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Insulin resistance and hair disorders, idiopathic hirsutism, and androgenic alopecia
P6446
P6548
Incidence of alopecia from endocrine therapies in cancer Vishal Saggar, New York University School of Medicine, New York, NY, United States; Mario E. Lacouture, MD, Memorial Sloan-Kettering Cancer Center, New York, NY, United States; Maura Dickler, MD, Memorial Sloan-Kettering Cancer Center, New York, NY, United States; Shenhong Wu, MD, PhD, Stony Brook University, Stony Brook, NY, United States
Minimal systemic exposure of a new topical triazole antifungal, efinaconazole 10% solution, in patients with severe onychomycosis following 28day treatment Christopher Crean, MS, Valeant Pharmaceuticals North America LLC, Durham, NC, United States; Akinori Aoyama, MS, Kaken Pharmaceutical Co Ltd, Shizuoka, Japan; Alexander Oh, PhD, Valeant Pharmaceuticals North America LLC, Bridgewater, NJ, United States; Robert Kang, MS, Valeant Pharmaceuticals North America LLC, Durham, NC, United States
Background: Whereas alopecia to cytotoxic chemotherapies is a well described event, hair loss in patients treated with endocrine therapies (antiestrogens, aromatase inhibitors) has not been systematically investigated. These agents are widely used in the treatment and prevention of many types of solid tumors, including breast and prostate cancers. We performed a systematic analysis of the literature in order to determine the frequency of alopecia for each of these drugs, in order to provide information that is critical for counseling and interventions against alopecia, a major quality of life issue for many patients. Methods: Relevant publications were identified from a PubMed search confined to phase II and III clinical trials, from 1966-2012. Keywords used in the search were ‘‘fulvestrant, octreotide, fluoxymesterone, nilutamide, flutamide, bicalutamide, estradiol, medroxyprogesterone, megestrol, leuprolide, anastrozole, letrozole, exemestane, tamoxifen, toremifene, and raloxifene.’’ Results: Of 1384 search results, 35 (2.5%) trials were found that included rates of alopecia, without confounding variables such as concurrent treatment with additional biologic therapy or chemotherapy. Data from a total of 14,769 patients were analyzed. Alopecia was reported with the use of the aromatase inhibitors anastrozole, letrozole, and exemestane, ranging from 0 to 9.4%, the LHRH agonist leuprolide, in 9.5% of patients, fulvestrant, ranging from 0% to 8%, megestrol, ranging from 0.5% to 11%, and tamoxifen, ranging from 0% to 17%. The types of cancer in which agents were reported to cause alopecia were breast (74%), hepatocellular (5.7%), ovarian (5.7%), prostate (5.7%), endometrial (2.8%), renal (2.8%), and meningioma (2.8%). Conclusion: Alopecia is a common, yet underreported side effect secondary to endocrine agents used against cancer, especially those of the breast and prostate. The long-term use of these agents heightens the importance of this adverse event on patients’ quality of life. Knowledge of the incidence of alopecia represents the first step towards the understanding and management of this frequently occurring untoward event that may affect many people receiving these therapies. Commercial support: None identified.
Background: Onychomycosis is a common fungal infection of toenails with oral medication preferred as first line therapy. However this approach may be limited in some patients by potential drugedrug interactions, systemic safety concerns (eg, liver toxicity), and by the potential need for laboratory monitoring. A topical treatment may be preferable, but the cure rates reported are much lower than those observed with systemic treatments and to date no topical treatment has been approved as monotherapy in the United States. Objective: To evaluate the safety and systemic exposure of once daily topically applied efinaconazole 10% solution in subjects with severe onychomycosis of the toenails. Methods: Single center, open-label study in 19 subjects (21-70 years old) with severe onychomycosis (approximately 90% of the toenail affected with a positive KOH). Efinaconazole 10% solution (0.42 mL) was applied once daily for 28 days under maximal exposure conditions (to all 10 toenails), with a 2-week posttreatment follow-up. Pharmacokinetic evaluations of efinaconazole and its metabolites (H3 and H4) were conducted during 3 separate periods: day 1-2, day 14-15, and day 28-29. Evaluations of safety were conducted throughout the study. Results: Efinaconazole Cmax increased slightly at each assessment period from 0.23 ng/mL on day 1, to 0.67 ng/mL on day 29. H3 metabolite Cmax increased from 0.09 ng/mL on day 1, to 2.36 ng/mL on day 28. The H4 metabolite was not quantifiable on day 1 and Cmax was 0.045 ng/mL on day 28. Plasma concentrations versus time curves were generally flat for efinaconazole and H3. Mean total exposure levels (AUCt) of efinaconazole, H3, and H4 were very low at 12, 46, and 2.0 ngh/mL, respectively, on day 28. A total of 4 adverse events (AEs) were reported; none were serious, related to study drug or resulted in study discontinuation. There were no clinically meaningful changes in laboratory parameters and no reports of swelling or vesiculation. One subject reported mild redness on day 7 following application of effinaconazole and there were a few (10%) reports of burning and/or itching, but these were not considered AEs. Conclusion: Efinaconazole 10% solution provided low systemic exposures to efinaconazole and its metabolites when applied once daily for 28 days to all 10 toenails. Efinaconazole was safe and well tolerated in adult subjects with severe distal lateral subungual onychomycosis affecting both great toenails. 100% sponsored by Valeant Dermatology a division of Valeant Pharmaceuticals North America LLC.
P6362 Onychomatricoma with classic features: Case report and review of the literature John Kelly, MD, PhD, University of Connecticut Health Center, Farmington, CT, United States; Adrienne Berke, MD, University of Connecticut Health Center, Farmington, CT, United States; Arni Kristjansson, MD, University of Connecticut Health Center, Farmington, CT, United States; Douglas Leone, MD, Great Lakes Dermatology, Racine, WI, United States; Siobhan Collins, MD, Dermatology Surgical Associates, Farmington, CT, United States
Background: Insulin resistance is becoming a focused cause in hair disorder such as idiopathic hirsutism that is characterized by hirsutism with normal ovulatory function in females and androgenic alopecia which is known to be androgen dependent in males since insulin has found in hair follicles and may play a role in regulation of hair growth cycle. Objective: To evaluate the accuracy of this hypothesis we conduct a case control study to evaluate the relation between metabolic syndrome factors and androgenic alopecia (AGA) in a male group and idiopathic hirsutism (IH) in a female group and control groups. Methods: This study conducted as a case control assay with 33 females with IH and 35 nonobese female control group and 97 males with AGA and 87 males as a control group. Results: Serum fasting insulin level, FBG, serum total cholesterol, triglyceride, HDL show no significant difference between cases and controls in male group, meanwhile fasting insulin level, HOMA, free androgen in IH group were higher than control subjects but it still it was not meaningful. Conclusion: Our study shows no significant relation between insulin resistance neither with idiopathic hirsutism nor with androgenic alopecia. However, it might be recommendable to consider this relationship more cautiously.
A 63-year-old white man presented to the dermatology clinic for the evaluation of nail dystrophy of the left pollex. It initially appeared 7 years earlier, with no preceding trauma, and had been consistently asymptomatic. Physical examination revealed a nontender, ill-defined subungal mass distorting the distal left pollex. There was partial onychodystrophy with splitting, longitudinal ridging, thickening, splinter hemorrhages, increased transverse curvature, and yellow discoloration of the nail plate. Radiographic studies revealed only minor degenerative changes of the IP joint. Diagnostic surgical biopsy revealed a very firm, exophytic, white, 5-mm nodule of the nail matrix with multiple soft filiform extensions projecting distally over the nail bed. Hematoxylineeosin staining showed a polypoid lesion. The matrix epithelium had deep projection into the underlying dermis and stroma, which was organized into two layers: (1) a superficial, highly-cellular layer with prominent fibrillary collagen, fibroblasts and mast cells and (2) a deeper, less-cellular layer with thicker collagen fibers. In addition, there were small nail plate extensions forming glove-like projections at the end of proximal nail plate. Immunohistochemistry revealed staining of stromal cells with CD34 and factor XIIIA and no staining with S100, Mart-1, EMA, and CD56. This analysis and clinical picture were consistent with the definitive diagnosis of onychomatricoma, a rare, benign, subungual tumor that produces deformity through autonomous production of nail plate keratin. The patient was successfully treated via elective surgical excision and has remained free from recurrence. As of 2012 approximately 70 cases of definitive onychomatricoma have been identified worldwide, with nearly 2/3 of patients being European and sporadic reports from North and South America. The female:male ratio is ;1:1.8, and nearly every digit has been reported affected at least once. Age at presentation varies widely, from 24 to 70 years old (excluding a single pediatric report), and most patients have had an indolent tumor for several years before seeking medical attention. While there is some histologic variation suggesting potential for malignant transformation, there are no reports of malignancy arising from an onychomatricoma, though there are a handful of cases that have relapsed following surgical resection.
Commercial support: None identified.
Commercial support: None identified.
P6603 Insulin resistance and hair disorders, idiopathic hirsutism, and androgenic alopecia Gita Meshkat Razavi, MD, Gita Meshkat Razavi, Palo Alto, CA, United States; Gity Meshkat Razavi, MD, Gity Meshkat Razavi, Palo Alto, CA, United States
APRIL 2013
J AM ACAD DERMATOL
AB107
P6548
Incidence of alopecia from endocrine therapies in cancer Vishal Saggar, New York University School of Medicine, New York, NY, United States; Mario E. Lacouture, MD, Memorial Sloan-Kettering Cancer Center, New York, NY, United States; Maura Dickler, MD, Memorial Sloan-Kettering Cancer Center, New York, NY, United States; Shenhong Wu, MD, PhD, Stony Brook University, Stony Brook, NY, United States
Minimal systemic exposure of a new topical triazole antifungal, efinaconazole 10% solution, in patients with severe onychomycosis following 28day treatment Christopher Crean, MS, Valeant Pharmaceuticals North America LLC, Durham, NC, United States; Akinori Aoyama, MS, Kaken Pharmaceutical Co Ltd, Shizuoka, Japan; Alexander Oh, PhD, Valeant Pharmaceuticals North America LLC, Bridgewater, NJ, United States; Robert Kang, MS, Valeant Pharmaceuticals North America LLC, Durham, NC, United States
Background: Whereas alopecia to cytotoxic chemotherapies is a well described event, hair loss in patients treated with endocrine therapies (antiestrogens, aromatase inhibitors) has not been systematically investigated. These agents are widely used in the treatment and prevention of many types of solid tumors, including breast and prostate cancers. We performed a systematic analysis of the literature in order to determine the frequency of alopecia for each of these drugs, in order to provide information that is critical for counseling and interventions against alopecia, a major quality of life issue for many patients. Methods: Relevant publications were identified from a PubMed search confined to phase II and III clinical trials, from 1966-2012. Keywords used in the search were ‘‘fulvestrant, octreotide, fluoxymesterone, nilutamide, flutamide, bicalutamide, estradiol, medroxyprogesterone, megestrol, leuprolide, anastrozole, letrozole, exemestane, tamoxifen, toremifene, and raloxifene.’’ Results: Of 1384 search results, 35 (2.5%) trials were found that included rates of alopecia, without confounding variables such as concurrent treatment with additional biologic therapy or chemotherapy. Data from a total of 14,769 patients were analyzed. Alopecia was reported with the use of the aromatase inhibitors anastrozole, letrozole, and exemestane, ranging from 0 to 9.4%, the LHRH agonist leuprolide, in 9.5% of patients, fulvestrant, ranging from 0% to 8%, megestrol, ranging from 0.5% to 11%, and tamoxifen, ranging from 0% to 17%. The types of cancer in which agents were reported to cause alopecia were breast (74%), hepatocellular (5.7%), ovarian (5.7%), prostate (5.7%), endometrial (2.8%), renal (2.8%), and meningioma (2.8%). Conclusion: Alopecia is a common, yet underreported side effect secondary to endocrine agents used against cancer, especially those of the breast and prostate. The long-term use of these agents heightens the importance of this adverse event on patients’ quality of life. Knowledge of the incidence of alopecia represents the first step towards the understanding and management of this frequently occurring untoward event that may affect many people receiving these therapies. Commercial support: None identified.
Background: Onychomycosis is a common fungal infection of toenails with oral medication preferred as first line therapy. However this approach may be limited in some patients by potential drugedrug interactions, systemic safety concerns (eg, liver toxicity), and by the potential need for laboratory monitoring. A topical treatment may be preferable, but the cure rates reported are much lower than those observed with systemic treatments and to date no topical treatment has been approved as monotherapy in the United States. Objective: To evaluate the safety and systemic exposure of once daily topically applied efinaconazole 10% solution in subjects with severe onychomycosis of the toenails. Methods: Single center, open-label study in 19 subjects (21-70 years old) with severe onychomycosis (approximately 90% of the toenail affected with a positive KOH). Efinaconazole 10% solution (0.42 mL) was applied once daily for 28 days under maximal exposure conditions (to all 10 toenails), with a 2-week posttreatment follow-up. Pharmacokinetic evaluations of efinaconazole and its metabolites (H3 and H4) were conducted during 3 separate periods: day 1-2, day 14-15, and day 28-29. Evaluations of safety were conducted throughout the study. Results: Efinaconazole Cmax increased slightly at each assessment period from 0.23 ng/mL on day 1, to 0.67 ng/mL on day 29. H3 metabolite Cmax increased from 0.09 ng/mL on day 1, to 2.36 ng/mL on day 28. The H4 metabolite was not quantifiable on day 1 and Cmax was 0.045 ng/mL on day 28. Plasma concentrations versus time curves were generally flat for efinaconazole and H3. Mean total exposure levels (AUCt) of efinaconazole, H3, and H4 were very low at 12, 46, and 2.0 ngh/mL, respectively, on day 28. A total of 4 adverse events (AEs) were reported; none were serious, related to study drug or resulted in study discontinuation. There were no clinically meaningful changes in laboratory parameters and no reports of swelling or vesiculation. One subject reported mild redness on day 7 following application of effinaconazole and there were a few (10%) reports of burning and/or itching, but these were not considered AEs. Conclusion: Efinaconazole 10% solution provided low systemic exposures to efinaconazole and its metabolites when applied once daily for 28 days to all 10 toenails. Efinaconazole was safe and well tolerated in adult subjects with severe distal lateral subungual onychomycosis affecting both great toenails. 100% sponsored by Valeant Dermatology a division of Valeant Pharmaceuticals North America LLC.
P6362 Onychomatricoma with classic features: Case report and review of the literature John Kelly, MD, PhD, University of Connecticut Health Center, Farmington, CT, United States; Adrienne Berke, MD, University of Connecticut Health Center, Farmington, CT, United States; Arni Kristjansson, MD, University of Connecticut Health Center, Farmington, CT, United States; Douglas Leone, MD, Great Lakes Dermatology, Racine, WI, United States; Siobhan Collins, MD, Dermatology Surgical Associates, Farmington, CT, United States
Background: Insulin resistance is becoming a focused cause in hair disorder such as idiopathic hirsutism that is characterized by hirsutism with normal ovulatory function in females and androgenic alopecia which is known to be androgen dependent in males since insulin has found in hair follicles and may play a role in regulation of hair growth cycle. Objective: To evaluate the accuracy of this hypothesis we conduct a case control study to evaluate the relation between metabolic syndrome factors and androgenic alopecia (AGA) in a male group and idiopathic hirsutism (IH) in a female group and control groups. Methods: This study conducted as a case control assay with 33 females with IH and 35 nonobese female control group and 97 males with AGA and 87 males as a control group. Results: Serum fasting insulin level, FBG, serum total cholesterol, triglyceride, HDL show no significant difference between cases and controls in male group, meanwhile fasting insulin level, HOMA, free androgen in IH group were higher than control subjects but it still it was not meaningful. Conclusion: Our study shows no significant relation between insulin resistance neither with idiopathic hirsutism nor with androgenic alopecia. However, it might be recommendable to consider this relationship more cautiously.
A 63-year-old white man presented to the dermatology clinic for the evaluation of nail dystrophy of the left pollex. It initially appeared 7 years earlier, with no preceding trauma, and had been consistently asymptomatic. Physical examination revealed a nontender, ill-defined subungal mass distorting the distal left pollex. There was partial onychodystrophy with splitting, longitudinal ridging, thickening, splinter hemorrhages, increased transverse curvature, and yellow discoloration of the nail plate. Radiographic studies revealed only minor degenerative changes of the IP joint. Diagnostic surgical biopsy revealed a very firm, exophytic, white, 5-mm nodule of the nail matrix with multiple soft filiform extensions projecting distally over the nail bed. Hematoxylineeosin staining showed a polypoid lesion. The matrix epithelium had deep projection into the underlying dermis and stroma, which was organized into two layers: (1) a superficial, highly-cellular layer with prominent fibrillary collagen, fibroblasts and mast cells and (2) a deeper, less-cellular layer with thicker collagen fibers. In addition, there were small nail plate extensions forming glove-like projections at the end of proximal nail plate. Immunohistochemistry revealed staining of stromal cells with CD34 and factor XIIIA and no staining with S100, Mart-1, EMA, and CD56. This analysis and clinical picture were consistent with the definitive diagnosis of onychomatricoma, a rare, benign, subungual tumor that produces deformity through autonomous production of nail plate keratin. The patient was successfully treated via elective surgical excision and has remained free from recurrence. As of 2012 approximately 70 cases of definitive onychomatricoma have been identified worldwide, with nearly 2/3 of patients being European and sporadic reports from North and South America. The female:male ratio is ;1:1.8, and nearly every digit has been reported affected at least once. Age at presentation varies widely, from 24 to 70 years old (excluding a single pediatric report), and most patients have had an indolent tumor for several years before seeking medical attention. While there is some histologic variation suggesting potential for malignant transformation, there are no reports of malignancy arising from an onychomatricoma, though there are a handful of cases that have relapsed following surgical resection.
Commercial support: None identified.
Commercial support: None identified.
P6603 Insulin resistance and hair disorders, idiopathic hirsutism, and androgenic alopecia Gita Meshkat Razavi, MD, Gita Meshkat Razavi, Palo Alto, CA, United States; Gity Meshkat Razavi, MD, Gity Meshkat Razavi, Palo Alto, CA, United States
APRIL 2013
J AM ACAD DERMATOL
AB107