variety of histopathologic findings. Further clinicohistologic correlation studies are needed.

Original languageEnglish (US)
Pages (from-to)5078-5083
Number of pages6
JournalCancer
Volume118
Issue number20
DOIs
StatePublished - Oct 15 2012
Externally publishedYes

Fingerprint

Sirolimus
Exanthema
Neoplasms
Symptom Assessment
Dermatitis
Dermatology
Scalp
Neck
Therapeutics
Extremities
Skin
Everolimus
temsirolimus

Keywords

  • adverse event
  • everolimus
  • mammalian target of rapamycin
  • rash
  • temsirolimus

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Balagula, Y., Rosen, A., Tan, B. H., Busam, K. J., Pulitzer, M. P., Motzer, R. J., ... Lacouture, M. E. (2012). Clinical and histopathologic characteristics of rash in cancer patients treated with mammalian target of rapamycin inhibitors. Cancer, 118(20), 5078-5083. https://doi.org/10.1002/cncr.27505

Clinical and histopathologic characteristics of rash in cancer patients treated with mammalian target of rapamycin inhibitors. / Balagula, Yevgeniy; Rosen, Alyx; Tan, Belinda H.; Busam, Klaus J.; Pulitzer, Melissa P.; Motzer, Robert J.; Feldman, Darren R.; Konner, Jason A.; Reidy-Lagunes, Diane; Myskowski, Patricia L.; Lacouture, Mario E.

In: Cancer, Vol. 118, No. 20, 15.10.2012, p. 5078-5083.

Research output: Contribution to journalArticle

Balagula, Y, Rosen, A, Tan, BH, Busam, KJ, Pulitzer, MP, Motzer, RJ, Feldman, DR, Konner, JA, Reidy-Lagunes, D, Myskowski, PL & Lacouture, ME 2012, 'Clinical and histopathologic characteristics of rash in cancer patients treated with mammalian target of rapamycin inhibitors', Cancer, vol. 118, no. 20, pp. 5078-5083. https://doi.org/10.1002/cncr.27505
Balagula, Yevgeniy ; Rosen, Alyx ; Tan, Belinda H. ; Busam, Klaus J. ; Pulitzer, Melissa P. ; Motzer, Robert J. ; Feldman, Darren R. ; Konner, Jason A. ; Reidy-Lagunes, Diane ; Myskowski, Patricia L. ; Lacouture, Mario E. / Clinical and histopathologic characteristics of rash in cancer patients treated with mammalian target of rapamycin inhibitors. In: Cancer. 2012 ; Vol. 118, No. 20. pp. 5078-5083.
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abstract = "BACKGROUND: Dermatologic adverse events stemming from anticancer therapies have become an increasingly frequent clinical problem. Inhibitors of mammalian target of rapamycin (mTOR), such as temsirolimus and everolimus, have been associated with a high rate of skin eruptions, but their clinical and histopathologic characteristics have not been explored. METHODS: A retrospective analysis of patients who were referred to the Dermatology Service for diagnosis and management of rash in the setting of therapy with the mTOR inhibitors everolimus and temsirolimus was performed. The parameters that were studied included the time to onset, clinical presentation at the time of dermatologic evaluation, associated symptoms, evolution, results of microbiologic studies, concomitant medications, the need for dose reduction and/or treatment interruption because of rash, and routine histopathology. RESULTS: In total, 13 patients were analyzed. Most rashes were mild (grade 1; 31{\%}) and moderate (grade 2; 54{\%}) in severity, and grade 3 rashes were observed only in 2 patients (15{\%}). The trunk was the most frequently affected region (77{\%}), with the scalp (23{\%}), face (38{\%}), neck (54{\%}), and extremities (69{\%}) also commonly involved. Erythematous papules and pustules constituted the predominant primary lesion morphology (62{\%}). No unique or uniform histopathologic reaction pattern was observed. The most common reaction pattern was that of a mixed, spongiotic interface and perivascular dermatitis, which was observed in 7 of 11 patients (63{\%}). CONCLUSIONS: Although mTOR inhibitors may commonly induce erythematous papules and pustules, they are associated with a spectrum of lesion morphologies and a variety of histopathologic findings. Further clinicohistologic correlation studies are needed.",
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AU - Balagula, Yevgeniy

AU - Rosen, Alyx

AU - Tan, Belinda H.

AU - Busam, Klaus J.

AU - Pulitzer, Melissa P.

AU - Motzer, Robert J.

AU - Feldman, Darren R.

AU - Konner, Jason A.

AU - Reidy-Lagunes, Diane

AU - Myskowski, Patricia L.

AU - Lacouture, Mario E.

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N2 - BACKGROUND: Dermatologic adverse events stemming from anticancer therapies have become an increasingly frequent clinical problem. Inhibitors of mammalian target of rapamycin (mTOR), such as temsirolimus and everolimus, have been associated with a high rate of skin eruptions, but their clinical and histopathologic characteristics have not been explored. METHODS: A retrospective analysis of patients who were referred to the Dermatology Service for diagnosis and management of rash in the setting of therapy with the mTOR inhibitors everolimus and temsirolimus was performed. The parameters that were studied included the time to onset, clinical presentation at the time of dermatologic evaluation, associated symptoms, evolution, results of microbiologic studies, concomitant medications, the need for dose reduction and/or treatment interruption because of rash, and routine histopathology. RESULTS: In total, 13 patients were analyzed. Most rashes were mild (grade 1; 31%) and moderate (grade 2; 54%) in severity, and grade 3 rashes were observed only in 2 patients (15%). The trunk was the most frequently affected region (77%), with the scalp (23%), face (38%), neck (54%), and extremities (69%) also commonly involved. Erythematous papules and pustules constituted the predominant primary lesion morphology (62%). No unique or uniform histopathologic reaction pattern was observed. The most common reaction pattern was that of a mixed, spongiotic interface and perivascular dermatitis, which was observed in 7 of 11 patients (63%). CONCLUSIONS: Although mTOR inhibitors may commonly induce erythematous papules and pustules, they are associated with a spectrum of lesion morphologies and a variety of histopathologic findings. Further clinicohistologic correlation studies are needed.

AB - BACKGROUND: Dermatologic adverse events stemming from anticancer therapies have become an increasingly frequent clinical problem. Inhibitors of mammalian target of rapamycin (mTOR), such as temsirolimus and everolimus, have been associated with a high rate of skin eruptions, but their clinical and histopathologic characteristics have not been explored. METHODS: A retrospective analysis of patients who were referred to the Dermatology Service for diagnosis and management of rash in the setting of therapy with the mTOR inhibitors everolimus and temsirolimus was performed. The parameters that were studied included the time to onset, clinical presentation at the time of dermatologic evaluation, associated symptoms, evolution, results of microbiologic studies, concomitant medications, the need for dose reduction and/or treatment interruption because of rash, and routine histopathology. RESULTS: In total, 13 patients were analyzed. Most rashes were mild (grade 1; 31%) and moderate (grade 2; 54%) in severity, and grade 3 rashes were observed only in 2 patients (15%). The trunk was the most frequently affected region (77%), with the scalp (23%), face (38%), neck (54%), and extremities (69%) also commonly involved. Erythematous papules and pustules constituted the predominant primary lesion morphology (62%). No unique or uniform histopathologic reaction pattern was observed. The most common reaction pattern was that of a mixed, spongiotic interface and perivascular dermatitis, which was observed in 7 of 11 patients (63%). CONCLUSIONS: Although mTOR inhibitors may commonly induce erythematous papules and pustules, they are associated with a spectrum of lesion morphologies and a variety of histopathologic findings. Further clinicohistologic correlation studies are needed.

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