Skin Disease Education Foundation (SDEF) 2011: Hawaii Dermatology Seminar

Sentinel lymph node biopsy is an important but greatly underused tool for staging and prognosis of Merkel cell carcinoma, according a recent multicenter analysis of 5,823 cases of the aggressive skin cancer.

This massive study led to the first consensus staging system for Merkel cell carcinoma. The new system replaces five conflicting staging systems published in the last 17 years, none of which were based upon more than 251 cases.

"The situation was a complete mess. If a person said, 'stage III Merkel cell carcinoma,' you didn’t know if they were talking about a deep primary, nodal disease, or distant metastatic disease," recalled Dr. Paul Nghiem, senior author of the analysis and new staging system.

The crucial difference between the new staging system and the prior ones lies in its emphasis on determining the pathological status of the nodes, according to Dr. Nghiem, a dermatologist at the University of Washington, Seattle.

Prior studies had established that roughly one-third of patients with clinically node-negative Merkel cell carcinoma (MCC) have microscopic nodal disease. Yet pathological nodal evaluation hasn’t been the norm; indeed, it wasn’t performed in more than two-thirds of the 5,823 cases of MCC obtained from the prospective National Cancer Data Base, which served as the basis for the new staging system.

Dr. Nghiem and his coworkers demonstrated that pathological nodal evaluation is a clinically important unused resource. For example, 5-year relative survival was 79% in patients with Stage IA disease under the new system, defined as local disease not more than 2 cm in diameter and with negative lymph nodes by pathological exam.

In contrast, survival in stage IB patients – local disease not greater than 2 cm, but with nodes that were negative only by clinical evaluation – was only 60%. The same pattern was seen in stage II and III disease under the new system.

Pathological lymph node evaluation not only results in more accurate staging and determination of prognosis, it also has important therapeutic implications.

"If the biopsy is positive, nodal treatment reduces recurrences in that nodal bed," Dr. Nghiem said.

He and his coworkers have shown that lymph node adjuvant radiation therapy and completion lymphadenectomy are similarly highly effective therapies for both microscopic and palpable lymph node involvement (Cancer 2010;116:1783-90). So treatment of the node bed in sentinel lymph node-positive disease should be either radiotherapy or surgery, but not both. It doesn’t make sense to subject patients to the added side effects of dual therapy when either therapy alone is so effective, he continued.

The only circumstances in which he and his colleagues don’t perform sentinel lymph node biopsy in MCC are when they’re planning to do radiation therapy anyway, if prognostic data simply aren’t important to the patient, or when the tumor is in the parotid region where for technical reasons the false-negative rate is substantial.

The best local therapy for MCC is excision with or without adjuvant radiation therapy. The only conditions in which adjuvant radiotherapy can be dispensed with are when a patient has all of five features signaling a low risk for local recurrence: negative sentinel lymph node biopsy, a primary tumor 1 cm or less in diameter, pathologically negative surgical margins, no lymphovascular invasion in the primary tumor, and no profoundly immunosuppressive comorbid conditions. If all five of those features are met, the risk of recurrence is probably less than 10% and may not justify the down sides of radiation, according to Dr. Nghiem.

The immunosuppressive conditions that are particularly problematic include chronic lymphocytic leukemia, which has been associated with a 30- to 50-fold increased risk of MCC; being a solid organ transplant recipient, which carries a 10-fold risk; and HIV positive status, which has been reported to increase the risk of MCC 13-fold.

It’s typically necessary to ask the pathologist if lymphovascular invasion is present in the primary tumor, as this is information not usually included in the report, the dermatologist explained at the 35th annual Hawaii Dermatology Seminar sponsored by Skin Disease Education Foundation.

Development of the new MCC consensus staging system (J. Am. Acad. Dermatol. 2010;63:751-61) was supported by the National Institutes of Health and American Cancer Society. Dr. Nghiem declared having no financial conflicts. Skin Disease Education Foundation and this news organization are owned by Elsevier.

Sentinel lymph node biopsy is an important but greatly underused tool for staging and prognosis of Merkel cell carcinoma, according a recent multicenter analysis of 5,823 cases of the aggressive skin cancer.

This massive study led to the first consensus staging system for Merkel cell carcinoma. The new system replaces five conflicting staging systems published in the last 17 years, none of which were based upon more than 251 cases.

"The situation was a complete mess. If a person said, 'stage III Merkel cell carcinoma,' you didn’t know if they were talking about a deep primary, nodal disease, or distant metastatic disease," recalled Dr. Paul Nghiem, senior author of the analysis and new staging system.

The crucial difference between the new staging system and the prior ones lies in its emphasis on determining the pathological status of the nodes, according to Dr. Nghiem, a dermatologist at the University of Washington, Seattle.

Prior studies had established that roughly one-third of patients with clinically node-negative Merkel cell carcinoma (MCC) have microscopic nodal disease. Yet pathological nodal evaluation hasn’t been the norm; indeed, it wasn’t performed in more than two-thirds of the 5,823 cases of MCC obtained from the prospective National Cancer Data Base, which served as the basis for the new staging system.

Dr. Nghiem and his coworkers demonstrated that pathological nodal evaluation is a clinically important unused resource. For example, 5-year relative survival was 79% in patients with Stage IA disease under the new system, defined as local disease not more than 2 cm in diameter and with negative lymph nodes by pathological exam.

In contrast, survival in stage IB patients – local disease not greater than 2 cm, but with nodes that were negative only by clinical evaluation – was only 60%. The same pattern was seen in stage II and III disease under the new system.

Pathological lymph node evaluation not only results in more accurate staging and determination of prognosis, it also has important therapeutic implications.

"If the biopsy is positive, nodal treatment reduces recurrences in that nodal bed," Dr. Nghiem said.

He and his coworkers have shown that lymph node adjuvant radiation therapy and completion lymphadenectomy are similarly highly effective therapies for both microscopic and palpable lymph node involvement (Cancer 2010;116:1783-90). So treatment of the node bed in sentinel lymph node-positive disease should be either radiotherapy or surgery, but not both. It doesn’t make sense to subject patients to the added side effects of dual therapy when either therapy alone is so effective, he continued.

The only circumstances in which he and his colleagues don’t perform sentinel lymph node biopsy in MCC are when they’re planning to do radiation therapy anyway, if prognostic data simply aren’t important to the patient, or when the tumor is in the parotid region where for technical reasons the false-negative rate is substantial.

The best local therapy for MCC is excision with or without adjuvant radiation therapy. The only conditions in which adjuvant radiotherapy can be dispensed with are when a patient has all of five features signaling a low risk for local recurrence: negative sentinel lymph node biopsy, a primary tumor 1 cm or less in diameter, pathologically negative surgical margins, no lymphovascular invasion in the primary tumor, and no profoundly immunosuppressive comorbid conditions. If all five of those features are met, the risk of recurrence is probably less than 10% and may not justify the down sides of radiation, according to Dr. Nghiem.

The immunosuppressive conditions that are particularly problematic include chronic lymphocytic leukemia, which has been associated with a 30- to 50-fold increased risk of MCC; being a solid organ transplant recipient, which carries a 10-fold risk; and HIV positive status, which has been reported to increase the risk of MCC 13-fold.

It’s typically necessary to ask the pathologist if lymphovascular invasion is present in the primary tumor, as this is information not usually included in the report, the dermatologist explained at the 35th annual Hawaii Dermatology Seminar sponsored by Skin Disease Education Foundation.

Development of the new MCC consensus staging system (J. Am. Acad. Dermatol. 2010;63:751-61) was supported by the National Institutes of Health and American Cancer Society. Dr. Nghiem declared having no financial conflicts. Skin Disease Education Foundation and this news organization are owned by Elsevier.

Sentinel lymph node biopsy is an important but greatly underused tool for staging and prognosis of Merkel cell carcinoma, according a recent multicenter analysis of 5,823 cases of the aggressive skin cancer.

This massive study led to the first consensus staging system for Merkel cell carcinoma. The new system replaces five conflicting staging systems published in the last 17 years, none of which were based upon more than 251 cases.

"The situation was a complete mess. If a person said, 'stage III Merkel cell carcinoma,' you didn’t know if they were talking about a deep primary, nodal disease, or distant metastatic disease," recalled Dr. Paul Nghiem, senior author of the analysis and new staging system.

The crucial difference between the new staging system and the prior ones lies in its emphasis on determining the pathological status of the nodes, according to Dr. Nghiem, a dermatologist at the University of Washington, Seattle.

Prior studies had established that roughly one-third of patients with clinically node-negative Merkel cell carcinoma (MCC) have microscopic nodal disease. Yet pathological nodal evaluation hasn’t been the norm; indeed, it wasn’t performed in more than two-thirds of the 5,823 cases of MCC obtained from the prospective National Cancer Data Base, which served as the basis for the new staging system.

Dr. Nghiem and his coworkers demonstrated that pathological nodal evaluation is a clinically important unused resource. For example, 5-year relative survival was 79% in patients with Stage IA disease under the new system, defined as local disease not more than 2 cm in diameter and with negative lymph nodes by pathological exam.

In contrast, survival in stage IB patients – local disease not greater than 2 cm, but with nodes that were negative only by clinical evaluation – was only 60%. The same pattern was seen in stage II and III disease under the new system.

Pathological lymph node evaluation not only results in more accurate staging and determination of prognosis, it also has important therapeutic implications.

"If the biopsy is positive, nodal treatment reduces recurrences in that nodal bed," Dr. Nghiem said.

He and his coworkers have shown that lymph node adjuvant radiation therapy and completion lymphadenectomy are similarly highly effective therapies for both microscopic and palpable lymph node involvement (Cancer 2010;116:1783-90). So treatment of the node bed in sentinel lymph node-positive disease should be either radiotherapy or surgery, but not both. It doesn’t make sense to subject patients to the added side effects of dual therapy when either therapy alone is so effective, he continued.

The only circumstances in which he and his colleagues don’t perform sentinel lymph node biopsy in MCC are when they’re planning to do radiation therapy anyway, if prognostic data simply aren’t important to the patient, or when the tumor is in the parotid region where for technical reasons the false-negative rate is substantial.

The best local therapy for MCC is excision with or without adjuvant radiation therapy. The only conditions in which adjuvant radiotherapy can be dispensed with are when a patient has all of five features signaling a low risk for local recurrence: negative sentinel lymph node biopsy, a primary tumor 1 cm or less in diameter, pathologically negative surgical margins, no lymphovascular invasion in the primary tumor, and no profoundly immunosuppressive comorbid conditions. If all five of those features are met, the risk of recurrence is probably less than 10% and may not justify the down sides of radiation, according to Dr. Nghiem.

The immunosuppressive conditions that are particularly problematic include chronic lymphocytic leukemia, which has been associated with a 30- to 50-fold increased risk of MCC; being a solid organ transplant recipient, which carries a 10-fold risk; and HIV positive status, which has been reported to increase the risk of MCC 13-fold.

It’s typically necessary to ask the pathologist if lymphovascular invasion is present in the primary tumor, as this is information not usually included in the report, the dermatologist explained at the 35th annual Hawaii Dermatology Seminar sponsored by Skin Disease Education Foundation.

Development of the new MCC consensus staging system (J. Am. Acad. Dermatol. 2010;63:751-61) was supported by the National Institutes of Health and American Cancer Society. Dr. Nghiem declared having no financial conflicts. Skin Disease Education Foundation and this news organization are owned by Elsevier.

Sequential topical therapy with clobetasol propionate spray followed by calcitriol ointment has joined the ranks of therapies that can boast documented safety and efficacy for moderate to severe plaque psoriasis.

The treatment strategy here is to wallop the disease initially with the super-high-potency corticosteroid to quickly quell an emerging flare, then turn to the safer, slower-acting metabolically active topical vitamin D to reduce the frequency of recurrent flare-ups.

This strategy proved effective and was well tolerated in a recent open-label multicenter study involving 170 patients. They received clobetasol propionate 0.05% spray (Clobex) twice daily for 4 weeks, then calcitriol 3 mcg/g (Vectical) twice daily for the next 8 weeks.

Eighty percent of patients were rated clear, almost clear, or mild at week 2, as were 93% at week 4, 92% at week 8, and 74% at week 12. Treatment success, defined as at least a one grade improvement in a five-point overall disease severity score at week 12, was accomplished in 84% of subjects. Body surface area involvement decreased significantly from 7.1% at baseline to 3.9% at week 12.

Side effects consisted mainly of mild telangiectasias and stinging and burning. Less than 1% of subjects had signs of skin atrophy.

This sequential regimen is attractive because patients only have to remember to take one drug at a time, and also because topical vitamin D and its analogs are at present the only available agents targeting the abnormal keratinocyte differentiation that's a core feature of psoriasis, Dr. James Q. Del Rosso noted at the annual Hawaii Dermatology Seminar sponsored by Skin Disease Education Foundation.

"Abnormal differentiation of keratinocytes is the one place where we have only one therapy. You really have to decide if that's important enough to you that you think it needs to be built into your treatment of psoriasis pretty much all of the time. You have to decide that for yourself," said Dr. Del Rosso of the University of Nevada, Las Vegas.

Dr. Del Rosso is a consultant to a number of pharmaceutical companies, including Galderma Laboratories, which funded the recently published open-label study (J. Drugs Dermatol. 2011;10:158-64).

SDEF and this publication are owned by Elsevier.

Sequential topical therapy with clobetasol propionate spray followed by calcitriol ointment has joined the ranks of therapies that can boast documented safety and efficacy for moderate to severe plaque psoriasis.

The treatment strategy here is to wallop the disease initially with the super-high-potency corticosteroid to quickly quell an emerging flare, then turn to the safer, slower-acting metabolically active topical vitamin D to reduce the frequency of recurrent flare-ups.

This strategy proved effective and was well tolerated in a recent open-label multicenter study involving 170 patients. They received clobetasol propionate 0.05% spray (Clobex) twice daily for 4 weeks, then calcitriol 3 mcg/g (Vectical) twice daily for the next 8 weeks.

Eighty percent of patients were rated clear, almost clear, or mild at week 2, as were 93% at week 4, 92% at week 8, and 74% at week 12. Treatment success, defined as at least a one grade improvement in a five-point overall disease severity score at week 12, was accomplished in 84% of subjects. Body surface area involvement decreased significantly from 7.1% at baseline to 3.9% at week 12.

Side effects consisted mainly of mild telangiectasias and stinging and burning. Less than 1% of subjects had signs of skin atrophy.

This sequential regimen is attractive because patients only have to remember to take one drug at a time, and also because topical vitamin D and its analogs are at present the only available agents targeting the abnormal keratinocyte differentiation that's a core feature of psoriasis, Dr. James Q. Del Rosso noted at the annual Hawaii Dermatology Seminar sponsored by Skin Disease Education Foundation.

"Abnormal differentiation of keratinocytes is the one place where we have only one therapy. You really have to decide if that's important enough to you that you think it needs to be built into your treatment of psoriasis pretty much all of the time. You have to decide that for yourself," said Dr. Del Rosso of the University of Nevada, Las Vegas.

Dr. Del Rosso is a consultant to a number of pharmaceutical companies, including Galderma Laboratories, which funded the recently published open-label study (J. Drugs Dermatol. 2011;10:158-64).

SDEF and this publication are owned by Elsevier.

Sequential topical therapy with clobetasol propionate spray followed by calcitriol ointment has joined the ranks of therapies that can boast documented safety and efficacy for moderate to severe plaque psoriasis.

The treatment strategy here is to wallop the disease initially with the super-high-potency corticosteroid to quickly quell an emerging flare, then turn to the safer, slower-acting metabolically active topical vitamin D to reduce the frequency of recurrent flare-ups.

This strategy proved effective and was well tolerated in a recent open-label multicenter study involving 170 patients. They received clobetasol propionate 0.05% spray (Clobex) twice daily for 4 weeks, then calcitriol 3 mcg/g (Vectical) twice daily for the next 8 weeks.

Eighty percent of patients were rated clear, almost clear, or mild at week 2, as were 93% at week 4, 92% at week 8, and 74% at week 12. Treatment success, defined as at least a one grade improvement in a five-point overall disease severity score at week 12, was accomplished in 84% of subjects. Body surface area involvement decreased significantly from 7.1% at baseline to 3.9% at week 12.

Side effects consisted mainly of mild telangiectasias and stinging and burning. Less than 1% of subjects had signs of skin atrophy.

This sequential regimen is attractive because patients only have to remember to take one drug at a time, and also because topical vitamin D and its analogs are at present the only available agents targeting the abnormal keratinocyte differentiation that's a core feature of psoriasis, Dr. James Q. Del Rosso noted at the annual Hawaii Dermatology Seminar sponsored by Skin Disease Education Foundation.

"Abnormal differentiation of keratinocytes is the one place where we have only one therapy. You really have to decide if that's important enough to you that you think it needs to be built into your treatment of psoriasis pretty much all of the time. You have to decide that for yourself," said Dr. Del Rosso of the University of Nevada, Las Vegas.

Dr. Del Rosso is a consultant to a number of pharmaceutical companies, including Galderma Laboratories, which funded the recently published open-label study (J. Drugs Dermatol. 2011;10:158-64).

SDEF and this publication are owned by Elsevier.

WAILEA, HAWAII – Moderate to severe psoriasis is an independent risk factor for a variety of adverse pregnancy outcomes, according to Dr. Jennifer C. Cather.

Yet much remains unknown about the impact of psoriasis and its treatment in pregnancy. For this reason, every psoriasis patient who becomes pregnant while on a biologic agent should be strongly encouraged to enter one of the pregnancy registries, Dr. Cather said at the Hawaii Dermatology Seminar sponsored by Skin Disease Education Foundation (SDEF).

She recommended the Organization of Teratology Information Specialists (OTIS), because the group helps inform concerned patients. OTIS operates pregnancy registries for women taking etanercept (Enbrel) or adalimumab (Humira). In addition, pharmaceutical companies that market biologics maintain pregnancy registries for their agents.

The Food and Drug Administration rates methotrexate and acitretin as pregnancy category X drugs and cyclosporine as a category C drug. The anti–tumor necrosis factor agents are category B – meaning animal studies have shown no fetal risk – as are alefacept (Amevive) and ustekinumab (Stelara).

"That doesn’t mean I think you should give a category B agent to people who are pregnant or are planning pregnancy, because I think that the best drug in pregnancy is probably no drug, or light treatment if you can get away with that," said Dr. Cather, who is in private practice in Dallas.

Still, there is sometimes no satisfactory alternative to using a biologic agent in pregnancy. Two of the toughest challenges Dr. Cather said she encounters in her clinical practice arise in such situations. One involves the psoriasis patient who calls and says that her ob.gyn. told her to come off the biologic therapy immediately.

The other challenge is the patient whose psoriasis worsens during pregnancy to the extent that she needs to start on a biologic agent or switch to another one. This is not an uncommon situation, Dr. Cather noted, citing a University of California, Irvine, study which found that while psoriasis improved during pregnancy in 55% of pregnant patients, it worsened in 23%. Postpartum, psoriasis worsened in 65% (Arch. Dermatol. 2005;141:601-6).

A recent retrospective matched cohort study of pregnancy outcomes in psoriasis patients involved 68 deliveries in 35 women with moderate to severe psoriasis and 237 deliveries in 236 controls in Israel.

The incidence of pregnancy-induced hypertensive diseases was 7.4% in the psoriasis patients, significantly greater than the 2.1% rate in controls. Premature rupture of membranes occurred in 16% of psoriasis patients, compared with 5.5% of controls. The 24% incidence of large-for-gestational-age newborns among the psoriasis patients’ babies was twice that of controls. Macrosomia occurred in 13% of the babies of women with psoriasis, compared with 4.2% of matched controls.

In this multivariate analysis, moderate to severe psoriasis was also an independent risk factor for previous spontaneous and induced abortions (J. Eur. Acad. Dermatol. Venereol. 2010 Nov. 25 doi: 10.1111/j.1468-3083.2010.03917.x]).

Dr. Cather’s biologics of choice for psoriasis and psoriatic arthritis, whether during pregnancy or not, are TNF-antagonists. She has been monitoring her own psoriasis patients who have been on biologic agents during pregnancy and has not noted any increase in adverse outcomes. While she finds this somewhat reassuring, the definitive answers will come from the large pregnancy registries.

Nursing mothers on methotrexate, acitretin, or cyclosporine should not breast-feed. The risk of using anti–tumor necrosis factor agents during breast-feeding is "probably negligible," she said.

Psoriasis patients have a below-average rate of childbearing. Theories abound as to why. Possibilities include an increased infertility rate, voluntary childlessness due to concern about genetic transmission of psoriasis to the next generation, and the interference with sexual activity that has been documented in patients with active disease.

"I do have people who say they never want to have children because of their disease. That’s a very sad conversation," Dr. Cather said.

Intriguingly, there is some recent evidence to suggest anti-TNF therapy may improve the results of in vitro fertilization in women with infertility and recurrent spontaneous abortion. The therapeutic rationale is that TNF-alpha has been shown to have antireproductive effects.

In a nonrandomized study involving 75 women without psoriasis under age 38 with Th1/Th2 cytokine elevation undergoing IVF for infertility, investigators found that implantation, clinical pregnancy, and live birth rates were significantly higher in those on adalimumab and IVIG than in patients on neither (Am. J. Repro. Immunol. 2009;61:113-20). This is a controversial study among assisted reproduction specialists, Dr. Cather noted.

She disclosed that she serves as a consultant to Amgen (manufacturer of Enbrel), Abbott (manufacturer of Humira), and Centocor (manufacturer of Stelara) and has received research grants from Amgen, Celgene, and Pfizer.

SDEF and this news organization are owned by Elsevier.

WAILEA, HAWAII – Moderate to severe psoriasis is an independent risk factor for a variety of adverse pregnancy outcomes, according to Dr. Jennifer C. Cather.

Yet much remains unknown about the impact of psoriasis and its treatment in pregnancy. For this reason, every psoriasis patient who becomes pregnant while on a biologic agent should be strongly encouraged to enter one of the pregnancy registries, Dr. Cather said at the Hawaii Dermatology Seminar sponsored by Skin Disease Education Foundation (SDEF).

She recommended the Organization of Teratology Information Specialists (OTIS), because the group helps inform concerned patients. OTIS operates pregnancy registries for women taking etanercept (Enbrel) or adalimumab (Humira). In addition, pharmaceutical companies that market biologics maintain pregnancy registries for their agents.

The Food and Drug Administration rates methotrexate and acitretin as pregnancy category X drugs and cyclosporine as a category C drug. The anti–tumor necrosis factor agents are category B – meaning animal studies have shown no fetal risk – as are alefacept (Amevive) and ustekinumab (Stelara).

"That doesn’t mean I think you should give a category B agent to people who are pregnant or are planning pregnancy, because I think that the best drug in pregnancy is probably no drug, or light treatment if you can get away with that," said Dr. Cather, who is in private practice in Dallas.

Still, there is sometimes no satisfactory alternative to using a biologic agent in pregnancy. Two of the toughest challenges Dr. Cather said she encounters in her clinical practice arise in such situations. One involves the psoriasis patient who calls and says that her ob.gyn. told her to come off the biologic therapy immediately.

The other challenge is the patient whose psoriasis worsens during pregnancy to the extent that she needs to start on a biologic agent or switch to another one. This is not an uncommon situation, Dr. Cather noted, citing a University of California, Irvine, study which found that while psoriasis improved during pregnancy in 55% of pregnant patients, it worsened in 23%. Postpartum, psoriasis worsened in 65% (Arch. Dermatol. 2005;141:601-6).

A recent retrospective matched cohort study of pregnancy outcomes in psoriasis patients involved 68 deliveries in 35 women with moderate to severe psoriasis and 237 deliveries in 236 controls in Israel.

The incidence of pregnancy-induced hypertensive diseases was 7.4% in the psoriasis patients, significantly greater than the 2.1% rate in controls. Premature rupture of membranes occurred in 16% of psoriasis patients, compared with 5.5% of controls. The 24% incidence of large-for-gestational-age newborns among the psoriasis patients’ babies was twice that of controls. Macrosomia occurred in 13% of the babies of women with psoriasis, compared with 4.2% of matched controls.

In this multivariate analysis, moderate to severe psoriasis was also an independent risk factor for previous spontaneous and induced abortions (J. Eur. Acad. Dermatol. Venereol. 2010 Nov. 25 doi: 10.1111/j.1468-3083.2010.03917.x]).

Dr. Cather’s biologics of choice for psoriasis and psoriatic arthritis, whether during pregnancy or not, are TNF-antagonists. She has been monitoring her own psoriasis patients who have been on biologic agents during pregnancy and has not noted any increase in adverse outcomes. While she finds this somewhat reassuring, the definitive answers will come from the large pregnancy registries.

Nursing mothers on methotrexate, acitretin, or cyclosporine should not breast-feed. The risk of using anti–tumor necrosis factor agents during breast-feeding is "probably negligible," she said.

Psoriasis patients have a below-average rate of childbearing. Theories abound as to why. Possibilities include an increased infertility rate, voluntary childlessness due to concern about genetic transmission of psoriasis to the next generation, and the interference with sexual activity that has been documented in patients with active disease.

"I do have people who say they never want to have children because of their disease. That’s a very sad conversation," Dr. Cather said.

Intriguingly, there is some recent evidence to suggest anti-TNF therapy may improve the results of in vitro fertilization in women with infertility and recurrent spontaneous abortion. The therapeutic rationale is that TNF-alpha has been shown to have antireproductive effects.

In a nonrandomized study involving 75 women without psoriasis under age 38 with Th1/Th2 cytokine elevation undergoing IVF for infertility, investigators found that implantation, clinical pregnancy, and live birth rates were significantly higher in those on adalimumab and IVIG than in patients on neither (Am. J. Repro. Immunol. 2009;61:113-20). This is a controversial study among assisted reproduction specialists, Dr. Cather noted.

She disclosed that she serves as a consultant to Amgen (manufacturer of Enbrel), Abbott (manufacturer of Humira), and Centocor (manufacturer of Stelara) and has received research grants from Amgen, Celgene, and Pfizer.

SDEF and this news organization are owned by Elsevier.

WAILEA, HAWAII – Moderate to severe psoriasis is an independent risk factor for a variety of adverse pregnancy outcomes, according to Dr. Jennifer C. Cather.

Yet much remains unknown about the impact of psoriasis and its treatment in pregnancy. For this reason, every psoriasis patient who becomes pregnant while on a biologic agent should be strongly encouraged to enter one of the pregnancy registries, Dr. Cather said at the Hawaii Dermatology Seminar sponsored by Skin Disease Education Foundation (SDEF).

She recommended the Organization of Teratology Information Specialists (OTIS), because the group helps inform concerned patients. OTIS operates pregnancy registries for women taking etanercept (Enbrel) or adalimumab (Humira). In addition, pharmaceutical companies that market biologics maintain pregnancy registries for their agents.

The Food and Drug Administration rates methotrexate and acitretin as pregnancy category X drugs and cyclosporine as a category C drug. The anti–tumor necrosis factor agents are category B – meaning animal studies have shown no fetal risk – as are alefacept (Amevive) and ustekinumab (Stelara).

"That doesn’t mean I think you should give a category B agent to people who are pregnant or are planning pregnancy, because I think that the best drug in pregnancy is probably no drug, or light treatment if you can get away with that," said Dr. Cather, who is in private practice in Dallas.

Still, there is sometimes no satisfactory alternative to using a biologic agent in pregnancy. Two of the toughest challenges Dr. Cather said she encounters in her clinical practice arise in such situations. One involves the psoriasis patient who calls and says that her ob.gyn. told her to come off the biologic therapy immediately.

The other challenge is the patient whose psoriasis worsens during pregnancy to the extent that she needs to start on a biologic agent or switch to another one. This is not an uncommon situation, Dr. Cather noted, citing a University of California, Irvine, study which found that while psoriasis improved during pregnancy in 55% of pregnant patients, it worsened in 23%. Postpartum, psoriasis worsened in 65% (Arch. Dermatol. 2005;141:601-6).

A recent retrospective matched cohort study of pregnancy outcomes in psoriasis patients involved 68 deliveries in 35 women with moderate to severe psoriasis and 237 deliveries in 236 controls in Israel.

The incidence of pregnancy-induced hypertensive diseases was 7.4% in the psoriasis patients, significantly greater than the 2.1% rate in controls. Premature rupture of membranes occurred in 16% of psoriasis patients, compared with 5.5% of controls. The 24% incidence of large-for-gestational-age newborns among the psoriasis patients’ babies was twice that of controls. Macrosomia occurred in 13% of the babies of women with psoriasis, compared with 4.2% of matched controls.

In this multivariate analysis, moderate to severe psoriasis was also an independent risk factor for previous spontaneous and induced abortions (J. Eur. Acad. Dermatol. Venereol. 2010 Nov. 25 doi: 10.1111/j.1468-3083.2010.03917.x]).

Dr. Cather’s biologics of choice for psoriasis and psoriatic arthritis, whether during pregnancy or not, are TNF-antagonists. She has been monitoring her own psoriasis patients who have been on biologic agents during pregnancy and has not noted any increase in adverse outcomes. While she finds this somewhat reassuring, the definitive answers will come from the large pregnancy registries.

Nursing mothers on methotrexate, acitretin, or cyclosporine should not breast-feed. The risk of using anti–tumor necrosis factor agents during breast-feeding is "probably negligible," she said.

Psoriasis patients have a below-average rate of childbearing. Theories abound as to why. Possibilities include an increased infertility rate, voluntary childlessness due to concern about genetic transmission of psoriasis to the next generation, and the interference with sexual activity that has been documented in patients with active disease.

"I do have people who say they never want to have children because of their disease. That’s a very sad conversation," Dr. Cather said.

Intriguingly, there is some recent evidence to suggest anti-TNF therapy may improve the results of in vitro fertilization in women with infertility and recurrent spontaneous abortion. The therapeutic rationale is that TNF-alpha has been shown to have antireproductive effects.

In a nonrandomized study involving 75 women without psoriasis under age 38 with Th1/Th2 cytokine elevation undergoing IVF for infertility, investigators found that implantation, clinical pregnancy, and live birth rates were significantly higher in those on adalimumab and IVIG than in patients on neither (Am. J. Repro. Immunol. 2009;61:113-20). This is a controversial study among assisted reproduction specialists, Dr. Cather noted.

She disclosed that she serves as a consultant to Amgen (manufacturer of Enbrel), Abbott (manufacturer of Humira), and Centocor (manufacturer of Stelara) and has received research grants from Amgen, Celgene, and Pfizer.

SDEF and this news organization are owned by Elsevier.

WAILEA, HAWAII – Moderate to severe psoriasis is an independent risk factor for a variety of adverse pregnancy outcomes, according to Dr. Jennifer C. Cather.

Yet much remains unknown about the impact of psoriasis and its treatment in pregnancy. For this reason, every psoriasis patient who becomes pregnant while on a biologic agent should be strongly encouraged to enter one of the pregnancy registries, Dr. Cather said at the Hawaii Dermatology Seminar sponsored by Skin Disease Education Foundation (SDEF).

She recommended the Organization of Teratology Information Specialists (OTIS), because the group helps inform concerned patients. OTIS operates pregnancy registries for women taking etanercept (Enbrel) or adalimumab (Humira). In addition, pharmaceutical companies that market biologics maintain pregnancy registries for their agents.

The Food and Drug Administration rates methotrexate and acitretin as pregnancy category X drugs and cyclosporine as a category C drug. The anti–tumor necrosis factor agents are category B – meaning animal studies have shown no fetal risk – as are alefacept (Amevive) and ustekinumab (Stelara).

"That doesn’t mean I think you should give a category B agent to people who are pregnant or are planning pregnancy, because I think that the best drug in pregnancy is probably no drug, or light treatment if you can get away with that," said Dr. Cather, who is in private practice in Dallas.

Still, there is sometimes no satisfactory alternative to using a biologic agent in pregnancy. Two of the toughest challenges Dr. Cather said she encounters in her clinical practice arise in such situations. One involves the psoriasis patient who calls and says that her ob.gyn. told her to come off the biologic therapy immediately.

The other challenge is the patient whose psoriasis worsens during pregnancy to the extent that she needs to start on a biologic agent or switch to another one. This is not an uncommon situation, Dr. Cather noted, citing a University of California, Irvine, study which found that while psoriasis improved during pregnancy in 55% of pregnant patients, it worsened in 23%. Postpartum, psoriasis worsened in 65% (Arch. Dermatol. 2005;141:601-6).

A recent retrospective matched cohort study of pregnancy outcomes in psoriasis patients involved 68 deliveries in 35 women with moderate to severe psoriasis and 237 deliveries in 236 controls in Israel.

The incidence of pregnancy-induced hypertensive diseases was 7.4% in the psoriasis patients, significantly greater than the 2.1% rate in controls. Premature rupture of membranes occurred in 16% of psoriasis patients, compared with 5.5% of controls. The 24% incidence of large-for-gestational-age newborns among the psoriasis patients’ babies was twice that of controls. Macrosomia occurred in 13% of the babies of women with psoriasis, compared with 4.2% of matched controls.

In this multivariate analysis, moderate to severe psoriasis was also an independent risk factor for previous spontaneous and induced abortions (J. Eur. Acad. Dermatol. Venereol. 2010 Nov. 25 doi: 10.1111/j.1468-3083.2010.03917.x]).

Dr. Cather’s biologics of choice for psoriasis and psoriatic arthritis, whether during pregnancy or not, are TNF-antagonists. She has been monitoring her own psoriasis patients who have been on biologic agents during pregnancy and has not noted any increase in adverse outcomes. While she finds this somewhat reassuring, the definitive answers will come from the large pregnancy registries.

Nursing mothers on methotrexate, acitretin, or cyclosporine should not breast-feed. The risk of using anti–tumor necrosis factor agents during breast-feeding is "probably negligible," she said.

Psoriasis patients have a below-average rate of childbearing. Theories abound as to why. Possibilities include an increased infertility rate, voluntary childlessness due to concern about genetic transmission of psoriasis to the next generation, and the interference with sexual activity that has been documented in patients with active disease.

"I do have people who say they never want to have children because of their disease. That’s a very sad conversation," Dr. Cather said.

Intriguingly, there is some recent evidence to suggest anti-TNF therapy may improve the results of in vitro fertilization in women with infertility and recurrent spontaneous abortion. The therapeutic rationale is that TNF-alpha has been shown to have antireproductive effects.

In a nonrandomized study involving 75 women without psoriasis under age 38 with Th1/Th2 cytokine elevation undergoing IVF for infertility, investigators found that implantation, clinical pregnancy, and live birth rates were significantly higher in those on adalimumab and IVIG than in patients on neither (Am. J. Repro. Immunol. 2009;61:113-20). This is a controversial study among assisted reproduction specialists, Dr. Cather noted.

She disclosed that she serves as a consultant to Amgen (manufacturer of Enbrel), Abbott (manufacturer of Humira), and Centocor (manufacturer of Stelara) and has received research grants from Amgen, Celgene, and Pfizer.

SDEF and this news organization are owned by Elsevier.

WAILEA, HAWAII – Moderate to severe psoriasis is an independent risk factor for a variety of adverse pregnancy outcomes, according to Dr. Jennifer C. Cather.

Yet much remains unknown about the impact of psoriasis and its treatment in pregnancy. For this reason, every psoriasis patient who becomes pregnant while on a biologic agent should be strongly encouraged to enter one of the pregnancy registries, Dr. Cather said at the Hawaii Dermatology Seminar sponsored by Skin Disease Education Foundation (SDEF).

She recommended the Organization of Teratology Information Specialists (OTIS), because the group helps inform concerned patients. OTIS operates pregnancy registries for women taking etanercept (Enbrel) or adalimumab (Humira). In addition, pharmaceutical companies that market biologics maintain pregnancy registries for their agents.

The Food and Drug Administration rates methotrexate and acitretin as pregnancy category X drugs and cyclosporine as a category C drug. The anti–tumor necrosis factor agents are category B – meaning animal studies have shown no fetal risk – as are alefacept (Amevive) and ustekinumab (Stelara).

"That doesn’t mean I think you should give a category B agent to people who are pregnant or are planning pregnancy, because I think that the best drug in pregnancy is probably no drug, or light treatment if you can get away with that," said Dr. Cather, who is in private practice in Dallas.

Still, there is sometimes no satisfactory alternative to using a biologic agent in pregnancy. Two of the toughest challenges Dr. Cather said she encounters in her clinical practice arise in such situations. One involves the psoriasis patient who calls and says that her ob.gyn. told her to come off the biologic therapy immediately.

The other challenge is the patient whose psoriasis worsens during pregnancy to the extent that she needs to start on a biologic agent or switch to another one. This is not an uncommon situation, Dr. Cather noted, citing a University of California, Irvine, study which found that while psoriasis improved during pregnancy in 55% of pregnant patients, it worsened in 23%. Postpartum, psoriasis worsened in 65% (Arch. Dermatol. 2005;141:601-6).

A recent retrospective matched cohort study of pregnancy outcomes in psoriasis patients involved 68 deliveries in 35 women with moderate to severe psoriasis and 237 deliveries in 236 controls in Israel.

The incidence of pregnancy-induced hypertensive diseases was 7.4% in the psoriasis patients, significantly greater than the 2.1% rate in controls. Premature rupture of membranes occurred in 16% of psoriasis patients, compared with 5.5% of controls. The 24% incidence of large-for-gestational-age newborns among the psoriasis patients’ babies was twice that of controls. Macrosomia occurred in 13% of the babies of women with psoriasis, compared with 4.2% of matched controls.

In this multivariate analysis, moderate to severe psoriasis was also an independent risk factor for previous spontaneous and induced abortions (J. Eur. Acad. Dermatol. Venereol. 2010 Nov. 25 doi: 10.1111/j.1468-3083.2010.03917.x]).

Dr. Cather’s biologics of choice for psoriasis and psoriatic arthritis, whether during pregnancy or not, are TNF-antagonists. She has been monitoring her own psoriasis patients who have been on biologic agents during pregnancy and has not noted any increase in adverse outcomes. While she finds this somewhat reassuring, the definitive answers will come from the large pregnancy registries.

Nursing mothers on methotrexate, acitretin, or cyclosporine should not breast-feed. The risk of using anti–tumor necrosis factor agents during breast-feeding is "probably negligible," she said.

Psoriasis patients have a below-average rate of childbearing. Theories abound as to why. Possibilities include an increased infertility rate, voluntary childlessness due to concern about genetic transmission of psoriasis to the next generation, and the interference with sexual activity that has been documented in patients with active disease.

"I do have people who say they never want to have children because of their disease. That’s a very sad conversation," Dr. Cather said.

Intriguingly, there is some recent evidence to suggest anti-TNF therapy may improve the results of in vitro fertilization in women with infertility and recurrent spontaneous abortion. The therapeutic rationale is that TNF-alpha has been shown to have antireproductive effects.

In a nonrandomized study involving 75 women without psoriasis under age 38 with Th1/Th2 cytokine elevation undergoing IVF for infertility, investigators found that implantation, clinical pregnancy, and live birth rates were significantly higher in those on adalimumab and IVIG than in patients on neither (Am. J. Repro. Immunol. 2009;61:113-20). This is a controversial study among assisted reproduction specialists, Dr. Cather noted.

She disclosed that she serves as a consultant to Amgen (manufacturer of Enbrel), Abbott (manufacturer of Humira), and Centocor (manufacturer of Stelara) and has received research grants from Amgen, Celgene, and Pfizer.

SDEF and this news organization are owned by Elsevier.

WAILEA, HAWAII – Moderate to severe psoriasis is an independent risk factor for a variety of adverse pregnancy outcomes, according to Dr. Jennifer C. Cather.

Yet much remains unknown about the impact of psoriasis and its treatment in pregnancy. For this reason, every psoriasis patient who becomes pregnant while on a biologic agent should be strongly encouraged to enter one of the pregnancy registries, Dr. Cather said at the Hawaii Dermatology Seminar sponsored by Skin Disease Education Foundation (SDEF).

She recommended the Organization of Teratology Information Specialists (OTIS), because the group helps inform concerned patients. OTIS operates pregnancy registries for women taking etanercept (Enbrel) or adalimumab (Humira). In addition, pharmaceutical companies that market biologics maintain pregnancy registries for their agents.

The Food and Drug Administration rates methotrexate and acitretin as pregnancy category X drugs and cyclosporine as a category C drug. The anti–tumor necrosis factor agents are category B – meaning animal studies have shown no fetal risk – as are alefacept (Amevive) and ustekinumab (Stelara).

"That doesn’t mean I think you should give a category B agent to people who are pregnant or are planning pregnancy, because I think that the best drug in pregnancy is probably no drug, or light treatment if you can get away with that," said Dr. Cather, who is in private practice in Dallas.

Still, there is sometimes no satisfactory alternative to using a biologic agent in pregnancy. Two of the toughest challenges Dr. Cather said she encounters in her clinical practice arise in such situations. One involves the psoriasis patient who calls and says that her ob.gyn. told her to come off the biologic therapy immediately.

The other challenge is the patient whose psoriasis worsens during pregnancy to the extent that she needs to start on a biologic agent or switch to another one. This is not an uncommon situation, Dr. Cather noted, citing a University of California, Irvine, study which found that while psoriasis improved during pregnancy in 55% of pregnant patients, it worsened in 23%. Postpartum, psoriasis worsened in 65% (Arch. Dermatol. 2005;141:601-6).

A recent retrospective matched cohort study of pregnancy outcomes in psoriasis patients involved 68 deliveries in 35 women with moderate to severe psoriasis and 237 deliveries in 236 controls in Israel.

The incidence of pregnancy-induced hypertensive diseases was 7.4% in the psoriasis patients, significantly greater than the 2.1% rate in controls. Premature rupture of membranes occurred in 16% of psoriasis patients, compared with 5.5% of controls. The 24% incidence of large-for-gestational-age newborns among the psoriasis patients’ babies was twice that of controls. Macrosomia occurred in 13% of the babies of women with psoriasis, compared with 4.2% of matched controls.

In this multivariate analysis, moderate to severe psoriasis was also an independent risk factor for previous spontaneous and induced abortions (J. Eur. Acad. Dermatol. Venereol. 2010 Nov. 25 doi: 10.1111/j.1468-3083.2010.03917.x]).

Dr. Cather’s biologics of choice for psoriasis and psoriatic arthritis, whether during pregnancy or not, are TNF-antagonists. She has been monitoring her own psoriasis patients who have been on biologic agents during pregnancy and has not noted any increase in adverse outcomes. While she finds this somewhat reassuring, the definitive answers will come from the large pregnancy registries.

Nursing mothers on methotrexate, acitretin, or cyclosporine should not breast-feed. The risk of using anti–tumor necrosis factor agents during breast-feeding is "probably negligible," she said.

Psoriasis patients have a below-average rate of childbearing. Theories abound as to why. Possibilities include an increased infertility rate, voluntary childlessness due to concern about genetic transmission of psoriasis to the next generation, and the interference with sexual activity that has been documented in patients with active disease.

"I do have people who say they never want to have children because of their disease. That’s a very sad conversation," Dr. Cather said.

Intriguingly, there is some recent evidence to suggest anti-TNF therapy may improve the results of in vitro fertilization in women with infertility and recurrent spontaneous abortion. The therapeutic rationale is that TNF-alpha has been shown to have antireproductive effects.

In a nonrandomized study involving 75 women without psoriasis under age 38 with Th1/Th2 cytokine elevation undergoing IVF for infertility, investigators found that implantation, clinical pregnancy, and live birth rates were significantly higher in those on adalimumab and IVIG than in patients on neither (Am. J. Repro. Immunol. 2009;61:113-20). This is a controversial study among assisted reproduction specialists, Dr. Cather noted.

She disclosed that she serves as a consultant to Amgen (manufacturer of Enbrel), Abbott (manufacturer of Humira), and Centocor (manufacturer of Stelara) and has received research grants from Amgen, Celgene, and Pfizer.

SDEF and this news organization are owned by Elsevier.

WAILEA, HAWAII – There is good news and bad news regarding the highly publicized bedbug resurgence.

The good news is that the much-loathed creatures are not effective vectors for disease transmission. To date, there have been no documented cases of disease transmission to humans via bedbug bites. Studies using animal models have also consistently been negative, Dr. Albert C. Yan said at the Hawaii Dermatology Seminar sponsored by Skin Disease Education Foundation (SDEF).

The bad news is pesticide resistance among bedbugs is a growing problem worldwide. One of the mutations in voltage-sensitive sodium channel alpha subunits associated with reduced bedbug neuronal sensitivity to pesticides has also been noted in permethrin-resistant head lice.

Bedbugs, or Cimex lectularius, are wingless, nocturnal, oval-shaped insects 3-5 mm in size. They are photophobic, hiding in protected places until they come out to feed on blood, typically between 2 and 4 a.m. Feeding takes only a few minutes and is painless because the insects smooth the way by injecting their anticoagulant-rich saliva. Their hosts rarely see them.

Treatment of the skin lesions is straightforward and symptomatic: hydroxyzine or diphenhydramine for the itch, along with a midpotency topical steroid. Guiding the patient to an experienced exterminator is also a big help.

Diagnosing Bites

Bedbug bites appear clinically as juicy pruritic papules that are often excoriated and arrayed in a line. The face and bare arms and shoulders are common locations.

"They tend not to crawl under clothing, so you only see bites on exposed surfaces," explained Dr. Yan, a pediatric dermatologist at Children’s Hospital of Philadelphia.

Courtesy of CDC/Piotr Naskrecki

Only one-third to two-thirds of people will generate a cutaneous reaction when bitten by bedbugs, which is why it is not uncommon for just one of two people sleeping in the same infested bed to develop lesions.

Fecal blood stains on bedding are a clue that bites are due to bedbugs rather than some other insect. When the bedbug becomes loaded with blood it defecates at the feeding site.

Detecting Infestation

It is not hard to locate a significant infestation. Bedbugs give off a distinctive sweet, musty odor. They like to nest along mattress seams, between the mattress and box springs, in cracks in wallpaper near the head of the bed, and in furniture crevices.

When traveling, Dr. Yan routinely strips hotel bed sheets and peers behind headboards and picture frames, he said. If he spots evidence of bedbug activity he simply requests another room. It is unusual for an infestation to take over an entire hotel, he said.

Also, it is a good idea to use the metal luggage stand that is present in most hotel rooms. It lessens the chance that the critters will crawl up into the suitcase at night and hitch a ride in luggage or clothing.

Eradication

"It is very difficult to eliminate an infestation on your own," said Dr. Yan.

Eradication does not come cheap. Licensed exterminators typically charge $250-$1,000 per treated room. Pyrethroids are the treatment of choice, although it is not a terribly effective therapy because of the high resistance rate. Retreatment is necessary after several weeks in order to kill the hatched instars.

With the growing problem of pesticide resistance, new methods of eradicating bedbug infestations are needed. One environmentally friendly, pesticide-free approach involves thermal treatment.

Courtesy of Andybrookestar/Wikimedia Commons/Creative Commons

Exterminators place a heater in every room in the house and gradually raise the ambient temperature to around 135  F, holding it there for several hours to kill the bedbugs and their eggs. Plants, pets, medications, candles, oil paintings, and the like must first be removed. While an intriguing approach, Dr. Yan said he has yet to see any studies in the entomologic literature validating its long-term effectiveness.

Do-It-Yourself Bedbug Detection

Before embarking on an expensive extermination program – or to verify its effectiveness – it makes sense to establish that bedbugs are actually present. When the insects are not found on a room search, professional exterminators will place a couple of commercial traps in the room overnight, typically charging $200 or more. But Dr. Yan noted that entomologist Wan-Tien Tsai, Ph.D., of Rutgers University in New Brunswick has come up with a do-it-yourself bedbug detector that patients can easily assemble for about $15.

Her homemade trap involves placing 2.5 pounds of CO₂ pellets in a one-third-gallon-size insulated jug or thermos obtainable at a camping supply store. The pour hole is left not quite closed, allowing CO₂ to leak out for about 11 hours. Bedbugs are attracted to the gas. The jug is placed in the middle of a plastic cat food dish whose bowl is dusted with talcum powder so that once bedbugs slide in, they cannot crawl out. A paper ramp is taped to the rim of the food dish to assist the bugs in climbing in. The trap is placed overnight near a bedpost.

Dr. Yan said he had no relevant financial disclosures. SDEF and this news organization are owned by Elsevier.

WAILEA, HAWAII – There is good news and bad news regarding the highly publicized bedbug resurgence.

The good news is that the much-loathed creatures are not effective vectors for disease transmission. To date, there have been no documented cases of disease transmission to humans via bedbug bites. Studies using animal models have also consistently been negative, Dr. Albert C. Yan said at the Hawaii Dermatology Seminar sponsored by Skin Disease Education Foundation (SDEF).

The bad news is pesticide resistance among bedbugs is a growing problem worldwide. One of the mutations in voltage-sensitive sodium channel alpha subunits associated with reduced bedbug neuronal sensitivity to pesticides has also been noted in permethrin-resistant head lice.

Bedbugs, or Cimex lectularius, are wingless, nocturnal, oval-shaped insects 3-5 mm in size. They are photophobic, hiding in protected places until they come out to feed on blood, typically between 2 and 4 a.m. Feeding takes only a few minutes and is painless because the insects smooth the way by injecting their anticoagulant-rich saliva. Their hosts rarely see them.

Treatment of the skin lesions is straightforward and symptomatic: hydroxyzine or diphenhydramine for the itch, along with a midpotency topical steroid. Guiding the patient to an experienced exterminator is also a big help.

Diagnosing Bites

Bedbug bites appear clinically as juicy pruritic papules that are often excoriated and arrayed in a line. The face and bare arms and shoulders are common locations.

"They tend not to crawl under clothing, so you only see bites on exposed surfaces," explained Dr. Yan, a pediatric dermatologist at Children’s Hospital of Philadelphia.

Courtesy of CDC/Piotr Naskrecki

Only one-third to two-thirds of people will generate a cutaneous reaction when bitten by bedbugs, which is why it is not uncommon for just one of two people sleeping in the same infested bed to develop lesions.

Fecal blood stains on bedding are a clue that bites are due to bedbugs rather than some other insect. When the bedbug becomes loaded with blood it defecates at the feeding site.

Detecting Infestation

It is not hard to locate a significant infestation. Bedbugs give off a distinctive sweet, musty odor. They like to nest along mattress seams, between the mattress and box springs, in cracks in wallpaper near the head of the bed, and in furniture crevices.

When traveling, Dr. Yan routinely strips hotel bed sheets and peers behind headboards and picture frames, he said. If he spots evidence of bedbug activity he simply requests another room. It is unusual for an infestation to take over an entire hotel, he said.

Also, it is a good idea to use the metal luggage stand that is present in most hotel rooms. It lessens the chance that the critters will crawl up into the suitcase at night and hitch a ride in luggage or clothing.

Eradication

"It is very difficult to eliminate an infestation on your own," said Dr. Yan.

Eradication does not come cheap. Licensed exterminators typically charge $250-$1,000 per treated room. Pyrethroids are the treatment of choice, although it is not a terribly effective therapy because of the high resistance rate. Retreatment is necessary after several weeks in order to kill the hatched instars.

With the growing problem of pesticide resistance, new methods of eradicating bedbug infestations are needed. One environmentally friendly, pesticide-free approach involves thermal treatment.

Courtesy of Andybrookestar/Wikimedia Commons/Creative Commons

Exterminators place a heater in every room in the house and gradually raise the ambient temperature to around 135  F, holding it there for several hours to kill the bedbugs and their eggs. Plants, pets, medications, candles, oil paintings, and the like must first be removed. While an intriguing approach, Dr. Yan said he has yet to see any studies in the entomologic literature validating its long-term effectiveness.

Do-It-Yourself Bedbug Detection

Before embarking on an expensive extermination program – or to verify its effectiveness – it makes sense to establish that bedbugs are actually present. When the insects are not found on a room search, professional exterminators will place a couple of commercial traps in the room overnight, typically charging $200 or more. But Dr. Yan noted that entomologist Wan-Tien Tsai, Ph.D., of Rutgers University in New Brunswick has come up with a do-it-yourself bedbug detector that patients can easily assemble for about $15.

Her homemade trap involves placing 2.5 pounds of CO₂ pellets in a one-third-gallon-size insulated jug or thermos obtainable at a camping supply store. The pour hole is left not quite closed, allowing CO₂ to leak out for about 11 hours. Bedbugs are attracted to the gas. The jug is placed in the middle of a plastic cat food dish whose bowl is dusted with talcum powder so that once bedbugs slide in, they cannot crawl out. A paper ramp is taped to the rim of the food dish to assist the bugs in climbing in. The trap is placed overnight near a bedpost.

Dr. Yan said he had no relevant financial disclosures. SDEF and this news organization are owned by Elsevier.

WAILEA, HAWAII – There is good news and bad news regarding the highly publicized bedbug resurgence.

The good news is that the much-loathed creatures are not effective vectors for disease transmission. To date, there have been no documented cases of disease transmission to humans via bedbug bites. Studies using animal models have also consistently been negative, Dr. Albert C. Yan said at the Hawaii Dermatology Seminar sponsored by Skin Disease Education Foundation (SDEF).

The bad news is pesticide resistance among bedbugs is a growing problem worldwide. One of the mutations in voltage-sensitive sodium channel alpha subunits associated with reduced bedbug neuronal sensitivity to pesticides has also been noted in permethrin-resistant head lice.

Bedbugs, or Cimex lectularius, are wingless, nocturnal, oval-shaped insects 3-5 mm in size. They are photophobic, hiding in protected places until they come out to feed on blood, typically between 2 and 4 a.m. Feeding takes only a few minutes and is painless because the insects smooth the way by injecting their anticoagulant-rich saliva. Their hosts rarely see them.

Treatment of the skin lesions is straightforward and symptomatic: hydroxyzine or diphenhydramine for the itch, along with a midpotency topical steroid. Guiding the patient to an experienced exterminator is also a big help.

Diagnosing Bites

Bedbug bites appear clinically as juicy pruritic papules that are often excoriated and arrayed in a line. The face and bare arms and shoulders are common locations.

"They tend not to crawl under clothing, so you only see bites on exposed surfaces," explained Dr. Yan, a pediatric dermatologist at Children’s Hospital of Philadelphia.

Courtesy of CDC/Piotr Naskrecki

Only one-third to two-thirds of people will generate a cutaneous reaction when bitten by bedbugs, which is why it is not uncommon for just one of two people sleeping in the same infested bed to develop lesions.

Fecal blood stains on bedding are a clue that bites are due to bedbugs rather than some other insect. When the bedbug becomes loaded with blood it defecates at the feeding site.

Detecting Infestation

It is not hard to locate a significant infestation. Bedbugs give off a distinctive sweet, musty odor. They like to nest along mattress seams, between the mattress and box springs, in cracks in wallpaper near the head of the bed, and in furniture crevices.

When traveling, Dr. Yan routinely strips hotel bed sheets and peers behind headboards and picture frames, he said. If he spots evidence of bedbug activity he simply requests another room. It is unusual for an infestation to take over an entire hotel, he said.

Also, it is a good idea to use the metal luggage stand that is present in most hotel rooms. It lessens the chance that the critters will crawl up into the suitcase at night and hitch a ride in luggage or clothing.

Eradication

"It is very difficult to eliminate an infestation on your own," said Dr. Yan.

Eradication does not come cheap. Licensed exterminators typically charge $250-$1,000 per treated room. Pyrethroids are the treatment of choice, although it is not a terribly effective therapy because of the high resistance rate. Retreatment is necessary after several weeks in order to kill the hatched instars.

With the growing problem of pesticide resistance, new methods of eradicating bedbug infestations are needed. One environmentally friendly, pesticide-free approach involves thermal treatment.

Courtesy of Andybrookestar/Wikimedia Commons/Creative Commons

Exterminators place a heater in every room in the house and gradually raise the ambient temperature to around 135  F, holding it there for several hours to kill the bedbugs and their eggs. Plants, pets, medications, candles, oil paintings, and the like must first be removed. While an intriguing approach, Dr. Yan said he has yet to see any studies in the entomologic literature validating its long-term effectiveness.

Do-It-Yourself Bedbug Detection

Before embarking on an expensive extermination program – or to verify its effectiveness – it makes sense to establish that bedbugs are actually present. When the insects are not found on a room search, professional exterminators will place a couple of commercial traps in the room overnight, typically charging $200 or more. But Dr. Yan noted that entomologist Wan-Tien Tsai, Ph.D., of Rutgers University in New Brunswick has come up with a do-it-yourself bedbug detector that patients can easily assemble for about $15.

Her homemade trap involves placing 2.5 pounds of CO₂ pellets in a one-third-gallon-size insulated jug or thermos obtainable at a camping supply store. The pour hole is left not quite closed, allowing CO₂ to leak out for about 11 hours. Bedbugs are attracted to the gas. The jug is placed in the middle of a plastic cat food dish whose bowl is dusted with talcum powder so that once bedbugs slide in, they cannot crawl out. A paper ramp is taped to the rim of the food dish to assist the bugs in climbing in. The trap is placed overnight near a bedpost.

Dr. Yan said he had no relevant financial disclosures. SDEF and this news organization are owned by Elsevier.

WAILEA, HAWAII – There is good news and bad news regarding the highly publicized bedbug resurgence.

The good news is that the much-loathed creatures are not effective vectors for disease transmission. To date, there have been no documented cases of disease transmission to humans via bedbug bites. Studies using animal models have also consistently been negative, Dr. Albert C. Yan said at the Hawaii Dermatology Seminar sponsored by Skin Disease Education Foundation (SDEF).

The bad news is pesticide resistance among bedbugs is a growing problem worldwide. One of the mutations in voltage-sensitive sodium channel alpha subunits associated with reduced bedbug neuronal sensitivity to pesticides has also been noted in permethrin-resistant head lice.

Bedbugs, or Cimex lectularius, are wingless, nocturnal, oval-shaped insects 3-5 mm in size. They are photophobic, hiding in protected places until they come out to feed on blood, typically between 2 and 4 a.m. Feeding takes only a few minutes and is painless because the insects smooth the way by injecting their anticoagulant-rich saliva. Their hosts rarely see them.

Treatment of the skin lesions is straightforward and symptomatic: hydroxyzine or diphenhydramine for the itch, along with a midpotency topical steroid. Guiding the patient to an experienced exterminator is also a big help.

Diagnosing Bites

Bedbug bites appear clinically as juicy pruritic papules that are often excoriated and arrayed in a line. The face and bare arms and shoulders are common locations.

"They tend not to crawl under clothing, so you only see bites on exposed surfaces," explained Dr. Yan, a pediatric dermatologist at Children’s Hospital of Philadelphia.

Courtesy of CDC/Piotr Naskrecki

Only one-third to two-thirds of people will generate a cutaneous reaction when bitten by bedbugs, which is why it is not uncommon for just one of two people sleeping in the same infested bed to develop lesions.

Fecal blood stains on bedding are a clue that bites are due to bedbugs rather than some other insect. When the bedbug becomes loaded with blood it defecates at the feeding site.

Detecting Infestation

It is not hard to locate a significant infestation. Bedbugs give off a distinctive sweet, musty odor. They like to nest along mattress seams, between the mattress and box springs, in cracks in wallpaper near the head of the bed, and in furniture crevices.

When traveling, Dr. Yan routinely strips hotel bed sheets and peers behind headboards and picture frames, he said. If he spots evidence of bedbug activity he simply requests another room. It is unusual for an infestation to take over an entire hotel, he said.

Also, it is a good idea to use the metal luggage stand that is present in most hotel rooms. It lessens the chance that the critters will crawl up into the suitcase at night and hitch a ride in luggage or clothing.

Eradication

"It is very difficult to eliminate an infestation on your own," said Dr. Yan.

Eradication does not come cheap. Licensed exterminators typically charge $250-$1,000 per treated room. Pyrethroids are the treatment of choice, although it is not a terribly effective therapy because of the high resistance rate. Retreatment is necessary after several weeks in order to kill the hatched instars.

With the growing problem of pesticide resistance, new methods of eradicating bedbug infestations are needed. One environmentally friendly, pesticide-free approach involves thermal treatment.

Courtesy of Andybrookestar/Wikimedia Commons/Creative Commons

Exterminators place a heater in every room in the house and gradually raise the ambient temperature to around 135  F, holding it there for several hours to kill the bedbugs and their eggs. Plants, pets, medications, candles, oil paintings, and the like must first be removed. While an intriguing approach, Dr. Yan said he has yet to see any studies in the entomologic literature validating its long-term effectiveness.

Do-It-Yourself Bedbug Detection

Before embarking on an expensive extermination program – or to verify its effectiveness – it makes sense to establish that bedbugs are actually present. When the insects are not found on a room search, professional exterminators will place a couple of commercial traps in the room overnight, typically charging $200 or more. But Dr. Yan noted that entomologist Wan-Tien Tsai, Ph.D., of Rutgers University in New Brunswick has come up with a do-it-yourself bedbug detector that patients can easily assemble for about $15.

Her homemade trap involves placing 2.5 pounds of CO₂ pellets in a one-third-gallon-size insulated jug or thermos obtainable at a camping supply store. The pour hole is left not quite closed, allowing CO₂ to leak out for about 11 hours. Bedbugs are attracted to the gas. The jug is placed in the middle of a plastic cat food dish whose bowl is dusted with talcum powder so that once bedbugs slide in, they cannot crawl out. A paper ramp is taped to the rim of the food dish to assist the bugs in climbing in. The trap is placed overnight near a bedpost.

Dr. Yan said he had no relevant financial disclosures. SDEF and this news organization are owned by Elsevier.

WAILEA, HAWAII – There is good news and bad news regarding the highly publicized bedbug resurgence.

The good news is that the much-loathed creatures are not effective vectors for disease transmission. To date, there have been no documented cases of disease transmission to humans via bedbug bites. Studies using animal models have also consistently been negative, Dr. Albert C. Yan said at the Hawaii Dermatology Seminar sponsored by Skin Disease Education Foundation (SDEF).

The bad news is pesticide resistance among bedbugs is a growing problem worldwide. One of the mutations in voltage-sensitive sodium channel alpha subunits associated with reduced bedbug neuronal sensitivity to pesticides has also been noted in permethrin-resistant head lice.

Bedbugs, or Cimex lectularius, are wingless, nocturnal, oval-shaped insects 3-5 mm in size. They are photophobic, hiding in protected places until they come out to feed on blood, typically between 2 and 4 a.m. Feeding takes only a few minutes and is painless because the insects smooth the way by injecting their anticoagulant-rich saliva. Their hosts rarely see them.

Treatment of the skin lesions is straightforward and symptomatic: hydroxyzine or diphenhydramine for the itch, along with a midpotency topical steroid. Guiding the patient to an experienced exterminator is also a big help.

Diagnosing Bites

Bedbug bites appear clinically as juicy pruritic papules that are often excoriated and arrayed in a line. The face and bare arms and shoulders are common locations.

"They tend not to crawl under clothing, so you only see bites on exposed surfaces," explained Dr. Yan, a pediatric dermatologist at Children’s Hospital of Philadelphia.

Courtesy of CDC/Piotr Naskrecki

Only one-third to two-thirds of people will generate a cutaneous reaction when bitten by bedbugs, which is why it is not uncommon for just one of two people sleeping in the same infested bed to develop lesions.

Fecal blood stains on bedding are a clue that bites are due to bedbugs rather than some other insect. When the bedbug becomes loaded with blood it defecates at the feeding site.

Detecting Infestation

It is not hard to locate a significant infestation. Bedbugs give off a distinctive sweet, musty odor. They like to nest along mattress seams, between the mattress and box springs, in cracks in wallpaper near the head of the bed, and in furniture crevices.

When traveling, Dr. Yan routinely strips hotel bed sheets and peers behind headboards and picture frames, he said. If he spots evidence of bedbug activity he simply requests another room. It is unusual for an infestation to take over an entire hotel, he said.

Also, it is a good idea to use the metal luggage stand that is present in most hotel rooms. It lessens the chance that the critters will crawl up into the suitcase at night and hitch a ride in luggage or clothing.

Eradication

"It is very difficult to eliminate an infestation on your own," said Dr. Yan.

Eradication does not come cheap. Licensed exterminators typically charge $250-$1,000 per treated room. Pyrethroids are the treatment of choice, although it is not a terribly effective therapy because of the high resistance rate. Retreatment is necessary after several weeks in order to kill the hatched instars.

With the growing problem of pesticide resistance, new methods of eradicating bedbug infestations are needed. One environmentally friendly, pesticide-free approach involves thermal treatment.

Courtesy of Andybrookestar/Wikimedia Commons/Creative Commons

Exterminators place a heater in every room in the house and gradually raise the ambient temperature to around 135  F, holding it there for several hours to kill the bedbugs and their eggs. Plants, pets, medications, candles, oil paintings, and the like must first be removed. While an intriguing approach, Dr. Yan said he has yet to see any studies in the entomologic literature validating its long-term effectiveness.

Do-It-Yourself Bedbug Detection

Before embarking on an expensive extermination program – or to verify its effectiveness – it makes sense to establish that bedbugs are actually present. When the insects are not found on a room search, professional exterminators will place a couple of commercial traps in the room overnight, typically charging $200 or more. But Dr. Yan noted that entomologist Wan-Tien Tsai, Ph.D., of Rutgers University in New Brunswick has come up with a do-it-yourself bedbug detector that patients can easily assemble for about $15.

Her homemade trap involves placing 2.5 pounds of CO₂ pellets in a one-third-gallon-size insulated jug or thermos obtainable at a camping supply store. The pour hole is left not quite closed, allowing CO₂ to leak out for about 11 hours. Bedbugs are attracted to the gas. The jug is placed in the middle of a plastic cat food dish whose bowl is dusted with talcum powder so that once bedbugs slide in, they cannot crawl out. A paper ramp is taped to the rim of the food dish to assist the bugs in climbing in. The trap is placed overnight near a bedpost.

Dr. Yan said he had no relevant financial disclosures. SDEF and this news organization are owned by Elsevier.

WAILEA, HAWAII – There is good news and bad news regarding the highly publicized bedbug resurgence.

The good news is that the much-loathed creatures are not effective vectors for disease transmission. To date, there have been no documented cases of disease transmission to humans via bedbug bites. Studies using animal models have also consistently been negative, Dr. Albert C. Yan said at the Hawaii Dermatology Seminar sponsored by Skin Disease Education Foundation (SDEF).

The bad news is pesticide resistance among bedbugs is a growing problem worldwide. One of the mutations in voltage-sensitive sodium channel alpha subunits associated with reduced bedbug neuronal sensitivity to pesticides has also been noted in permethrin-resistant head lice.

Bedbugs, or Cimex lectularius, are wingless, nocturnal, oval-shaped insects 3-5 mm in size. They are photophobic, hiding in protected places until they come out to feed on blood, typically between 2 and 4 a.m. Feeding takes only a few minutes and is painless because the insects smooth the way by injecting their anticoagulant-rich saliva. Their hosts rarely see them.

Treatment of the skin lesions is straightforward and symptomatic: hydroxyzine or diphenhydramine for the itch, along with a midpotency topical steroid. Guiding the patient to an experienced exterminator is also a big help.

Diagnosing Bites

Bedbug bites appear clinically as juicy pruritic papules that are often excoriated and arrayed in a line. The face and bare arms and shoulders are common locations.

"They tend not to crawl under clothing, so you only see bites on exposed surfaces," explained Dr. Yan, a pediatric dermatologist at Children’s Hospital of Philadelphia.

Courtesy of CDC/Piotr Naskrecki

Only one-third to two-thirds of people will generate a cutaneous reaction when bitten by bedbugs, which is why it is not uncommon for just one of two people sleeping in the same infested bed to develop lesions.

Fecal blood stains on bedding are a clue that bites are due to bedbugs rather than some other insect. When the bedbug becomes loaded with blood it defecates at the feeding site.

Detecting Infestation

It is not hard to locate a significant infestation. Bedbugs give off a distinctive sweet, musty odor. They like to nest along mattress seams, between the mattress and box springs, in cracks in wallpaper near the head of the bed, and in furniture crevices.

When traveling, Dr. Yan routinely strips hotel bed sheets and peers behind headboards and picture frames, he said. If he spots evidence of bedbug activity he simply requests another room. It is unusual for an infestation to take over an entire hotel, he said.

Also, it is a good idea to use the metal luggage stand that is present in most hotel rooms. It lessens the chance that the critters will crawl up into the suitcase at night and hitch a ride in luggage or clothing.

Eradication

"It is very difficult to eliminate an infestation on your own," said Dr. Yan.

Eradication does not come cheap. Licensed exterminators typically charge $250-$1,000 per treated room. Pyrethroids are the treatment of choice, although it is not a terribly effective therapy because of the high resistance rate. Retreatment is necessary after several weeks in order to kill the hatched instars.

With the growing problem of pesticide resistance, new methods of eradicating bedbug infestations are needed. One environmentally friendly, pesticide-free approach involves thermal treatment.

Courtesy of Andybrookestar/Wikimedia Commons/Creative Commons

Exterminators place a heater in every room in the house and gradually raise the ambient temperature to around 135  F, holding it there for several hours to kill the bedbugs and their eggs. Plants, pets, medications, candles, oil paintings, and the like must first be removed. While an intriguing approach, Dr. Yan said he has yet to see any studies in the entomologic literature validating its long-term effectiveness.

Do-It-Yourself Bedbug Detection

Before embarking on an expensive extermination program – or to verify its effectiveness – it makes sense to establish that bedbugs are actually present. When the insects are not found on a room search, professional exterminators will place a couple of commercial traps in the room overnight, typically charging $200 or more. But Dr. Yan noted that entomologist Wan-Tien Tsai, Ph.D., of Rutgers University in New Brunswick has come up with a do-it-yourself bedbug detector that patients can easily assemble for about $15.

Her homemade trap involves placing 2.5 pounds of CO₂ pellets in a one-third-gallon-size insulated jug or thermos obtainable at a camping supply store. The pour hole is left not quite closed, allowing CO₂ to leak out for about 11 hours. Bedbugs are attracted to the gas. The jug is placed in the middle of a plastic cat food dish whose bowl is dusted with talcum powder so that once bedbugs slide in, they cannot crawl out. A paper ramp is taped to the rim of the food dish to assist the bugs in climbing in. The trap is placed overnight near a bedpost.

Dr. Yan said he had no relevant financial disclosures. SDEF and this news organization are owned by Elsevier.

WAILEA, HAWAII – There is good news and bad news regarding the highly publicized bedbug resurgence.

The good news is that the much-loathed creatures are not effective vectors for disease transmission. To date, there have been no documented cases of disease transmission to humans via bedbug bites. Studies using animal models have also consistently been negative, Dr. Albert C. Yan said at the Hawaii Dermatology Seminar sponsored by Skin Disease Education Foundation (SDEF).

The bad news is pesticide resistance among bedbugs is a growing problem worldwide. One of the mutations in voltage-sensitive sodium channel alpha subunits associated with reduced bedbug neuronal sensitivity to pesticides has also been noted in permethrin-resistant head lice.

Bedbugs, or Cimex lectularius, are wingless, nocturnal, oval-shaped insects 3-5 mm in size. They are photophobic, hiding in protected places until they come out to feed on blood, typically between 2 and 4 a.m. Feeding takes only a few minutes and is painless because the insects smooth the way by injecting their anticoagulant-rich saliva. Their hosts rarely see them.

Treatment of the skin lesions is straightforward and symptomatic: hydroxyzine or diphenhydramine for the itch, along with a midpotency topical steroid. Guiding the patient to an experienced exterminator is also a big help.

Diagnosing Bites

Bedbug bites appear clinically as juicy pruritic papules that are often excoriated and arrayed in a line. The face and bare arms and shoulders are common locations.

"They tend not to crawl under clothing, so you only see bites on exposed surfaces," explained Dr. Yan, a pediatric dermatologist at Children’s Hospital of Philadelphia.

Courtesy of CDC/Piotr Naskrecki

Only one-third to two-thirds of people will generate a cutaneous reaction when bitten by bedbugs, which is why it is not uncommon for just one of two people sleeping in the same infested bed to develop lesions.

Fecal blood stains on bedding are a clue that bites are due to bedbugs rather than some other insect. When the bedbug becomes loaded with blood it defecates at the feeding site.

Detecting Infestation

It is not hard to locate a significant infestation. Bedbugs give off a distinctive sweet, musty odor. They like to nest along mattress seams, between the mattress and box springs, in cracks in wallpaper near the head of the bed, and in furniture crevices.

When traveling, Dr. Yan routinely strips hotel bed sheets and peers behind headboards and picture frames, he said. If he spots evidence of bedbug activity he simply requests another room. It is unusual for an infestation to take over an entire hotel, he said.

Also, it is a good idea to use the metal luggage stand that is present in most hotel rooms. It lessens the chance that the critters will crawl up into the suitcase at night and hitch a ride in luggage or clothing.

Eradication

"It is very difficult to eliminate an infestation on your own," said Dr. Yan.

Eradication does not come cheap. Licensed exterminators typically charge $250-$1,000 per treated room. Pyrethroids are the treatment of choice, although it is not a terribly effective therapy because of the high resistance rate. Retreatment is necessary after several weeks in order to kill the hatched instars.

With the growing problem of pesticide resistance, new methods of eradicating bedbug infestations are needed. One environmentally friendly, pesticide-free approach involves thermal treatment.

Courtesy of Andybrookestar/Wikimedia Commons/Creative Commons

Exterminators place a heater in every room in the house and gradually raise the ambient temperature to around 135  F, holding it there for several hours to kill the bedbugs and their eggs. Plants, pets, medications, candles, oil paintings, and the like must first be removed. While an intriguing approach, Dr. Yan said he has yet to see any studies in the entomologic literature validating its long-term effectiveness.

Do-It-Yourself Bedbug Detection

Before embarking on an expensive extermination program – or to verify its effectiveness – it makes sense to establish that bedbugs are actually present. When the insects are not found on a room search, professional exterminators will place a couple of commercial traps in the room overnight, typically charging $200 or more. But Dr. Yan noted that entomologist Wan-Tien Tsai, Ph.D., of Rutgers University in New Brunswick has come up with a do-it-yourself bedbug detector that patients can easily assemble for about $15.

Her homemade trap involves placing 2.5 pounds of CO₂ pellets in a one-third-gallon-size insulated jug or thermos obtainable at a camping supply store. The pour hole is left not quite closed, allowing CO₂ to leak out for about 11 hours. Bedbugs are attracted to the gas. The jug is placed in the middle of a plastic cat food dish whose bowl is dusted with talcum powder so that once bedbugs slide in, they cannot crawl out. A paper ramp is taped to the rim of the food dish to assist the bugs in climbing in. The trap is placed overnight near a bedpost.

Dr. Yan said he had no relevant financial disclosures. SDEF and this news organization are owned by Elsevier.

WAILEA, HAWAII – There is good news and bad news regarding the highly publicized bedbug resurgence.

The good news is that the much-loathed creatures are not effective vectors for disease transmission. To date, there have been no documented cases of disease transmission to humans via bedbug bites. Studies using animal models have also consistently been negative, Dr. Albert C. Yan said at the Hawaii Dermatology Seminar sponsored by Skin Disease Education Foundation (SDEF).

The bad news is pesticide resistance among bedbugs is a growing problem worldwide. One of the mutations in voltage-sensitive sodium channel alpha subunits associated with reduced bedbug neuronal sensitivity to pesticides has also been noted in permethrin-resistant head lice.

Bedbugs, or Cimex lectularius, are wingless, nocturnal, oval-shaped insects 3-5 mm in size. They are photophobic, hiding in protected places until they come out to feed on blood, typically between 2 and 4 a.m. Feeding takes only a few minutes and is painless because the insects smooth the way by injecting their anticoagulant-rich saliva. Their hosts rarely see them.

Treatment of the skin lesions is straightforward and symptomatic: hydroxyzine or diphenhydramine for the itch, along with a midpotency topical steroid. Guiding the patient to an experienced exterminator is also a big help.

Diagnosing Bites

Bedbug bites appear clinically as juicy pruritic papules that are often excoriated and arrayed in a line. The face and bare arms and shoulders are common locations.

"They tend not to crawl under clothing, so you only see bites on exposed surfaces," explained Dr. Yan, a pediatric dermatologist at Children’s Hospital of Philadelphia.

Courtesy of CDC/Piotr Naskrecki

Only one-third to two-thirds of people will generate a cutaneous reaction when bitten by bedbugs, which is why it is not uncommon for just one of two people sleeping in the same infested bed to develop lesions.

Fecal blood stains on bedding are a clue that bites are due to bedbugs rather than some other insect. When the bedbug becomes loaded with blood it defecates at the feeding site.

Detecting Infestation

It is not hard to locate a significant infestation. Bedbugs give off a distinctive sweet, musty odor. They like to nest along mattress seams, between the mattress and box springs, in cracks in wallpaper near the head of the bed, and in furniture crevices.

When traveling, Dr. Yan routinely strips hotel bed sheets and peers behind headboards and picture frames, he said. If he spots evidence of bedbug activity he simply requests another room. It is unusual for an infestation to take over an entire hotel, he said.

Also, it is a good idea to use the metal luggage stand that is present in most hotel rooms. It lessens the chance that the critters will crawl up into the suitcase at night and hitch a ride in luggage or clothing.

Eradication

"It is very difficult to eliminate an infestation on your own," said Dr. Yan.

Eradication does not come cheap. Licensed exterminators typically charge $250-$1,000 per treated room. Pyrethroids are the treatment of choice, although it is not a terribly effective therapy because of the high resistance rate. Retreatment is necessary after several weeks in order to kill the hatched instars.

With the growing problem of pesticide resistance, new methods of eradicating bedbug infestations are needed. One environmentally friendly, pesticide-free approach involves thermal treatment.

Courtesy of Andybrookestar/Wikimedia Commons/Creative Commons

Exterminators place a heater in every room in the house and gradually raise the ambient temperature to around 135  F, holding it there for several hours to kill the bedbugs and their eggs. Plants, pets, medications, candles, oil paintings, and the like must first be removed. While an intriguing approach, Dr. Yan said he has yet to see any studies in the entomologic literature validating its long-term effectiveness.

Do-It-Yourself Bedbug Detection

Before embarking on an expensive extermination program – or to verify its effectiveness – it makes sense to establish that bedbugs are actually present. When the insects are not found on a room search, professional exterminators will place a couple of commercial traps in the room overnight, typically charging $200 or more. But Dr. Yan noted that entomologist Wan-Tien Tsai, Ph.D., of Rutgers University in New Brunswick has come up with a do-it-yourself bedbug detector that patients can easily assemble for about $15.

Her homemade trap involves placing 2.5 pounds of CO₂ pellets in a one-third-gallon-size insulated jug or thermos obtainable at a camping supply store. The pour hole is left not quite closed, allowing CO₂ to leak out for about 11 hours. Bedbugs are attracted to the gas. The jug is placed in the middle of a plastic cat food dish whose bowl is dusted with talcum powder so that once bedbugs slide in, they cannot crawl out. A paper ramp is taped to the rim of the food dish to assist the bugs in climbing in. The trap is placed overnight near a bedpost.

Dr. Yan said he had no relevant financial disclosures. SDEF and this news organization are owned by Elsevier.

WAILEA, HAWAII – There is good news and bad news regarding the highly publicized bedbug resurgence.

The good news is that the much-loathed creatures are not effective vectors for disease transmission. To date, there have been no documented cases of disease transmission to humans via bedbug bites. Studies using animal models have also consistently been negative, Dr. Albert C. Yan said at the Hawaii Dermatology Seminar sponsored by Skin Disease Education Foundation (SDEF).

The bad news is pesticide resistance among bedbugs is a growing problem worldwide. One of the mutations in voltage-sensitive sodium channel alpha subunits associated with reduced bedbug neuronal sensitivity to pesticides has also been noted in permethrin-resistant head lice.

Bedbugs, or Cimex lectularius, are wingless, nocturnal, oval-shaped insects 3-5 mm in size. They are photophobic, hiding in protected places until they come out to feed on blood, typically between 2 and 4 a.m. Feeding takes only a few minutes and is painless because the insects smooth the way by injecting their anticoagulant-rich saliva. Their hosts rarely see them.

Treatment of the skin lesions is straightforward and symptomatic: hydroxyzine or diphenhydramine for the itch, along with a midpotency topical steroid. Guiding the patient to an experienced exterminator is also a big help.

Diagnosing Bites

Bedbug bites appear clinically as juicy pruritic papules that are often excoriated and arrayed in a line. The face and bare arms and shoulders are common locations.

"They tend not to crawl under clothing, so you only see bites on exposed surfaces," explained Dr. Yan, a pediatric dermatologist at Children’s Hospital of Philadelphia.

Courtesy of CDC/Piotr Naskrecki

Only one-third to two-thirds of people will generate a cutaneous reaction when bitten by bedbugs, which is why it is not uncommon for just one of two people sleeping in the same infested bed to develop lesions.

Fecal blood stains on bedding are a clue that bites are due to bedbugs rather than some other insect. When the bedbug becomes loaded with blood it defecates at the feeding site.

Detecting Infestation

It is not hard to locate a significant infestation. Bedbugs give off a distinctive sweet, musty odor. They like to nest along mattress seams, between the mattress and box springs, in cracks in wallpaper near the head of the bed, and in furniture crevices.

When traveling, Dr. Yan routinely strips hotel bed sheets and peers behind headboards and picture frames, he said. If he spots evidence of bedbug activity he simply requests another room. It is unusual for an infestation to take over an entire hotel, he said.

Also, it is a good idea to use the metal luggage stand that is present in most hotel rooms. It lessens the chance that the critters will crawl up into the suitcase at night and hitch a ride in luggage or clothing.

Eradication

"It is very difficult to eliminate an infestation on your own," said Dr. Yan.

Eradication does not come cheap. Licensed exterminators typically charge $250-$1,000 per treated room. Pyrethroids are the treatment of choice, although it is not a terribly effective therapy because of the high resistance rate. Retreatment is necessary after several weeks in order to kill the hatched instars.

With the growing problem of pesticide resistance, new methods of eradicating bedbug infestations are needed. One environmentally friendly, pesticide-free approach involves thermal treatment.

Courtesy of Andybrookestar/Wikimedia Commons/Creative Commons

Exterminators place a heater in every room in the house and gradually raise the ambient temperature to around 135  F, holding it there for several hours to kill the bedbugs and their eggs. Plants, pets, medications, candles, oil paintings, and the like must first be removed. While an intriguing approach, Dr. Yan said he has yet to see any studies in the entomologic literature validating its long-term effectiveness.

Do-It-Yourself Bedbug Detection

Before embarking on an expensive extermination program – or to verify its effectiveness – it makes sense to establish that bedbugs are actually present. When the insects are not found on a room search, professional exterminators will place a couple of commercial traps in the room overnight, typically charging $200 or more. But Dr. Yan noted that entomologist Wan-Tien Tsai, Ph.D., of Rutgers University in New Brunswick has come up with a do-it-yourself bedbug detector that patients can easily assemble for about $15.

Her homemade trap involves placing 2.5 pounds of CO₂ pellets in a one-third-gallon-size insulated jug or thermos obtainable at a camping supply store. The pour hole is left not quite closed, allowing CO₂ to leak out for about 11 hours. Bedbugs are attracted to the gas. The jug is placed in the middle of a plastic cat food dish whose bowl is dusted with talcum powder so that once bedbugs slide in, they cannot crawl out. A paper ramp is taped to the rim of the food dish to assist the bugs in climbing in. The trap is placed overnight near a bedpost.

Dr. Yan said he had no relevant financial disclosures. SDEF and this news organization are owned by Elsevier.

WAILEA, HAWAII – Large numbers of children with atopic dermatitis have been diagnosed with food allergy and placed on strict food-elimination diets on the basis of positive serum immunoglobulin E tests, when in fact oral food challenges conducted in such patients indicate that the vast majority of foods that are being shunned can safely be returned to the diet.

"A shocking number of these kids have false-positive labels of food allergy," Dr. Lawrence F. Eichenfield said at the Hawaii Dermatology Seminar sponsored by Skin Disease Education Foundation (SDEF).

These food-elimination diets can lead to poor weight gain and chronic malnutrition, added Dr. Eichenfield, chief of pediatric and adolescent dermatology at Rady Children's Hospital, San Diego, and professor of pediatrics and medicine (dermatology) at the University of California, San Diego.

"This is an issue that we face in our offices, especially with our moderate to severe atopic dermatitis individuals. We need to have a real sense of the disability that goes on because of empiric food elimination or elimination based on serum IgE tests and nonstandardized tests. Let's consider working with enlightened allergists in the community on giving appropriate challenges or repeating of these foods, because many times they're not a factor at all in the atopic dermatitis," he said.

He cited a recent study by investigators at Denver's renowned National Jewish Health. The study involved 125 children aged 1-19 years (median, 4 years), with atopic dermatitis who were on elimination diets based upon positive serum IgE immunoassay results. The children were hospitalized for medically supervised oral food challenges in which they were given 6-10 doses of a food at intervals of 15-30 minutes.

A negative challenge was defined as no reaction or worsening of atopic dermatitis within a 2-hour observation period, when IgE-mediated symptoms would be expected to become manifest. No challenges were done using foods for which the child had a history of anaphylaxis.

Overall, 93% of the oral food challenges were negative, meaning that those foods could be safely returned to the diet. In all, 100% of challenges to meat, egg, oat, shellfish, and vegetables in the 34 patients on elimination diets involving those foods proved to be negative.

"The results of this retrospective study demonstrate that a primary reliance on serum food-specific IgE testing to determine the need for food elimination diets in children, especially those with atopic dermatitis, is not sufficient," the investigators concluded (J. Pediatr. 2011;158:578-83).

Dr. Eichenfield noted that this conclusion is entirely consistent with the thrust of important new guidelines on the diagnosis and management of food allergy released by a National Institute of Allergy and Infectious Diseases–sponsored expert panel. The guidelines recommend against food avoidance to manage atopic dermatitis, asthma, or eosinophilic esophagitis in the absence of documented or proven food allergy. Furthermore, the guidelines state that serum IgE tests and skin-prick tests are not diagnostic of food allergy, although they can be of assistance in the work-up. Hair analysis, electrodermal tests, kinesiology, and other nonstandardized tests are not recommended.

The new guidelines suggest that only under certain specific conditions should children younger than age 5 years with moderate to severe atopic dermatitis be considered for food allergy evaluation for milk, egg, peanut, wheat, and soy – the handful of foods in which IgE levels and skin-prick testing have the greatest validity in predicting a positive challenge. To be a candidate for this limited food-allergy evaluation, the child needs to have persistent atopic dermatitis despite optimized management and topical therapy, and/or a reliable history of an immediate reaction after consuming a specific food (J. Allergy Clin. Immunol. 2010;126(suppl. 6):S1-58).

"I'd say that this is a new standard for dermatology," Dr. Eichenfield commented. "If a child has a history of a specific food reaction, you want to consider specific food testing because that individual could be at risk for a life-threatening reaction in the future."

"But you don't want to get caught up in a secret allergen search," he added. "Continue to emphasize eczema care as the primary approach to atopic dermatitis."

Dr. Eichenfield serves as a consultant to Coria, Galderma, Promius Pharma, Intendis, and Ortho Dermatologics. He is an uncompensated investigator for numerous pharmaceutical companies. SDEF and this news organization are owned by Elsevier.

WAILEA, HAWAII – Large numbers of children with atopic dermatitis have been diagnosed with food allergy and placed on strict food-elimination diets on the basis of positive serum immunoglobulin E tests, when in fact oral food challenges conducted in such patients indicate that the vast majority of foods that are being shunned can safely be returned to the diet.

"A shocking number of these kids have false-positive labels of food allergy," Dr. Lawrence F. Eichenfield said at the Hawaii Dermatology Seminar sponsored by Skin Disease Education Foundation (SDEF).

These food-elimination diets can lead to poor weight gain and chronic malnutrition, added Dr. Eichenfield, chief of pediatric and adolescent dermatology at Rady Children's Hospital, San Diego, and professor of pediatrics and medicine (dermatology) at the University of California, San Diego.

"This is an issue that we face in our offices, especially with our moderate to severe atopic dermatitis individuals. We need to have a real sense of the disability that goes on because of empiric food elimination or elimination based on serum IgE tests and nonstandardized tests. Let's consider working with enlightened allergists in the community on giving appropriate challenges or repeating of these foods, because many times they're not a factor at all in the atopic dermatitis," he said.

He cited a recent study by investigators at Denver's renowned National Jewish Health. The study involved 125 children aged 1-19 years (median, 4 years), with atopic dermatitis who were on elimination diets based upon positive serum IgE immunoassay results. The children were hospitalized for medically supervised oral food challenges in which they were given 6-10 doses of a food at intervals of 15-30 minutes.

A negative challenge was defined as no reaction or worsening of atopic dermatitis within a 2-hour observation period, when IgE-mediated symptoms would be expected to become manifest. No challenges were done using foods for which the child had a history of anaphylaxis.

Overall, 93% of the oral food challenges were negative, meaning that those foods could be safely returned to the diet. In all, 100% of challenges to meat, egg, oat, shellfish, and vegetables in the 34 patients on elimination diets involving those foods proved to be negative.

"The results of this retrospective study demonstrate that a primary reliance on serum food-specific IgE testing to determine the need for food elimination diets in children, especially those with atopic dermatitis, is not sufficient," the investigators concluded (J. Pediatr. 2011;158:578-83).

Dr. Eichenfield noted that this conclusion is entirely consistent with the thrust of important new guidelines on the diagnosis and management of food allergy released by a National Institute of Allergy and Infectious Diseases–sponsored expert panel. The guidelines recommend against food avoidance to manage atopic dermatitis, asthma, or eosinophilic esophagitis in the absence of documented or proven food allergy. Furthermore, the guidelines state that serum IgE tests and skin-prick tests are not diagnostic of food allergy, although they can be of assistance in the work-up. Hair analysis, electrodermal tests, kinesiology, and other nonstandardized tests are not recommended.

The new guidelines suggest that only under certain specific conditions should children younger than age 5 years with moderate to severe atopic dermatitis be considered for food allergy evaluation for milk, egg, peanut, wheat, and soy – the handful of foods in which IgE levels and skin-prick testing have the greatest validity in predicting a positive challenge. To be a candidate for this limited food-allergy evaluation, the child needs to have persistent atopic dermatitis despite optimized management and topical therapy, and/or a reliable history of an immediate reaction after consuming a specific food (J. Allergy Clin. Immunol. 2010;126(suppl. 6):S1-58).

"I'd say that this is a new standard for dermatology," Dr. Eichenfield commented. "If a child has a history of a specific food reaction, you want to consider specific food testing because that individual could be at risk for a life-threatening reaction in the future."

"But you don't want to get caught up in a secret allergen search," he added. "Continue to emphasize eczema care as the primary approach to atopic dermatitis."

Dr. Eichenfield serves as a consultant to Coria, Galderma, Promius Pharma, Intendis, and Ortho Dermatologics. He is an uncompensated investigator for numerous pharmaceutical companies. SDEF and this news organization are owned by Elsevier.

WAILEA, HAWAII – Large numbers of children with atopic dermatitis have been diagnosed with food allergy and placed on strict food-elimination diets on the basis of positive serum immunoglobulin E tests, when in fact oral food challenges conducted in such patients indicate that the vast majority of foods that are being shunned can safely be returned to the diet.

"A shocking number of these kids have false-positive labels of food allergy," Dr. Lawrence F. Eichenfield said at the Hawaii Dermatology Seminar sponsored by Skin Disease Education Foundation (SDEF).

These food-elimination diets can lead to poor weight gain and chronic malnutrition, added Dr. Eichenfield, chief of pediatric and adolescent dermatology at Rady Children's Hospital, San Diego, and professor of pediatrics and medicine (dermatology) at the University of California, San Diego.

"This is an issue that we face in our offices, especially with our moderate to severe atopic dermatitis individuals. We need to have a real sense of the disability that goes on because of empiric food elimination or elimination based on serum IgE tests and nonstandardized tests. Let's consider working with enlightened allergists in the community on giving appropriate challenges or repeating of these foods, because many times they're not a factor at all in the atopic dermatitis," he said.

He cited a recent study by investigators at Denver's renowned National Jewish Health. The study involved 125 children aged 1-19 years (median, 4 years), with atopic dermatitis who were on elimination diets based upon positive serum IgE immunoassay results. The children were hospitalized for medically supervised oral food challenges in which they were given 6-10 doses of a food at intervals of 15-30 minutes.

A negative challenge was defined as no reaction or worsening of atopic dermatitis within a 2-hour observation period, when IgE-mediated symptoms would be expected to become manifest. No challenges were done using foods for which the child had a history of anaphylaxis.

Overall, 93% of the oral food challenges were negative, meaning that those foods could be safely returned to the diet. In all, 100% of challenges to meat, egg, oat, shellfish, and vegetables in the 34 patients on elimination diets involving those foods proved to be negative.

"The results of this retrospective study demonstrate that a primary reliance on serum food-specific IgE testing to determine the need for food elimination diets in children, especially those with atopic dermatitis, is not sufficient," the investigators concluded (J. Pediatr. 2011;158:578-83).

Dr. Eichenfield noted that this conclusion is entirely consistent with the thrust of important new guidelines on the diagnosis and management of food allergy released by a National Institute of Allergy and Infectious Diseases–sponsored expert panel. The guidelines recommend against food avoidance to manage atopic dermatitis, asthma, or eosinophilic esophagitis in the absence of documented or proven food allergy. Furthermore, the guidelines state that serum IgE tests and skin-prick tests are not diagnostic of food allergy, although they can be of assistance in the work-up. Hair analysis, electrodermal tests, kinesiology, and other nonstandardized tests are not recommended.

The new guidelines suggest that only under certain specific conditions should children younger than age 5 years with moderate to severe atopic dermatitis be considered for food allergy evaluation for milk, egg, peanut, wheat, and soy – the handful of foods in which IgE levels and skin-prick testing have the greatest validity in predicting a positive challenge. To be a candidate for this limited food-allergy evaluation, the child needs to have persistent atopic dermatitis despite optimized management and topical therapy, and/or a reliable history of an immediate reaction after consuming a specific food (J. Allergy Clin. Immunol. 2010;126(suppl. 6):S1-58).

"I'd say that this is a new standard for dermatology," Dr. Eichenfield commented. "If a child has a history of a specific food reaction, you want to consider specific food testing because that individual could be at risk for a life-threatening reaction in the future."

"But you don't want to get caught up in a secret allergen search," he added. "Continue to emphasize eczema care as the primary approach to atopic dermatitis."

Dr. Eichenfield serves as a consultant to Coria, Galderma, Promius Pharma, Intendis, and Ortho Dermatologics. He is an uncompensated investigator for numerous pharmaceutical companies. SDEF and this news organization are owned by Elsevier.

WAILEA, MAUI – Large numbers of children with atopic dermatitis have been diagnosed with food allergy and placed on strict food-elimination diets on the basis of positive serum immunoglobulin E tests, when in fact oral food challenges conducted in such patients indicate that the vast majority of foods that are being shunned can safely be returned to the diet.

"A shocking number of these kids have false-positive labels of food allergy," Dr. Lawrence F. Eichenfield said at the Hawaii Dermatology Seminar sponsored by Skin Disease Education Foundation (SDEF).

These food-elimination diets can lead to poor weight gain and chronic malnutrition, added Dr. Eichenfield, chief of pediatric and adolescent dermatology at Rady Children’s Hospital, San Diego, and professor of pediatrics and medicine (dermatology) at the University of California, San Diego.

"This is an issue that we face in our offices, especially with our moderate to severe atopic dermatitis individuals. We need to have a real sense of the disability that goes on because of empiric food elimination or elimination based on serum IgE tests and nonstandardized tests. Let’s consider working with enlightened allergists in the community on giving appropriate challenges or repeating of these foods, because many times they’re not a factor at all in the atopic dermatitis," he said.

He cited a recent study by investigators at Denver’s renowned National Jewish Health. The study involved 125 children aged 1-19 years (median, 4 years), with atopic dermatitis who were on elimination diets based upon positive serum IgE immunoassay results. The children were hospitalized for medically supervised oral food challenges in which they were given 6-10 doses of a food at intervals of 15-30 minutes. A negative challenge was defined as no reaction or worsening of atopic dermatitis within a 2-hour observation period, when IgE-mediated symptoms would be expected to become manifest. No challenges were done using foods for which the child had a history of anaphylaxis.

Overall, 93% of the oral food challenges were negative, meaning that those foods could be safely returned to the diet. In all, 100% of challenges to meat, egg, oat, shellfish, and vegetables in the 34 patients on elimination diets involving those foods proved to be negative.

"The results of this retrospective study demonstrate that a primary reliance on serum food-specific IgE testing to determine the need for food elimination diets in children, especially those with atopic dermatitis, is not sufficient," the investigators concluded (J. Pediatr. 2011;158:578-83).

Dr. Eichenfield noted that this conclusion is entirely consistent with the thrust of important new guidelines on the diagnosis and management of food allergy released by a National Institute of Allergy and Infectious Diseases–sponsored expert panel. The guidelines recommend against food avoidance to manage atopic dermatitis, asthma, or eosinophilic esophagitis in the absence of documented or proven food allergy. Furthermore, the guidelines state that serum IgE tests and skin-prick tests are not diagnostic of food allergy, although they can be of assistance in the work-up. Hair analysis, electrodermal tests, kinesiology, and other nonstandardized tests are not recommended.

The new guidelines suggest that only under certain specific conditions should children younger than age 5 years with moderate to severe atopic dermatitis be considered for food allergy evaluation for milk, egg, peanut, wheat, and soy – the handful of foods in which IgE levels and skin-prick testing have the greatest validity in predicting a positive challenge. To be a candidate for this limited food-allergy evaluation, the child needs to have persistent atopic dermatitis despite optimized management and topical therapy, and/or a reliable history of an immediate reaction after consuming a specific food (J. Allergy Clin. Immunol. 2010;126(suppl. 6):S1-58).

"I’d say that this is a new standard for dermatology," Dr. Eichenfield commented. "If a child has a history of a specific food reaction, you want to consider specific food testing because that individual could be at risk for a life-threatening reaction in the future."

"But you don’t want to get caught up in a secret allergen search," he added. "Continue to emphasize eczema care as the primary approach to atopic dermatitis."

Dr. Eichenfield serves as a consultant to Coria, Galderma, Promius Pharma, Intendis, and Ortho Dermatologics. He is an uncompensated investigator for numerous pharmaceutical companies. SDEF and this news organization are owned by Elsevier.

WAILEA, MAUI – Large numbers of children with atopic dermatitis have been diagnosed with food allergy and placed on strict food-elimination diets on the basis of positive serum immunoglobulin E tests, when in fact oral food challenges conducted in such patients indicate that the vast majority of foods that are being shunned can safely be returned to the diet.

"A shocking number of these kids have false-positive labels of food allergy," Dr. Lawrence F. Eichenfield said at the Hawaii Dermatology Seminar sponsored by Skin Disease Education Foundation (SDEF).

These food-elimination diets can lead to poor weight gain and chronic malnutrition, added Dr. Eichenfield, chief of pediatric and adolescent dermatology at Rady Children’s Hospital, San Diego, and professor of pediatrics and medicine (dermatology) at the University of California, San Diego.

"This is an issue that we face in our offices, especially with our moderate to severe atopic dermatitis individuals. We need to have a real sense of the disability that goes on because of empiric food elimination or elimination based on serum IgE tests and nonstandardized tests. Let’s consider working with enlightened allergists in the community on giving appropriate challenges or repeating of these foods, because many times they’re not a factor at all in the atopic dermatitis," he said.

He cited a recent study by investigators at Denver’s renowned National Jewish Health. The study involved 125 children aged 1-19 years (median, 4 years), with atopic dermatitis who were on elimination diets based upon positive serum IgE immunoassay results. The children were hospitalized for medically supervised oral food challenges in which they were given 6-10 doses of a food at intervals of 15-30 minutes. A negative challenge was defined as no reaction or worsening of atopic dermatitis within a 2-hour observation period, when IgE-mediated symptoms would be expected to become manifest. No challenges were done using foods for which the child had a history of anaphylaxis.

Overall, 93% of the oral food challenges were negative, meaning that those foods could be safely returned to the diet. In all, 100% of challenges to meat, egg, oat, shellfish, and vegetables in the 34 patients on elimination diets involving those foods proved to be negative.

"The results of this retrospective study demonstrate that a primary reliance on serum food-specific IgE testing to determine the need for food elimination diets in children, especially those with atopic dermatitis, is not sufficient," the investigators concluded (J. Pediatr. 2011;158:578-83).

Dr. Eichenfield noted that this conclusion is entirely consistent with the thrust of important new guidelines on the diagnosis and management of food allergy released by a National Institute of Allergy and Infectious Diseases–sponsored expert panel. The guidelines recommend against food avoidance to manage atopic dermatitis, asthma, or eosinophilic esophagitis in the absence of documented or proven food allergy. Furthermore, the guidelines state that serum IgE tests and skin-prick tests are not diagnostic of food allergy, although they can be of assistance in the work-up. Hair analysis, electrodermal tests, kinesiology, and other nonstandardized tests are not recommended.

The new guidelines suggest that only under certain specific conditions should children younger than age 5 years with moderate to severe atopic dermatitis be considered for food allergy evaluation for milk, egg, peanut, wheat, and soy – the handful of foods in which IgE levels and skin-prick testing have the greatest validity in predicting a positive challenge. To be a candidate for this limited food-allergy evaluation, the child needs to have persistent atopic dermatitis despite optimized management and topical therapy, and/or a reliable history of an immediate reaction after consuming a specific food (J. Allergy Clin. Immunol. 2010;126(suppl. 6):S1-58).

"I’d say that this is a new standard for dermatology," Dr. Eichenfield commented. "If a child has a history of a specific food reaction, you want to consider specific food testing because that individual could be at risk for a life-threatening reaction in the future."

"But you don’t want to get caught up in a secret allergen search," he added. "Continue to emphasize eczema care as the primary approach to atopic dermatitis."

Dr. Eichenfield serves as a consultant to Coria, Galderma, Promius Pharma, Intendis, and Ortho Dermatologics. He is an uncompensated investigator for numerous pharmaceutical companies. SDEF and this news organization are owned by Elsevier.

WAILEA, MAUI – Large numbers of children with atopic dermatitis have been diagnosed with food allergy and placed on strict food-elimination diets on the basis of positive serum immunoglobulin E tests, when in fact oral food challenges conducted in such patients indicate that the vast majority of foods that are being shunned can safely be returned to the diet.

"A shocking number of these kids have false-positive labels of food allergy," Dr. Lawrence F. Eichenfield said at the Hawaii Dermatology Seminar sponsored by Skin Disease Education Foundation (SDEF).

These food-elimination diets can lead to poor weight gain and chronic malnutrition, added Dr. Eichenfield, chief of pediatric and adolescent dermatology at Rady Children’s Hospital, San Diego, and professor of pediatrics and medicine (dermatology) at the University of California, San Diego.

"This is an issue that we face in our offices, especially with our moderate to severe atopic dermatitis individuals. We need to have a real sense of the disability that goes on because of empiric food elimination or elimination based on serum IgE tests and nonstandardized tests. Let’s consider working with enlightened allergists in the community on giving appropriate challenges or repeating of these foods, because many times they’re not a factor at all in the atopic dermatitis," he said.

He cited a recent study by investigators at Denver’s renowned National Jewish Health. The study involved 125 children aged 1-19 years (median, 4 years), with atopic dermatitis who were on elimination diets based upon positive serum IgE immunoassay results. The children were hospitalized for medically supervised oral food challenges in which they were given 6-10 doses of a food at intervals of 15-30 minutes. A negative challenge was defined as no reaction or worsening of atopic dermatitis within a 2-hour observation period, when IgE-mediated symptoms would be expected to become manifest. No challenges were done using foods for which the child had a history of anaphylaxis.

Overall, 93% of the oral food challenges were negative, meaning that those foods could be safely returned to the diet. In all, 100% of challenges to meat, egg, oat, shellfish, and vegetables in the 34 patients on elimination diets involving those foods proved to be negative.

"The results of this retrospective study demonstrate that a primary reliance on serum food-specific IgE testing to determine the need for food elimination diets in children, especially those with atopic dermatitis, is not sufficient," the investigators concluded (J. Pediatr. 2011;158:578-83).

Dr. Eichenfield noted that this conclusion is entirely consistent with the thrust of important new guidelines on the diagnosis and management of food allergy released by a National Institute of Allergy and Infectious Diseases–sponsored expert panel. The guidelines recommend against food avoidance to manage atopic dermatitis, asthma, or eosinophilic esophagitis in the absence of documented or proven food allergy. Furthermore, the guidelines state that serum IgE tests and skin-prick tests are not diagnostic of food allergy, although they can be of assistance in the work-up. Hair analysis, electrodermal tests, kinesiology, and other nonstandardized tests are not recommended.

The new guidelines suggest that only under certain specific conditions should children younger than age 5 years with moderate to severe atopic dermatitis be considered for food allergy evaluation for milk, egg, peanut, wheat, and soy – the handful of foods in which IgE levels and skin-prick testing have the greatest validity in predicting a positive challenge. To be a candidate for this limited food-allergy evaluation, the child needs to have persistent atopic dermatitis despite optimized management and topical therapy, and/or a reliable history of an immediate reaction after consuming a specific food (J. Allergy Clin. Immunol. 2010;126(suppl. 6):S1-58).

"I’d say that this is a new standard for dermatology," Dr. Eichenfield commented. "If a child has a history of a specific food reaction, you want to consider specific food testing because that individual could be at risk for a life-threatening reaction in the future."

"But you don’t want to get caught up in a secret allergen search," he added. "Continue to emphasize eczema care as the primary approach to atopic dermatitis."

Dr. Eichenfield serves as a consultant to Coria, Galderma, Promius Pharma, Intendis, and Ortho Dermatologics. He is an uncompensated investigator for numerous pharmaceutical companies. SDEF and this news organization are owned by Elsevier.

WAILEA, HAWAII – Physicians will likely gain a novel short-course field therapy for multiple actinic keratoses next year.

Ingenol mebutate (Leo Pharmaceuticals) hit all of its end points in two phase III clinical trials. One trial was conducted in patients treated for fields of multiple actinic keratoses (AKs) on the head and neck, the other in patients with clusters of AKs anywhere else, Dr. Theodore Rosen said at the Hawaii Dermatology Seminar sponsored by Skin Disease Education Foundation (SDEF).

Median reductions in AKs in these pivotal trials were comparable to results reported with other field therapies, such as imiquimod and 5-fluorouracil. What is remarkable about ingenol mebutate, however, is these outcomes were achieved with only 2 days of once-daily therapy for non–head and neck AKs and 3 days of therapy at a lower concentration for AKs on the head and neck, noted Dr. Rosen, professor of dermatology at Baylor College of Medicine, Houston.

In contrast, the original regimen for the 5% imiquimod dermatologists have been using since its 2004 marketing approval for AKs entails a full 16 weeks of twice-weekly therapy. That being said, last year, the FDA approved a new, shorter-duration formulation of imiquimod which Dr. Rosen said was a better product than the traditional 5% version.

Ingenol mebutate is a diterpene ester derived from the sap of a plant, Euphorbia peplus, traditionally used by Australian aborigines for topical treatment of various skin ailments. Ingenol mebutate's mechanism of action is not fully understood, but involves initial cell necrosis because of mitochondrial disruption followed by granulocyte-dependent cytotoxicity. Immune upregulation also appears to be involved, Dr. Rosen explained.

Non–Head and Neck AK Study

The phase III non–head and neck AK study involved 256 patients randomized to 2 consecutive days of once-daily ingenol mebutate 0.05% gel or placebo applied to up to a 25-cm² area of skin with four to eight visible AKs. The ingenol mebutate group showed a complete clearance rate at day 57 of 27.8%, compared with 4.7% for placebo, and a median 67% reduction in AKs.

The 27.8% complete clearance rate is nothing to write home about, but the 67% reduction in AKs is quite impressive, particularly for a 2-day therapy, according to Dr. Rosen, who was an investigator in these and other AK clinical trials.

"That 67% median reduction is very nice, and it’s really the most accurate measurement because it tells you how many of these things are going to go away by treating the field," Dr. Rosen said.

The complete clearance rate was highest on the chest, followed by the arms, legs, back of hand, and back.

Side effect rates were low at 1%-2%, and consisted of burning, irritation, pain, and other symptoms that are associated with most field therapies for AKs. Interestingly, the peak incidence of the skin side effects was not until day 8.

"You'll have to prepare patients for the fact that almost a week after they’re done with therapy, they may suddenly look worse," he noted.

The product labeling will limit treatment to areas of 25 cm² or less because that is how the pivotal trials were done. "If you want to treat more than 25 cm², you’ll probably be off-label, but we do that all the time," he said.

In an exploratory trial in which investigators treated AK fields of 25, 50, 75, and 100 cm² on the dorsal arms using 0.05% ingenol mebutate applied once daily for 2 days, cumulative local skin reaction scores correlated with the size of the area treated. Even in patients who underwent treatment of 100 cm² of involved skin, side-effect scores returned to baseline by 2 months. Most patients tolerated even the most severe reactions, he noted.

Head and Neck AK Study

The phase III head and neck AK trial involved treatment of areas up to 25 cm² in 264 patients. This trial featured several drug concentrations and durations; the one that produced the best outcomes and will move forward to the marketplace is 0.015% once daily for 3 days. It yielded a complete clearance rate of 50% on day 57, and an 85% median reduction in AKs, according to Dr. Rosen.

With two different concentrations of ingenol mebutate likely to be approved for application at different sites, physicians will need to remain vigilant regarding possible dispensing errors or patient misuse, he said.

Imiquimod

While ingenol mebutate's duration of efficacy remains unknown, that is not the case with imiquimod.

The new imiquimod 3.75% cream (Zyclara), approved last year for treatment of AKs, provides clear benefits over the older 5% formulation in terms of convenience, and with comparable efficacy.

Instead of the traditional 16 weeks of therapy, the 3.75% cream is used daily for 2 weeks, followed by a 2-week rest, then another 2 weeks of therapy, for a total 6-week treatment course. And the imiquimod 3.75% cream is approved for treatment of the full face or balding scalp, unlike imiquimod 5%, whose approved indication is limited to a much smaller area of 25 cm², Dr. Rosen said.

In the pivotal trial for imiquimod 3.75%, 160 treated patients showed a complete clearance rate of 35.6% and a median 81.8% reduction in AKs 8 weeks after the final treatment. That is near-identical to the 83.3% reduction noted in an earlier trial of 215 patients treated with imiquimod 5%.

Dr. Rosen said field therapy makes sound sense in patients with multiple AKs in the same area of the skin.

"When you have a patient with [a lot of] AKs, then all the skin in between those AKs is no more normal than the AK skin; it just hasn’t manifest yet. That’s where field therapy comes in," he explained.

As much as he likes field therapy, though, Dr. Rosen stressed that the emerging new paradigm for treatment of patients with multiple AKs is combination therapy. This can take the form of either a field therapy followed by individual lesion-directed therapy such as cryotherapy, or lesion-directed therapy followed by a field therapy. There are numerous possible combinations. Insurance reimbursement can be a problem for now, but payers will eventually have to come around to the new paradigm.

"The bottom line is for every study where field therapy is combined with lesion-directed therapy or with another field therapy, the combination proved superior to monotherapy," Dr. Rosen said. "It's a little more work, but in the end I think it's probably the best thing for your patient."

Other Agents in the AK Pipeline

AK remains an active target for new drug development. Among the wide range of drugs in the developmental pipeline, albeit still years away from the marketplace, are:

Resiquimod and sotirimod. These are the most promising of the more than 1,000 known analogues of imiquimod. Like the parent compound, they work via immune upregulation, said Dr. Rosen.

Betulin. A triterpene isolated from the extract of birch bark. It eliminates actinic keratoses through cytotoxicity.

Perillyl alcohol. A monoterpene isolated from essential oils of peppermint, spearmint, lavender, and other plants. Its mechanism of action involves induction of apoptosis in rapidly dividing cells without affecting normal cells.

Difluoromethylornithine. Irreversibly inhibits ornithine decarboxylase, which regulates cell division. DFMO is already marketed in a topical formulation for the treatment of facial hirsutism, and as an injectable drug for treatment of African trypanosomiasis.

Afamelanotide. This synthetic analogue of melanocyte-stimulating hormone is under development as a treatment for a diverse collection of skin diseases, including polymorphous light eruption, solar urticaria, and squamous cell carcinoma, as well as AKs.

T4 endonuclease V. This drug enhances repair of UV-induced DNA damage. "It might help prevent future AKs, but not existing ones," Dr. Rosen said.

Why does AK therapy remain such a busy area of new drug development? Simple: A substantial portion of the public continues to be casual about sun protection or disregards it altogether, and with the graying of the baby boomer generation, AKs are more common than ever, he said.

"Everybody in Texas has AKs, including me. I just found one on my hand, and now I need to go treat it," he said.

Dr. Rosen is on the speaker's bureau for Graceway and is a consultant to Graceway and Leo Pharmaceuticals. SDEF and this news organization are owned by Elsevier.

WAILEA, HAWAII – Physicians will likely gain a novel short-course field therapy for multiple actinic keratoses next year.

Ingenol mebutate (Leo Pharmaceuticals) hit all of its end points in two phase III clinical trials. One trial was conducted in patients treated for fields of multiple actinic keratoses (AKs) on the head and neck, the other in patients with clusters of AKs anywhere else, Dr. Theodore Rosen said at the Hawaii Dermatology Seminar sponsored by Skin Disease Education Foundation (SDEF).

Median reductions in AKs in these pivotal trials were comparable to results reported with other field therapies, such as imiquimod and 5-fluorouracil. What is remarkable about ingenol mebutate, however, is these outcomes were achieved with only 2 days of once-daily therapy for non–head and neck AKs and 3 days of therapy at a lower concentration for AKs on the head and neck, noted Dr. Rosen, professor of dermatology at Baylor College of Medicine, Houston.

In contrast, the original regimen for the 5% imiquimod dermatologists have been using since its 2004 marketing approval for AKs entails a full 16 weeks of twice-weekly therapy. That being said, last year, the FDA approved a new, shorter-duration formulation of imiquimod which Dr. Rosen said was a better product than the traditional 5% version.

Ingenol mebutate is a diterpene ester derived from the sap of a plant, Euphorbia peplus, traditionally used by Australian aborigines for topical treatment of various skin ailments. Ingenol mebutate's mechanism of action is not fully understood, but involves initial cell necrosis because of mitochondrial disruption followed by granulocyte-dependent cytotoxicity. Immune upregulation also appears to be involved, Dr. Rosen explained.

Non–Head and Neck AK Study

The phase III non–head and neck AK study involved 256 patients randomized to 2 consecutive days of once-daily ingenol mebutate 0.05% gel or placebo applied to up to a 25-cm² area of skin with four to eight visible AKs. The ingenol mebutate group showed a complete clearance rate at day 57 of 27.8%, compared with 4.7% for placebo, and a median 67% reduction in AKs.

The 27.8% complete clearance rate is nothing to write home about, but the 67% reduction in AKs is quite impressive, particularly for a 2-day therapy, according to Dr. Rosen, who was an investigator in these and other AK clinical trials.

"That 67% median reduction is very nice, and it’s really the most accurate measurement because it tells you how many of these things are going to go away by treating the field," Dr. Rosen said.

The complete clearance rate was highest on the chest, followed by the arms, legs, back of hand, and back.

Side effect rates were low at 1%-2%, and consisted of burning, irritation, pain, and other symptoms that are associated with most field therapies for AKs. Interestingly, the peak incidence of the skin side effects was not until day 8.

"You'll have to prepare patients for the fact that almost a week after they’re done with therapy, they may suddenly look worse," he noted.

The product labeling will limit treatment to areas of 25 cm² or less because that is how the pivotal trials were done. "If you want to treat more than 25 cm², you’ll probably be off-label, but we do that all the time," he said.

In an exploratory trial in which investigators treated AK fields of 25, 50, 75, and 100 cm² on the dorsal arms using 0.05% ingenol mebutate applied once daily for 2 days, cumulative local skin reaction scores correlated with the size of the area treated. Even in patients who underwent treatment of 100 cm² of involved skin, side-effect scores returned to baseline by 2 months. Most patients tolerated even the most severe reactions, he noted.

Head and Neck AK Study

The phase III head and neck AK trial involved treatment of areas up to 25 cm² in 264 patients. This trial featured several drug concentrations and durations; the one that produced the best outcomes and will move forward to the marketplace is 0.015% once daily for 3 days. It yielded a complete clearance rate of 50% on day 57, and an 85% median reduction in AKs, according to Dr. Rosen.

With two different concentrations of ingenol mebutate likely to be approved for application at different sites, physicians will need to remain vigilant regarding possible dispensing errors or patient misuse, he said.

Imiquimod

While ingenol mebutate's duration of efficacy remains unknown, that is not the case with imiquimod.

The new imiquimod 3.75% cream (Zyclara), approved last year for treatment of AKs, provides clear benefits over the older 5% formulation in terms of convenience, and with comparable efficacy.

Instead of the traditional 16 weeks of therapy, the 3.75% cream is used daily for 2 weeks, followed by a 2-week rest, then another 2 weeks of therapy, for a total 6-week treatment course. And the imiquimod 3.75% cream is approved for treatment of the full face or balding scalp, unlike imiquimod 5%, whose approved indication is limited to a much smaller area of 25 cm², Dr. Rosen said.

In the pivotal trial for imiquimod 3.75%, 160 treated patients showed a complete clearance rate of 35.6% and a median 81.8% reduction in AKs 8 weeks after the final treatment. That is near-identical to the 83.3% reduction noted in an earlier trial of 215 patients treated with imiquimod 5%.

Dr. Rosen said field therapy makes sound sense in patients with multiple AKs in the same area of the skin.

"When you have a patient with [a lot of] AKs, then all the skin in between those AKs is no more normal than the AK skin; it just hasn’t manifest yet. That’s where field therapy comes in," he explained.

As much as he likes field therapy, though, Dr. Rosen stressed that the emerging new paradigm for treatment of patients with multiple AKs is combination therapy. This can take the form of either a field therapy followed by individual lesion-directed therapy such as cryotherapy, or lesion-directed therapy followed by a field therapy. There are numerous possible combinations. Insurance reimbursement can be a problem for now, but payers will eventually have to come around to the new paradigm.

"The bottom line is for every study where field therapy is combined with lesion-directed therapy or with another field therapy, the combination proved superior to monotherapy," Dr. Rosen said. "It's a little more work, but in the end I think it's probably the best thing for your patient."

Other Agents in the AK Pipeline

AK remains an active target for new drug development. Among the wide range of drugs in the developmental pipeline, albeit still years away from the marketplace, are:

Resiquimod and sotirimod. These are the most promising of the more than 1,000 known analogues of imiquimod. Like the parent compound, they work via immune upregulation, said Dr. Rosen.

Betulin. A triterpene isolated from the extract of birch bark. It eliminates actinic keratoses through cytotoxicity.

Perillyl alcohol. A monoterpene isolated from essential oils of peppermint, spearmint, lavender, and other plants. Its mechanism of action involves induction of apoptosis in rapidly dividing cells without affecting normal cells.

Difluoromethylornithine. Irreversibly inhibits ornithine decarboxylase, which regulates cell division. DFMO is already marketed in a topical formulation for the treatment of facial hirsutism, and as an injectable drug for treatment of African trypanosomiasis.

Afamelanotide. This synthetic analogue of melanocyte-stimulating hormone is under development as a treatment for a diverse collection of skin diseases, including polymorphous light eruption, solar urticaria, and squamous cell carcinoma, as well as AKs.

T4 endonuclease V. This drug enhances repair of UV-induced DNA damage. "It might help prevent future AKs, but not existing ones," Dr. Rosen said.

Why does AK therapy remain such a busy area of new drug development? Simple: A substantial portion of the public continues to be casual about sun protection or disregards it altogether, and with the graying of the baby boomer generation, AKs are more common than ever, he said.

"Everybody in Texas has AKs, including me. I just found one on my hand, and now I need to go treat it," he said.

Dr. Rosen is on the speaker's bureau for Graceway and is a consultant to Graceway and Leo Pharmaceuticals. SDEF and this news organization are owned by Elsevier.

WAILEA, HAWAII – Physicians will likely gain a novel short-course field therapy for multiple actinic keratoses next year.

Ingenol mebutate (Leo Pharmaceuticals) hit all of its end points in two phase III clinical trials. One trial was conducted in patients treated for fields of multiple actinic keratoses (AKs) on the head and neck, the other in patients with clusters of AKs anywhere else, Dr. Theodore Rosen said at the Hawaii Dermatology Seminar sponsored by Skin Disease Education Foundation (SDEF).

Median reductions in AKs in these pivotal trials were comparable to results reported with other field therapies, such as imiquimod and 5-fluorouracil. What is remarkable about ingenol mebutate, however, is these outcomes were achieved with only 2 days of once-daily therapy for non–head and neck AKs and 3 days of therapy at a lower concentration for AKs on the head and neck, noted Dr. Rosen, professor of dermatology at Baylor College of Medicine, Houston.

In contrast, the original regimen for the 5% imiquimod dermatologists have been using since its 2004 marketing approval for AKs entails a full 16 weeks of twice-weekly therapy. That being said, last year, the FDA approved a new, shorter-duration formulation of imiquimod which Dr. Rosen said was a better product than the traditional 5% version.

Ingenol mebutate is a diterpene ester derived from the sap of a plant, Euphorbia peplus, traditionally used by Australian aborigines for topical treatment of various skin ailments. Ingenol mebutate's mechanism of action is not fully understood, but involves initial cell necrosis because of mitochondrial disruption followed by granulocyte-dependent cytotoxicity. Immune upregulation also appears to be involved, Dr. Rosen explained.

Non–Head and Neck AK Study

The phase III non–head and neck AK study involved 256 patients randomized to 2 consecutive days of once-daily ingenol mebutate 0.05% gel or placebo applied to up to a 25-cm² area of skin with four to eight visible AKs. The ingenol mebutate group showed a complete clearance rate at day 57 of 27.8%, compared with 4.7% for placebo, and a median 67% reduction in AKs.

The 27.8% complete clearance rate is nothing to write home about, but the 67% reduction in AKs is quite impressive, particularly for a 2-day therapy, according to Dr. Rosen, who was an investigator in these and other AK clinical trials.

"That 67% median reduction is very nice, and it’s really the most accurate measurement because it tells you how many of these things are going to go away by treating the field," Dr. Rosen said.

The complete clearance rate was highest on the chest, followed by the arms, legs, back of hand, and back.

Side effect rates were low at 1%-2%, and consisted of burning, irritation, pain, and other symptoms that are associated with most field therapies for AKs. Interestingly, the peak incidence of the skin side effects was not until day 8.

"You'll have to prepare patients for the fact that almost a week after they’re done with therapy, they may suddenly look worse," he noted.

The product labeling will limit treatment to areas of 25 cm² or less because that is how the pivotal trials were done. "If you want to treat more than 25 cm², you’ll probably be off-label, but we do that all the time," he said.

In an exploratory trial in which investigators treated AK fields of 25, 50, 75, and 100 cm² on the dorsal arms using 0.05% ingenol mebutate applied once daily for 2 days, cumulative local skin reaction scores correlated with the size of the area treated. Even in patients who underwent treatment of 100 cm² of involved skin, side-effect scores returned to baseline by 2 months. Most patients tolerated even the most severe reactions, he noted.

Head and Neck AK Study

The phase III head and neck AK trial involved treatment of areas up to 25 cm² in 264 patients. This trial featured several drug concentrations and durations; the one that produced the best outcomes and will move forward to the marketplace is 0.015% once daily for 3 days. It yielded a complete clearance rate of 50% on day 57, and an 85% median reduction in AKs, according to Dr. Rosen.

With two different concentrations of ingenol mebutate likely to be approved for application at different sites, physicians will need to remain vigilant regarding possible dispensing errors or patient misuse, he said.

Imiquimod

While ingenol mebutate's duration of efficacy remains unknown, that is not the case with imiquimod.

The new imiquimod 3.75% cream (Zyclara), approved last year for treatment of AKs, provides clear benefits over the older 5% formulation in terms of convenience, and with comparable efficacy.

Instead of the traditional 16 weeks of therapy, the 3.75% cream is used daily for 2 weeks, followed by a 2-week rest, then another 2 weeks of therapy, for a total 6-week treatment course. And the imiquimod 3.75% cream is approved for treatment of the full face or balding scalp, unlike imiquimod 5%, whose approved indication is limited to a much smaller area of 25 cm², Dr. Rosen said.

In the pivotal trial for imiquimod 3.75%, 160 treated patients showed a complete clearance rate of 35.6% and a median 81.8% reduction in AKs 8 weeks after the final treatment. That is near-identical to the 83.3% reduction noted in an earlier trial of 215 patients treated with imiquimod 5%.

Dr. Rosen said field therapy makes sound sense in patients with multiple AKs in the same area of the skin.

"When you have a patient with [a lot of] AKs, then all the skin in between those AKs is no more normal than the AK skin; it just hasn’t manifest yet. That’s where field therapy comes in," he explained.

As much as he likes field therapy, though, Dr. Rosen stressed that the emerging new paradigm for treatment of patients with multiple AKs is combination therapy. This can take the form of either a field therapy followed by individual lesion-directed therapy such as cryotherapy, or lesion-directed therapy followed by a field therapy. There are numerous possible combinations. Insurance reimbursement can be a problem for now, but payers will eventually have to come around to the new paradigm.

"The bottom line is for every study where field therapy is combined with lesion-directed therapy or with another field therapy, the combination proved superior to monotherapy," Dr. Rosen said. "It's a little more work, but in the end I think it's probably the best thing for your patient."

Other Agents in the AK Pipeline

AK remains an active target for new drug development. Among the wide range of drugs in the developmental pipeline, albeit still years away from the marketplace, are:

Resiquimod and sotirimod. These are the most promising of the more than 1,000 known analogues of imiquimod. Like the parent compound, they work via immune upregulation, said Dr. Rosen.

Betulin. A triterpene isolated from the extract of birch bark. It eliminates actinic keratoses through cytotoxicity.

Perillyl alcohol. A monoterpene isolated from essential oils of peppermint, spearmint, lavender, and other plants. Its mechanism of action involves induction of apoptosis in rapidly dividing cells without affecting normal cells.

Difluoromethylornithine. Irreversibly inhibits ornithine decarboxylase, which regulates cell division. DFMO is already marketed in a topical formulation for the treatment of facial hirsutism, and as an injectable drug for treatment of African trypanosomiasis.

Afamelanotide. This synthetic analogue of melanocyte-stimulating hormone is under development as a treatment for a diverse collection of skin diseases, including polymorphous light eruption, solar urticaria, and squamous cell carcinoma, as well as AKs.

T4 endonuclease V. This drug enhances repair of UV-induced DNA damage. "It might help prevent future AKs, but not existing ones," Dr. Rosen said.

Why does AK therapy remain such a busy area of new drug development? Simple: A substantial portion of the public continues to be casual about sun protection or disregards it altogether, and with the graying of the baby boomer generation, AKs are more common than ever, he said.

"Everybody in Texas has AKs, including me. I just found one on my hand, and now I need to go treat it," he said.

Dr. Rosen is on the speaker's bureau for Graceway and is a consultant to Graceway and Leo Pharmaceuticals. SDEF and this news organization are owned by Elsevier.