AAD Summer Academy 2011

NEW YORK  – Bullous pemphigoid has a sharply increased incidence in the elderly, and can sometimes be challenging to diagnose because of atypical presentation.

Results from a recent review of 117 patients newly diagnosed with bullous pemphigoid (BP) in Switzerland during 2001-2002 showed that 20% of the patients had atypical manifestations. Among the patients with atypical BP, the time to a correct diagnosis rose by 50%, compared with patients who had typical presentations (an average increased time to diagnosis of 3 months), Dr. Luca Borradori said at the meeting.

Photos courtesy Dr. Luca Borradori

BP "is an extremely polymorphic disease," he added. When it presents with classic, generalized bullous lesions it’s easily diagnosed, but when it is localized and presents with nonbullous lesions the diagnosis is challenging and often delayed, said Dr. Borradori, a professor of dermatology at the University Hospital in Bern, Switzerland. The elderly are so susceptible to BP that an aggressive approach to diagnosis works best.

"Always consider BP for elderly patients with relapsing, itchy, cutaneous lesions," he said.

His recommended diagnostic criteria include using direct immunofluorescence microscopy to identify linear deposits of IgG or complement component C3 in the epidermal basement membrane zone in patients with subepidermal blistering. Patients with these deposits should also have at least three of the following four criteria to receive a BP diagnosis: no atrophic scarring, no mucosal involvement, no head and neck involvement, and age older than 70 years. This approach had a positive predictive value of 95%, a sensitivity of 86%, and a specificity of 90%, Dr. Borradori said.

Patients with nonbullous lesions pose the hardest diagnostic challenge. These cases can present with eczematous and urticated lesions; scaly and crusted lesions; localized bullae, erosions, or vegetating lesions; persistent mucosal lesions; and lesions with skin fragility or atrophic scarring.

Dr. Borradori and his associates have documented the role of older age in boosting the incidence of BP. In their study of all new presenting BP cases in Switzerland during 2001-2002, they found an overall BP incidence of about 12 new cases/year for every 1 million people. But among men aged 70-79 the average annual rate jumped to roughly 175 new cases per 1 million people, and for those aged 80 or older the incidence rose to 250 new cases per 1 million people per year.

In contrast, among men or women 50-59 the annual rate ran less than 10 new cases per 1 million people, and among people younger than 50 years old the annual incidence barely rose above one new case per 1 million people.

The clear choice for treatment of mild or localized BP is potent topical steroids, as well as for extensive and persistent cutaneous disease. The oral corticosteroid prednisone was also validated for treating extensive and persistent cutaneous BP in a prospective randomized trial. However, no treatments have been proven in a trial to work for treatment-resistant and challenging cases. "Aggressive, non-validated therapies should be avoided," Dr. Borradori said. Blinded, randomized trials are "urgently needed" to investigate the efficacy of novel biologic therapies.

Dr. Borradori reported having no disclosures.

NEW YORK  – Bullous pemphigoid has a sharply increased incidence in the elderly, and can sometimes be challenging to diagnose because of atypical presentation.

Results from a recent review of 117 patients newly diagnosed with bullous pemphigoid (BP) in Switzerland during 2001-2002 showed that 20% of the patients had atypical manifestations. Among the patients with atypical BP, the time to a correct diagnosis rose by 50%, compared with patients who had typical presentations (an average increased time to diagnosis of 3 months), Dr. Luca Borradori said at the meeting.

Photos courtesy Dr. Luca Borradori

BP "is an extremely polymorphic disease," he added. When it presents with classic, generalized bullous lesions it’s easily diagnosed, but when it is localized and presents with nonbullous lesions the diagnosis is challenging and often delayed, said Dr. Borradori, a professor of dermatology at the University Hospital in Bern, Switzerland. The elderly are so susceptible to BP that an aggressive approach to diagnosis works best.

"Always consider BP for elderly patients with relapsing, itchy, cutaneous lesions," he said.

His recommended diagnostic criteria include using direct immunofluorescence microscopy to identify linear deposits of IgG or complement component C3 in the epidermal basement membrane zone in patients with subepidermal blistering. Patients with these deposits should also have at least three of the following four criteria to receive a BP diagnosis: no atrophic scarring, no mucosal involvement, no head and neck involvement, and age older than 70 years. This approach had a positive predictive value of 95%, a sensitivity of 86%, and a specificity of 90%, Dr. Borradori said.

Patients with nonbullous lesions pose the hardest diagnostic challenge. These cases can present with eczematous and urticated lesions; scaly and crusted lesions; localized bullae, erosions, or vegetating lesions; persistent mucosal lesions; and lesions with skin fragility or atrophic scarring.

Dr. Borradori and his associates have documented the role of older age in boosting the incidence of BP. In their study of all new presenting BP cases in Switzerland during 2001-2002, they found an overall BP incidence of about 12 new cases/year for every 1 million people. But among men aged 70-79 the average annual rate jumped to roughly 175 new cases per 1 million people, and for those aged 80 or older the incidence rose to 250 new cases per 1 million people per year.

In contrast, among men or women 50-59 the annual rate ran less than 10 new cases per 1 million people, and among people younger than 50 years old the annual incidence barely rose above one new case per 1 million people.

The clear choice for treatment of mild or localized BP is potent topical steroids, as well as for extensive and persistent cutaneous disease. The oral corticosteroid prednisone was also validated for treating extensive and persistent cutaneous BP in a prospective randomized trial. However, no treatments have been proven in a trial to work for treatment-resistant and challenging cases. "Aggressive, non-validated therapies should be avoided," Dr. Borradori said. Blinded, randomized trials are "urgently needed" to investigate the efficacy of novel biologic therapies.

Dr. Borradori reported having no disclosures.

NEW YORK  – Bullous pemphigoid has a sharply increased incidence in the elderly, and can sometimes be challenging to diagnose because of atypical presentation.

Results from a recent review of 117 patients newly diagnosed with bullous pemphigoid (BP) in Switzerland during 2001-2002 showed that 20% of the patients had atypical manifestations. Among the patients with atypical BP, the time to a correct diagnosis rose by 50%, compared with patients who had typical presentations (an average increased time to diagnosis of 3 months), Dr. Luca Borradori said at the meeting.

Photos courtesy Dr. Luca Borradori

BP "is an extremely polymorphic disease," he added. When it presents with classic, generalized bullous lesions it’s easily diagnosed, but when it is localized and presents with nonbullous lesions the diagnosis is challenging and often delayed, said Dr. Borradori, a professor of dermatology at the University Hospital in Bern, Switzerland. The elderly are so susceptible to BP that an aggressive approach to diagnosis works best.

"Always consider BP for elderly patients with relapsing, itchy, cutaneous lesions," he said.

His recommended diagnostic criteria include using direct immunofluorescence microscopy to identify linear deposits of IgG or complement component C3 in the epidermal basement membrane zone in patients with subepidermal blistering. Patients with these deposits should also have at least three of the following four criteria to receive a BP diagnosis: no atrophic scarring, no mucosal involvement, no head and neck involvement, and age older than 70 years. This approach had a positive predictive value of 95%, a sensitivity of 86%, and a specificity of 90%, Dr. Borradori said.

Patients with nonbullous lesions pose the hardest diagnostic challenge. These cases can present with eczematous and urticated lesions; scaly and crusted lesions; localized bullae, erosions, or vegetating lesions; persistent mucosal lesions; and lesions with skin fragility or atrophic scarring.

Dr. Borradori and his associates have documented the role of older age in boosting the incidence of BP. In their study of all new presenting BP cases in Switzerland during 2001-2002, they found an overall BP incidence of about 12 new cases/year for every 1 million people. But among men aged 70-79 the average annual rate jumped to roughly 175 new cases per 1 million people, and for those aged 80 or older the incidence rose to 250 new cases per 1 million people per year.

In contrast, among men or women 50-59 the annual rate ran less than 10 new cases per 1 million people, and among people younger than 50 years old the annual incidence barely rose above one new case per 1 million people.

The clear choice for treatment of mild or localized BP is potent topical steroids, as well as for extensive and persistent cutaneous disease. The oral corticosteroid prednisone was also validated for treating extensive and persistent cutaneous BP in a prospective randomized trial. However, no treatments have been proven in a trial to work for treatment-resistant and challenging cases. "Aggressive, non-validated therapies should be avoided," Dr. Borradori said. Blinded, randomized trials are "urgently needed" to investigate the efficacy of novel biologic therapies.

Dr. Borradori reported having no disclosures.

NEW YORK – Can cosmetic dermatologists work with other specialists to create a multidisciplinary care clinic?

A pilot survey says it might just work – and that both physicians and patients could benefit from the arrangement, Dr. Steven R. Feldman and his colleagues reported in a poster presented at the American Academy of Dermatology’s Summer Academy Meeting.

The researchers wanted to find out if academic physicians at Wake Forest University Baptist Medical Center, Winston-Salem, N.C., would be interested in participating in a clinic that would include dermatologists, plastic surgeons, and specialists in otolaryngology and ophthalmology. Dr. Feldman, professor of dermatology at Wake Forest, and his colleagues surveyed six faculty members – two plastic surgeons, an otolaryngologist (ENT), an ophthalmologist, a general dermatologist, and a dermatologic surgeon – to assess their interest, and to find out what they foresaw as possible pitfalls in such collaboration. Five of the respondents reported performing cosmetic procedures.

The survey included 7 multiple-choice opinion statements and 15 open-ended questions, which allowed the participants to freely express their thoughts.

On average, the respondents agreed that patients would benefit from such a clinic, that they would be willing to work at one, and that their involvement would be a wise investment.

They reported that they did feel market competition could be a problem and that the professional relationship among providers in such a clinic could be contentious.

Opinions on who should perform which procedure were stronger. The group strongly agreed that "Certain procedures should only be performed by board-certified members of [each] subspecialty." But there was strong disagreement that only specialists who develop certain procedures should be licensed to perform them, suggesting that teaching could be a vital part of a collaborative clinic.

Overall, the ENT and general dermatologist were most in favor of such a project. The dermatologic and plastic surgeons were least in favor. The overall score for supporting the idea was positive.

Respondents were more cautious on the idea of a successful collaboration. Again, the ENT and dermatologic surgeon had the most positive view on this, while the ophthalmologist and plastic surgeons were less enthusiastic. The overall collaboration score was neutral. Dr. Feldman and his associates said the combination of the two scores among all respondents was neutral.

Responses to open-ended questions were diverse, the investigators noted. The ENT said it would be important for major institutions to offer such a program, while the dermatologic surgeon stressed the teaching possibilities. The plastic surgeons expressed concern about clear definition of roles.

The ENT saw a potential pitfall: ego, fear of competition, jealousy, sharing of expenses, resources, and referrals. One plastic surgeon said a major problem would be "increasing competition for a defined group of patients. No other specialty is bringing anything to the table other than more patients than we already have."

The general dermatologist was more positive about the idea, citing the ability to increase patient care possibilities with high-reward cosmetic procedures, the opportunity for teaching residents, and the center’s ability to provide the ethical delivery of advice to patients interested in purchasing a cosmetic service.

In voicing other concerns about such a program, one plastic surgeon was skeptical. "Plastic surgery can do anything that other specialists can provide. [They are] self reliant." Working with physicians who don’t work at the same level or achieve the same results would be an issue, the surgeon noted. And since reputations would be linked, physicians would need to watch for "subpar standards."

Overall, the investigators concluded, "Academic physicians are interested in participating in a multidisciplinary cosmetic center. This survey, although small, helps to reveal potential pitfalls of such a center, which is an important step toward constructing a practice model that minimizes conflict between specialists and maximizes cooperation and collaboration, [and] ultimately optimizes patient care and outcomes."

None of the authors noted any financial conflicts.

NEW YORK – Can cosmetic dermatologists work with other specialists to create a multidisciplinary care clinic?

A pilot survey says it might just work – and that both physicians and patients could benefit from the arrangement, Dr. Steven R. Feldman and his colleagues reported in a poster presented at the American Academy of Dermatology’s Summer Academy Meeting.

The researchers wanted to find out if academic physicians at Wake Forest University Baptist Medical Center, Winston-Salem, N.C., would be interested in participating in a clinic that would include dermatologists, plastic surgeons, and specialists in otolaryngology and ophthalmology. Dr. Feldman, professor of dermatology at Wake Forest, and his colleagues surveyed six faculty members – two plastic surgeons, an otolaryngologist (ENT), an ophthalmologist, a general dermatologist, and a dermatologic surgeon – to assess their interest, and to find out what they foresaw as possible pitfalls in such collaboration. Five of the respondents reported performing cosmetic procedures.

The survey included 7 multiple-choice opinion statements and 15 open-ended questions, which allowed the participants to freely express their thoughts.

On average, the respondents agreed that patients would benefit from such a clinic, that they would be willing to work at one, and that their involvement would be a wise investment.

They reported that they did feel market competition could be a problem and that the professional relationship among providers in such a clinic could be contentious.

Opinions on who should perform which procedure were stronger. The group strongly agreed that "Certain procedures should only be performed by board-certified members of [each] subspecialty." But there was strong disagreement that only specialists who develop certain procedures should be licensed to perform them, suggesting that teaching could be a vital part of a collaborative clinic.

Overall, the ENT and general dermatologist were most in favor of such a project. The dermatologic and plastic surgeons were least in favor. The overall score for supporting the idea was positive.

Respondents were more cautious on the idea of a successful collaboration. Again, the ENT and dermatologic surgeon had the most positive view on this, while the ophthalmologist and plastic surgeons were less enthusiastic. The overall collaboration score was neutral. Dr. Feldman and his associates said the combination of the two scores among all respondents was neutral.

Responses to open-ended questions were diverse, the investigators noted. The ENT said it would be important for major institutions to offer such a program, while the dermatologic surgeon stressed the teaching possibilities. The plastic surgeons expressed concern about clear definition of roles.

The ENT saw a potential pitfall: ego, fear of competition, jealousy, sharing of expenses, resources, and referrals. One plastic surgeon said a major problem would be "increasing competition for a defined group of patients. No other specialty is bringing anything to the table other than more patients than we already have."

The general dermatologist was more positive about the idea, citing the ability to increase patient care possibilities with high-reward cosmetic procedures, the opportunity for teaching residents, and the center’s ability to provide the ethical delivery of advice to patients interested in purchasing a cosmetic service.

In voicing other concerns about such a program, one plastic surgeon was skeptical. "Plastic surgery can do anything that other specialists can provide. [They are] self reliant." Working with physicians who don’t work at the same level or achieve the same results would be an issue, the surgeon noted. And since reputations would be linked, physicians would need to watch for "subpar standards."

Overall, the investigators concluded, "Academic physicians are interested in participating in a multidisciplinary cosmetic center. This survey, although small, helps to reveal potential pitfalls of such a center, which is an important step toward constructing a practice model that minimizes conflict between specialists and maximizes cooperation and collaboration, [and] ultimately optimizes patient care and outcomes."

None of the authors noted any financial conflicts.

NEW YORK – Can cosmetic dermatologists work with other specialists to create a multidisciplinary care clinic?

A pilot survey says it might just work – and that both physicians and patients could benefit from the arrangement, Dr. Steven R. Feldman and his colleagues reported in a poster presented at the American Academy of Dermatology’s Summer Academy Meeting.

The researchers wanted to find out if academic physicians at Wake Forest University Baptist Medical Center, Winston-Salem, N.C., would be interested in participating in a clinic that would include dermatologists, plastic surgeons, and specialists in otolaryngology and ophthalmology. Dr. Feldman, professor of dermatology at Wake Forest, and his colleagues surveyed six faculty members – two plastic surgeons, an otolaryngologist (ENT), an ophthalmologist, a general dermatologist, and a dermatologic surgeon – to assess their interest, and to find out what they foresaw as possible pitfalls in such collaboration. Five of the respondents reported performing cosmetic procedures.

The survey included 7 multiple-choice opinion statements and 15 open-ended questions, which allowed the participants to freely express their thoughts.

On average, the respondents agreed that patients would benefit from such a clinic, that they would be willing to work at one, and that their involvement would be a wise investment.

They reported that they did feel market competition could be a problem and that the professional relationship among providers in such a clinic could be contentious.

Opinions on who should perform which procedure were stronger. The group strongly agreed that "Certain procedures should only be performed by board-certified members of [each] subspecialty." But there was strong disagreement that only specialists who develop certain procedures should be licensed to perform them, suggesting that teaching could be a vital part of a collaborative clinic.

Overall, the ENT and general dermatologist were most in favor of such a project. The dermatologic and plastic surgeons were least in favor. The overall score for supporting the idea was positive.

Respondents were more cautious on the idea of a successful collaboration. Again, the ENT and dermatologic surgeon had the most positive view on this, while the ophthalmologist and plastic surgeons were less enthusiastic. The overall collaboration score was neutral. Dr. Feldman and his associates said the combination of the two scores among all respondents was neutral.

Responses to open-ended questions were diverse, the investigators noted. The ENT said it would be important for major institutions to offer such a program, while the dermatologic surgeon stressed the teaching possibilities. The plastic surgeons expressed concern about clear definition of roles.

The ENT saw a potential pitfall: ego, fear of competition, jealousy, sharing of expenses, resources, and referrals. One plastic surgeon said a major problem would be "increasing competition for a defined group of patients. No other specialty is bringing anything to the table other than more patients than we already have."

The general dermatologist was more positive about the idea, citing the ability to increase patient care possibilities with high-reward cosmetic procedures, the opportunity for teaching residents, and the center’s ability to provide the ethical delivery of advice to patients interested in purchasing a cosmetic service.

In voicing other concerns about such a program, one plastic surgeon was skeptical. "Plastic surgery can do anything that other specialists can provide. [They are] self reliant." Working with physicians who don’t work at the same level or achieve the same results would be an issue, the surgeon noted. And since reputations would be linked, physicians would need to watch for "subpar standards."

Overall, the investigators concluded, "Academic physicians are interested in participating in a multidisciplinary cosmetic center. This survey, although small, helps to reveal potential pitfalls of such a center, which is an important step toward constructing a practice model that minimizes conflict between specialists and maximizes cooperation and collaboration, [and] ultimately optimizes patient care and outcomes."

None of the authors noted any financial conflicts.

NEW YORK – Sentinel lymph node biopsy continues to aid the management of about 30% of melanoma patients, though its role in the future will depend on ongoing follow-up of a major trial that started nearly 20 years ago to assess the effect of SLNB on patient survival.

But SLNB’s role could soon be upstaged by molecular profiling and the identification of specific genetic mutations that drive various melanoma subtypes, Dr. Timothy M. Johnson said at the American Academy of Dermatology’s Summer Academy Meeting.

"In the future, I hope we can do molecular profiling on melanoma and [based on that] tell patients who will benefit [from various targeted treatments] and who won’t. We are already doing this [on an investigational basis] with several new molecular profiling tests such as BRAF mutations" and treatment with vemurafenib, said Dr. Johnson, a professor of dermatology at the University of Michigan in Ann Arbor.

For the time being, melanoma patients should be counseled regarding SLNB if their tumors are at least 0.75 mm in Breslow depth and if they meet certain other criteria.

Even patients with thinner tumors should be counseled on the pros and cons of SLNB, because they will likely hear or know about the technique and may have questions. That is the approach taken at the University of Michigan and other centers, he said.

"SLN status is a powerful predictor of survival in the relatively small subset of patients where SLNB is indicated," he said. Reasons not to do SLNB include thin primary melanomas generally less than 0.75 mm with a low probability of a positive SLNB, high comorbidities, and maybe prior wide local excision, certainly in areas of ambiguous lymphatic drainage or following a local flap. This group includes about 70% of all U.S. melanoma patients. Albeit rarely, these thin lesions may be at higher risk when they have greater degrees of adverse features or positive deep margins on shave biopsy.

Melanoma patients with primary tumors that are 0.75-0.99 mm generally need an additional risk factor, such as ulceration, young age – up to about 40 years old, an increased mitotic rate, or angiolymphatic invasion to justify SLNB. When patients have additional risk factors, "we have a discussion with the patient to help them decide," he said. "We tell them the likely rate of positive lymph nodes based on our best information."

A clearer role for SLNB exists for patients with tumors with a Breslow thickness of 1 mm or greater. In these patients, exclusions from SLNB include "highly significant" medical comorbidities, a prior wide excision of the tumor, and tumors in "ambiguous" lymphatic drainage areas, such as the central back or central chest. Even in these cases, exclusion from SLNB "usually occurs but not always," Dr. Johnson noted.

Patients whose tumors have a Breslow thickness of more than 4 mm are also candidates for SLNB. In these cases, SLNB can help refine the patient’s prognosis, and may also aid the choice of adjuvant therapy.

Historically, patients with tumors 4 mm or larger were considered likely to have distant metastatic disease and a poor prognosis, and, hence, no benefit from SLNB. But Dr. Johnson and his colleagues showed a substantial difference in survival rate between patients with positive and negative SLNs even when they had thicker primary tumors.

In a series of 227 patients with melanomas at least 4 mm thick and no clinically or radiologically-apparent distant disease, patients with a positive SLNB had a 5-year overall survival rate of 47%, while patients with negative SLNs had a 5-year survival rate of 80%, a statistically significant difference (P less than .0001). The difference in 5-year distant disease-free survival rates ran slightly larger, 85% in the node-negative patients and 48% in the node-positive patients (P less than .0001) (Cancer 2009;115:5752-60). Following this study, supporting evidence has come from several other research groups.

The ongoing Multicenter Selective Lymphadenectomy Trial (MSLT) should provide more definitive evidence on the survival effects of SLNB. The interim, 5-year follow-up data from 1,327 patients at 18 worldwide centers reported in 2006 included patients with primary-tumor Breslow thicknesses of 1.2-3.5 mm. Although the study’s primary endpoint of the 5-year melanoma-specific survival rate was similar in the patients randomized to SLNB or wide local excision (87%), the prespecified secondary endpoint of 5-year disease-free survival ran 78% in patients who underwent SLNB and 73% in the wide excision group, a statistically-significant difference (P = .009) (N. Engl. J. Med. 2006;355:1307-17).

"The question is, can we identify a subset of patients with occult nodal disease with SLNB, intervene early, and improve outcomes? At face value, the third interim analysis data [the 2006 report] suggests potentially yes. However, this is a subset analysis and its validity can be debated. The data certainly support the potential for a subset benefit in node-positive patients," said Dr. Johnson. Updated survival results from a longer-term, fourth interim analysis of the MSLT survival outcomes are expected within the next year, and will help answer this question.

In addition to the disease-free survival benefit shown in the MSLT, the 30% of melanoma patients who are candidates for SLNB stand to gain useful prognostic information from the procedure. On average, about 20% of patients who are eligible for SLNB have a positive SLN, and this subgroup of patients also stand to benefit from more durable regional control of their disease with better quality of life. The survival benefit most likely occurs in a subset, perhaps 20%, of the node-positive patients, he said.

In summary, Dr. Johnson said the main reasons to consider SLNB are prognosis, durable regional control, and potential survival benefit in a select subset. These factors should be presented in "an honest discussion with the patient and family about the risks and benefits of SLNB, to help them make a best informed decision," he said.

Although many cancer centers currently use SLNB for melanoma in the way outlined by Dr. Johnson, with "not much controversy" among the "mainstream" of physicians and surgeons who treat melanoma, he noted that "there is posturing and emotion with this procedure," with controversy among some clinicians about the proper role.

"Some dermatologists don’t believe that SLNB should be used for anybody, and some surgeons overuse it on everybody. The answer [on when to use SLNB] is somewhere in between," he said in an interview. The forthcoming, longer-term follow-up data from MSLT may help clinicians how best to use SLNB most appropriately, he added.

Dr. Johnson said that he had no disclosures.

NEW YORK – Sentinel lymph node biopsy continues to aid the management of about 30% of melanoma patients, though its role in the future will depend on ongoing follow-up of a major trial that started nearly 20 years ago to assess the effect of SLNB on patient survival.

But SLNB’s role could soon be upstaged by molecular profiling and the identification of specific genetic mutations that drive various melanoma subtypes, Dr. Timothy M. Johnson said at the American Academy of Dermatology’s Summer Academy Meeting.

"In the future, I hope we can do molecular profiling on melanoma and [based on that] tell patients who will benefit [from various targeted treatments] and who won’t. We are already doing this [on an investigational basis] with several new molecular profiling tests such as BRAF mutations" and treatment with vemurafenib, said Dr. Johnson, a professor of dermatology at the University of Michigan in Ann Arbor.

For the time being, melanoma patients should be counseled regarding SLNB if their tumors are at least 0.75 mm in Breslow depth and if they meet certain other criteria.

Even patients with thinner tumors should be counseled on the pros and cons of SLNB, because they will likely hear or know about the technique and may have questions. That is the approach taken at the University of Michigan and other centers, he said.

"SLN status is a powerful predictor of survival in the relatively small subset of patients where SLNB is indicated," he said. Reasons not to do SLNB include thin primary melanomas generally less than 0.75 mm with a low probability of a positive SLNB, high comorbidities, and maybe prior wide local excision, certainly in areas of ambiguous lymphatic drainage or following a local flap. This group includes about 70% of all U.S. melanoma patients. Albeit rarely, these thin lesions may be at higher risk when they have greater degrees of adverse features or positive deep margins on shave biopsy.

Melanoma patients with primary tumors that are 0.75-0.99 mm generally need an additional risk factor, such as ulceration, young age – up to about 40 years old, an increased mitotic rate, or angiolymphatic invasion to justify SLNB. When patients have additional risk factors, "we have a discussion with the patient to help them decide," he said. "We tell them the likely rate of positive lymph nodes based on our best information."

A clearer role for SLNB exists for patients with tumors with a Breslow thickness of 1 mm or greater. In these patients, exclusions from SLNB include "highly significant" medical comorbidities, a prior wide excision of the tumor, and tumors in "ambiguous" lymphatic drainage areas, such as the central back or central chest. Even in these cases, exclusion from SLNB "usually occurs but not always," Dr. Johnson noted.

Patients whose tumors have a Breslow thickness of more than 4 mm are also candidates for SLNB. In these cases, SLNB can help refine the patient’s prognosis, and may also aid the choice of adjuvant therapy.

Historically, patients with tumors 4 mm or larger were considered likely to have distant metastatic disease and a poor prognosis, and, hence, no benefit from SLNB. But Dr. Johnson and his colleagues showed a substantial difference in survival rate between patients with positive and negative SLNs even when they had thicker primary tumors.

In a series of 227 patients with melanomas at least 4 mm thick and no clinically or radiologically-apparent distant disease, patients with a positive SLNB had a 5-year overall survival rate of 47%, while patients with negative SLNs had a 5-year survival rate of 80%, a statistically significant difference (P less than .0001). The difference in 5-year distant disease-free survival rates ran slightly larger, 85% in the node-negative patients and 48% in the node-positive patients (P less than .0001) (Cancer 2009;115:5752-60). Following this study, supporting evidence has come from several other research groups.

The ongoing Multicenter Selective Lymphadenectomy Trial (MSLT) should provide more definitive evidence on the survival effects of SLNB. The interim, 5-year follow-up data from 1,327 patients at 18 worldwide centers reported in 2006 included patients with primary-tumor Breslow thicknesses of 1.2-3.5 mm. Although the study’s primary endpoint of the 5-year melanoma-specific survival rate was similar in the patients randomized to SLNB or wide local excision (87%), the prespecified secondary endpoint of 5-year disease-free survival ran 78% in patients who underwent SLNB and 73% in the wide excision group, a statistically-significant difference (P = .009) (N. Engl. J. Med. 2006;355:1307-17).

"The question is, can we identify a subset of patients with occult nodal disease with SLNB, intervene early, and improve outcomes? At face value, the third interim analysis data [the 2006 report] suggests potentially yes. However, this is a subset analysis and its validity can be debated. The data certainly support the potential for a subset benefit in node-positive patients," said Dr. Johnson. Updated survival results from a longer-term, fourth interim analysis of the MSLT survival outcomes are expected within the next year, and will help answer this question.

In addition to the disease-free survival benefit shown in the MSLT, the 30% of melanoma patients who are candidates for SLNB stand to gain useful prognostic information from the procedure. On average, about 20% of patients who are eligible for SLNB have a positive SLN, and this subgroup of patients also stand to benefit from more durable regional control of their disease with better quality of life. The survival benefit most likely occurs in a subset, perhaps 20%, of the node-positive patients, he said.

In summary, Dr. Johnson said the main reasons to consider SLNB are prognosis, durable regional control, and potential survival benefit in a select subset. These factors should be presented in "an honest discussion with the patient and family about the risks and benefits of SLNB, to help them make a best informed decision," he said.

Although many cancer centers currently use SLNB for melanoma in the way outlined by Dr. Johnson, with "not much controversy" among the "mainstream" of physicians and surgeons who treat melanoma, he noted that "there is posturing and emotion with this procedure," with controversy among some clinicians about the proper role.

"Some dermatologists don’t believe that SLNB should be used for anybody, and some surgeons overuse it on everybody. The answer [on when to use SLNB] is somewhere in between," he said in an interview. The forthcoming, longer-term follow-up data from MSLT may help clinicians how best to use SLNB most appropriately, he added.

Dr. Johnson said that he had no disclosures.

NEW YORK – Sentinel lymph node biopsy continues to aid the management of about 30% of melanoma patients, though its role in the future will depend on ongoing follow-up of a major trial that started nearly 20 years ago to assess the effect of SLNB on patient survival.

But SLNB’s role could soon be upstaged by molecular profiling and the identification of specific genetic mutations that drive various melanoma subtypes, Dr. Timothy M. Johnson said at the American Academy of Dermatology’s Summer Academy Meeting.

"In the future, I hope we can do molecular profiling on melanoma and [based on that] tell patients who will benefit [from various targeted treatments] and who won’t. We are already doing this [on an investigational basis] with several new molecular profiling tests such as BRAF mutations" and treatment with vemurafenib, said Dr. Johnson, a professor of dermatology at the University of Michigan in Ann Arbor.

For the time being, melanoma patients should be counseled regarding SLNB if their tumors are at least 0.75 mm in Breslow depth and if they meet certain other criteria.

Even patients with thinner tumors should be counseled on the pros and cons of SLNB, because they will likely hear or know about the technique and may have questions. That is the approach taken at the University of Michigan and other centers, he said.

"SLN status is a powerful predictor of survival in the relatively small subset of patients where SLNB is indicated," he said. Reasons not to do SLNB include thin primary melanomas generally less than 0.75 mm with a low probability of a positive SLNB, high comorbidities, and maybe prior wide local excision, certainly in areas of ambiguous lymphatic drainage or following a local flap. This group includes about 70% of all U.S. melanoma patients. Albeit rarely, these thin lesions may be at higher risk when they have greater degrees of adverse features or positive deep margins on shave biopsy.

Melanoma patients with primary tumors that are 0.75-0.99 mm generally need an additional risk factor, such as ulceration, young age – up to about 40 years old, an increased mitotic rate, or angiolymphatic invasion to justify SLNB. When patients have additional risk factors, "we have a discussion with the patient to help them decide," he said. "We tell them the likely rate of positive lymph nodes based on our best information."

A clearer role for SLNB exists for patients with tumors with a Breslow thickness of 1 mm or greater. In these patients, exclusions from SLNB include "highly significant" medical comorbidities, a prior wide excision of the tumor, and tumors in "ambiguous" lymphatic drainage areas, such as the central back or central chest. Even in these cases, exclusion from SLNB "usually occurs but not always," Dr. Johnson noted.

Patients whose tumors have a Breslow thickness of more than 4 mm are also candidates for SLNB. In these cases, SLNB can help refine the patient’s prognosis, and may also aid the choice of adjuvant therapy.

Historically, patients with tumors 4 mm or larger were considered likely to have distant metastatic disease and a poor prognosis, and, hence, no benefit from SLNB. But Dr. Johnson and his colleagues showed a substantial difference in survival rate between patients with positive and negative SLNs even when they had thicker primary tumors.

In a series of 227 patients with melanomas at least 4 mm thick and no clinically or radiologically-apparent distant disease, patients with a positive SLNB had a 5-year overall survival rate of 47%, while patients with negative SLNs had a 5-year survival rate of 80%, a statistically significant difference (P less than .0001). The difference in 5-year distant disease-free survival rates ran slightly larger, 85% in the node-negative patients and 48% in the node-positive patients (P less than .0001) (Cancer 2009;115:5752-60). Following this study, supporting evidence has come from several other research groups.

The ongoing Multicenter Selective Lymphadenectomy Trial (MSLT) should provide more definitive evidence on the survival effects of SLNB. The interim, 5-year follow-up data from 1,327 patients at 18 worldwide centers reported in 2006 included patients with primary-tumor Breslow thicknesses of 1.2-3.5 mm. Although the study’s primary endpoint of the 5-year melanoma-specific survival rate was similar in the patients randomized to SLNB or wide local excision (87%), the prespecified secondary endpoint of 5-year disease-free survival ran 78% in patients who underwent SLNB and 73% in the wide excision group, a statistically-significant difference (P = .009) (N. Engl. J. Med. 2006;355:1307-17).

"The question is, can we identify a subset of patients with occult nodal disease with SLNB, intervene early, and improve outcomes? At face value, the third interim analysis data [the 2006 report] suggests potentially yes. However, this is a subset analysis and its validity can be debated. The data certainly support the potential for a subset benefit in node-positive patients," said Dr. Johnson. Updated survival results from a longer-term, fourth interim analysis of the MSLT survival outcomes are expected within the next year, and will help answer this question.

In addition to the disease-free survival benefit shown in the MSLT, the 30% of melanoma patients who are candidates for SLNB stand to gain useful prognostic information from the procedure. On average, about 20% of patients who are eligible for SLNB have a positive SLN, and this subgroup of patients also stand to benefit from more durable regional control of their disease with better quality of life. The survival benefit most likely occurs in a subset, perhaps 20%, of the node-positive patients, he said.

In summary, Dr. Johnson said the main reasons to consider SLNB are prognosis, durable regional control, and potential survival benefit in a select subset. These factors should be presented in "an honest discussion with the patient and family about the risks and benefits of SLNB, to help them make a best informed decision," he said.

Although many cancer centers currently use SLNB for melanoma in the way outlined by Dr. Johnson, with "not much controversy" among the "mainstream" of physicians and surgeons who treat melanoma, he noted that "there is posturing and emotion with this procedure," with controversy among some clinicians about the proper role.

"Some dermatologists don’t believe that SLNB should be used for anybody, and some surgeons overuse it on everybody. The answer [on when to use SLNB] is somewhere in between," he said in an interview. The forthcoming, longer-term follow-up data from MSLT may help clinicians how best to use SLNB most appropriately, he added.

Dr. Johnson said that he had no disclosures.

NEW YORK – Teenage girls who used tanning beds in the 1990s are behind the sharp increase in melanoma in young women, according to Dr. Darrell S. Rigel.

The rise in melanoma from this often prom-driven surge in tanning has shown up as increased cases in women aged 25-34 years, Dr. Rigel said at the American Academy of Dermatology’s Summer Academy meeting.

"All the melanoma I see in women in their 20s and 30s, virtually every one of them has gone to a tanning salon, and we’re seeing a lot more" melanoma in women in this age group, said Dr. Rigel, a dermatologist at New York University. In addition, the primary melanomas seen in young women "often occur where the sun doesn’t shine but the tanning beds do," on breasts and near the genitalia, he said. "There definitely is a causal relationship."

Documentation of the rising rate of melanoma in young women includes data collected by the National Cancer Institute’s SEER (Surveillance, Epidemiology, and End Results) program. Data collected by SEER for U.S. melanoma incidence rates showed that during 2004-2006, white women aged 25-29 had a 14.3 per 100,000 incidence of melanoma, a 4% absolute and 42% relative jump from the rate in similarly aged women in 1994-1996. Among white women aged 30-34, the 2004-2006 SEER rate was 16.4 per 100,000 cases, also a 4% absolute and 32% relative jump from the rate in 1994-1996.

Recent increases in melanoma incidence among young white women have been "especially rapid," according to comments published earlier this year (J. Natl. Cancer Inst. 2011;103:171). Since 1995, the annual incidence of melanoma among young, white U.S. women rose by an average of 3.8%, compared with each preceding year.

Increased melanoma incidence since the 1990s links with the greater popularity of tanning beds among teens that first reached high levels in the 1990s. The first commercial U.S. tanning salon opened in 1978, and today there are about 60,000, with about 1 million Americans using a tanning bed daily and about 28 million using a tanning bed at least once each year, Dr. Rigel said. Women patronize tanning salons about sevenfold times more often than men, and other statistics show that more than a third of white, U.S. teens aged 17-18 have had a tanning session at least once in the prior year, he said.

"Major marketing is targeted at these women prior to proms," Dr. Rigel said in an interview. Young women aged 17-18 are "particularly susceptible," to the effects of artificial UV tanning radiation in the development of skin cancer. "This will take a broad sea change. We need models who are not tan in magazines aimed at young women. The pale look has to be in. It’s still cool to be tan. We’re working against that, and against their not being worried about skin cancer, and about how they’ll look at age 50. It’s just not there."

The spike in cases appearing in women once they have reached 25 years or older "is exactly when you’d expect to see the melanomas" based on high-level exposure at age 17-18, he added. The latency period from the time of intensified exposure to the appearance of melanoma is 5-20 years, he said.

"Twenty years ago, it was rare to see a woman in her 20s with melanoma, and we also did not see a lot among women in their 30s. Now, we commonly see cases in women in their 20s, and every one of them has a tanning history. The foremost issue for melanoma in women is tanning beds. For the first time, we’re seeing an increased incidence of melanoma in young women in their 20s and 30s, and the only thing they appear to do differently than young men is go to tanning salons."

Primary care physicians who see women in their 20s and 30s should examine their skin for signs of melanoma when they have the chance during physical examination, and should ask about a history of tanning-bed use. Results from several studies show that even a single tanning episode can significantly increase the risk for melanoma, so all a physician has to ask is, "Have you ever gone to a tanning salon?" to know whether a patient has an increased melanoma risk.

In addition to increased awareness, physicians need to educate teenage girls and the general public about the danger from tanning beds. "It’s very analogous to cigarette smoking. All we can do is get the word out, and hope that people do less harm to themselves."

Dr. Rigel said that he had no relevant disclosures.

NEW YORK – Teenage girls who used tanning beds in the 1990s are behind the sharp increase in melanoma in young women, according to Dr. Darrell S. Rigel.

The rise in melanoma from this often prom-driven surge in tanning has shown up as increased cases in women aged 25-34 years, Dr. Rigel said at the American Academy of Dermatology’s Summer Academy meeting.

"All the melanoma I see in women in their 20s and 30s, virtually every one of them has gone to a tanning salon, and we’re seeing a lot more" melanoma in women in this age group, said Dr. Rigel, a dermatologist at New York University. In addition, the primary melanomas seen in young women "often occur where the sun doesn’t shine but the tanning beds do," on breasts and near the genitalia, he said. "There definitely is a causal relationship."

Documentation of the rising rate of melanoma in young women includes data collected by the National Cancer Institute’s SEER (Surveillance, Epidemiology, and End Results) program. Data collected by SEER for U.S. melanoma incidence rates showed that during 2004-2006, white women aged 25-29 had a 14.3 per 100,000 incidence of melanoma, a 4% absolute and 42% relative jump from the rate in similarly aged women in 1994-1996. Among white women aged 30-34, the 2004-2006 SEER rate was 16.4 per 100,000 cases, also a 4% absolute and 32% relative jump from the rate in 1994-1996.

Recent increases in melanoma incidence among young white women have been "especially rapid," according to comments published earlier this year (J. Natl. Cancer Inst. 2011;103:171). Since 1995, the annual incidence of melanoma among young, white U.S. women rose by an average of 3.8%, compared with each preceding year.

Increased melanoma incidence since the 1990s links with the greater popularity of tanning beds among teens that first reached high levels in the 1990s. The first commercial U.S. tanning salon opened in 1978, and today there are about 60,000, with about 1 million Americans using a tanning bed daily and about 28 million using a tanning bed at least once each year, Dr. Rigel said. Women patronize tanning salons about sevenfold times more often than men, and other statistics show that more than a third of white, U.S. teens aged 17-18 have had a tanning session at least once in the prior year, he said.

"Major marketing is targeted at these women prior to proms," Dr. Rigel said in an interview. Young women aged 17-18 are "particularly susceptible," to the effects of artificial UV tanning radiation in the development of skin cancer. "This will take a broad sea change. We need models who are not tan in magazines aimed at young women. The pale look has to be in. It’s still cool to be tan. We’re working against that, and against their not being worried about skin cancer, and about how they’ll look at age 50. It’s just not there."

The spike in cases appearing in women once they have reached 25 years or older "is exactly when you’d expect to see the melanomas" based on high-level exposure at age 17-18, he added. The latency period from the time of intensified exposure to the appearance of melanoma is 5-20 years, he said.

"Twenty years ago, it was rare to see a woman in her 20s with melanoma, and we also did not see a lot among women in their 30s. Now, we commonly see cases in women in their 20s, and every one of them has a tanning history. The foremost issue for melanoma in women is tanning beds. For the first time, we’re seeing an increased incidence of melanoma in young women in their 20s and 30s, and the only thing they appear to do differently than young men is go to tanning salons."

Primary care physicians who see women in their 20s and 30s should examine their skin for signs of melanoma when they have the chance during physical examination, and should ask about a history of tanning-bed use. Results from several studies show that even a single tanning episode can significantly increase the risk for melanoma, so all a physician has to ask is, "Have you ever gone to a tanning salon?" to know whether a patient has an increased melanoma risk.

In addition to increased awareness, physicians need to educate teenage girls and the general public about the danger from tanning beds. "It’s very analogous to cigarette smoking. All we can do is get the word out, and hope that people do less harm to themselves."

Dr. Rigel said that he had no relevant disclosures.

NEW YORK – Teenage girls who used tanning beds in the 1990s are behind the sharp increase in melanoma in young women, according to Dr. Darrell S. Rigel.

The rise in melanoma from this often prom-driven surge in tanning has shown up as increased cases in women aged 25-34 years, Dr. Rigel said at the American Academy of Dermatology’s Summer Academy meeting.

"All the melanoma I see in women in their 20s and 30s, virtually every one of them has gone to a tanning salon, and we’re seeing a lot more" melanoma in women in this age group, said Dr. Rigel, a dermatologist at New York University. In addition, the primary melanomas seen in young women "often occur where the sun doesn’t shine but the tanning beds do," on breasts and near the genitalia, he said. "There definitely is a causal relationship."

Documentation of the rising rate of melanoma in young women includes data collected by the National Cancer Institute’s SEER (Surveillance, Epidemiology, and End Results) program. Data collected by SEER for U.S. melanoma incidence rates showed that during 2004-2006, white women aged 25-29 had a 14.3 per 100,000 incidence of melanoma, a 4% absolute and 42% relative jump from the rate in similarly aged women in 1994-1996. Among white women aged 30-34, the 2004-2006 SEER rate was 16.4 per 100,000 cases, also a 4% absolute and 32% relative jump from the rate in 1994-1996.

Recent increases in melanoma incidence among young white women have been "especially rapid," according to comments published earlier this year (J. Natl. Cancer Inst. 2011;103:171). Since 1995, the annual incidence of melanoma among young, white U.S. women rose by an average of 3.8%, compared with each preceding year.

Increased melanoma incidence since the 1990s links with the greater popularity of tanning beds among teens that first reached high levels in the 1990s. The first commercial U.S. tanning salon opened in 1978, and today there are about 60,000, with about 1 million Americans using a tanning bed daily and about 28 million using a tanning bed at least once each year, Dr. Rigel said. Women patronize tanning salons about sevenfold times more often than men, and other statistics show that more than a third of white, U.S. teens aged 17-18 have had a tanning session at least once in the prior year, he said.

"Major marketing is targeted at these women prior to proms," Dr. Rigel said in an interview. Young women aged 17-18 are "particularly susceptible," to the effects of artificial UV tanning radiation in the development of skin cancer. "This will take a broad sea change. We need models who are not tan in magazines aimed at young women. The pale look has to be in. It’s still cool to be tan. We’re working against that, and against their not being worried about skin cancer, and about how they’ll look at age 50. It’s just not there."

The spike in cases appearing in women once they have reached 25 years or older "is exactly when you’d expect to see the melanomas" based on high-level exposure at age 17-18, he added. The latency period from the time of intensified exposure to the appearance of melanoma is 5-20 years, he said.

"Twenty years ago, it was rare to see a woman in her 20s with melanoma, and we also did not see a lot among women in their 30s. Now, we commonly see cases in women in their 20s, and every one of them has a tanning history. The foremost issue for melanoma in women is tanning beds. For the first time, we’re seeing an increased incidence of melanoma in young women in their 20s and 30s, and the only thing they appear to do differently than young men is go to tanning salons."

Primary care physicians who see women in their 20s and 30s should examine their skin for signs of melanoma when they have the chance during physical examination, and should ask about a history of tanning-bed use. Results from several studies show that even a single tanning episode can significantly increase the risk for melanoma, so all a physician has to ask is, "Have you ever gone to a tanning salon?" to know whether a patient has an increased melanoma risk.

In addition to increased awareness, physicians need to educate teenage girls and the general public about the danger from tanning beds. "It’s very analogous to cigarette smoking. All we can do is get the word out, and hope that people do less harm to themselves."

Dr. Rigel said that he had no relevant disclosures.

NEW YORK – U.S. patients who were treated for actinic keratosis via cryosurgery or fluorouracil failed to receive optimal treatment with these agents, based on a review of more than 16 million patients treated in 2001-2008.

The results "reveal a gap between practice and the evidence in the treatment of AKs [actinic keratoses] by both dermatologists and nondermatologists," reported Dr. Steven R. Feldman and his associates in a poster at the American Academy of Dermatology’s Summer Academy meeting.

"Combination therapy with cryosurgery and topical fluorouracil is underutilized," and when topical fluorouracil is used to treat AKs, "the 0.5% rather than the 5.0% formulation may be preferable to maximize adherence and to minimize cost and adverse events," they wrote.

Their analysis found cryosurgery alone to be the most commonly used treatment in 59% of patients. Neither cryosurgery nor fluorouracil was used in 35% of U.S. patients in 2001-2008. Among the 5% of patients who were treated with a fluorouracil formulation, 3% received the 0.5% formulation, whereas the other 2% received a different formulation (most often the 5.0% strength), reported Dr. Feldman, professor of dermatology and director of the center for dermatology research at Wake Forest University in Winston-Salem, N.C.

Although other treatments for actinic keratosis exist, the researchers noted, "evidence-based medicine supports the use of 0.5% fluorouracil, rather than the 5.0% formulation, for treatment of actinic keratosis. Evidence, including head-to-head clinical trials, indicates that 0.5% fluorouracil has comparable efficacy, greater tolerability, and lower cost, compared with 5.0% fluorouracil. Similar compelling data support the use of combination cryotherapy plus topical fluorouracil rather than either modality alone." (Arch. Dermaol. 2009;145:203-5; Cutis. 2008;81:509-16; J. Drugs Dermatol. 2006;5:133-9). They performed their new analysis "to determine whether current practice reflects the evidence."

They reviewed data from the Centers for Disease Control and Prevention’s National Ambulatory Medical Care Survey. They identified more than 16 million U.S. patients seen with actinic keratosis during the years of 2001-2008 based on ICD-9 coding. Two-thirds of patients received treatment of their actinic keratosis during an office visit.

Dermatologists saw about 90% of these patients. During the period studied, the annual number of patients with AK seen by all physicians and by dermatologists significantly increased, whereas the number seen by nondermatologists did not significantly change.

The data showed that dermatologists did a better job using 0.5% fluorouracil and cryosurgery, compared with nondermatologists. Dermatologists used cryosurgery alone on 62% of their AK patients; they treated 3% with 0.5% fluorouracil, 2% with 5.0% fluorouracil, and 1% with a combination of fluorouracil and cryosurgery.

"Despite the better tolerability and lower cost of the 0.5% fluorouracil formulation, dermatologists prescribed the 5% formulation in over 392,000 patient visits for AK" in 2001-2008. In contrast, nondermatologists used cryosurgery alone on 32% of their AK patients, 0.5% fluorouracil on no patients, 5.0% fluorouracil on 3%, and a combination of fluorouracil and cryosurgery on no patients. Treatments other than cryosurgery or fluorouracil were used by 32% of the dermatologists and by 63% of the nondermatologists.

"Efforts need to be taken to increase physician awareness of the advantages of 0.5% fluorouracil relative to other formulations, and the value of combination therapy," they reported. "Providers who manage AKs should reassess their current treatment practices and adapt them to be consistent with current evidence."

The study was funded by Sanofi-Aventis, which markets a 0.5% formulation of fluorouracil (Carac). Dr. Feldman said that he has received speaking, consulting, or research support from Abbott, Amgen, Astellas, Aventis, Biogen, Centocor, Connetics, Galderma, Genentech, GlaxoSmithKline (Stiefel), Leo, National Biological, Roche, Warner Chilcott, and 3M.

NEW YORK – U.S. patients who were treated for actinic keratosis via cryosurgery or fluorouracil failed to receive optimal treatment with these agents, based on a review of more than 16 million patients treated in 2001-2008.

The results "reveal a gap between practice and the evidence in the treatment of AKs [actinic keratoses] by both dermatologists and nondermatologists," reported Dr. Steven R. Feldman and his associates in a poster at the American Academy of Dermatology’s Summer Academy meeting.

"Combination therapy with cryosurgery and topical fluorouracil is underutilized," and when topical fluorouracil is used to treat AKs, "the 0.5% rather than the 5.0% formulation may be preferable to maximize adherence and to minimize cost and adverse events," they wrote.

Their analysis found cryosurgery alone to be the most commonly used treatment in 59% of patients. Neither cryosurgery nor fluorouracil was used in 35% of U.S. patients in 2001-2008. Among the 5% of patients who were treated with a fluorouracil formulation, 3% received the 0.5% formulation, whereas the other 2% received a different formulation (most often the 5.0% strength), reported Dr. Feldman, professor of dermatology and director of the center for dermatology research at Wake Forest University in Winston-Salem, N.C.

Although other treatments for actinic keratosis exist, the researchers noted, "evidence-based medicine supports the use of 0.5% fluorouracil, rather than the 5.0% formulation, for treatment of actinic keratosis. Evidence, including head-to-head clinical trials, indicates that 0.5% fluorouracil has comparable efficacy, greater tolerability, and lower cost, compared with 5.0% fluorouracil. Similar compelling data support the use of combination cryotherapy plus topical fluorouracil rather than either modality alone." (Arch. Dermaol. 2009;145:203-5; Cutis. 2008;81:509-16; J. Drugs Dermatol. 2006;5:133-9). They performed their new analysis "to determine whether current practice reflects the evidence."

They reviewed data from the Centers for Disease Control and Prevention’s National Ambulatory Medical Care Survey. They identified more than 16 million U.S. patients seen with actinic keratosis during the years of 2001-2008 based on ICD-9 coding. Two-thirds of patients received treatment of their actinic keratosis during an office visit.

Dermatologists saw about 90% of these patients. During the period studied, the annual number of patients with AK seen by all physicians and by dermatologists significantly increased, whereas the number seen by nondermatologists did not significantly change.

The data showed that dermatologists did a better job using 0.5% fluorouracil and cryosurgery, compared with nondermatologists. Dermatologists used cryosurgery alone on 62% of their AK patients; they treated 3% with 0.5% fluorouracil, 2% with 5.0% fluorouracil, and 1% with a combination of fluorouracil and cryosurgery.

"Despite the better tolerability and lower cost of the 0.5% fluorouracil formulation, dermatologists prescribed the 5% formulation in over 392,000 patient visits for AK" in 2001-2008. In contrast, nondermatologists used cryosurgery alone on 32% of their AK patients, 0.5% fluorouracil on no patients, 5.0% fluorouracil on 3%, and a combination of fluorouracil and cryosurgery on no patients. Treatments other than cryosurgery or fluorouracil were used by 32% of the dermatologists and by 63% of the nondermatologists.

"Efforts need to be taken to increase physician awareness of the advantages of 0.5% fluorouracil relative to other formulations, and the value of combination therapy," they reported. "Providers who manage AKs should reassess their current treatment practices and adapt them to be consistent with current evidence."

The study was funded by Sanofi-Aventis, which markets a 0.5% formulation of fluorouracil (Carac). Dr. Feldman said that he has received speaking, consulting, or research support from Abbott, Amgen, Astellas, Aventis, Biogen, Centocor, Connetics, Galderma, Genentech, GlaxoSmithKline (Stiefel), Leo, National Biological, Roche, Warner Chilcott, and 3M.

NEW YORK – U.S. patients who were treated for actinic keratosis via cryosurgery or fluorouracil failed to receive optimal treatment with these agents, based on a review of more than 16 million patients treated in 2001-2008.

The results "reveal a gap between practice and the evidence in the treatment of AKs [actinic keratoses] by both dermatologists and nondermatologists," reported Dr. Steven R. Feldman and his associates in a poster at the American Academy of Dermatology’s Summer Academy meeting.

"Combination therapy with cryosurgery and topical fluorouracil is underutilized," and when topical fluorouracil is used to treat AKs, "the 0.5% rather than the 5.0% formulation may be preferable to maximize adherence and to minimize cost and adverse events," they wrote.

Their analysis found cryosurgery alone to be the most commonly used treatment in 59% of patients. Neither cryosurgery nor fluorouracil was used in 35% of U.S. patients in 2001-2008. Among the 5% of patients who were treated with a fluorouracil formulation, 3% received the 0.5% formulation, whereas the other 2% received a different formulation (most often the 5.0% strength), reported Dr. Feldman, professor of dermatology and director of the center for dermatology research at Wake Forest University in Winston-Salem, N.C.

Although other treatments for actinic keratosis exist, the researchers noted, "evidence-based medicine supports the use of 0.5% fluorouracil, rather than the 5.0% formulation, for treatment of actinic keratosis. Evidence, including head-to-head clinical trials, indicates that 0.5% fluorouracil has comparable efficacy, greater tolerability, and lower cost, compared with 5.0% fluorouracil. Similar compelling data support the use of combination cryotherapy plus topical fluorouracil rather than either modality alone." (Arch. Dermaol. 2009;145:203-5; Cutis. 2008;81:509-16; J. Drugs Dermatol. 2006;5:133-9). They performed their new analysis "to determine whether current practice reflects the evidence."

They reviewed data from the Centers for Disease Control and Prevention’s National Ambulatory Medical Care Survey. They identified more than 16 million U.S. patients seen with actinic keratosis during the years of 2001-2008 based on ICD-9 coding. Two-thirds of patients received treatment of their actinic keratosis during an office visit.

Dermatologists saw about 90% of these patients. During the period studied, the annual number of patients with AK seen by all physicians and by dermatologists significantly increased, whereas the number seen by nondermatologists did not significantly change.

The data showed that dermatologists did a better job using 0.5% fluorouracil and cryosurgery, compared with nondermatologists. Dermatologists used cryosurgery alone on 62% of their AK patients; they treated 3% with 0.5% fluorouracil, 2% with 5.0% fluorouracil, and 1% with a combination of fluorouracil and cryosurgery.

"Despite the better tolerability and lower cost of the 0.5% fluorouracil formulation, dermatologists prescribed the 5% formulation in over 392,000 patient visits for AK" in 2001-2008. In contrast, nondermatologists used cryosurgery alone on 32% of their AK patients, 0.5% fluorouracil on no patients, 5.0% fluorouracil on 3%, and a combination of fluorouracil and cryosurgery on no patients. Treatments other than cryosurgery or fluorouracil were used by 32% of the dermatologists and by 63% of the nondermatologists.

"Efforts need to be taken to increase physician awareness of the advantages of 0.5% fluorouracil relative to other formulations, and the value of combination therapy," they reported. "Providers who manage AKs should reassess their current treatment practices and adapt them to be consistent with current evidence."

The study was funded by Sanofi-Aventis, which markets a 0.5% formulation of fluorouracil (Carac). Dr. Feldman said that he has received speaking, consulting, or research support from Abbott, Amgen, Astellas, Aventis, Biogen, Centocor, Connetics, Galderma, Genentech, GlaxoSmithKline (Stiefel), Leo, National Biological, Roche, Warner Chilcott, and 3M.

NEW YORK – Since its introduction in 2007, performance-improvement CME has become a key part of dermatology’s maintenance of certification, but many dermatologists still need to set up their personal program.

"Don’t wait to start on point-of-care and performance-improvement [PI] CME projects," Dr. Erik J. Stratman said at the meeting. "If you’re not yet in the first phase of a PICME program, you better do it. It may take a while to accumulate enough patients to run an analysis," said Dr. Stratman, a dermatologist and medical director of the division of education at the Marshfield Clinic of the University of Wisconsin–Madison.

Dr. Stratman also advised dermatologists to "take control" of their maintenance of certification (MOC) timeline, and to be patient as new forms of CME programs roll out in the near future. "In 2009, there were at least four major overhauls to the MOC requirements. "The MOC dermatology program continues to change with time," he said.

PICME arrived on the CME scene as part of a trend toward programs that do a better job of closing practice gaps, the difference between optimal practice and what physicians actually do. Closing practice gaps involves four steps, he said: changing physician knowledge, changing their competence, changing physician performance, and changing patient outcomes. Measuring changes in performance and changes in patient outcomes requires a patient-oriented program like PICME. "When there is a gap in performance there is an opportunity to improve, and that is the future of CME," he said. Physicians "need to become more practice-gap savvy and more alert when they read the literature, by asking themselves whether it contains something that changes practice."

A PICME program has three phases. First is measurement of what is done in the practice at baseline, second is devising a plan to improve performance, and third is later measuring how well the CME program worked to improve practice. A PICME can satisfy 20 CME credits for component 4, the practice assessment and quality improvement portion of MOC.

The American Academy of Dermatology (AAD) sells PICME program modules for three common dermatology practice areas: acne, atopic dermatitis, and melanoma. A fourth module on biopsies is planned. The AAD has called these modules its Clinical Performance Assessment Tools (CPAT), "but the name may change to better reflect the PICME aspect," said Dr. Stratman. He also noted that PICME tools will soon become available from other sources, too.

"We expect to see more and more PICME activities," he said in an interview. "The academy is a leader in the initial response to the MOC requirements, but I hope that many other organizations and institutions will develop PICME modules, too," said Dr. Stratman, who is chairman of the AAD’s Council on Education. He noted that the institution where he works, the Marshfield Clinic, will soon make PICME modules available.

"It’s far better for physicians to select PICME activities that are locally relevant rather than look at national products, because they know where in their practice they need the most help. It will start at the bigger institutions, but it will then spread to private practice offices. I think the American Board of Dermatology is interested in having many different groups apply that are not linked to the Academy."

Dr. Stratman also said that PICME programs are feasible for small practices; they will not require a lot of technology support that only big societies or institutions can afford. Creating a PICME module "is not as hard as integrating an electronic medical record into a practice. It does not involve hard-to-manage data."

Another emerging CME style is point of care. When physicians face a patient-care related question that requires a literature search they can earn 0.5 CME credits by simply documenting the search and the result it produced. "It takes about 5 minutes [to write the documentation] to earn the half credit of CME," he said. "There is a good likelihood that soon we will all be required to have point-of-care CME as a percent of annual CME."

Dr. Stratman said that he had no disclosures.

NEW YORK – Since its introduction in 2007, performance-improvement CME has become a key part of dermatology’s maintenance of certification, but many dermatologists still need to set up their personal program.

"Don’t wait to start on point-of-care and performance-improvement [PI] CME projects," Dr. Erik J. Stratman said at the meeting. "If you’re not yet in the first phase of a PICME program, you better do it. It may take a while to accumulate enough patients to run an analysis," said Dr. Stratman, a dermatologist and medical director of the division of education at the Marshfield Clinic of the University of Wisconsin–Madison.

Dr. Stratman also advised dermatologists to "take control" of their maintenance of certification (MOC) timeline, and to be patient as new forms of CME programs roll out in the near future. "In 2009, there were at least four major overhauls to the MOC requirements. "The MOC dermatology program continues to change with time," he said.

PICME arrived on the CME scene as part of a trend toward programs that do a better job of closing practice gaps, the difference between optimal practice and what physicians actually do. Closing practice gaps involves four steps, he said: changing physician knowledge, changing their competence, changing physician performance, and changing patient outcomes. Measuring changes in performance and changes in patient outcomes requires a patient-oriented program like PICME. "When there is a gap in performance there is an opportunity to improve, and that is the future of CME," he said. Physicians "need to become more practice-gap savvy and more alert when they read the literature, by asking themselves whether it contains something that changes practice."

A PICME program has three phases. First is measurement of what is done in the practice at baseline, second is devising a plan to improve performance, and third is later measuring how well the CME program worked to improve practice. A PICME can satisfy 20 CME credits for component 4, the practice assessment and quality improvement portion of MOC.

The American Academy of Dermatology (AAD) sells PICME program modules for three common dermatology practice areas: acne, atopic dermatitis, and melanoma. A fourth module on biopsies is planned. The AAD has called these modules its Clinical Performance Assessment Tools (CPAT), "but the name may change to better reflect the PICME aspect," said Dr. Stratman. He also noted that PICME tools will soon become available from other sources, too.

"We expect to see more and more PICME activities," he said in an interview. "The academy is a leader in the initial response to the MOC requirements, but I hope that many other organizations and institutions will develop PICME modules, too," said Dr. Stratman, who is chairman of the AAD’s Council on Education. He noted that the institution where he works, the Marshfield Clinic, will soon make PICME modules available.

"It’s far better for physicians to select PICME activities that are locally relevant rather than look at national products, because they know where in their practice they need the most help. It will start at the bigger institutions, but it will then spread to private practice offices. I think the American Board of Dermatology is interested in having many different groups apply that are not linked to the Academy."

Dr. Stratman also said that PICME programs are feasible for small practices; they will not require a lot of technology support that only big societies or institutions can afford. Creating a PICME module "is not as hard as integrating an electronic medical record into a practice. It does not involve hard-to-manage data."

Another emerging CME style is point of care. When physicians face a patient-care related question that requires a literature search they can earn 0.5 CME credits by simply documenting the search and the result it produced. "It takes about 5 minutes [to write the documentation] to earn the half credit of CME," he said. "There is a good likelihood that soon we will all be required to have point-of-care CME as a percent of annual CME."

Dr. Stratman said that he had no disclosures.

NEW YORK – Since its introduction in 2007, performance-improvement CME has become a key part of dermatology’s maintenance of certification, but many dermatologists still need to set up their personal program.

"Don’t wait to start on point-of-care and performance-improvement [PI] CME projects," Dr. Erik J. Stratman said at the meeting. "If you’re not yet in the first phase of a PICME program, you better do it. It may take a while to accumulate enough patients to run an analysis," said Dr. Stratman, a dermatologist and medical director of the division of education at the Marshfield Clinic of the University of Wisconsin–Madison.

Dr. Stratman also advised dermatologists to "take control" of their maintenance of certification (MOC) timeline, and to be patient as new forms of CME programs roll out in the near future. "In 2009, there were at least four major overhauls to the MOC requirements. "The MOC dermatology program continues to change with time," he said.

PICME arrived on the CME scene as part of a trend toward programs that do a better job of closing practice gaps, the difference between optimal practice and what physicians actually do. Closing practice gaps involves four steps, he said: changing physician knowledge, changing their competence, changing physician performance, and changing patient outcomes. Measuring changes in performance and changes in patient outcomes requires a patient-oriented program like PICME. "When there is a gap in performance there is an opportunity to improve, and that is the future of CME," he said. Physicians "need to become more practice-gap savvy and more alert when they read the literature, by asking themselves whether it contains something that changes practice."

A PICME program has three phases. First is measurement of what is done in the practice at baseline, second is devising a plan to improve performance, and third is later measuring how well the CME program worked to improve practice. A PICME can satisfy 20 CME credits for component 4, the practice assessment and quality improvement portion of MOC.

The American Academy of Dermatology (AAD) sells PICME program modules for three common dermatology practice areas: acne, atopic dermatitis, and melanoma. A fourth module on biopsies is planned. The AAD has called these modules its Clinical Performance Assessment Tools (CPAT), "but the name may change to better reflect the PICME aspect," said Dr. Stratman. He also noted that PICME tools will soon become available from other sources, too.

"We expect to see more and more PICME activities," he said in an interview. "The academy is a leader in the initial response to the MOC requirements, but I hope that many other organizations and institutions will develop PICME modules, too," said Dr. Stratman, who is chairman of the AAD’s Council on Education. He noted that the institution where he works, the Marshfield Clinic, will soon make PICME modules available.

"It’s far better for physicians to select PICME activities that are locally relevant rather than look at national products, because they know where in their practice they need the most help. It will start at the bigger institutions, but it will then spread to private practice offices. I think the American Board of Dermatology is interested in having many different groups apply that are not linked to the Academy."

Dr. Stratman also said that PICME programs are feasible for small practices; they will not require a lot of technology support that only big societies or institutions can afford. Creating a PICME module "is not as hard as integrating an electronic medical record into a practice. It does not involve hard-to-manage data."

Another emerging CME style is point of care. When physicians face a patient-care related question that requires a literature search they can earn 0.5 CME credits by simply documenting the search and the result it produced. "It takes about 5 minutes [to write the documentation] to earn the half credit of CME," he said. "There is a good likelihood that soon we will all be required to have point-of-care CME as a percent of annual CME."

Dr. Stratman said that he had no disclosures.

NEW YORK – The number of dermatologic procedures more than doubled from 1995 to 2008, and the average number of procedures done by each U.S. dermatologist jumped by more than 60% in the same period.

The majority of the increase occurred in noncosmetic procedures, which rose from roughly 14 million in 1995 to more than 30 million in 2008, Dr. Steven R. Feldman and his associates reported in a poster at the American Academy of Dermatology’s Summer Academy meeting.

Despite the 62% rise in the average number of procedures per dermatologist, from a mean of 1,111 per physician in 1995 to 1,795 per physician in 2008, the percent of all dermatologic procedures done by dermatologists in 1995-2008 stood at 55%, down from 69% in 1993-1994, said Dr. Feldman, professor of dermatology and director of the Center for Dermatology Research at Wake Forest University in Winston-Salem, N.C.

In contrast, during the same two periods the percent of all dermatologic procedures done by general and family physicians rose, from 15% in 1993-1994 to 19% in 1995-2008.

The different trends seen among dermatologists and other physicians "may be due to a shortage in the dermatology workforce, rather than changes in the general and family physicians’ practices of treating and referring skin conditions," Dr. Feldman and his associates reported.

The analysis used data collected by the Centers for Disease Control and Prevention in the National Ambulatory Medical Care Survey. The researchers tallied cosmetic and noncosmetic dermatologic procedures using ICD-9 codes for the years 1995-2004 and for 2007-2008. They omitted data from 2005-2006 because of ICD-9 coding discrepancies.

During the 12 years included in the calculation, U.S. clinicians performed 298 million total dermatologic procedures in 258 million patients, 56% of them women. Dermatologists performed a majority, 55%, of the procedures, followed by general or family practice physicians, who performed 19%.

The most common procedure was tissue or lesion destruction, 51% of all procedures, followed by biopsies, 15% of the total. Dermatologists dominated as providers for both of these procedures, performing two-thirds of all the destructions and more than three-quarters of the biopsies. Most of the remaining procedures, 27% of the total, included a wide-ranging mix in which each procedure failed to reach even 2% of the total.

Cosmetic procedures constituted 9% of the total, with 42% performed by dermatologists and 26% performed by plastic surgeons. The annual number of cosmetic procedures also roughly doubled during the period studied, rising from about 2 million procedures in 1995 to about 4 million in 2008. The most common cosmetic procedure (and the fifth most common procedure overall) was botulinum toxin injection, a notable achievement given that the Food and Drug Administration’s approval for this use did not occur until April 2002, the investigators noted.

Dr. Feldman said that he has received speaking, consultant, or research support from Abbott, Amgen, Astellas, Aventis, Biogen, Centocor, Connetics, Galderma, Genentech, GlaxoSmithKline (Stiefel), Leo, National Biological, Roche, Warner Chilcott, and 3M.

NEW YORK – The number of dermatologic procedures more than doubled from 1995 to 2008, and the average number of procedures done by each U.S. dermatologist jumped by more than 60% in the same period.

The majority of the increase occurred in noncosmetic procedures, which rose from roughly 14 million in 1995 to more than 30 million in 2008, Dr. Steven R. Feldman and his associates reported in a poster at the American Academy of Dermatology’s Summer Academy meeting.

Despite the 62% rise in the average number of procedures per dermatologist, from a mean of 1,111 per physician in 1995 to 1,795 per physician in 2008, the percent of all dermatologic procedures done by dermatologists in 1995-2008 stood at 55%, down from 69% in 1993-1994, said Dr. Feldman, professor of dermatology and director of the Center for Dermatology Research at Wake Forest University in Winston-Salem, N.C.

In contrast, during the same two periods the percent of all dermatologic procedures done by general and family physicians rose, from 15% in 1993-1994 to 19% in 1995-2008.

The different trends seen among dermatologists and other physicians "may be due to a shortage in the dermatology workforce, rather than changes in the general and family physicians’ practices of treating and referring skin conditions," Dr. Feldman and his associates reported.

The analysis used data collected by the Centers for Disease Control and Prevention in the National Ambulatory Medical Care Survey. The researchers tallied cosmetic and noncosmetic dermatologic procedures using ICD-9 codes for the years 1995-2004 and for 2007-2008. They omitted data from 2005-2006 because of ICD-9 coding discrepancies.

During the 12 years included in the calculation, U.S. clinicians performed 298 million total dermatologic procedures in 258 million patients, 56% of them women. Dermatologists performed a majority, 55%, of the procedures, followed by general or family practice physicians, who performed 19%.

The most common procedure was tissue or lesion destruction, 51% of all procedures, followed by biopsies, 15% of the total. Dermatologists dominated as providers for both of these procedures, performing two-thirds of all the destructions and more than three-quarters of the biopsies. Most of the remaining procedures, 27% of the total, included a wide-ranging mix in which each procedure failed to reach even 2% of the total.

Cosmetic procedures constituted 9% of the total, with 42% performed by dermatologists and 26% performed by plastic surgeons. The annual number of cosmetic procedures also roughly doubled during the period studied, rising from about 2 million procedures in 1995 to about 4 million in 2008. The most common cosmetic procedure (and the fifth most common procedure overall) was botulinum toxin injection, a notable achievement given that the Food and Drug Administration’s approval for this use did not occur until April 2002, the investigators noted.

Dr. Feldman said that he has received speaking, consultant, or research support from Abbott, Amgen, Astellas, Aventis, Biogen, Centocor, Connetics, Galderma, Genentech, GlaxoSmithKline (Stiefel), Leo, National Biological, Roche, Warner Chilcott, and 3M.

NEW YORK – The number of dermatologic procedures more than doubled from 1995 to 2008, and the average number of procedures done by each U.S. dermatologist jumped by more than 60% in the same period.

The majority of the increase occurred in noncosmetic procedures, which rose from roughly 14 million in 1995 to more than 30 million in 2008, Dr. Steven R. Feldman and his associates reported in a poster at the American Academy of Dermatology’s Summer Academy meeting.

Despite the 62% rise in the average number of procedures per dermatologist, from a mean of 1,111 per physician in 1995 to 1,795 per physician in 2008, the percent of all dermatologic procedures done by dermatologists in 1995-2008 stood at 55%, down from 69% in 1993-1994, said Dr. Feldman, professor of dermatology and director of the Center for Dermatology Research at Wake Forest University in Winston-Salem, N.C.

In contrast, during the same two periods the percent of all dermatologic procedures done by general and family physicians rose, from 15% in 1993-1994 to 19% in 1995-2008.

The different trends seen among dermatologists and other physicians "may be due to a shortage in the dermatology workforce, rather than changes in the general and family physicians’ practices of treating and referring skin conditions," Dr. Feldman and his associates reported.

The analysis used data collected by the Centers for Disease Control and Prevention in the National Ambulatory Medical Care Survey. The researchers tallied cosmetic and noncosmetic dermatologic procedures using ICD-9 codes for the years 1995-2004 and for 2007-2008. They omitted data from 2005-2006 because of ICD-9 coding discrepancies.

During the 12 years included in the calculation, U.S. clinicians performed 298 million total dermatologic procedures in 258 million patients, 56% of them women. Dermatologists performed a majority, 55%, of the procedures, followed by general or family practice physicians, who performed 19%.

The most common procedure was tissue or lesion destruction, 51% of all procedures, followed by biopsies, 15% of the total. Dermatologists dominated as providers for both of these procedures, performing two-thirds of all the destructions and more than three-quarters of the biopsies. Most of the remaining procedures, 27% of the total, included a wide-ranging mix in which each procedure failed to reach even 2% of the total.

Cosmetic procedures constituted 9% of the total, with 42% performed by dermatologists and 26% performed by plastic surgeons. The annual number of cosmetic procedures also roughly doubled during the period studied, rising from about 2 million procedures in 1995 to about 4 million in 2008. The most common cosmetic procedure (and the fifth most common procedure overall) was botulinum toxin injection, a notable achievement given that the Food and Drug Administration’s approval for this use did not occur until April 2002, the investigators noted.

Dr. Feldman said that he has received speaking, consultant, or research support from Abbott, Amgen, Astellas, Aventis, Biogen, Centocor, Connetics, Galderma, Genentech, GlaxoSmithKline (Stiefel), Leo, National Biological, Roche, Warner Chilcott, and 3M.

NEW YORK – Raynaud’s phenomenon can cause nipple pain in breastfeeding mothers – but a small case series found that it is almost always misdiagnosed.

Of 86 women in the series – the largest ever accrued – 24 patients had Raynaud’s, all of whom were misdiagnosed as having fungal mastitis, Dr. Honor Fullerton Stone and her colleagues reported in a poster presented at the American Academy of Dermatology’s Summer Academy Meeting.

Although the physical exam can be complicated by other factors – a flare of atopic dermatitis or a fungal or bacterial superinfection – Raynaud’s should always be considered in the differential diagnosis of lactating women with nipple pain, according to Dr. Fullerton Stone of Stanford (Calif.) University.

She presented a chart review of 86 lactating women complaining of nipple pain; the cases were accrued from 2004 to 2010 in a single medical center. Of these, 24 (28%) were diagnosed with Raynaud’s, based on the presence of at least two of the following diagnostic characteristics:

– Color changes of the nipple (blue, white, or red), especially with exposure to cold.

– Cold sensitivity or color changes of acral surfaces with cold exposure.

– Chronic deep breast pain for 4 weeks or longer and failed therapy with oral antifungals and/or antibiotics.

All 24 women with Raynaud’s presented with enlarged breasts, mild to moderate erythema of the areola, and desquamation of one or both nipples. Two also had plugged milk ducts.

All were initially diagnosed as having a candida breast infection. Ten of them reported that their babies had experienced an episode of oral thrush. And 20 of the 24 (83%) had been unsuccessfully treated with topical or oral antifungals, including at least one course of fluconazole (18; 75%).

Two also had a skin superinfection, growing Staphylococcus aureus on a bacterial culture; these women also received a course of oral antibiotics.

After being diagnosed with Raynaud’s, about 16 (67%) received a course of nifedipine; 3 discontinued the drug because of headache, dizziness, or nausea. Of the 13 who continued the drug, 10 (77%) reported a decrease or elimination of their nipple pain.

Other Raynaud’s-specific treatment included advice to wear warm clothing, to take hot showers before nursing, and to avoid caffeine and other vasoconstrictive drugs that could precipitate symptoms.

In addition to the Raynaud’s-specific treatment, all of the women were treated for accompanying issues, including breast dermatitis and antifungal therapy.

All received a prescription for a low- or moderate-strength hydrocortisone butyrate cream or alclometasone dipropionate to be applied twice a day for 2 weeks. They were also told to apply Aquaphor two or three times daily, over the steroid cream. Most (23) also had an additional standard course of oral fluconazole (400 mg on day 1 followed by 200 mg daily for the next 8-10 days).

Twenty women participated in a follow-up survey. Most (15, 75%) also reported that they had cold sensitivity or color changes in their hands and feet. Two reported having been diagnosed with an autoimmune disease – either lupus or Sjögren’s syndrome, and two reported having had a breast cyst removed.

They also described the pain they experienced during a Raynaud’s episode of the nipple. All said the pain continued throughout breastfeeding; 25% said that the pain increased during the beginning of lactation. Most, however, (75%) said the pain occurred before, during, and after breastfeeding.

Since the physical exam may be inconclusive, the quality of the pain can be a diagnostic clue to Raynaud’s in the nursing mother, Dr. Fullerton Stone noted. Letdown pain is more common in the weeks after birth, and usually improves. It is typically experienced as a mild pain during the first minutes of breast feeding, which may continue for 12-15 minutes afterward.

Candida infections are described as causing moderate, burning pain that is worse when the baby latches on for a nursing session. The pain can radiate from the nipple throughout the breast; it typically improves dramatically within the first few days of oral antifungal treatment.

Raynaud’s is usually described as moderate sharp, shocking-type, or throbbing pain before, during, and after nursing. As is typically observed with Raynaud’s of the hands and feet, there is a color change that signifies the vasoconstriction characteristic of the disorder.

Dr. Fullerton Stone said she had no financial declarations with regard to her work.

NEW YORK – Raynaud’s phenomenon can cause nipple pain in breastfeeding mothers – but a small case series found that it is almost always misdiagnosed.

Of 86 women in the series – the largest ever accrued – 24 patients had Raynaud’s, all of whom were misdiagnosed as having fungal mastitis, Dr. Honor Fullerton Stone and her colleagues reported in a poster presented at the American Academy of Dermatology’s Summer Academy Meeting.

Although the physical exam can be complicated by other factors – a flare of atopic dermatitis or a fungal or bacterial superinfection – Raynaud’s should always be considered in the differential diagnosis of lactating women with nipple pain, according to Dr. Fullerton Stone of Stanford (Calif.) University.

She presented a chart review of 86 lactating women complaining of nipple pain; the cases were accrued from 2004 to 2010 in a single medical center. Of these, 24 (28%) were diagnosed with Raynaud’s, based on the presence of at least two of the following diagnostic characteristics:

– Color changes of the nipple (blue, white, or red), especially with exposure to cold.

– Cold sensitivity or color changes of acral surfaces with cold exposure.

– Chronic deep breast pain for 4 weeks or longer and failed therapy with oral antifungals and/or antibiotics.

All 24 women with Raynaud’s presented with enlarged breasts, mild to moderate erythema of the areola, and desquamation of one or both nipples. Two also had plugged milk ducts.

All were initially diagnosed as having a candida breast infection. Ten of them reported that their babies had experienced an episode of oral thrush. And 20 of the 24 (83%) had been unsuccessfully treated with topical or oral antifungals, including at least one course of fluconazole (18; 75%).

Two also had a skin superinfection, growing Staphylococcus aureus on a bacterial culture; these women also received a course of oral antibiotics.

After being diagnosed with Raynaud’s, about 16 (67%) received a course of nifedipine; 3 discontinued the drug because of headache, dizziness, or nausea. Of the 13 who continued the drug, 10 (77%) reported a decrease or elimination of their nipple pain.

Other Raynaud’s-specific treatment included advice to wear warm clothing, to take hot showers before nursing, and to avoid caffeine and other vasoconstrictive drugs that could precipitate symptoms.

In addition to the Raynaud’s-specific treatment, all of the women were treated for accompanying issues, including breast dermatitis and antifungal therapy.

All received a prescription for a low- or moderate-strength hydrocortisone butyrate cream or alclometasone dipropionate to be applied twice a day for 2 weeks. They were also told to apply Aquaphor two or three times daily, over the steroid cream. Most (23) also had an additional standard course of oral fluconazole (400 mg on day 1 followed by 200 mg daily for the next 8-10 days).

Twenty women participated in a follow-up survey. Most (15, 75%) also reported that they had cold sensitivity or color changes in their hands and feet. Two reported having been diagnosed with an autoimmune disease – either lupus or Sjögren’s syndrome, and two reported having had a breast cyst removed.

They also described the pain they experienced during a Raynaud’s episode of the nipple. All said the pain continued throughout breastfeeding; 25% said that the pain increased during the beginning of lactation. Most, however, (75%) said the pain occurred before, during, and after breastfeeding.

Since the physical exam may be inconclusive, the quality of the pain can be a diagnostic clue to Raynaud’s in the nursing mother, Dr. Fullerton Stone noted. Letdown pain is more common in the weeks after birth, and usually improves. It is typically experienced as a mild pain during the first minutes of breast feeding, which may continue for 12-15 minutes afterward.

Candida infections are described as causing moderate, burning pain that is worse when the baby latches on for a nursing session. The pain can radiate from the nipple throughout the breast; it typically improves dramatically within the first few days of oral antifungal treatment.

Raynaud’s is usually described as moderate sharp, shocking-type, or throbbing pain before, during, and after nursing. As is typically observed with Raynaud’s of the hands and feet, there is a color change that signifies the vasoconstriction characteristic of the disorder.

Dr. Fullerton Stone said she had no financial declarations with regard to her work.

NEW YORK – Raynaud’s phenomenon can cause nipple pain in breastfeeding mothers – but a small case series found that it is almost always misdiagnosed.

Of 86 women in the series – the largest ever accrued – 24 patients had Raynaud’s, all of whom were misdiagnosed as having fungal mastitis, Dr. Honor Fullerton Stone and her colleagues reported in a poster presented at the American Academy of Dermatology’s Summer Academy Meeting.

Although the physical exam can be complicated by other factors – a flare of atopic dermatitis or a fungal or bacterial superinfection – Raynaud’s should always be considered in the differential diagnosis of lactating women with nipple pain, according to Dr. Fullerton Stone of Stanford (Calif.) University.

She presented a chart review of 86 lactating women complaining of nipple pain; the cases were accrued from 2004 to 2010 in a single medical center. Of these, 24 (28%) were diagnosed with Raynaud’s, based on the presence of at least two of the following diagnostic characteristics:

– Color changes of the nipple (blue, white, or red), especially with exposure to cold.

– Cold sensitivity or color changes of acral surfaces with cold exposure.

– Chronic deep breast pain for 4 weeks or longer and failed therapy with oral antifungals and/or antibiotics.

All 24 women with Raynaud’s presented with enlarged breasts, mild to moderate erythema of the areola, and desquamation of one or both nipples. Two also had plugged milk ducts.

All were initially diagnosed as having a candida breast infection. Ten of them reported that their babies had experienced an episode of oral thrush. And 20 of the 24 (83%) had been unsuccessfully treated with topical or oral antifungals, including at least one course of fluconazole (18; 75%).

Two also had a skin superinfection, growing Staphylococcus aureus on a bacterial culture; these women also received a course of oral antibiotics.

After being diagnosed with Raynaud’s, about 16 (67%) received a course of nifedipine; 3 discontinued the drug because of headache, dizziness, or nausea. Of the 13 who continued the drug, 10 (77%) reported a decrease or elimination of their nipple pain.

Other Raynaud’s-specific treatment included advice to wear warm clothing, to take hot showers before nursing, and to avoid caffeine and other vasoconstrictive drugs that could precipitate symptoms.

In addition to the Raynaud’s-specific treatment, all of the women were treated for accompanying issues, including breast dermatitis and antifungal therapy.

All received a prescription for a low- or moderate-strength hydrocortisone butyrate cream or alclometasone dipropionate to be applied twice a day for 2 weeks. They were also told to apply Aquaphor two or three times daily, over the steroid cream. Most (23) also had an additional standard course of oral fluconazole (400 mg on day 1 followed by 200 mg daily for the next 8-10 days).

Twenty women participated in a follow-up survey. Most (15, 75%) also reported that they had cold sensitivity or color changes in their hands and feet. Two reported having been diagnosed with an autoimmune disease – either lupus or Sjögren’s syndrome, and two reported having had a breast cyst removed.

They also described the pain they experienced during a Raynaud’s episode of the nipple. All said the pain continued throughout breastfeeding; 25% said that the pain increased during the beginning of lactation. Most, however, (75%) said the pain occurred before, during, and after breastfeeding.

Since the physical exam may be inconclusive, the quality of the pain can be a diagnostic clue to Raynaud’s in the nursing mother, Dr. Fullerton Stone noted. Letdown pain is more common in the weeks after birth, and usually improves. It is typically experienced as a mild pain during the first minutes of breast feeding, which may continue for 12-15 minutes afterward.

Candida infections are described as causing moderate, burning pain that is worse when the baby latches on for a nursing session. The pain can radiate from the nipple throughout the breast; it typically improves dramatically within the first few days of oral antifungal treatment.

Raynaud’s is usually described as moderate sharp, shocking-type, or throbbing pain before, during, and after nursing. As is typically observed with Raynaud’s of the hands and feet, there is a color change that signifies the vasoconstriction characteristic of the disorder.

Dr. Fullerton Stone said she had no financial declarations with regard to her work.

NEW YORK – The genotyping era of melanoma management is poised to launch.

The era will start with genetic assessment of every patient with advanced-stage melanoma becoming the standard of care, as soon as the Food and Drug Administration approves marketing of vemurafenib, the small-molecule inhibitor of a mutated form of the BRAF gene.

Reuters reports that approval is imminent, based on strikingly good results from a phase III study presented in June at the annual meeting of the American Society of Clinical Oncology, and published in the New England Journal of Medicine (2011;364:2507-16).

"If and when [vemurafenib] is approved by the FDA, we will need some sort of commercially available test to assess patients [with unresectable stage IIIC or stage IV melanoma] for BRAF [mutations]," Dr. Richard D. Carvajal said in an interview after speaking at the American Academy of Dermatology's Summer Academy meeting. "In a large, phase III trial, vemurafenib impacted survival in patients with tumors with a BRAF mutation. You'll need to know the BRAF status to use [vemurafenib]."

In May, Genentech, a Roche subsidiary developing vemurafenib with Daiichi Sankyo subsidiary Plexxikon, announced that it had submitted a new drug approval application to the FDA.

"At my institution and at others, it's becoming standard of care to do genotyping on these patients. We need to know how to prioritize them to experimental or standard treatments," said Dr. Carvajal, a medical oncologist specializing in melanoma and sarcomas at Memorial Sloan-Kettering Cancer Center in New York. "In the not too distant future, it will be standard to get a panel" of genotyping results, probably also including NRAS, KIT, and several other oncogenes now emerging as important players in the genetic progression of metastatic melanoma.

"As these markers become relevant for choosing treatment, they will be available in CLIA-certified tests," Dr. Carvajal said. Genotyping "should be done on all [advanced melanoma] patients; it's just a matter of how you pay for it. The panel of genes we’ll need to look at will grow with time."

Results from genotyping studies of metastatic melanoma tumors have shown a BRAF mutation prevalence of about 43% and a NRAS mutation prevalence of about 14%, with the remaining 43% of tumors having wild type forms of both genes, Dr. Nancy E. Thomas said in a separate talk at the meeting.

The BRAF and NRAS mutations, as well as several others found with less frequency, appear mutually exclusive, so that, for example, essentially all studied tumors with BRAF mutations are wild type for NRAS, and essentially all tumors with a NRAS mutation have wild type BRAF, said Dr. Thomas, professor of dermatology at the University of North Carolina at Chapel Hill.

When vemurafenib gets U.S. marketing approval, it will also muddy the treatment algorithm for metastatic melanoma. For the time being, ipilimumab (Yervoy), an immunotherapy approved for treating advanced-stage melanoma in March 2011, is unrivaled for survival benefits as first-line therapy.

"Ipilimumab is the only FDA-approved drug [for advanced melanoma] that has demonstrated an improvement in overall survival. Right now, it's the standard of care," Dr. Carvajal said.

But ipilimumab also has some drawbacks. The evidence base to date gives no guidance on whether ipilimumab can be targeted to certain genotypic subgroups of melanoma, and it works relatively slowly, which makes it problematic for patients with rapidly progressing disease or a large disease burden.

The ipilimumab studies done so far enrolled patients regardless of their genotype status, so no information exists on whether tumors with specific gene mutations respond especially well or poorly.

"When vemurafenib is approved, the question will be how to sequence these two drugs in patients with BRAF mutations. That's something we're struggling with," Dr. Carvajal said.

Despite that, the success scored so far by both ipilimumab and vemurafenib represents major advances at least for certain, responsive patients, Dr. Carvajal said. "For both drugs we can see tumor shrinkage, but what we really look for is prolongation of life. A significant proportion of patients will have benefit from treatment that lasts years and years."

Dr. Carvajal said that he has been a consultant to Novartis.

NEW YORK – The genotyping era of melanoma management is poised to launch.

The era will start with genetic assessment of every patient with advanced-stage melanoma becoming the standard of care, as soon as the Food and Drug Administration approves marketing of vemurafenib, the small-molecule inhibitor of a mutated form of the BRAF gene.

Reuters reports that approval is imminent, based on strikingly good results from a phase III study presented in June at the annual meeting of the American Society of Clinical Oncology, and published in the New England Journal of Medicine (2011;364:2507-16).

"If and when [vemurafenib] is approved by the FDA, we will need some sort of commercially available test to assess patients [with unresectable stage IIIC or stage IV melanoma] for BRAF [mutations]," Dr. Richard D. Carvajal said in an interview after speaking at the American Academy of Dermatology's Summer Academy meeting. "In a large, phase III trial, vemurafenib impacted survival in patients with tumors with a BRAF mutation. You'll need to know the BRAF status to use [vemurafenib]."

In May, Genentech, a Roche subsidiary developing vemurafenib with Daiichi Sankyo subsidiary Plexxikon, announced that it had submitted a new drug approval application to the FDA.

"At my institution and at others, it's becoming standard of care to do genotyping on these patients. We need to know how to prioritize them to experimental or standard treatments," said Dr. Carvajal, a medical oncologist specializing in melanoma and sarcomas at Memorial Sloan-Kettering Cancer Center in New York. "In the not too distant future, it will be standard to get a panel" of genotyping results, probably also including NRAS, KIT, and several other oncogenes now emerging as important players in the genetic progression of metastatic melanoma.

"As these markers become relevant for choosing treatment, they will be available in CLIA-certified tests," Dr. Carvajal said. Genotyping "should be done on all [advanced melanoma] patients; it's just a matter of how you pay for it. The panel of genes we’ll need to look at will grow with time."

Results from genotyping studies of metastatic melanoma tumors have shown a BRAF mutation prevalence of about 43% and a NRAS mutation prevalence of about 14%, with the remaining 43% of tumors having wild type forms of both genes, Dr. Nancy E. Thomas said in a separate talk at the meeting.

The BRAF and NRAS mutations, as well as several others found with less frequency, appear mutually exclusive, so that, for example, essentially all studied tumors with BRAF mutations are wild type for NRAS, and essentially all tumors with a NRAS mutation have wild type BRAF, said Dr. Thomas, professor of dermatology at the University of North Carolina at Chapel Hill.

When vemurafenib gets U.S. marketing approval, it will also muddy the treatment algorithm for metastatic melanoma. For the time being, ipilimumab (Yervoy), an immunotherapy approved for treating advanced-stage melanoma in March 2011, is unrivaled for survival benefits as first-line therapy.

"Ipilimumab is the only FDA-approved drug [for advanced melanoma] that has demonstrated an improvement in overall survival. Right now, it's the standard of care," Dr. Carvajal said.

But ipilimumab also has some drawbacks. The evidence base to date gives no guidance on whether ipilimumab can be targeted to certain genotypic subgroups of melanoma, and it works relatively slowly, which makes it problematic for patients with rapidly progressing disease or a large disease burden.

The ipilimumab studies done so far enrolled patients regardless of their genotype status, so no information exists on whether tumors with specific gene mutations respond especially well or poorly.

"When vemurafenib is approved, the question will be how to sequence these two drugs in patients with BRAF mutations. That's something we're struggling with," Dr. Carvajal said.

Despite that, the success scored so far by both ipilimumab and vemurafenib represents major advances at least for certain, responsive patients, Dr. Carvajal said. "For both drugs we can see tumor shrinkage, but what we really look for is prolongation of life. A significant proportion of patients will have benefit from treatment that lasts years and years."

Dr. Carvajal said that he has been a consultant to Novartis.

NEW YORK – The genotyping era of melanoma management is poised to launch.

The era will start with genetic assessment of every patient with advanced-stage melanoma becoming the standard of care, as soon as the Food and Drug Administration approves marketing of vemurafenib, the small-molecule inhibitor of a mutated form of the BRAF gene.

Reuters reports that approval is imminent, based on strikingly good results from a phase III study presented in June at the annual meeting of the American Society of Clinical Oncology, and published in the New England Journal of Medicine (2011;364:2507-16).

"If and when [vemurafenib] is approved by the FDA, we will need some sort of commercially available test to assess patients [with unresectable stage IIIC or stage IV melanoma] for BRAF [mutations]," Dr. Richard D. Carvajal said in an interview after speaking at the American Academy of Dermatology's Summer Academy meeting. "In a large, phase III trial, vemurafenib impacted survival in patients with tumors with a BRAF mutation. You'll need to know the BRAF status to use [vemurafenib]."

In May, Genentech, a Roche subsidiary developing vemurafenib with Daiichi Sankyo subsidiary Plexxikon, announced that it had submitted a new drug approval application to the FDA.

"At my institution and at others, it's becoming standard of care to do genotyping on these patients. We need to know how to prioritize them to experimental or standard treatments," said Dr. Carvajal, a medical oncologist specializing in melanoma and sarcomas at Memorial Sloan-Kettering Cancer Center in New York. "In the not too distant future, it will be standard to get a panel" of genotyping results, probably also including NRAS, KIT, and several other oncogenes now emerging as important players in the genetic progression of metastatic melanoma.

"As these markers become relevant for choosing treatment, they will be available in CLIA-certified tests," Dr. Carvajal said. Genotyping "should be done on all [advanced melanoma] patients; it's just a matter of how you pay for it. The panel of genes we’ll need to look at will grow with time."

Results from genotyping studies of metastatic melanoma tumors have shown a BRAF mutation prevalence of about 43% and a NRAS mutation prevalence of about 14%, with the remaining 43% of tumors having wild type forms of both genes, Dr. Nancy E. Thomas said in a separate talk at the meeting.

The BRAF and NRAS mutations, as well as several others found with less frequency, appear mutually exclusive, so that, for example, essentially all studied tumors with BRAF mutations are wild type for NRAS, and essentially all tumors with a NRAS mutation have wild type BRAF, said Dr. Thomas, professor of dermatology at the University of North Carolina at Chapel Hill.

When vemurafenib gets U.S. marketing approval, it will also muddy the treatment algorithm for metastatic melanoma. For the time being, ipilimumab (Yervoy), an immunotherapy approved for treating advanced-stage melanoma in March 2011, is unrivaled for survival benefits as first-line therapy.

"Ipilimumab is the only FDA-approved drug [for advanced melanoma] that has demonstrated an improvement in overall survival. Right now, it's the standard of care," Dr. Carvajal said.

But ipilimumab also has some drawbacks. The evidence base to date gives no guidance on whether ipilimumab can be targeted to certain genotypic subgroups of melanoma, and it works relatively slowly, which makes it problematic for patients with rapidly progressing disease or a large disease burden.

The ipilimumab studies done so far enrolled patients regardless of their genotype status, so no information exists on whether tumors with specific gene mutations respond especially well or poorly.

"When vemurafenib is approved, the question will be how to sequence these two drugs in patients with BRAF mutations. That's something we're struggling with," Dr. Carvajal said.

Despite that, the success scored so far by both ipilimumab and vemurafenib represents major advances at least for certain, responsive patients, Dr. Carvajal said. "For both drugs we can see tumor shrinkage, but what we really look for is prolongation of life. A significant proportion of patients will have benefit from treatment that lasts years and years."

Dr. Carvajal said that he has been a consultant to Novartis.

NEW YORK – Zinc oxide and titanium dioxide have a long history of use – from paint pigment to diaper rash remedy. They’ve even made a beach-side fashion statement among sun seekers who protect their ears and nose with a thick, white slathering of the light-reflecting mineral cream.

But these inert particles may someday form the basis of the "perfect sunscreen," Dr. Zoe Draelos said at the American Academy of Dermatology’s Summer Academy meeting. Such a compound would completely protect against both ultraviolet B and the more-damaging ultraviolet A while being completely invisible on skin types I-VI.

©Corbis/Fotolia.com

Nanoparticles are highly refined substances with a particle size of 15-100 nm. Theoretically, Dr. Draelos said, nanoparticulate zinc oxide and titanium dioxide could be dispersed in a comfortable vehicle that would be invisible even on dark skin, easy to apply, last a long time, and provide full-spectrum protection – all attributes that could increase user compliance and, therefore, overall skin safety.

Unfortunately, like most things that seem too good to be true, nanoparticles lug around some potentially serious baggage, said Dr. Draelos, a clinical dermatologist and researcher in High Point, N.C.

"We already know that some nanoparticles cause health risks," she said. "The smog that we breathed in on the way to this meeting contained carbon and other nanoparticles, which are so small that they escape phagocytosis, making it virtually impossible for the body to ever remove them."

Prolonged exposure to inhaled nanoparticles can contribute to lung disease, and there is even preliminary research that smog and some nanoparticles may even impact cardiovascular function.

"Because we already know some things about the potential harm of inhaled nanoparticles, it’s very important that any topical products don’t contain nanoparticles that could be absorbed into the skin," said Dr. Draelos, who is also vice president-elect of the American Academy of Dermatology.

To address the issue, the Food and Drug Administration established a nanotechnology task force in 2007, she said. "But no one has heard from them since." Other groups have cited environmental concerns, pushing the issue to the forefront. But scientific literature about skin absorption has come to conflicting results, some of which may not be applicable to humans.

Risks Associated With Nanoparticles

A 2009 study suggested that titanium dioxide nanoparticles, applied topically to pigs’ ears and to hairless mice, not only penetrated the stratum corneum but later showed up in other organs, including the liver and the brain. The study "indicates that nano-sized titanium dioxide may pose a health risk to humans after dermal exposure over a relative long time period" (Toxicol. Lett. 2009;191:1-8).

But a review published the same year found conflicting evidence (Dermatoendocrinol. 2009;1:197-206). The review examined the absorption of various nanoparticle types, including titanium dioxide and zinc oxide. Citing nine studies on humans, pigs, and mice, the authors concluded that the minerals in sizes of 10-100 nm did not penetrate the human stratum corneum beyond five layers, although they could be seen in the openings of the hair follicles.

Any nanoparticle smaller than 13 nm could potentially penetrate the stratum corneum, Dr. Draelos said, but anything larger would stay on the surface.

"The follicular infundibulum is about 170 micrometers, so nanoparticles can get in there but, as sebum is produced, the particles are washed out onto the skin’s surface. If you had a nanoparticle that was really soluble, it could dissolve into the sebum, but nanoparticles made of these metal oxides don’t dissolve."

Applying a nanoparticle sunscreen to damaged skin could potentially increase the likelihood of absorption, and no one is quite sure what would happen when such a compound concentrates in the body’s creases and folds. Would the additional pressure on the inside of the elbow, for example, facilitate absorption? "No one really knows," she said.

For a sunscreen to remain invisible on all skin types, the nanoparticles would have to be no larger than 10 nm, "putting us right back where we started. So it’s going to be difficult to make an effective nanoparticle sunscreen that will be invisible on all skin types," she added.

To further complicate matters, nanoparticles themselves can be damaging. "When a photon of ultraviolet B radiation strikes a nanoparticle, the particle undergoes photocatalysis, which generates secondary free radicals," said Dr. Draelos. Researchers are trying to tackle this problem with polyester or nylon coatings that block the process.

Although research continues, no nanoparticle sunscreens are available in the United States. Two can be found in Europe. "One uses a 15% concentration of 50-nm zinc oxide and the other, a 5% concentration of 30-nm titanium dioxide," she noted

The Swedish government, however, has blocked 10 companies from marketing such sunscreens because of possible toxicity to aquatic flora, said Dr. Draelos. "These compounds can be toxic to organisms at the bottom of the food chain, including photo- and phytoplankton. The European Union countries have also said that labels must state whether the product contains nanoparticles."

The scientific jury is still out on how to make cosmetically acceptable sunscreens that offer optimal UVA protection while being physically and environmentally safe, Dr. Draelos said. "But we can’t ignore the opportunities they create for novel formulations."

Dr. Draelos disclosed financial relationships with numerous pharmaceutical companies.

NEW YORK – Zinc oxide and titanium dioxide have a long history of use – from paint pigment to diaper rash remedy. They’ve even made a beach-side fashion statement among sun seekers who protect their ears and nose with a thick, white slathering of the light-reflecting mineral cream.

But these inert particles may someday form the basis of the "perfect sunscreen," Dr. Zoe Draelos said at the American Academy of Dermatology’s Summer Academy meeting. Such a compound would completely protect against both ultraviolet B and the more-damaging ultraviolet A while being completely invisible on skin types I-VI.

©Corbis/Fotolia.com

Nanoparticles are highly refined substances with a particle size of 15-100 nm. Theoretically, Dr. Draelos said, nanoparticulate zinc oxide and titanium dioxide could be dispersed in a comfortable vehicle that would be invisible even on dark skin, easy to apply, last a long time, and provide full-spectrum protection – all attributes that could increase user compliance and, therefore, overall skin safety.

Unfortunately, like most things that seem too good to be true, nanoparticles lug around some potentially serious baggage, said Dr. Draelos, a clinical dermatologist and researcher in High Point, N.C.

"We already know that some nanoparticles cause health risks," she said. "The smog that we breathed in on the way to this meeting contained carbon and other nanoparticles, which are so small that they escape phagocytosis, making it virtually impossible for the body to ever remove them."

Prolonged exposure to inhaled nanoparticles can contribute to lung disease, and there is even preliminary research that smog and some nanoparticles may even impact cardiovascular function.

"Because we already know some things about the potential harm of inhaled nanoparticles, it’s very important that any topical products don’t contain nanoparticles that could be absorbed into the skin," said Dr. Draelos, who is also vice president-elect of the American Academy of Dermatology.

To address the issue, the Food and Drug Administration established a nanotechnology task force in 2007, she said. "But no one has heard from them since." Other groups have cited environmental concerns, pushing the issue to the forefront. But scientific literature about skin absorption has come to conflicting results, some of which may not be applicable to humans.

Risks Associated With Nanoparticles

A 2009 study suggested that titanium dioxide nanoparticles, applied topically to pigs’ ears and to hairless mice, not only penetrated the stratum corneum but later showed up in other organs, including the liver and the brain. The study "indicates that nano-sized titanium dioxide may pose a health risk to humans after dermal exposure over a relative long time period" (Toxicol. Lett. 2009;191:1-8).

But a review published the same year found conflicting evidence (Dermatoendocrinol. 2009;1:197-206). The review examined the absorption of various nanoparticle types, including titanium dioxide and zinc oxide. Citing nine studies on humans, pigs, and mice, the authors concluded that the minerals in sizes of 10-100 nm did not penetrate the human stratum corneum beyond five layers, although they could be seen in the openings of the hair follicles.

Any nanoparticle smaller than 13 nm could potentially penetrate the stratum corneum, Dr. Draelos said, but anything larger would stay on the surface.

"The follicular infundibulum is about 170 micrometers, so nanoparticles can get in there but, as sebum is produced, the particles are washed out onto the skin’s surface. If you had a nanoparticle that was really soluble, it could dissolve into the sebum, but nanoparticles made of these metal oxides don’t dissolve."

Applying a nanoparticle sunscreen to damaged skin could potentially increase the likelihood of absorption, and no one is quite sure what would happen when such a compound concentrates in the body’s creases and folds. Would the additional pressure on the inside of the elbow, for example, facilitate absorption? "No one really knows," she said.

For a sunscreen to remain invisible on all skin types, the nanoparticles would have to be no larger than 10 nm, "putting us right back where we started. So it’s going to be difficult to make an effective nanoparticle sunscreen that will be invisible on all skin types," she added.

To further complicate matters, nanoparticles themselves can be damaging. "When a photon of ultraviolet B radiation strikes a nanoparticle, the particle undergoes photocatalysis, which generates secondary free radicals," said Dr. Draelos. Researchers are trying to tackle this problem with polyester or nylon coatings that block the process.

Although research continues, no nanoparticle sunscreens are available in the United States. Two can be found in Europe. "One uses a 15% concentration of 50-nm zinc oxide and the other, a 5% concentration of 30-nm titanium dioxide," she noted

The Swedish government, however, has blocked 10 companies from marketing such sunscreens because of possible toxicity to aquatic flora, said Dr. Draelos. "These compounds can be toxic to organisms at the bottom of the food chain, including photo- and phytoplankton. The European Union countries have also said that labels must state whether the product contains nanoparticles."

The scientific jury is still out on how to make cosmetically acceptable sunscreens that offer optimal UVA protection while being physically and environmentally safe, Dr. Draelos said. "But we can’t ignore the opportunities they create for novel formulations."

Dr. Draelos disclosed financial relationships with numerous pharmaceutical companies.

NEW YORK – Zinc oxide and titanium dioxide have a long history of use – from paint pigment to diaper rash remedy. They’ve even made a beach-side fashion statement among sun seekers who protect their ears and nose with a thick, white slathering of the light-reflecting mineral cream.

But these inert particles may someday form the basis of the "perfect sunscreen," Dr. Zoe Draelos said at the American Academy of Dermatology’s Summer Academy meeting. Such a compound would completely protect against both ultraviolet B and the more-damaging ultraviolet A while being completely invisible on skin types I-VI.

©Corbis/Fotolia.com

Nanoparticles are highly refined substances with a particle size of 15-100 nm. Theoretically, Dr. Draelos said, nanoparticulate zinc oxide and titanium dioxide could be dispersed in a comfortable vehicle that would be invisible even on dark skin, easy to apply, last a long time, and provide full-spectrum protection – all attributes that could increase user compliance and, therefore, overall skin safety.

Unfortunately, like most things that seem too good to be true, nanoparticles lug around some potentially serious baggage, said Dr. Draelos, a clinical dermatologist and researcher in High Point, N.C.

"We already know that some nanoparticles cause health risks," she said. "The smog that we breathed in on the way to this meeting contained carbon and other nanoparticles, which are so small that they escape phagocytosis, making it virtually impossible for the body to ever remove them."

Prolonged exposure to inhaled nanoparticles can contribute to lung disease, and there is even preliminary research that smog and some nanoparticles may even impact cardiovascular function.

"Because we already know some things about the potential harm of inhaled nanoparticles, it’s very important that any topical products don’t contain nanoparticles that could be absorbed into the skin," said Dr. Draelos, who is also vice president-elect of the American Academy of Dermatology.

To address the issue, the Food and Drug Administration established a nanotechnology task force in 2007, she said. "But no one has heard from them since." Other groups have cited environmental concerns, pushing the issue to the forefront. But scientific literature about skin absorption has come to conflicting results, some of which may not be applicable to humans.

Risks Associated With Nanoparticles

A 2009 study suggested that titanium dioxide nanoparticles, applied topically to pigs’ ears and to hairless mice, not only penetrated the stratum corneum but later showed up in other organs, including the liver and the brain. The study "indicates that nano-sized titanium dioxide may pose a health risk to humans after dermal exposure over a relative long time period" (Toxicol. Lett. 2009;191:1-8).

But a review published the same year found conflicting evidence (Dermatoendocrinol. 2009;1:197-206). The review examined the absorption of various nanoparticle types, including titanium dioxide and zinc oxide. Citing nine studies on humans, pigs, and mice, the authors concluded that the minerals in sizes of 10-100 nm did not penetrate the human stratum corneum beyond five layers, although they could be seen in the openings of the hair follicles.

Any nanoparticle smaller than 13 nm could potentially penetrate the stratum corneum, Dr. Draelos said, but anything larger would stay on the surface.

"The follicular infundibulum is about 170 micrometers, so nanoparticles can get in there but, as sebum is produced, the particles are washed out onto the skin’s surface. If you had a nanoparticle that was really soluble, it could dissolve into the sebum, but nanoparticles made of these metal oxides don’t dissolve."

Applying a nanoparticle sunscreen to damaged skin could potentially increase the likelihood of absorption, and no one is quite sure what would happen when such a compound concentrates in the body’s creases and folds. Would the additional pressure on the inside of the elbow, for example, facilitate absorption? "No one really knows," she said.

For a sunscreen to remain invisible on all skin types, the nanoparticles would have to be no larger than 10 nm, "putting us right back where we started. So it’s going to be difficult to make an effective nanoparticle sunscreen that will be invisible on all skin types," she added.

To further complicate matters, nanoparticles themselves can be damaging. "When a photon of ultraviolet B radiation strikes a nanoparticle, the particle undergoes photocatalysis, which generates secondary free radicals," said Dr. Draelos. Researchers are trying to tackle this problem with polyester or nylon coatings that block the process.

Although research continues, no nanoparticle sunscreens are available in the United States. Two can be found in Europe. "One uses a 15% concentration of 50-nm zinc oxide and the other, a 5% concentration of 30-nm titanium dioxide," she noted

The Swedish government, however, has blocked 10 companies from marketing such sunscreens because of possible toxicity to aquatic flora, said Dr. Draelos. "These compounds can be toxic to organisms at the bottom of the food chain, including photo- and phytoplankton. The European Union countries have also said that labels must state whether the product contains nanoparticles."

The scientific jury is still out on how to make cosmetically acceptable sunscreens that offer optimal UVA protection while being physically and environmentally safe, Dr. Draelos said. "But we can’t ignore the opportunities they create for novel formulations."

Dr. Draelos disclosed financial relationships with numerous pharmaceutical companies.