- Email: [email protected]
Extramammary Paget disease: Failure to respond to topical imiquimod 5%
J AM ACAD DERMATOL
656 Letters
SEPTEMBER 2011
4. List A, Kurtin S, Roe DJ, Buresh A, Mahadeven D, Fuchs D, et al. Efficacy of lenalidomide in myelodysplastic syndromes. N Engl J Med 2005;352:549-57. 5. Bartlett JB, Dredge K, Dalgleish AG. The evolution of thalidomide and its IMID derivatives as anticancer agents. Nature Rev Cancer 2004;4:314-22. 6. Bartlett JB, Michael A, Clarke IA, Dredge K, Nicholson S, Kristeleit H, et al. Phase I study to determine the safety, tolerability and immunostimulatory activity of thalidomide analogue CC-5013 in patients with metastatic malignant melanoma and other advanced cancers. Br J Cancer 2004;90:955-61. 7. Horwitz SM. Novel therapies for cutaneous T-cell lymphomas. Clin Lymphoma Myeloma 2008;8(Suppl 5):S187-192. 8. Shah A, Albrecht J, Bonilla-Martinez Z, Okawa J, Rose M, Rosenbach M, et al. Lenalidomide for the treatment of resistant discoid lupus erythematosus. Arch Dermatol 2009;145:303-6. 9. Rajkumar SV, Hayman SR, Lacy MQ, Dispenzieri A, Geyer SM, Kabat B, et al. Combination therapy with lenalidomide plus dexamethasone (Rev/Dex) for newly diagnosed myeloma. Blood 2005;106:4050-3. 10. Hall VC, El-Azhary RA, Bouwhuis S, Rajkumar SV. Dermatologic side effects of thalidomide in patients with multiple myeloma. J Am Acad Dermatol 2003;48:548-52. 11. Sviggum HP, Davis MDP, Rajkumar SV, Dispenzieri A. Dermatologic adverse effects of lenalidomide therapy for amyloidosis and multiple myeloma. Arch Dermatol 2006;142:1298-302. 12. Thieu KP, Rosenbach M, Xu X, Kist JM. Neutrophilic dermatosis complicating lenalidomide therapy. J Am Acad Dermatol 2009;61:709-10. 13. Susser WS, Whitaker-Worth DL, Grant-Kels JM. Mucocutaneous reactions to chemotherapy. J Am Acad Dermatol 1999;40:367-98. 14. Goon AT, McFadden JP, McCann M, Royds C, Rycroft RJ. Allergic contact dermatitis from melphalan and chlorambucil: cross-sensitivity or cosensitization? Contact Dermatitis 2002;47:309-14. doi:10.1016/j.jaad.2010.04.034
Extramammary Paget disease: Failure to respond to topical imiquimod 5% To the Editor: Extramammary Paget disease (EMPD) is a rare malignant adenocarcinoma characterized by Paget cells within the epidermis. EMPD is classified as primary (within the epidermis) or secondary (arising from underlying malignancies in the gastrointestinal tract, bladder, or apocrine glands) and most commonly occurs in the vulvar region of elderly white women. Scrotal involvement is rare, particularly in Asians. Cytochemistry is necessary to delineate the nature of Paget cells and rule out squamous cell carcinoma and melanoma. EMPD presents as a pruritic, erythematous, scaly plaque or patch that is frequently misdiagnosed as an inflammatory or infectious disease. Surgery remains the treatment of choice, but other treatment options are available. We report two elderly Asian men with primary EMPD involving the scrotum that failed to respond to a 4- to 6-month trial of topical imiquimod 5%. Imiquimod 5% was selected because of the large
Fig 1. Eczematous lesion with poorly defined margins involving the right scrotal, inguinal, and perineal region. Note the site of the biopsy.
scrotal surfaces involved, the age of the patients, advice against surgical treatment by the surgeon, and recent successful treatment with imiquimod 5% in the literature.1-5 Case 1 was a 75-year-old Chinese man with a 1-year history of an eczematous dermatitis involving the right scrotum. His previous treatments included antifungal and corticosteroid creams, oral antibiotics, and oral corticosteroids. The physical examination revealed an eczematous plaque on the right side of his scrotum extending to the inguinal area. A biopsy specimen revealed Paget cells in the epidermis, which were CK-7 positive and S-100 negative. Routine laboratory examinations included a normal urinalysis, stool guaiac, and prostate-specific antigen (PSA) levels. A surgeon did not recommend surgical removal because of the extent of involvement and the patient’s age. Alternative treatments were discussed with the patient and imiquimod 5% was selected. Imiquimod 5% was applied twice a day, 3 days a week for 6 months. He had a vigorous inflammatory reaction but failed to respond after a 6-month trial. He then began radiation therapy, receiving 60 Gy in 30 fractions over a 7-week period. Three months after radiation, he was clinically clear. The second case was a 70-year-old Japanese man with 4-year history of progressive pruritic scrotal dermatitis treated previously with topical corticosteroids and antifungal and antibacterial creams without benefit. His medical history was significant for
J AM ACAD DERMATOL
Letters 657
VOLUME 65, NUMBER 3
benign prostatic hyperplasia (BPH) with elevated PSA levels (5.7-7.3 ng/mL; age-adjusted normal range 0-6.5 ng/mL) and confirmatory prostatic biopsy. His PSA normalized after treatment with dutasteride and finasteride. A stool guaiac and urinalysis were normal. The physical examination revealed a large weeping eczematous plaque on the right scrotum extending to the groin and perineum (Fig 1). A biopsy specimen revealed intraepithelial Paget cells, which were CK-7 positive and S-100 negative. Treatment options were discussed and he was started on a course of imiquimod 5%, used twice a day, 3 times a week for 4 months, accompanied by an inflammatory reaction, but he failed to respond to this therapy. A surgical consult advised against surgery; the patient is scheduled to receive radiation therapy. In conclusion, although there are at least three reports of successful treatment of scrotal EMPD with imiquimod 5%,1,5 our two cases failed to respond. Shelbi C. Jim On, BA,a and Allan K. Izumi, MDb Medical studenta and the Division of Dermatology,b Department of Medicine, University of Hawaii John A. Burns School of Medicine, Honolulu, Hawaii Funding sources: None. Conflicts of interest: None declared. Correspondence to: Allan K. Izumi, MD, Division of Dermatology, Department of Medicine, University of Hawaii John A. Burns School of Medicine, 1380 Lusitana St, Ste 412, Honolulu, HI 96813 E-mail: [email protected] REFERENCES 1. Cohen PR, Schulze KE, Tschen JA, Hetherington GW, Nelson BR. Treatment of extramammary Paget disease with topical imiquimod cream: case report and literature review. South Med J 2006;99:396-402. 2. Zampogna JC, Flowers FP, Roth WI, Hassenein AM. Treatment of primary limited cutaneous extramammary Paget’s disease with topical imiquimod monotherapy: two case reports. J Am Acad Dermatol 2002;47(suppl 4):S229-235. 3. Cecchi R, Pavesi M, Bartoli L, Brunetti L, Rapicano V. Perineal extramammary Paget disease responsive to topical imiquimod. J Dtsch Dermatol Ges 2010;8:38-40. 4. Vereecken P, Awada A, Ghanem G, Marques Da Costa C, Larsimont D, Simoens C, et al. A therapeutic approach to perianal extramammary Paget’s disease: topical imiquimod can be useful to prevent or defer surgery. Med Sci Monit 2007;13:75-7. 5. Berman B, Spencer J, Villa A, Poochareon V, Elgart G. Successful treatment of extramammary Paget’s disease of the scrotum with imiquimod 5% cream. Clin Exp Dermatol 2003;28(suppl 1):36-8. doi:10.1016/j.jaad.2010.04.035
Cyclophosphamide-associated acneiform drug eruption in a patient with multiple myeloma To the Editor: We report a patient with multiple myeloma (MM) who developed cyclophosphamideassociated neutrophilic folliculitis. To our knowledge, cyclophosphamide-associated neutrophilic, acneiform eruption in a seborrheic distribution has not been described. A 67-year-old man presented for evaluation of a progressive pustular eruption involving his scalp, face, neck, upper chest, and back of 4 weeks’ duration. The eruption began 3 days after he had started cyclophosphamide and dexamethasone for the MM. The patient’s medical history was significant for MM, amyloidosis, acute renal failure, adult-onset diabetes mellitus, and bilateral deep vein thrombosis. The patient had been taking oral renaphro, glimepiride, aspirin, warfarin, acyclovir, and fluconazole for many months before starting cyclophosphamide and dexamethasone. The patient was also undergoing hemodialysis 3 times a week. No topical medications or exposures to irritants or allergens occurred in the month before presentation. Upon examination, he had multiple erythematous 2- to 3-mm pustules symmetrically distributed throughout his face, scalp, ears, and central part of the chest (Fig 1). The eruption was most prominent on the face, where lesions coalesced into ill-defined plaques. There was accentuation of pustules along the eyebrows, nose, nasolabial creases, and within the beard area. He did not have any oral lesions or any other cutaneous findings. The patient had mild pruritus and burning sensation associated with this eruption. He denied subjective fever, chills, recent upper respiratory or urinary tract infections, prior cyclophosphamide exposure, or a similar rash in the past. Lesion cultures were negative for bacteria, herpes simplex virus, and herpes zoster virus. Histologic examination of one of the facial lesions showed a neutrophil-rich infiltrate with eosinophils involving the deeper dermis and surrounding hair follicles (Fig 2). Periodic acideSchiff with diastase (PAS-D) and gram stains for microorganisms were negative. The histologic findings were interpreted to be compatible with a ‘‘folliculitis-like’’ neutrophilic drug reaction. On the basis of his clinical presentation and the histopathologic correlation, the patient was diagnosed with probable cyclophosphamide drug eruption. Cyclophosphamide was discontinued and topical fluocinonide emollient cream was initiated. The eruption began to recede 1 day after discontinuation of cyclophosphamide and had completely resolved within 6 weeks. The patient’s medical oncologist initiated oral lenalidomide for his MM
656 Letters
SEPTEMBER 2011
4. List A, Kurtin S, Roe DJ, Buresh A, Mahadeven D, Fuchs D, et al. Efficacy of lenalidomide in myelodysplastic syndromes. N Engl J Med 2005;352:549-57. 5. Bartlett JB, Dredge K, Dalgleish AG. The evolution of thalidomide and its IMID derivatives as anticancer agents. Nature Rev Cancer 2004;4:314-22. 6. Bartlett JB, Michael A, Clarke IA, Dredge K, Nicholson S, Kristeleit H, et al. Phase I study to determine the safety, tolerability and immunostimulatory activity of thalidomide analogue CC-5013 in patients with metastatic malignant melanoma and other advanced cancers. Br J Cancer 2004;90:955-61. 7. Horwitz SM. Novel therapies for cutaneous T-cell lymphomas. Clin Lymphoma Myeloma 2008;8(Suppl 5):S187-192. 8. Shah A, Albrecht J, Bonilla-Martinez Z, Okawa J, Rose M, Rosenbach M, et al. Lenalidomide for the treatment of resistant discoid lupus erythematosus. Arch Dermatol 2009;145:303-6. 9. Rajkumar SV, Hayman SR, Lacy MQ, Dispenzieri A, Geyer SM, Kabat B, et al. Combination therapy with lenalidomide plus dexamethasone (Rev/Dex) for newly diagnosed myeloma. Blood 2005;106:4050-3. 10. Hall VC, El-Azhary RA, Bouwhuis S, Rajkumar SV. Dermatologic side effects of thalidomide in patients with multiple myeloma. J Am Acad Dermatol 2003;48:548-52. 11. Sviggum HP, Davis MDP, Rajkumar SV, Dispenzieri A. Dermatologic adverse effects of lenalidomide therapy for amyloidosis and multiple myeloma. Arch Dermatol 2006;142:1298-302. 12. Thieu KP, Rosenbach M, Xu X, Kist JM. Neutrophilic dermatosis complicating lenalidomide therapy. J Am Acad Dermatol 2009;61:709-10. 13. Susser WS, Whitaker-Worth DL, Grant-Kels JM. Mucocutaneous reactions to chemotherapy. J Am Acad Dermatol 1999;40:367-98. 14. Goon AT, McFadden JP, McCann M, Royds C, Rycroft RJ. Allergic contact dermatitis from melphalan and chlorambucil: cross-sensitivity or cosensitization? Contact Dermatitis 2002;47:309-14. doi:10.1016/j.jaad.2010.04.034
Extramammary Paget disease: Failure to respond to topical imiquimod 5% To the Editor: Extramammary Paget disease (EMPD) is a rare malignant adenocarcinoma characterized by Paget cells within the epidermis. EMPD is classified as primary (within the epidermis) or secondary (arising from underlying malignancies in the gastrointestinal tract, bladder, or apocrine glands) and most commonly occurs in the vulvar region of elderly white women. Scrotal involvement is rare, particularly in Asians. Cytochemistry is necessary to delineate the nature of Paget cells and rule out squamous cell carcinoma and melanoma. EMPD presents as a pruritic, erythematous, scaly plaque or patch that is frequently misdiagnosed as an inflammatory or infectious disease. Surgery remains the treatment of choice, but other treatment options are available. We report two elderly Asian men with primary EMPD involving the scrotum that failed to respond to a 4- to 6-month trial of topical imiquimod 5%. Imiquimod 5% was selected because of the large
Fig 1. Eczematous lesion with poorly defined margins involving the right scrotal, inguinal, and perineal region. Note the site of the biopsy.
scrotal surfaces involved, the age of the patients, advice against surgical treatment by the surgeon, and recent successful treatment with imiquimod 5% in the literature.1-5 Case 1 was a 75-year-old Chinese man with a 1-year history of an eczematous dermatitis involving the right scrotum. His previous treatments included antifungal and corticosteroid creams, oral antibiotics, and oral corticosteroids. The physical examination revealed an eczematous plaque on the right side of his scrotum extending to the inguinal area. A biopsy specimen revealed Paget cells in the epidermis, which were CK-7 positive and S-100 negative. Routine laboratory examinations included a normal urinalysis, stool guaiac, and prostate-specific antigen (PSA) levels. A surgeon did not recommend surgical removal because of the extent of involvement and the patient’s age. Alternative treatments were discussed with the patient and imiquimod 5% was selected. Imiquimod 5% was applied twice a day, 3 days a week for 6 months. He had a vigorous inflammatory reaction but failed to respond after a 6-month trial. He then began radiation therapy, receiving 60 Gy in 30 fractions over a 7-week period. Three months after radiation, he was clinically clear. The second case was a 70-year-old Japanese man with 4-year history of progressive pruritic scrotal dermatitis treated previously with topical corticosteroids and antifungal and antibacterial creams without benefit. His medical history was significant for
J AM ACAD DERMATOL
Letters 657
VOLUME 65, NUMBER 3
benign prostatic hyperplasia (BPH) with elevated PSA levels (5.7-7.3 ng/mL; age-adjusted normal range 0-6.5 ng/mL) and confirmatory prostatic biopsy. His PSA normalized after treatment with dutasteride and finasteride. A stool guaiac and urinalysis were normal. The physical examination revealed a large weeping eczematous plaque on the right scrotum extending to the groin and perineum (Fig 1). A biopsy specimen revealed intraepithelial Paget cells, which were CK-7 positive and S-100 negative. Treatment options were discussed and he was started on a course of imiquimod 5%, used twice a day, 3 times a week for 4 months, accompanied by an inflammatory reaction, but he failed to respond to this therapy. A surgical consult advised against surgery; the patient is scheduled to receive radiation therapy. In conclusion, although there are at least three reports of successful treatment of scrotal EMPD with imiquimod 5%,1,5 our two cases failed to respond. Shelbi C. Jim On, BA,a and Allan K. Izumi, MDb Medical studenta and the Division of Dermatology,b Department of Medicine, University of Hawaii John A. Burns School of Medicine, Honolulu, Hawaii Funding sources: None. Conflicts of interest: None declared. Correspondence to: Allan K. Izumi, MD, Division of Dermatology, Department of Medicine, University of Hawaii John A. Burns School of Medicine, 1380 Lusitana St, Ste 412, Honolulu, HI 96813 E-mail: [email protected] REFERENCES 1. Cohen PR, Schulze KE, Tschen JA, Hetherington GW, Nelson BR. Treatment of extramammary Paget disease with topical imiquimod cream: case report and literature review. South Med J 2006;99:396-402. 2. Zampogna JC, Flowers FP, Roth WI, Hassenein AM. Treatment of primary limited cutaneous extramammary Paget’s disease with topical imiquimod monotherapy: two case reports. J Am Acad Dermatol 2002;47(suppl 4):S229-235. 3. Cecchi R, Pavesi M, Bartoli L, Brunetti L, Rapicano V. Perineal extramammary Paget disease responsive to topical imiquimod. J Dtsch Dermatol Ges 2010;8:38-40. 4. Vereecken P, Awada A, Ghanem G, Marques Da Costa C, Larsimont D, Simoens C, et al. A therapeutic approach to perianal extramammary Paget’s disease: topical imiquimod can be useful to prevent or defer surgery. Med Sci Monit 2007;13:75-7. 5. Berman B, Spencer J, Villa A, Poochareon V, Elgart G. Successful treatment of extramammary Paget’s disease of the scrotum with imiquimod 5% cream. Clin Exp Dermatol 2003;28(suppl 1):36-8. doi:10.1016/j.jaad.2010.04.035
Cyclophosphamide-associated acneiform drug eruption in a patient with multiple myeloma To the Editor: We report a patient with multiple myeloma (MM) who developed cyclophosphamideassociated neutrophilic folliculitis. To our knowledge, cyclophosphamide-associated neutrophilic, acneiform eruption in a seborrheic distribution has not been described. A 67-year-old man presented for evaluation of a progressive pustular eruption involving his scalp, face, neck, upper chest, and back of 4 weeks’ duration. The eruption began 3 days after he had started cyclophosphamide and dexamethasone for the MM. The patient’s medical history was significant for MM, amyloidosis, acute renal failure, adult-onset diabetes mellitus, and bilateral deep vein thrombosis. The patient had been taking oral renaphro, glimepiride, aspirin, warfarin, acyclovir, and fluconazole for many months before starting cyclophosphamide and dexamethasone. The patient was also undergoing hemodialysis 3 times a week. No topical medications or exposures to irritants or allergens occurred in the month before presentation. Upon examination, he had multiple erythematous 2- to 3-mm pustules symmetrically distributed throughout his face, scalp, ears, and central part of the chest (Fig 1). The eruption was most prominent on the face, where lesions coalesced into ill-defined plaques. There was accentuation of pustules along the eyebrows, nose, nasolabial creases, and within the beard area. He did not have any oral lesions or any other cutaneous findings. The patient had mild pruritus and burning sensation associated with this eruption. He denied subjective fever, chills, recent upper respiratory or urinary tract infections, prior cyclophosphamide exposure, or a similar rash in the past. Lesion cultures were negative for bacteria, herpes simplex virus, and herpes zoster virus. Histologic examination of one of the facial lesions showed a neutrophil-rich infiltrate with eosinophils involving the deeper dermis and surrounding hair follicles (Fig 2). Periodic acideSchiff with diastase (PAS-D) and gram stains for microorganisms were negative. The histologic findings were interpreted to be compatible with a ‘‘folliculitis-like’’ neutrophilic drug reaction. On the basis of his clinical presentation and the histopathologic correlation, the patient was diagnosed with probable cyclophosphamide drug eruption. Cyclophosphamide was discontinued and topical fluocinonide emollient cream was initiated. The eruption began to recede 1 day after discontinuation of cyclophosphamide and had completely resolved within 6 weeks. The patient’s medical oncologist initiated oral lenalidomide for his MM