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Successful treatment of the erythema and flushing of rosacea using a topically applied selective α1 adrenergic receptor agonist, oxymetazoline
POSTER DISCUSSION SESSION 495—MEDICAL DERMATOLOGY P400 Successful treatment of the erythema and flushing of rosacea using a topically applied selective a1 adrenergic receptor agonist, oxymetazoline Stuart Shanler, MD, Las Cruces Dermatology, Las Cruces, NM, United States; Andrew Ondo, MD, Las Cruces Dermatology, Las Cruces, NM, United States Background: Rosacea is a common chronic cutaneous disorder affecting more than 40 million people worldwide. Type I, or erythematotelangiectatic rosacea (ETR), is the subtype of rosacea characterized by frequent episodes of transient facial erythema (flushing) and/or persistent erythema, and may be accompanied by facial edema, burning, or stinging. ETR in general responds poorly to treatment and there are no effective topical therapies directed towards the erythema and telangiectasias. While rosacea remains a disorder of uncertain etiology and pathogenesis, the abnormal flushing and persistent erythema have usually been theorized to arise from a progressive dysregulation of the cutaneous vasomotor response resulting in an abnormal and persistent dilation of facial blood vessels. The mechanism of such ‘‘dysregulation’’ has never been elucidated. The regulation of the cutaneous circulation is extremely complex and activation of adrenergic receptors (adrenoceptors) present on vascular smooth muscle may result in vasoactive changes that are difficult to predict. Recent studies, however, have demonstrated that the contraction of peripheral vascular smooth muscle is primarily mediated by a1A and a1D adrenoceptor subtypes, and certain experimental models indicate several a2 receptors may play a role as well. Objective: An attempt to treat ETR using topically applied oxymetazoline, an overthe-counter drug known to be a potent selective a1A and partially selective a2A adrenoceptor agonist—a potent vasoconstrictor—was undertaken. Methods: A commercially available preparation of oxymetazoline 0.05% solution was applied once daily to the faces of 4 patients with ETR. Clinical evaluation and high resolution digital photographs were performed pretreatment, 1, 3, and 24 hours after a single application and 1 and 3 months after initiating once daily application. Results: All 4 patients showed clinical improvement in the erythema, marked decrease in the erythematous flares (flushing), relief from the stinging/burning, and no adverse effects. The effect was noted within 1 hour of drug application, lasted more than 6 hours, and was maintained at 3-month follow-up. Conclusion: We propose that the erythema and flushing of ETR may be caused by an abnormal expression, function, distribution, or responsiveness of a adrenoceptors, likely of an a1 subtype, and that ETR may be successfully treated by the topical application of agonists selective for these receptors, such as oxymetazoline.
P1202 Incidence of nonmelanoma skin cancer in a cohort of 479 vitiligo patients Camile L. Hexsel, MD, Department of Dermatology, Henry Ford Hospital, Detroit, MI, United States; Melody Eide, MD, MPH, Department of Dermatology, Henry Ford Hospital, Detroit, MI, United States; Richard Krajenta, Christine C. Johnson, PhD, Department of Biostatistics and Epidemiology, Henry Ford Hospital, Detroit, MI, United States; Iltefat Hamzavi, Henry W. Lim, MD, Department of Dermatology, Henry Ford Hospital, Detroit, MI, United States Background: Despite the loss of melanin in vitiligo, the incidence of skin cancer is unknown. Objective: To quantify the incidence of skin cancer in a cohort of 479 vitiligo patients. Methods: Using the HFHS database, 518 patients were identified by the ICD-9 code for vitiligo recorded at least twice from January 2001-July 2006. Medical record abstraction was performed to validate cases of vitiligo (n ¼ 479, 92%) and to identify patients who developed biopsy-confirmed skin cancer within the inclusion period. The incidence rates were age-adjusted to the 2000 US standard million, and for the purpose of comparison, to previously reported incidence rates of nonmelanoma skin cancer in the United States, also standardized to the 1970 US standard million.1 Results: A total of 6 patients developed skin cancer, 4 basal cell carcinomas (all male), 2 squamous cell carcinomas (1 male, 1 female) diagnosed in both vitiliginous (n ¼ 2) and unaffected skin (n ¼ 4). All skin cancer patients were white ([61 yrs of age). Annual incidence rates in white vitiligo patients, age-adjusted to the 2000 and 1970 US Standard Million were: basal cell carcinoma (BCC) males, 772/100,000 and 627/100,000; squamous cell carcinoma (SCC), males 153/100,000 and 112/100,000; SCC, females 149/100,000 and 107/100,000. Incidence rates are higher than incidence rates of NMSC in the US white population derived from the KaiserPermanente database by Miller and Weinstock.1 Conclusion: Skin cancer incidence in the white vitiligo cohort was higher than white US rates. The risk of nonmelanoma skin cancer in white vitiligo patients should not be ignored. Because of the limited sample size, incidence in non-whites could not be assessed. Reference 1. Miller DL, Weinstock MA. Nonmelanoma skin cancer in the United States: incidence. J Am Acad Dermatol 1994;30:774-8. Commercial support: None identified.
Commercial support: None identified.
P805 Cutaneous metastases: Utility of skin biopsy in the diagnosis of non skin neoplasias Brenda Lopez Tintos, MD, Instituto Nacional de Ciencias Medicas y Nutricion, Mexico City, Mexico; Ana Ruelas Villavicencio, MD, Instituto Nacional de Ciencias Medicas y Nutricion, Mexico City, Mexico; Linda Garcia Hidalgo, MD, Instituto Nacional de Ciencias Medicas y Nutricion, Mexico City, Mexico; Rocio Orozco Scholtes, MD, Instituto Nacional de Ciencias Medicas y Nutricion, Mexico City, Mexico Background: Cutaneous metastases present in 2% to 10% of stage IV neoplasias. They are the initial presentation of neoplasia in 0.8%. Melanoma, breast, colon, and lung cancer are the most often found. The utility of skin biopsy in the diagnosis of primary tumors has not been quantified.
P1411
Objective: To describe the epidemiologic and clinical features of skin metastases and determine the utility of skin biopsy in the diagnosis of primary tumor. Methods: We reviewed the medical charts of patients with skin metastases or leucemic infiltration from 1979 to 2006. We excluded patients with primary cutaneous lymphoma or unavailable chart. Results: Patients: We found 40 patients (50% male) with a mean age of 57 years (617 yrs). Time elapsed from initial presentation of a skin metastasis to skin biopsy was 5.85 months (range, 0-96 mos). In patients who died, survival after skin biopsy was 5.43 months. Two patients reached cure (seminoma and breast carcinoma). Four patients with a follow-up of less than 5 months are still alive. Metastases: Most frequent primary tumors were: breast cancer (17.5%), gastrointestinal tract adenocarcinoma (20%), hematologic (17.5%), and primary unknown adenocarcinoma (after an exhaustive medical search; 12.5%). The most frequent sites included the thorax (27.5%) and abdomen (15%), scalp (10%), legs (12.5%), groin, neck, and surgical scar (7.5% each). Nodular metstases were 78.4% (13% erysipeloid). Skin biopsy utility: Skin biopsy diagnosed a previously unknown neoplasia in 45% patients, a metastasis of an already known tumor was confirmed in 40%, skin and primary tumor biopsies coincided in 10%, and there was an equivocal diagnosis of primary tumor with skin biopsy in 5%. In 3 cases, this method detected recurrence of neoplasia. Discussion: Skin metastases are found mostly in late stages of a neoplasia, and prognosis is usually ominous and short-term. However, depending of the type of neoplasia, there are still some cases that may be cured. In this study, we included diverse types of neoplasia and we confirmed the utility of skin biopsy for the initial diagnosis of a systemic neoplasia (up to 45% of cases obtained diagnosis by this method). This high incidence of new diagnosis of cancer by skin biopsy could also reflect a tendency of our population to search for health care in a delayed fashion. Conclusions: Skin biopsy is an accesible, fast, and useful method to diagnose a nonskin neoplasia. In some cases, it is still necessary to biopsy the primary tumor for confirmation of histology.
A phase II randomized bilateral comparison study of bexarotene 1% gel in alopecia areata Rakhshandra Talpur, MD, University of Texas MD Anderson Cancer Center, Houston, TX, United States; Roland Bassett, MS, University of Texas MD Anderson Cancer Center, Houston, TX, United States; Madeleine Duvic, MD, University of Texas MD Anderson Cancer Center, Houston, TX, United States; Victor Stevens, PhD, Ligand Pharmaceuticals, San Diego, CA, United States Alopecia areata (AA), a T-cell mediated autoimmune disease directed against hair follicles, can result in patchy (AA) or total loss (alopecia totalis [AT]) of scalp hair or loss of all hair (alopecia universalis [AU]), and is often refractory to therapy. Bexarotene (bex) is an RXR selective retinoid that induces T-cell apoptosis and is effective for the treatment of cutaneous T-cell lymphoma. We previously observed that bexarotene reversed alopecia in CTCL patients and therefore conducted a phase II study of topical targretin gel for AA. Forty-two patients (11 males, 31 females) with AT (n ¼ 3), AU (n ¼ 5) or patchy AA (n ¼ 34) were randomized to apply 1% topical bexarotene gel to one half of the scalp once daily for 2 weeks, then twice daily for 24 weeks. Responders were allowed continue therapy on both sides of the scalp for another 24 weeks. Assessments of index lesions, hair density, labs, and adverse events were performed monthly. Thirty-nine patients used the drug and were evaluable for response. Twelve patients of 39 (30.7%) had [50% partial hair regrowth: 6 improved on both sides including 1 with AT and 6 had responses limited to 1 side. Twenty patients had stable disease, 7 progressed while on therapy, and 3 patients withdrew after 2 weeks of study. Erythema, scaling, and/or itching caused by local irritation at the application site were experienced by 26 patients, and required a decreased application frequency in 8 patients. Four patients with no response were grade 3 dermal irritation. Five of 12 responders elected to continue treatment for 48 weeks: 3 achieved complete hair regrowth, 1 had bilateral partial responses, and 1 patient had a complete response on 1 side and stable disease on the other. Topical bex 1% is generally well tolerated with mild irritation and was associated with a 30% response in AA.
Commercial support: None identified.
Commercial support: None identified.
FEBRUARY 2008
J AM ACAD DERMATOL
AB9
P1202 Incidence of nonmelanoma skin cancer in a cohort of 479 vitiligo patients Camile L. Hexsel, MD, Department of Dermatology, Henry Ford Hospital, Detroit, MI, United States; Melody Eide, MD, MPH, Department of Dermatology, Henry Ford Hospital, Detroit, MI, United States; Richard Krajenta, Christine C. Johnson, PhD, Department of Biostatistics and Epidemiology, Henry Ford Hospital, Detroit, MI, United States; Iltefat Hamzavi, Henry W. Lim, MD, Department of Dermatology, Henry Ford Hospital, Detroit, MI, United States Background: Despite the loss of melanin in vitiligo, the incidence of skin cancer is unknown. Objective: To quantify the incidence of skin cancer in a cohort of 479 vitiligo patients. Methods: Using the HFHS database, 518 patients were identified by the ICD-9 code for vitiligo recorded at least twice from January 2001-July 2006. Medical record abstraction was performed to validate cases of vitiligo (n ¼ 479, 92%) and to identify patients who developed biopsy-confirmed skin cancer within the inclusion period. The incidence rates were age-adjusted to the 2000 US standard million, and for the purpose of comparison, to previously reported incidence rates of nonmelanoma skin cancer in the United States, also standardized to the 1970 US standard million.1 Results: A total of 6 patients developed skin cancer, 4 basal cell carcinomas (all male), 2 squamous cell carcinomas (1 male, 1 female) diagnosed in both vitiliginous (n ¼ 2) and unaffected skin (n ¼ 4). All skin cancer patients were white ([61 yrs of age). Annual incidence rates in white vitiligo patients, age-adjusted to the 2000 and 1970 US Standard Million were: basal cell carcinoma (BCC) males, 772/100,000 and 627/100,000; squamous cell carcinoma (SCC), males 153/100,000 and 112/100,000; SCC, females 149/100,000 and 107/100,000. Incidence rates are higher than incidence rates of NMSC in the US white population derived from the KaiserPermanente database by Miller and Weinstock.1 Conclusion: Skin cancer incidence in the white vitiligo cohort was higher than white US rates. The risk of nonmelanoma skin cancer in white vitiligo patients should not be ignored. Because of the limited sample size, incidence in non-whites could not be assessed. Reference 1. Miller DL, Weinstock MA. Nonmelanoma skin cancer in the United States: incidence. J Am Acad Dermatol 1994;30:774-8. Commercial support: None identified.
Commercial support: None identified.
P805 Cutaneous metastases: Utility of skin biopsy in the diagnosis of non skin neoplasias Brenda Lopez Tintos, MD, Instituto Nacional de Ciencias Medicas y Nutricion, Mexico City, Mexico; Ana Ruelas Villavicencio, MD, Instituto Nacional de Ciencias Medicas y Nutricion, Mexico City, Mexico; Linda Garcia Hidalgo, MD, Instituto Nacional de Ciencias Medicas y Nutricion, Mexico City, Mexico; Rocio Orozco Scholtes, MD, Instituto Nacional de Ciencias Medicas y Nutricion, Mexico City, Mexico Background: Cutaneous metastases present in 2% to 10% of stage IV neoplasias. They are the initial presentation of neoplasia in 0.8%. Melanoma, breast, colon, and lung cancer are the most often found. The utility of skin biopsy in the diagnosis of primary tumors has not been quantified.
P1411
Objective: To describe the epidemiologic and clinical features of skin metastases and determine the utility of skin biopsy in the diagnosis of primary tumor. Methods: We reviewed the medical charts of patients with skin metastases or leucemic infiltration from 1979 to 2006. We excluded patients with primary cutaneous lymphoma or unavailable chart. Results: Patients: We found 40 patients (50% male) with a mean age of 57 years (617 yrs). Time elapsed from initial presentation of a skin metastasis to skin biopsy was 5.85 months (range, 0-96 mos). In patients who died, survival after skin biopsy was 5.43 months. Two patients reached cure (seminoma and breast carcinoma). Four patients with a follow-up of less than 5 months are still alive. Metastases: Most frequent primary tumors were: breast cancer (17.5%), gastrointestinal tract adenocarcinoma (20%), hematologic (17.5%), and primary unknown adenocarcinoma (after an exhaustive medical search; 12.5%). The most frequent sites included the thorax (27.5%) and abdomen (15%), scalp (10%), legs (12.5%), groin, neck, and surgical scar (7.5% each). Nodular metstases were 78.4% (13% erysipeloid). Skin biopsy utility: Skin biopsy diagnosed a previously unknown neoplasia in 45% patients, a metastasis of an already known tumor was confirmed in 40%, skin and primary tumor biopsies coincided in 10%, and there was an equivocal diagnosis of primary tumor with skin biopsy in 5%. In 3 cases, this method detected recurrence of neoplasia. Discussion: Skin metastases are found mostly in late stages of a neoplasia, and prognosis is usually ominous and short-term. However, depending of the type of neoplasia, there are still some cases that may be cured. In this study, we included diverse types of neoplasia and we confirmed the utility of skin biopsy for the initial diagnosis of a systemic neoplasia (up to 45% of cases obtained diagnosis by this method). This high incidence of new diagnosis of cancer by skin biopsy could also reflect a tendency of our population to search for health care in a delayed fashion. Conclusions: Skin biopsy is an accesible, fast, and useful method to diagnose a nonskin neoplasia. In some cases, it is still necessary to biopsy the primary tumor for confirmation of histology.
A phase II randomized bilateral comparison study of bexarotene 1% gel in alopecia areata Rakhshandra Talpur, MD, University of Texas MD Anderson Cancer Center, Houston, TX, United States; Roland Bassett, MS, University of Texas MD Anderson Cancer Center, Houston, TX, United States; Madeleine Duvic, MD, University of Texas MD Anderson Cancer Center, Houston, TX, United States; Victor Stevens, PhD, Ligand Pharmaceuticals, San Diego, CA, United States Alopecia areata (AA), a T-cell mediated autoimmune disease directed against hair follicles, can result in patchy (AA) or total loss (alopecia totalis [AT]) of scalp hair or loss of all hair (alopecia universalis [AU]), and is often refractory to therapy. Bexarotene (bex) is an RXR selective retinoid that induces T-cell apoptosis and is effective for the treatment of cutaneous T-cell lymphoma. We previously observed that bexarotene reversed alopecia in CTCL patients and therefore conducted a phase II study of topical targretin gel for AA. Forty-two patients (11 males, 31 females) with AT (n ¼ 3), AU (n ¼ 5) or patchy AA (n ¼ 34) were randomized to apply 1% topical bexarotene gel to one half of the scalp once daily for 2 weeks, then twice daily for 24 weeks. Responders were allowed continue therapy on both sides of the scalp for another 24 weeks. Assessments of index lesions, hair density, labs, and adverse events were performed monthly. Thirty-nine patients used the drug and were evaluable for response. Twelve patients of 39 (30.7%) had [50% partial hair regrowth: 6 improved on both sides including 1 with AT and 6 had responses limited to 1 side. Twenty patients had stable disease, 7 progressed while on therapy, and 3 patients withdrew after 2 weeks of study. Erythema, scaling, and/or itching caused by local irritation at the application site were experienced by 26 patients, and required a decreased application frequency in 8 patients. Four patients with no response were grade 3 dermal irritation. Five of 12 responders elected to continue treatment for 48 weeks: 3 achieved complete hair regrowth, 1 had bilateral partial responses, and 1 patient had a complete response on 1 side and stable disease on the other. Topical bex 1% is generally well tolerated with mild irritation and was associated with a 30% response in AA.
Commercial support: None identified.
Commercial support: None identified.
FEBRUARY 2008
J AM ACAD DERMATOL
AB9