Michele G. Sullivan

Major Finding: Compared with saline injections, hyaluronic injections eased pain and improved function in 22% more patients.

Data Source: A double-blinded randomized controlled trial of 306 patients with knee osteoarthritis.

Disclosures: The study was supported by Tedec Meiji Farma SA. Dr. Navarro-Sarabia and coauthors received research funds from the company as study investigators. Two coauthors are Tedec Meiji Farma SA employees.

Repeated intra-articular injections of hyaluronic acid appear to lessen pain and improve function in knee osteoarthritis between treatment cycles, and for up to a year later.

The 40-month AMELIA (Osteoarthritis Modifying Effects of Long-Term Intra-Articular Adant) project found that, compared with those getting saline as a placebo injection, patients who got the treatment were 22% more likely to experience a clinical response – a 50% or greater improvement in pain or function (80% vs. 66%; risk ratio 1.22).

However, wrote Dr. Federico Navarro-Sarabia and his colleagues, the study could not determine why the improvement persisted as long as it did after treatments stopped.

“In this regard, it is not possible to establish whether this carry-over effect reflects a true disease remission or just a modification of the natural course of the disease,” the investigators wrote (Ann. Rheum. Dis. 2011 Aug. 17 [doi: 10.1136/ard.2011.152017]).

AMELIA comprised 306 patients with knee osteoarthritis. They were randomized to four cycles of five weekly injections. The treatment groups received 2.5 mL 1% sodium hyaluronate derived from Streptococcus zooepidemicus. The placebo group received saline injections. Patients and evaluators were both blinded to the treatments by using a blinded evaluator and an unblinded investigator to administer the injections.

Follow-up occurred during the 6 months after cycles 1 and 2; and 1 year after cycles 3 and 4. Patients were allowed to use aspirin or paracetamol, and short durations of nonsteroidal anti-inflammatories. “However, for 24 h and 1 week before efficacy evaluation, patients were required to abstain from any paracetamol or NSAID, respectively,” the researchers wrote. No corticosteroid injections were allowed in the treated knee throughout the entire study.

The patients were mostly women (87%), with a mean age of 63 years. The mean body mass index was 28 (kg/m

Of the 306 randomized, 109 in the treatment group and 94 in the placebo group completed the entire study. In the treatment group, discontinuation was due to lack of efficacy (8), patient decision (12), adverse events (12), and investigator decision (1). The rest were lost to follow-up or left for other reasons. In the placebo group, reasons were lack of efficacy (19), patient decision (13), adverse events (16), and investigator decision (1). The rest were lost to follow-up or left for other reasons. Outcomes were assessed in an intent-to-treat analysis.

At the end of the 40-month study period, 22% more treated patients than placebo patients were judged responders according to the Osteoarthritis Research Society International 2004 criteria – a significant difference.

However, the number of responders in the treatment group progressively increased after each cycle, from 71% after the first cycle to 80% after the last cycle. Response rates in the placebo group remained stable throughout the study (68% after the first cycle and 66% after the last cycle).

The chances of response seemed to increase as the study progressed, the authors noted. Among the nonresponders in the treatment group, 54% became responders later on. Similarly, 38% of the nonresponders in the placebo group eventually became responders.

The high placebo response is not an unusual finding in osteoarthritis trials, said Dr. Navarro-Sarabi of Hospital Universitario Virgen Macarena, Seville, Spain, and coauthors.

“In AMELIA, however, the success of the study was in fact accentuated by the high placebo efficacy detected, making the results found [80% vs. 68%] even more clinically meaningful and remarkable.”

Most of the patients (71% of each group) used either an NSAID or paracetamol as a rescue medication during the study. Among the 48% who took paracetamol over the study's course, the mean daily dose declined by 27% in the treatment group and 4% in the placebo group.

Twenty-nine adverse events occurred (15 in the treatment group and 14 in the placebo group), among 22 patients (11 in each group). These included allergic reaction (three in each treatment group), bleeding and pain at the injection site, arthralgia, and other events.

View on the News

Nonresponders Become Responders

I think this is a valuable study. It adds important information on the use of hyaluronic acid injections for osteoarthritis of the knee.

▸ First, under controlled conditions with a saline control parallel group, a series of four courses of repeat series of injections can provide significantly greater benefit than in the control group.

▸ Second, that the repeat series of injections were safe with this bacteria-derived product; there was no increase in adverse events.

▸ Third – which is a new finding to my knowledge – is that there is a subset of patients who don't respond to the initial series of injections but who did respond to repeat series of injections.

▸ Fourth – this is the first controlled study to my knowledge that has demonstrated benefit lasting for at least a year following the repeated series of injections.

Statistically, they used the OMERACT-OARSI responder criteria, a robust technique that separates responders and nonresponders.

This is the kind of study that reinforces the way I practice and may even change it. If I have someone with only a borderline response to the first injections, I now might give it a second try.

One thing I do question is the dropout rate. With a dropout rate of 27% in the treatment group and 39% in the saline group, you wonder if the significance of the findings would change if they had completed the trial.

ROY ALTMAN, M.D., is professor of rheumatology and immunology at the University of California, Los Angeles. He reported having no financial relationship to disclose relevant to Adant. Dr. Altman said that he consults for Ferring, Fidia, Novozyme, and Smith & Nephew/Q-Med, all of which make other hyaluronic acid products.

Vitals

Major Finding: Compared with saline injections, hyaluronic injections eased pain and improved function in 22% more patients.

Data Source: A double-blinded randomized controlled trial of 306 patients with knee osteoarthritis.

Disclosures: The study was supported by Tedec Meiji Farma SA. Dr. Navarro-Sarabia and coauthors received research funds from the company as study investigators. Two coauthors are Tedec Meiji Farma SA employees.

Repeated intra-articular injections of hyaluronic acid appear to lessen pain and improve function in knee osteoarthritis between treatment cycles, and for up to a year later.

The 40-month AMELIA (Osteoarthritis Modifying Effects of Long-Term Intra-Articular Adant) project found that, compared with those getting saline as a placebo injection, patients who got the treatment were 22% more likely to experience a clinical response – a 50% or greater improvement in pain or function (80% vs. 66%; risk ratio 1.22).

However, wrote Dr. Federico Navarro-Sarabia and his colleagues, the study could not determine why the improvement persisted as long as it did after treatments stopped.

“In this regard, it is not possible to establish whether this carry-over effect reflects a true disease remission or just a modification of the natural course of the disease,” the investigators wrote (Ann. Rheum. Dis. 2011 Aug. 17 [doi: 10.1136/ard.2011.152017]).

AMELIA comprised 306 patients with knee osteoarthritis. They were randomized to four cycles of five weekly injections. The treatment groups received 2.5 mL 1% sodium hyaluronate derived from Streptococcus zooepidemicus. The placebo group received saline injections. Patients and evaluators were both blinded to the treatments by using a blinded evaluator and an unblinded investigator to administer the injections.

Follow-up occurred during the 6 months after cycles 1 and 2; and 1 year after cycles 3 and 4. Patients were allowed to use aspirin or paracetamol, and short durations of nonsteroidal anti-inflammatories. “However, for 24 h and 1 week before efficacy evaluation, patients were required to abstain from any paracetamol or NSAID, respectively,” the researchers wrote. No corticosteroid injections were allowed in the treated knee throughout the entire study.

The patients were mostly women (87%), with a mean age of 63 years. The mean body mass index was 28 (kg/m

Of the 306 randomized, 109 in the treatment group and 94 in the placebo group completed the entire study. In the treatment group, discontinuation was due to lack of efficacy (8), patient decision (12), adverse events (12), and investigator decision (1). The rest were lost to follow-up or left for other reasons. In the placebo group, reasons were lack of efficacy (19), patient decision (13), adverse events (16), and investigator decision (1). The rest were lost to follow-up or left for other reasons. Outcomes were assessed in an intent-to-treat analysis.

At the end of the 40-month study period, 22% more treated patients than placebo patients were judged responders according to the Osteoarthritis Research Society International 2004 criteria – a significant difference.

However, the number of responders in the treatment group progressively increased after each cycle, from 71% after the first cycle to 80% after the last cycle. Response rates in the placebo group remained stable throughout the study (68% after the first cycle and 66% after the last cycle).

The chances of response seemed to increase as the study progressed, the authors noted. Among the nonresponders in the treatment group, 54% became responders later on. Similarly, 38% of the nonresponders in the placebo group eventually became responders.

The high placebo response is not an unusual finding in osteoarthritis trials, said Dr. Navarro-Sarabi of Hospital Universitario Virgen Macarena, Seville, Spain, and coauthors.

“In AMELIA, however, the success of the study was in fact accentuated by the high placebo efficacy detected, making the results found [80% vs. 68%] even more clinically meaningful and remarkable.”

Most of the patients (71% of each group) used either an NSAID or paracetamol as a rescue medication during the study. Among the 48% who took paracetamol over the study's course, the mean daily dose declined by 27% in the treatment group and 4% in the placebo group.

Twenty-nine adverse events occurred (15 in the treatment group and 14 in the placebo group), among 22 patients (11 in each group). These included allergic reaction (three in each treatment group), bleeding and pain at the injection site, arthralgia, and other events.

View on the News

Nonresponders Become Responders

I think this is a valuable study. It adds important information on the use of hyaluronic acid injections for osteoarthritis of the knee.

▸ First, under controlled conditions with a saline control parallel group, a series of four courses of repeat series of injections can provide significantly greater benefit than in the control group.

▸ Second, that the repeat series of injections were safe with this bacteria-derived product; there was no increase in adverse events.

▸ Third – which is a new finding to my knowledge – is that there is a subset of patients who don't respond to the initial series of injections but who did respond to repeat series of injections.

▸ Fourth – this is the first controlled study to my knowledge that has demonstrated benefit lasting for at least a year following the repeated series of injections.

Statistically, they used the OMERACT-OARSI responder criteria, a robust technique that separates responders and nonresponders.

This is the kind of study that reinforces the way I practice and may even change it. If I have someone with only a borderline response to the first injections, I now might give it a second try.

One thing I do question is the dropout rate. With a dropout rate of 27% in the treatment group and 39% in the saline group, you wonder if the significance of the findings would change if they had completed the trial.

ROY ALTMAN, M.D., is professor of rheumatology and immunology at the University of California, Los Angeles. He reported having no financial relationship to disclose relevant to Adant. Dr. Altman said that he consults for Ferring, Fidia, Novozyme, and Smith & Nephew/Q-Med, all of which make other hyaluronic acid products.

Vitals

Major Finding: Compared with saline injections, hyaluronic injections eased pain and improved function in 22% more patients.

Data Source: A double-blinded randomized controlled trial of 306 patients with knee osteoarthritis.

Disclosures: The study was supported by Tedec Meiji Farma SA. Dr. Navarro-Sarabia and coauthors received research funds from the company as study investigators. Two coauthors are Tedec Meiji Farma SA employees.

Repeated intra-articular injections of hyaluronic acid appear to lessen pain and improve function in knee osteoarthritis between treatment cycles, and for up to a year later.

The 40-month AMELIA (Osteoarthritis Modifying Effects of Long-Term Intra-Articular Adant) project found that, compared with those getting saline as a placebo injection, patients who got the treatment were 22% more likely to experience a clinical response – a 50% or greater improvement in pain or function (80% vs. 66%; risk ratio 1.22).

However, wrote Dr. Federico Navarro-Sarabia and his colleagues, the study could not determine why the improvement persisted as long as it did after treatments stopped.

“In this regard, it is not possible to establish whether this carry-over effect reflects a true disease remission or just a modification of the natural course of the disease,” the investigators wrote (Ann. Rheum. Dis. 2011 Aug. 17 [doi: 10.1136/ard.2011.152017]).

AMELIA comprised 306 patients with knee osteoarthritis. They were randomized to four cycles of five weekly injections. The treatment groups received 2.5 mL 1% sodium hyaluronate derived from Streptococcus zooepidemicus. The placebo group received saline injections. Patients and evaluators were both blinded to the treatments by using a blinded evaluator and an unblinded investigator to administer the injections.

Follow-up occurred during the 6 months after cycles 1 and 2; and 1 year after cycles 3 and 4. Patients were allowed to use aspirin or paracetamol, and short durations of nonsteroidal anti-inflammatories. “However, for 24 h and 1 week before efficacy evaluation, patients were required to abstain from any paracetamol or NSAID, respectively,” the researchers wrote. No corticosteroid injections were allowed in the treated knee throughout the entire study.

The patients were mostly women (87%), with a mean age of 63 years. The mean body mass index was 28 (kg/m

Of the 306 randomized, 109 in the treatment group and 94 in the placebo group completed the entire study. In the treatment group, discontinuation was due to lack of efficacy (8), patient decision (12), adverse events (12), and investigator decision (1). The rest were lost to follow-up or left for other reasons. In the placebo group, reasons were lack of efficacy (19), patient decision (13), adverse events (16), and investigator decision (1). The rest were lost to follow-up or left for other reasons. Outcomes were assessed in an intent-to-treat analysis.

At the end of the 40-month study period, 22% more treated patients than placebo patients were judged responders according to the Osteoarthritis Research Society International 2004 criteria – a significant difference.

However, the number of responders in the treatment group progressively increased after each cycle, from 71% after the first cycle to 80% after the last cycle. Response rates in the placebo group remained stable throughout the study (68% after the first cycle and 66% after the last cycle).

The chances of response seemed to increase as the study progressed, the authors noted. Among the nonresponders in the treatment group, 54% became responders later on. Similarly, 38% of the nonresponders in the placebo group eventually became responders.

The high placebo response is not an unusual finding in osteoarthritis trials, said Dr. Navarro-Sarabi of Hospital Universitario Virgen Macarena, Seville, Spain, and coauthors.

“In AMELIA, however, the success of the study was in fact accentuated by the high placebo efficacy detected, making the results found [80% vs. 68%] even more clinically meaningful and remarkable.”

Most of the patients (71% of each group) used either an NSAID or paracetamol as a rescue medication during the study. Among the 48% who took paracetamol over the study's course, the mean daily dose declined by 27% in the treatment group and 4% in the placebo group.

Twenty-nine adverse events occurred (15 in the treatment group and 14 in the placebo group), among 22 patients (11 in each group). These included allergic reaction (three in each treatment group), bleeding and pain at the injection site, arthralgia, and other events.

View on the News

Nonresponders Become Responders

I think this is a valuable study. It adds important information on the use of hyaluronic acid injections for osteoarthritis of the knee.

▸ First, under controlled conditions with a saline control parallel group, a series of four courses of repeat series of injections can provide significantly greater benefit than in the control group.

▸ Second, that the repeat series of injections were safe with this bacteria-derived product; there was no increase in adverse events.

▸ Third – which is a new finding to my knowledge – is that there is a subset of patients who don't respond to the initial series of injections but who did respond to repeat series of injections.

▸ Fourth – this is the first controlled study to my knowledge that has demonstrated benefit lasting for at least a year following the repeated series of injections.

Statistically, they used the OMERACT-OARSI responder criteria, a robust technique that separates responders and nonresponders.

This is the kind of study that reinforces the way I practice and may even change it. If I have someone with only a borderline response to the first injections, I now might give it a second try.

One thing I do question is the dropout rate. With a dropout rate of 27% in the treatment group and 39% in the saline group, you wonder if the significance of the findings would change if they had completed the trial.

ROY ALTMAN, M.D., is professor of rheumatology and immunology at the University of California, Los Angeles. He reported having no financial relationship to disclose relevant to Adant. Dr. Altman said that he consults for Ferring, Fidia, Novozyme, and Smith & Nephew/Q-Med, all of which make other hyaluronic acid products.

Vitals

Major Finding: All (24) lactating women with Raynaud's of the nipple were initially diagnosed as having a fungal breast infection.

Data Source: A retrospective review of 86 lactating women with a complaint of nipple pain; the cases were accrued from 2004 to 2010 in a single medical center.

Disclosures: Dr. Fullerton Stone had no financial disclosures.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Twenty women participated in a follow-up survey. Most (15, 75%) also reported that they had cold sensitivity or color changes in their hands and feet.

Two reported having been diagnosed with an autoimmune disease – either lupus or Sjögren's syndrome, and two reported having had a breast cyst removed.

They also described the pain they experienced during a Raynaud's episode of the nipple.

All said the pain continued throughout breastfeeding; 25% said that the pain increased during the beginning of lactation. Most, however, (75%) said the pain occurred before, during, and after breastfeeding.

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

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

Raynaud's is usually described as moderate sharp, shocking-type, or throbbing pain before, during, and after nursing.

As is typically observed with Raynaud's of the hands and feet, there is a color change that signifies the vasoconstriction characteristic of the disorder.

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

Major Finding: All (24) lactating women with Raynaud's of the nipple were initially diagnosed as having a fungal breast infection.

Data Source: A retrospective review of 86 lactating women with a complaint of nipple pain; the cases were accrued from 2004 to 2010 in a single medical center.

Disclosures: Dr. Fullerton Stone had no financial disclosures.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Twenty women participated in a follow-up survey. Most (15, 75%) also reported that they had cold sensitivity or color changes in their hands and feet.

Two reported having been diagnosed with an autoimmune disease – either lupus or Sjögren's syndrome, and two reported having had a breast cyst removed.

They also described the pain they experienced during a Raynaud's episode of the nipple.

All said the pain continued throughout breastfeeding; 25% said that the pain increased during the beginning of lactation. Most, however, (75%) said the pain occurred before, during, and after breastfeeding.

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

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

Raynaud's is usually described as moderate sharp, shocking-type, or throbbing pain before, during, and after nursing.

As is typically observed with Raynaud's of the hands and feet, there is a color change that signifies the vasoconstriction characteristic of the disorder.

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

Major Finding: All (24) lactating women with Raynaud's of the nipple were initially diagnosed as having a fungal breast infection.

Data Source: A retrospective review of 86 lactating women with a complaint of nipple pain; the cases were accrued from 2004 to 2010 in a single medical center.

Disclosures: Dr. Fullerton Stone had no financial disclosures.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Twenty women participated in a follow-up survey. Most (15, 75%) also reported that they had cold sensitivity or color changes in their hands and feet.

Two reported having been diagnosed with an autoimmune disease – either lupus or Sjögren's syndrome, and two reported having had a breast cyst removed.

They also described the pain they experienced during a Raynaud's episode of the nipple.

All said the pain continued throughout breastfeeding; 25% said that the pain increased during the beginning of lactation. Most, however, (75%) said the pain occurred before, during, and after breastfeeding.

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

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

Raynaud's is usually described as moderate sharp, shocking-type, or throbbing pain before, during, and after nursing.

As is typically observed with Raynaud's of the hands and feet, there is a color change that signifies the vasoconstriction characteristic of the disorder.

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

Major Finding: Therapeutic hypothermia for cardiac arrest patients – beginning in the field and completed in a hospital – was associated with good neurologic outcomes in 98% of patients who survived to hospital discharge.

Data Source: A 4-year prospective study of 140 patients with out-of-hospital cardiac arrest.

Disclosures: The study was sponsored by the Minneapolis Heart Institute Foundation. None of the authors declared any financial disclosures.

A protocol of in-field cooling quickly followed by rapid in-hospital hypothermia positively affected neurologic outcomes in patients with cardiac arrest – even among the elderly and those with non–ventricular fibrillation arrest and cardiogenic shock.

In a prospective study of 140 patients, 56% survived to hospital discharge. Of these, 92% had positive neurologic outcomes, compared with 77% of survivors before the hospital developed its integrated hypothermia program, wrote Dr. Michael Mooney and his colleagues (Circulation 2011 July 11 [doi:10.1161/circulationaha.110.986257]).

The study also determined that each 1-hour delay in initiating hypothermia among out-of-hospital cardiac arrest decreased the chance of survival by 20%. Therefore, the authors wrote, “it is recommended that therapeutic hypothermia protocols should include a prehospital cooling component. Education and resources should be directed toward emergency medical services and community hospitals to ensure execution of the simple but seemingly effective practice of initiating cooling with ice packs immediately on return of spontaneous circulation.”

Dr. Mooney, director of the therapeutic hypothermia program at the Minneapolis Heart Institute, and his colleagues tracked 140 patients with out-of-hospital cardiac arrest during 2006-2009. All patients remained unresponsive despite the return of spontaneous circulation. They were all treated according to the hospital's 2006 “Cool It” initiative – a multidisciplinary care system that allows EMS personnel to begin the cooling procedure after circulation returns and stresses rapid transfer to a hospital capable of therapeutic cooling.

The procedure begins with cardiac arrest guidelines established by the American Heart Association, followed by noninvasive body cooling. Ice packs are placed at the patient's groin, head, neck, and chest during the first phase of management and transport to a Minneapolis Heart Institute–affiliated hospital.

As soon as EMS identifies a candidate patient, the complementary hospital program kicks into gear. When a patient arrives, a cardiologist and intensivist are ready to implement the standardized therapeutic cooling protocol; if the patient arrives at a nonaffiliate hospital, the emergency department staff initiates the procedure and then transfers the patient to a facility capable of complete therapeutic cooling.

The target body temperature is 33° C. After 24 hours, rewarming proceeds at a rate of 0.5° C/hour until the core temperature reaches 37° C – usually 8 hours.

The mean age of the 140 patients followed was 62 years, with 30 being older than 75 years. Most (102) had ventricular fibrillation or tachycardia; other presenting factors included asystole or pulseless electrical activity (32), ST-segment myocardial infarction (68), and cardiogenic shock (61). EMS personnel initiated some kind of cooling in 43% of the patients.

Most (75%) were taken to a hospital not equipped to administer therapeutic cooling and were transferred to one of the target facilities; the mean transfer distance was 56 miles, although some traveled up to 173 miles. The median time from return of spontaneous circulation to in-hospital cooling was 117 minutes.

Invasive cardiac interventions were performed in most of the patients, with angiography in 101 and percutaneous coronary intervention in 56.

Of the entire cohort, 78 patients (56%) survived to discharge. Of these 78 survivors, 72 (92%) had a good neurologic outcome, defined as a Cerebral Performance Category score of 1 (good) or 2 (moderate disability). Mortality and poor neurologic outcome were significantly related to advanced age (more than 75 years), asystole, or pulseless electrical activity, and cardiogenic shock.

Survival rates were not significantly different among those who arrived at a hypothermia treatment facility and those who did not (52% vs. 57%).

Two other significant prognostic factors were time between arrest to the return of spontaneous circulation and time of returned circulation to application of therapeutic cooling. A total of 36% of those with a circulatory down time of more than 30 minutes survived to hospital discharge. When therapeutic cooling began more than 2.5 hours after circulation returned, patients were 65% less likely to survive.

“When modeled continuously, the relative hazard estimate for a 1-hour increase in time from return of spontaneous circulation to first cooling was 1.20, indicating that for every 1 hour in delay to initiation of cooling, the risk of death increased by 20%,” the authors wrote.

Over the study period, the authors also tracked their progress in time to cooling time. The median time from circulatory return to target temperature improved from 345 minutes to 258 minutes. The median time from circulatory return to first cooling shortened by 2 hours, “reflecting increased efforts to initiate early surface cooling,” the authors said.

“Through ongoing education and outreach, the proportion of cases receiving some cooling before arrival at [a therapeutic cooling facility] has risen consistently and dramatically, from [6% in year 1 to 69% in year 4],” they noted.

Major Finding: Therapeutic hypothermia for cardiac arrest patients – beginning in the field and completed in a hospital – was associated with good neurologic outcomes in 98% of patients who survived to hospital discharge.

Data Source: A 4-year prospective study of 140 patients with out-of-hospital cardiac arrest.

Disclosures: The study was sponsored by the Minneapolis Heart Institute Foundation. None of the authors declared any financial disclosures.

A protocol of in-field cooling quickly followed by rapid in-hospital hypothermia positively affected neurologic outcomes in patients with cardiac arrest – even among the elderly and those with non–ventricular fibrillation arrest and cardiogenic shock.

In a prospective study of 140 patients, 56% survived to hospital discharge. Of these, 92% had positive neurologic outcomes, compared with 77% of survivors before the hospital developed its integrated hypothermia program, wrote Dr. Michael Mooney and his colleagues (Circulation 2011 July 11 [doi:10.1161/circulationaha.110.986257]).

The study also determined that each 1-hour delay in initiating hypothermia among out-of-hospital cardiac arrest decreased the chance of survival by 20%. Therefore, the authors wrote, “it is recommended that therapeutic hypothermia protocols should include a prehospital cooling component. Education and resources should be directed toward emergency medical services and community hospitals to ensure execution of the simple but seemingly effective practice of initiating cooling with ice packs immediately on return of spontaneous circulation.”

Dr. Mooney, director of the therapeutic hypothermia program at the Minneapolis Heart Institute, and his colleagues tracked 140 patients with out-of-hospital cardiac arrest during 2006-2009. All patients remained unresponsive despite the return of spontaneous circulation. They were all treated according to the hospital's 2006 “Cool It” initiative – a multidisciplinary care system that allows EMS personnel to begin the cooling procedure after circulation returns and stresses rapid transfer to a hospital capable of therapeutic cooling.

The procedure begins with cardiac arrest guidelines established by the American Heart Association, followed by noninvasive body cooling. Ice packs are placed at the patient's groin, head, neck, and chest during the first phase of management and transport to a Minneapolis Heart Institute–affiliated hospital.

As soon as EMS identifies a candidate patient, the complementary hospital program kicks into gear. When a patient arrives, a cardiologist and intensivist are ready to implement the standardized therapeutic cooling protocol; if the patient arrives at a nonaffiliate hospital, the emergency department staff initiates the procedure and then transfers the patient to a facility capable of complete therapeutic cooling.

The target body temperature is 33° C. After 24 hours, rewarming proceeds at a rate of 0.5° C/hour until the core temperature reaches 37° C – usually 8 hours.

The mean age of the 140 patients followed was 62 years, with 30 being older than 75 years. Most (102) had ventricular fibrillation or tachycardia; other presenting factors included asystole or pulseless electrical activity (32), ST-segment myocardial infarction (68), and cardiogenic shock (61). EMS personnel initiated some kind of cooling in 43% of the patients.

Most (75%) were taken to a hospital not equipped to administer therapeutic cooling and were transferred to one of the target facilities; the mean transfer distance was 56 miles, although some traveled up to 173 miles. The median time from return of spontaneous circulation to in-hospital cooling was 117 minutes.

Invasive cardiac interventions were performed in most of the patients, with angiography in 101 and percutaneous coronary intervention in 56.

Of the entire cohort, 78 patients (56%) survived to discharge. Of these 78 survivors, 72 (92%) had a good neurologic outcome, defined as a Cerebral Performance Category score of 1 (good) or 2 (moderate disability). Mortality and poor neurologic outcome were significantly related to advanced age (more than 75 years), asystole, or pulseless electrical activity, and cardiogenic shock.

Survival rates were not significantly different among those who arrived at a hypothermia treatment facility and those who did not (52% vs. 57%).

Two other significant prognostic factors were time between arrest to the return of spontaneous circulation and time of returned circulation to application of therapeutic cooling. A total of 36% of those with a circulatory down time of more than 30 minutes survived to hospital discharge. When therapeutic cooling began more than 2.5 hours after circulation returned, patients were 65% less likely to survive.

“When modeled continuously, the relative hazard estimate for a 1-hour increase in time from return of spontaneous circulation to first cooling was 1.20, indicating that for every 1 hour in delay to initiation of cooling, the risk of death increased by 20%,” the authors wrote.

Over the study period, the authors also tracked their progress in time to cooling time. The median time from circulatory return to target temperature improved from 345 minutes to 258 minutes. The median time from circulatory return to first cooling shortened by 2 hours, “reflecting increased efforts to initiate early surface cooling,” the authors said.

“Through ongoing education and outreach, the proportion of cases receiving some cooling before arrival at [a therapeutic cooling facility] has risen consistently and dramatically, from [6% in year 1 to 69% in year 4],” they noted.

Major Finding: Therapeutic hypothermia for cardiac arrest patients – beginning in the field and completed in a hospital – was associated with good neurologic outcomes in 98% of patients who survived to hospital discharge.

Data Source: A 4-year prospective study of 140 patients with out-of-hospital cardiac arrest.

Disclosures: The study was sponsored by the Minneapolis Heart Institute Foundation. None of the authors declared any financial disclosures.

A protocol of in-field cooling quickly followed by rapid in-hospital hypothermia positively affected neurologic outcomes in patients with cardiac arrest – even among the elderly and those with non–ventricular fibrillation arrest and cardiogenic shock.

In a prospective study of 140 patients, 56% survived to hospital discharge. Of these, 92% had positive neurologic outcomes, compared with 77% of survivors before the hospital developed its integrated hypothermia program, wrote Dr. Michael Mooney and his colleagues (Circulation 2011 July 11 [doi:10.1161/circulationaha.110.986257]).

The study also determined that each 1-hour delay in initiating hypothermia among out-of-hospital cardiac arrest decreased the chance of survival by 20%. Therefore, the authors wrote, “it is recommended that therapeutic hypothermia protocols should include a prehospital cooling component. Education and resources should be directed toward emergency medical services and community hospitals to ensure execution of the simple but seemingly effective practice of initiating cooling with ice packs immediately on return of spontaneous circulation.”

Dr. Mooney, director of the therapeutic hypothermia program at the Minneapolis Heart Institute, and his colleagues tracked 140 patients with out-of-hospital cardiac arrest during 2006-2009. All patients remained unresponsive despite the return of spontaneous circulation. They were all treated according to the hospital's 2006 “Cool It” initiative – a multidisciplinary care system that allows EMS personnel to begin the cooling procedure after circulation returns and stresses rapid transfer to a hospital capable of therapeutic cooling.

The procedure begins with cardiac arrest guidelines established by the American Heart Association, followed by noninvasive body cooling. Ice packs are placed at the patient's groin, head, neck, and chest during the first phase of management and transport to a Minneapolis Heart Institute–affiliated hospital.

As soon as EMS identifies a candidate patient, the complementary hospital program kicks into gear. When a patient arrives, a cardiologist and intensivist are ready to implement the standardized therapeutic cooling protocol; if the patient arrives at a nonaffiliate hospital, the emergency department staff initiates the procedure and then transfers the patient to a facility capable of complete therapeutic cooling.

The target body temperature is 33° C. After 24 hours, rewarming proceeds at a rate of 0.5° C/hour until the core temperature reaches 37° C – usually 8 hours.

The mean age of the 140 patients followed was 62 years, with 30 being older than 75 years. Most (102) had ventricular fibrillation or tachycardia; other presenting factors included asystole or pulseless electrical activity (32), ST-segment myocardial infarction (68), and cardiogenic shock (61). EMS personnel initiated some kind of cooling in 43% of the patients.

Most (75%) were taken to a hospital not equipped to administer therapeutic cooling and were transferred to one of the target facilities; the mean transfer distance was 56 miles, although some traveled up to 173 miles. The median time from return of spontaneous circulation to in-hospital cooling was 117 minutes.

Invasive cardiac interventions were performed in most of the patients, with angiography in 101 and percutaneous coronary intervention in 56.

Of the entire cohort, 78 patients (56%) survived to discharge. Of these 78 survivors, 72 (92%) had a good neurologic outcome, defined as a Cerebral Performance Category score of 1 (good) or 2 (moderate disability). Mortality and poor neurologic outcome were significantly related to advanced age (more than 75 years), asystole, or pulseless electrical activity, and cardiogenic shock.

Survival rates were not significantly different among those who arrived at a hypothermia treatment facility and those who did not (52% vs. 57%).

Two other significant prognostic factors were time between arrest to the return of spontaneous circulation and time of returned circulation to application of therapeutic cooling. A total of 36% of those with a circulatory down time of more than 30 minutes survived to hospital discharge. When therapeutic cooling began more than 2.5 hours after circulation returned, patients were 65% less likely to survive.

“When modeled continuously, the relative hazard estimate for a 1-hour increase in time from return of spontaneous circulation to first cooling was 1.20, indicating that for every 1 hour in delay to initiation of cooling, the risk of death increased by 20%,” the authors wrote.

Over the study period, the authors also tracked their progress in time to cooling time. The median time from circulatory return to target temperature improved from 345 minutes to 258 minutes. The median time from circulatory return to first cooling shortened by 2 hours, “reflecting increased efforts to initiate early surface cooling,” the authors said.

“Through ongoing education and outreach, the proportion of cases receiving some cooling before arrival at [a therapeutic cooling facility] has risen consistently and dramatically, from [6% in year 1 to 69% in year 4],” they noted.

Major Finding: Heart attacks are significantly more likely than are strokes to occur in family clusters, with 21% of heart attack patients having at least one similarly affected sibling, compared with 8% of stroke patients.

Data Source: A subanalysis of more than 91,000 subjects who had experienced either a heart attack or stroke.

Disclosures: The study was primarily sponsored by the U.K. Medical Research Council. None of the authors had any financial disclosures.

People whose mother and father have both had a myocardial infarction are six times more likely to have one than are those without a parental history, according to a large, population-based study.

Strokes, on the other hand, do not seem related to genetic predisposition.

Because most risk-estimation models include both cardiovascular and cerebrovascular factors, the findings could influence the way such risks are calculated, Dr. Peter Rothwell and colleagues wrote.

“The way physicians predict the odds of a healthy person suffering a heart attack or stroke needs refining,” Dr. Rothwell, senior author and professor of neurology at Oxford (England) University, said in a press statement. “Currently, most risk models lump a patient's family history of stroke and heart attack together. We probably should model family history of stroke and heart attack separately in the future.”

Dr. Rothwell and his coauthors reported a subanalysis of the Oxford Vascular Study (OXVASC), a population-based study of transient ischemic attacks, strokes, acute coronary syndrome (ACS), and acute peripheral vascular events in 91,106 people. They focused on 1,921 patients who had ACS or stroke and had information on cardiovascular and cerebrovascular events in both their parents and siblings. Among these, 906 had experienced an ACS and 1,015 some kind of cerebrovascular event (Circ. Cardiovasc. Genet. 2011 July 26 [doi:10.1161/CIRCGENETICS. 110.959114]).

The authors found clusters of ACS in many families: 21% of patients (191) had at least one sibling who had had an MI and 7% (64) had at least two siblings with the event. There was also a strong parental influence. Nearly a third of patients (277) had one parent with a positive history of MI and in 5% (47) both parents had a positive history.

The associations were not as strong in patients with cerebrovascular events. Of these patients, 8% (82) had least one sibling with a stroke history and 1% (14) at least two siblings with a history. Twenty-one percent (216) of patients had one parent with a positive history, while 2% (21) had two parents with a positive history.

When the investigators considered the proband families, they found significant relationships between the number of affected parents and the number of affected siblings. The ACS patients' 2,601 siblings were 48% more likely to have had an ACS when one parent had a positive MI history and six times more likely when both parents did.

These associations were not significant among stroke patients, however. Among the 2,692 siblings of the stroke patients, there were no significant relationships with parental history of stroke (either one or both parents).

The study plays into the knowledge that atherosclerosis and plaque – the main risk factors of MI – are more heritable than thromboembolism and small-vessel disease, which are the main risk factors for stroke.

“Coronary disease may be a better indicator of generalized atherosclerosis than stroke, and therefore family history of MI may represent a greater risk factor for MI and stroke, whereas family history of stroke is not a strong risk factor for MI,” Dr. Rothwell and his associates said.

Nearly a third of ACS patients had one parent with a positive history of MI.

Source ©Kativ/iStockphoto

Major Finding: Heart attacks are significantly more likely than are strokes to occur in family clusters, with 21% of heart attack patients having at least one similarly affected sibling, compared with 8% of stroke patients.

Data Source: A subanalysis of more than 91,000 subjects who had experienced either a heart attack or stroke.

Disclosures: The study was primarily sponsored by the U.K. Medical Research Council. None of the authors had any financial disclosures.

People whose mother and father have both had a myocardial infarction are six times more likely to have one than are those without a parental history, according to a large, population-based study.

Strokes, on the other hand, do not seem related to genetic predisposition.

Because most risk-estimation models include both cardiovascular and cerebrovascular factors, the findings could influence the way such risks are calculated, Dr. Peter Rothwell and colleagues wrote.

“The way physicians predict the odds of a healthy person suffering a heart attack or stroke needs refining,” Dr. Rothwell, senior author and professor of neurology at Oxford (England) University, said in a press statement. “Currently, most risk models lump a patient's family history of stroke and heart attack together. We probably should model family history of stroke and heart attack separately in the future.”

Dr. Rothwell and his coauthors reported a subanalysis of the Oxford Vascular Study (OXVASC), a population-based study of transient ischemic attacks, strokes, acute coronary syndrome (ACS), and acute peripheral vascular events in 91,106 people. They focused on 1,921 patients who had ACS or stroke and had information on cardiovascular and cerebrovascular events in both their parents and siblings. Among these, 906 had experienced an ACS and 1,015 some kind of cerebrovascular event (Circ. Cardiovasc. Genet. 2011 July 26 [doi:10.1161/CIRCGENETICS. 110.959114]).

The authors found clusters of ACS in many families: 21% of patients (191) had at least one sibling who had had an MI and 7% (64) had at least two siblings with the event. There was also a strong parental influence. Nearly a third of patients (277) had one parent with a positive history of MI and in 5% (47) both parents had a positive history.

The associations were not as strong in patients with cerebrovascular events. Of these patients, 8% (82) had least one sibling with a stroke history and 1% (14) at least two siblings with a history. Twenty-one percent (216) of patients had one parent with a positive history, while 2% (21) had two parents with a positive history.

When the investigators considered the proband families, they found significant relationships between the number of affected parents and the number of affected siblings. The ACS patients' 2,601 siblings were 48% more likely to have had an ACS when one parent had a positive MI history and six times more likely when both parents did.

These associations were not significant among stroke patients, however. Among the 2,692 siblings of the stroke patients, there were no significant relationships with parental history of stroke (either one or both parents).

The study plays into the knowledge that atherosclerosis and plaque – the main risk factors of MI – are more heritable than thromboembolism and small-vessel disease, which are the main risk factors for stroke.

“Coronary disease may be a better indicator of generalized atherosclerosis than stroke, and therefore family history of MI may represent a greater risk factor for MI and stroke, whereas family history of stroke is not a strong risk factor for MI,” Dr. Rothwell and his associates said.

Nearly a third of ACS patients had one parent with a positive history of MI.

Source ©Kativ/iStockphoto

Major Finding: Heart attacks are significantly more likely than are strokes to occur in family clusters, with 21% of heart attack patients having at least one similarly affected sibling, compared with 8% of stroke patients.

Data Source: A subanalysis of more than 91,000 subjects who had experienced either a heart attack or stroke.

Disclosures: The study was primarily sponsored by the U.K. Medical Research Council. None of the authors had any financial disclosures.

People whose mother and father have both had a myocardial infarction are six times more likely to have one than are those without a parental history, according to a large, population-based study.

Strokes, on the other hand, do not seem related to genetic predisposition.

Because most risk-estimation models include both cardiovascular and cerebrovascular factors, the findings could influence the way such risks are calculated, Dr. Peter Rothwell and colleagues wrote.

“The way physicians predict the odds of a healthy person suffering a heart attack or stroke needs refining,” Dr. Rothwell, senior author and professor of neurology at Oxford (England) University, said in a press statement. “Currently, most risk models lump a patient's family history of stroke and heart attack together. We probably should model family history of stroke and heart attack separately in the future.”

Dr. Rothwell and his coauthors reported a subanalysis of the Oxford Vascular Study (OXVASC), a population-based study of transient ischemic attacks, strokes, acute coronary syndrome (ACS), and acute peripheral vascular events in 91,106 people. They focused on 1,921 patients who had ACS or stroke and had information on cardiovascular and cerebrovascular events in both their parents and siblings. Among these, 906 had experienced an ACS and 1,015 some kind of cerebrovascular event (Circ. Cardiovasc. Genet. 2011 July 26 [doi:10.1161/CIRCGENETICS. 110.959114]).

The authors found clusters of ACS in many families: 21% of patients (191) had at least one sibling who had had an MI and 7% (64) had at least two siblings with the event. There was also a strong parental influence. Nearly a third of patients (277) had one parent with a positive history of MI and in 5% (47) both parents had a positive history.

The associations were not as strong in patients with cerebrovascular events. Of these patients, 8% (82) had least one sibling with a stroke history and 1% (14) at least two siblings with a history. Twenty-one percent (216) of patients had one parent with a positive history, while 2% (21) had two parents with a positive history.

When the investigators considered the proband families, they found significant relationships between the number of affected parents and the number of affected siblings. The ACS patients' 2,601 siblings were 48% more likely to have had an ACS when one parent had a positive MI history and six times more likely when both parents did.

These associations were not significant among stroke patients, however. Among the 2,692 siblings of the stroke patients, there were no significant relationships with parental history of stroke (either one or both parents).

The study plays into the knowledge that atherosclerosis and plaque – the main risk factors of MI – are more heritable than thromboembolism and small-vessel disease, which are the main risk factors for stroke.

“Coronary disease may be a better indicator of generalized atherosclerosis than stroke, and therefore family history of MI may represent a greater risk factor for MI and stroke, whereas family history of stroke is not a strong risk factor for MI,” Dr. Rothwell and his associates said.

Nearly a third of ACS patients had one parent with a positive history of MI.

Source ©Kativ/iStockphoto

Tumor necrosis factor–inhibiting drugs may moderate atherosclerosis progression in patients with rheumatoid arthritis, a prospective study has suggested.

Compared with patients who did not get the drugs, those treated with TNF inhibitors had a 37% lower rate of plaque progression in the common carotid artery, Dr. Jon T. Giles and his colleagues reported in Arthritis & Rheumatism (2011 [doi:10.1002/art.30542]).

"Our observation that TNF-inhibitor treated patients [had a 37% reduction in arterial plaque] provides some human confirmation of a link between cytokines and atherosclerosis," wrote Dr. Giles of New York Presbyterian-Columbia University Medical Center, New York, and his coauthors. "However, it is unclear whether this effect is due to TNF inhibition per se, and is thus a unique effect of the TNF inhibitors, or is a general anti-inflammatory effect."

The study also found a significantly increased rate of progression with glucocorticoid exposure – a relationship that seemed to be attenuated by the concurrent use of statins.

The 3-year study was a subanalysis of the ESCAPE RA (Evaluation of Subclinical Cardiovascular Disease and Predictors of Events in Rheumatoid Arthritis) cohort study, which looked at subclinical cardiovascular disease. This analysis examined intima-medial thickness in the common and internal carotid arteries and the internal carotid artery bulb among 154 patients with rheumatoid arthritis, none of whom had prior cardiovascular disease. All underwent carotid ultrasound at 1 and 3 years.

The patients’ mean age was 59 years at baseline, and they had had rheumatoid arthritis for a mean of 8.5 years. In all, 42% were taking TNF inhibitors and 86% were taking a nonbiologic disease-modifying antirheumatic drug. The mean cumulative prednisone dose was 3.1 grams.

Overall, plaque deposits grew at a median rate of 16 mcm/year in the common carotid artery; 82% showed some level of increase. The median plaque increase in the internal carotid artery was 25 mcm/year; 82% of patients also showed some level of plaque increase in this artery.

At baseline, 38% of patients showed no stenosis in the internal carotid artery due to plaque, 55% showed plaque stenosis of up to 24%, and 7% had plaque stenosis of 35%-50%. There were no patients with arterial plaque stenosis of more than 50%.

Among the 58 patients without plaque at baseline, 8 (14%) showed some new plaque at 3 years – a progression rate of 4 patients per 100 person-years. Among the 96 patients with plaque at baseline, 5% (5) had increased plaque at 3 years – a progression rate of 1.6 patients per 100 person-years. In the remaining 91 patients with plaque at baseline, 89% had the same degree of plaque at 3 years and 6 patients (7%) showed less plaque stenosis, the authors noted.

In a multivariate analysis, two disease characteristics were significantly associated with plaque progression in the common carotid artery: disease duration and TNF-inhibitor use.

The rate of change in common carotid plaque was doubled in the first tertile of disease duration (up to 6 years), compared with the second or third tertiles (7-14 years and more than 14 years). The rate of change was not significantly different from the second to third tertiles of disease duration.

The Framingham risk score did significantly affect plaque change in the group with shortest disease duration, however. The rate of change was significantly higher among those with higher risk scores or diabetes than in those with lower risk scores (33 vs. 20 mcm/year). "In contrast ... progression rates were identical for RA patients with longer-standing disease, regardless of Framingham score," the authors wrote.

Statin therapy exerted a significant, positive effect on plaque progression in those with longer-standing disease. Compared with patients who were not taking a statin at baseline, those who were had significantly less annual progression of plaque (1 vs. 15 mcm/year). Statins exerted no significant effect on patients with the shortest disease duration.

Baseline use of TNF inhibitors reduced the annual progression rate by 37% compared with those not using the drugs at baseline (14 vs. 22 mcm/year). This difference remained significant even after adjusting for demographics, lifestyle characteristics, Framingham score, and other disease characteristics.

In the internal carotid artery, prior glucocorticoid exposure was significantly related to higher annual plaque change. "This association was modified by statin use, as the association of cumulative prednisone exposure with the adjusted average yearly change ... was attenuated, yet remained significant, in participants receiving statins at baseline," the authors noted.

For the internal carotid artery bulb, the authors found four significant predictors of plaque change: hormone replacement therapy, cumulative average swollen joint count, cumulative C-reactive protein level, and age. Neither exposure to TNF inhibitors nor exposure to glucocorticoids was related to plaque progression in the bulb.

C-reactive protein did not exert a linear effect on plaque progression or on the appearance of incident plaque until it reached 12 mg/L or more. This threshold of change was significantly lower in patients with higher Framingham scores or diabetes at baseline (5 mg/L)

The role of statins in modifying progression is complicated, the authors stated. "Notably, statin use was associated with almost no progression of [common carotid plaque] in RA patients with longer disease duration, an observation supporting the use of statins in RA," they said. "Interestingly, however, statin use was not associated with lower [common carotid progression] among participants with earlier disease. This may suggest differing mechanisms for [common carotid plaque] progression in early vs. late disease."

The additional finding that statins attenuated the risk exerted by glucocorticoid exposure "deserves additional study and, short of a confirmatory trial, suggests that statins could be considered in RA patients receiving glucocorticoids."

The ESCAPE RA trial was primarily sponsored by the National Institutes of Health. The subanalysis was sponsored by the American College of Rheumatology Research and Education Foundation. None of the authors reported any financial conflicts.

Tumor necrosis factor–inhibiting drugs may moderate atherosclerosis progression in patients with rheumatoid arthritis, a prospective study has suggested.

Compared with patients who did not get the drugs, those treated with TNF inhibitors had a 37% lower rate of plaque progression in the common carotid artery, Dr. Jon T. Giles and his colleagues reported in Arthritis & Rheumatism (2011 [doi:10.1002/art.30542]).

"Our observation that TNF-inhibitor treated patients [had a 37% reduction in arterial plaque] provides some human confirmation of a link between cytokines and atherosclerosis," wrote Dr. Giles of New York Presbyterian-Columbia University Medical Center, New York, and his coauthors. "However, it is unclear whether this effect is due to TNF inhibition per se, and is thus a unique effect of the TNF inhibitors, or is a general anti-inflammatory effect."

The study also found a significantly increased rate of progression with glucocorticoid exposure – a relationship that seemed to be attenuated by the concurrent use of statins.

The 3-year study was a subanalysis of the ESCAPE RA (Evaluation of Subclinical Cardiovascular Disease and Predictors of Events in Rheumatoid Arthritis) cohort study, which looked at subclinical cardiovascular disease. This analysis examined intima-medial thickness in the common and internal carotid arteries and the internal carotid artery bulb among 154 patients with rheumatoid arthritis, none of whom had prior cardiovascular disease. All underwent carotid ultrasound at 1 and 3 years.

The patients’ mean age was 59 years at baseline, and they had had rheumatoid arthritis for a mean of 8.5 years. In all, 42% were taking TNF inhibitors and 86% were taking a nonbiologic disease-modifying antirheumatic drug. The mean cumulative prednisone dose was 3.1 grams.

Overall, plaque deposits grew at a median rate of 16 mcm/year in the common carotid artery; 82% showed some level of increase. The median plaque increase in the internal carotid artery was 25 mcm/year; 82% of patients also showed some level of plaque increase in this artery.

At baseline, 38% of patients showed no stenosis in the internal carotid artery due to plaque, 55% showed plaque stenosis of up to 24%, and 7% had plaque stenosis of 35%-50%. There were no patients with arterial plaque stenosis of more than 50%.

Among the 58 patients without plaque at baseline, 8 (14%) showed some new plaque at 3 years – a progression rate of 4 patients per 100 person-years. Among the 96 patients with plaque at baseline, 5% (5) had increased plaque at 3 years – a progression rate of 1.6 patients per 100 person-years. In the remaining 91 patients with plaque at baseline, 89% had the same degree of plaque at 3 years and 6 patients (7%) showed less plaque stenosis, the authors noted.

In a multivariate analysis, two disease characteristics were significantly associated with plaque progression in the common carotid artery: disease duration and TNF-inhibitor use.

The rate of change in common carotid plaque was doubled in the first tertile of disease duration (up to 6 years), compared with the second or third tertiles (7-14 years and more than 14 years). The rate of change was not significantly different from the second to third tertiles of disease duration.

The Framingham risk score did significantly affect plaque change in the group with shortest disease duration, however. The rate of change was significantly higher among those with higher risk scores or diabetes than in those with lower risk scores (33 vs. 20 mcm/year). "In contrast ... progression rates were identical for RA patients with longer-standing disease, regardless of Framingham score," the authors wrote.

Statin therapy exerted a significant, positive effect on plaque progression in those with longer-standing disease. Compared with patients who were not taking a statin at baseline, those who were had significantly less annual progression of plaque (1 vs. 15 mcm/year). Statins exerted no significant effect on patients with the shortest disease duration.

Baseline use of TNF inhibitors reduced the annual progression rate by 37% compared with those not using the drugs at baseline (14 vs. 22 mcm/year). This difference remained significant even after adjusting for demographics, lifestyle characteristics, Framingham score, and other disease characteristics.

In the internal carotid artery, prior glucocorticoid exposure was significantly related to higher annual plaque change. "This association was modified by statin use, as the association of cumulative prednisone exposure with the adjusted average yearly change ... was attenuated, yet remained significant, in participants receiving statins at baseline," the authors noted.

For the internal carotid artery bulb, the authors found four significant predictors of plaque change: hormone replacement therapy, cumulative average swollen joint count, cumulative C-reactive protein level, and age. Neither exposure to TNF inhibitors nor exposure to glucocorticoids was related to plaque progression in the bulb.

C-reactive protein did not exert a linear effect on plaque progression or on the appearance of incident plaque until it reached 12 mg/L or more. This threshold of change was significantly lower in patients with higher Framingham scores or diabetes at baseline (5 mg/L)

The role of statins in modifying progression is complicated, the authors stated. "Notably, statin use was associated with almost no progression of [common carotid plaque] in RA patients with longer disease duration, an observation supporting the use of statins in RA," they said. "Interestingly, however, statin use was not associated with lower [common carotid progression] among participants with earlier disease. This may suggest differing mechanisms for [common carotid plaque] progression in early vs. late disease."

The additional finding that statins attenuated the risk exerted by glucocorticoid exposure "deserves additional study and, short of a confirmatory trial, suggests that statins could be considered in RA patients receiving glucocorticoids."

The ESCAPE RA trial was primarily sponsored by the National Institutes of Health. The subanalysis was sponsored by the American College of Rheumatology Research and Education Foundation. None of the authors reported any financial conflicts.

Tumor necrosis factor–inhibiting drugs may moderate atherosclerosis progression in patients with rheumatoid arthritis, a prospective study has suggested.

Compared with patients who did not get the drugs, those treated with TNF inhibitors had a 37% lower rate of plaque progression in the common carotid artery, Dr. Jon T. Giles and his colleagues reported in Arthritis & Rheumatism (2011 [doi:10.1002/art.30542]).

"Our observation that TNF-inhibitor treated patients [had a 37% reduction in arterial plaque] provides some human confirmation of a link between cytokines and atherosclerosis," wrote Dr. Giles of New York Presbyterian-Columbia University Medical Center, New York, and his coauthors. "However, it is unclear whether this effect is due to TNF inhibition per se, and is thus a unique effect of the TNF inhibitors, or is a general anti-inflammatory effect."

The study also found a significantly increased rate of progression with glucocorticoid exposure – a relationship that seemed to be attenuated by the concurrent use of statins.

The 3-year study was a subanalysis of the ESCAPE RA (Evaluation of Subclinical Cardiovascular Disease and Predictors of Events in Rheumatoid Arthritis) cohort study, which looked at subclinical cardiovascular disease. This analysis examined intima-medial thickness in the common and internal carotid arteries and the internal carotid artery bulb among 154 patients with rheumatoid arthritis, none of whom had prior cardiovascular disease. All underwent carotid ultrasound at 1 and 3 years.

The patients’ mean age was 59 years at baseline, and they had had rheumatoid arthritis for a mean of 8.5 years. In all, 42% were taking TNF inhibitors and 86% were taking a nonbiologic disease-modifying antirheumatic drug. The mean cumulative prednisone dose was 3.1 grams.

Overall, plaque deposits grew at a median rate of 16 mcm/year in the common carotid artery; 82% showed some level of increase. The median plaque increase in the internal carotid artery was 25 mcm/year; 82% of patients also showed some level of plaque increase in this artery.

At baseline, 38% of patients showed no stenosis in the internal carotid artery due to plaque, 55% showed plaque stenosis of up to 24%, and 7% had plaque stenosis of 35%-50%. There were no patients with arterial plaque stenosis of more than 50%.

Among the 58 patients without plaque at baseline, 8 (14%) showed some new plaque at 3 years – a progression rate of 4 patients per 100 person-years. Among the 96 patients with plaque at baseline, 5% (5) had increased plaque at 3 years – a progression rate of 1.6 patients per 100 person-years. In the remaining 91 patients with plaque at baseline, 89% had the same degree of plaque at 3 years and 6 patients (7%) showed less plaque stenosis, the authors noted.

In a multivariate analysis, two disease characteristics were significantly associated with plaque progression in the common carotid artery: disease duration and TNF-inhibitor use.

The rate of change in common carotid plaque was doubled in the first tertile of disease duration (up to 6 years), compared with the second or third tertiles (7-14 years and more than 14 years). The rate of change was not significantly different from the second to third tertiles of disease duration.

The Framingham risk score did significantly affect plaque change in the group with shortest disease duration, however. The rate of change was significantly higher among those with higher risk scores or diabetes than in those with lower risk scores (33 vs. 20 mcm/year). "In contrast ... progression rates were identical for RA patients with longer-standing disease, regardless of Framingham score," the authors wrote.

Statin therapy exerted a significant, positive effect on plaque progression in those with longer-standing disease. Compared with patients who were not taking a statin at baseline, those who were had significantly less annual progression of plaque (1 vs. 15 mcm/year). Statins exerted no significant effect on patients with the shortest disease duration.

Baseline use of TNF inhibitors reduced the annual progression rate by 37% compared with those not using the drugs at baseline (14 vs. 22 mcm/year). This difference remained significant even after adjusting for demographics, lifestyle characteristics, Framingham score, and other disease characteristics.

In the internal carotid artery, prior glucocorticoid exposure was significantly related to higher annual plaque change. "This association was modified by statin use, as the association of cumulative prednisone exposure with the adjusted average yearly change ... was attenuated, yet remained significant, in participants receiving statins at baseline," the authors noted.

For the internal carotid artery bulb, the authors found four significant predictors of plaque change: hormone replacement therapy, cumulative average swollen joint count, cumulative C-reactive protein level, and age. Neither exposure to TNF inhibitors nor exposure to glucocorticoids was related to plaque progression in the bulb.

C-reactive protein did not exert a linear effect on plaque progression or on the appearance of incident plaque until it reached 12 mg/L or more. This threshold of change was significantly lower in patients with higher Framingham scores or diabetes at baseline (5 mg/L)

The role of statins in modifying progression is complicated, the authors stated. "Notably, statin use was associated with almost no progression of [common carotid plaque] in RA patients with longer disease duration, an observation supporting the use of statins in RA," they said. "Interestingly, however, statin use was not associated with lower [common carotid progression] among participants with earlier disease. This may suggest differing mechanisms for [common carotid plaque] progression in early vs. late disease."

The additional finding that statins attenuated the risk exerted by glucocorticoid exposure "deserves additional study and, short of a confirmatory trial, suggests that statins could be considered in RA patients receiving glucocorticoids."

The ESCAPE RA trial was primarily sponsored by the National Institutes of Health. The subanalysis was sponsored by the American College of Rheumatology Research and Education Foundation. None of the authors reported any financial conflicts.

Vaccines do not cause autism in children who receive them, the Institute of Medicine has reported in an unprecedented review of medical literature.

"Our review found no tangible, credible evidence to support a conclusion that the MMR vaccine causes autism," Dr. Douglas Barrett, a member of the IOM’s review committee, said in an interview.

Although the scientific evidence against the relationship is solid, he said, it may not be enough to change entrenched ideology about the vaccine’s safety for children.

"This won’t preclude people from worrying about it or making a claim about it, but there is just no science behind those worries. But our charge was to look at the science and hard evidence, and that evidence is not there," he said.

© Yarinca/iStockphoto.com

The committee did, however, establish causal links between seven vaccines and 14 other adverse events, including seizures, inflammation of the brain, fainting, and anaphylaxis.

"Many of those findings support vaccine adverse events that are readily apparent, easily identified, or self-limited, transient conditions," said Dr. Barrett, a professor of pediatrics in the division of immunology, infectious disease, and rheumatology at the University of Florida, Gainesville.

The 18-member IOM Committee to Review Adverse Effects of Vaccines was not directed to make practice recommendations regarding vaccine administration. But, Dr. Barrett said, none of its findings is likely to change any current regimen. "However, that is a question for others to decide," he noted.

The report should be "extraordinarily helpful" to practicing physicians who administer vaccines," he said. "They are asked these questions day in and day out by patients relying on their expert opinion about these purported adverse events. This will provide them with today’s best evidence about whether or not there is an association."

The committee examined both epidemiologic and mechanistic evidence to pinpoint true vaccine-related adverse events – a process that highlighted the clinical importance of this interplay. In reviewing the evidence, the committee divided adverse events into four categories: convincingly supported, favoring acceptance, favoring rejection, and inadequate information to accept or reject.

The IOM asked the committee to consider evidence for 79 purported adverse events related to eight vaccines: MMR, varicella, influenza, hepatitis A, hepatitis B, human papillomavirus, meningococcal, and vaccines that contain diphtheria, tetanus or pertussis components.

The evidence convincingly supported the following associations:

• Disseminated Oka varicella zoster virus (VZV) and Oka VZV viral reactivation with varicella vaccine.

• Measles inclusion body encephalitis with MMR vaccine.

• Febrile seizures with MMR vaccine.

• Hypersensitivity and anaphylaxis with MMR, varicella, influenza, hepatitis B, meningococcal, and tetanus toxoid vaccines.

• Syncope and deltoid bursitis with the injection of any vaccine, regardless of antigen.

The committee found evidence that favored acceptance of the following four associations:

• Anaphylaxis and HPV vaccine.

• Transient arthralgia in female adults with the MMR vaccine.

• Transient arthralgia in children with the MMR vaccine.

• Mild, temporary oculorespiratory syndrome with certain trivalent influenza vaccines used in Canada.

The committee found evidence that favored rejecting the following associations:

• Type 1 diabetes with MMR or with the diphtheria, tetanus, acellular pertussis vaccine (DTaP).

• Autism with MMR.

• Asthma exacerbation, reactive airway disease episodes, and Bell’s palsy with inactivated influenza vaccine.

However, the report stated, "The vast majority of causality conclusions in this report are that the evidence was inadequate to accept or reject a causal relationship. Some might interpret that to mean either of the following statements: Because the committee did not find convincing evidence that the vaccine does cause the adverse event, the vaccine is safe. Or, because the committee did not find convincing evidence that the vaccine does not cause the adverse event, the vaccine is unsafe. Neither of these interpretations is correct. Inadequate to accept or reject means just that – inadequate."

The report represents the best currently available information on these vaccines and any adverse events associated with them, Dr. Barrett reiterated. "From my perspective, the process was incredibly rigorous [and] objective, and included significant debate from a variety of perspectives – that of practicing doctors, public health epidemiologists, basic scientists, and people who understand legal systems. So the rigor of the review process, and the care and detail of the analysis was extraordinary."

The report was funded by the U.S. Department of Health and Human Services. None of the authors reported any financial conflicts.

Vaccines do not cause autism in children who receive them, the Institute of Medicine has reported in an unprecedented review of medical literature.

"Our review found no tangible, credible evidence to support a conclusion that the MMR vaccine causes autism," Dr. Douglas Barrett, a member of the IOM’s review committee, said in an interview.

Although the scientific evidence against the relationship is solid, he said, it may not be enough to change entrenched ideology about the vaccine’s safety for children.

"This won’t preclude people from worrying about it or making a claim about it, but there is just no science behind those worries. But our charge was to look at the science and hard evidence, and that evidence is not there," he said.

© Yarinca/iStockphoto.com

The committee did, however, establish causal links between seven vaccines and 14 other adverse events, including seizures, inflammation of the brain, fainting, and anaphylaxis.

"Many of those findings support vaccine adverse events that are readily apparent, easily identified, or self-limited, transient conditions," said Dr. Barrett, a professor of pediatrics in the division of immunology, infectious disease, and rheumatology at the University of Florida, Gainesville.

The 18-member IOM Committee to Review Adverse Effects of Vaccines was not directed to make practice recommendations regarding vaccine administration. But, Dr. Barrett said, none of its findings is likely to change any current regimen. "However, that is a question for others to decide," he noted.

The report should be "extraordinarily helpful" to practicing physicians who administer vaccines," he said. "They are asked these questions day in and day out by patients relying on their expert opinion about these purported adverse events. This will provide them with today’s best evidence about whether or not there is an association."

The committee examined both epidemiologic and mechanistic evidence to pinpoint true vaccine-related adverse events – a process that highlighted the clinical importance of this interplay. In reviewing the evidence, the committee divided adverse events into four categories: convincingly supported, favoring acceptance, favoring rejection, and inadequate information to accept or reject.

The IOM asked the committee to consider evidence for 79 purported adverse events related to eight vaccines: MMR, varicella, influenza, hepatitis A, hepatitis B, human papillomavirus, meningococcal, and vaccines that contain diphtheria, tetanus or pertussis components.

The evidence convincingly supported the following associations:

• Disseminated Oka varicella zoster virus (VZV) and Oka VZV viral reactivation with varicella vaccine.

• Measles inclusion body encephalitis with MMR vaccine.

• Febrile seizures with MMR vaccine.

• Hypersensitivity and anaphylaxis with MMR, varicella, influenza, hepatitis B, meningococcal, and tetanus toxoid vaccines.

• Syncope and deltoid bursitis with the injection of any vaccine, regardless of antigen.

The committee found evidence that favored acceptance of the following four associations:

• Anaphylaxis and HPV vaccine.

• Transient arthralgia in female adults with the MMR vaccine.

• Transient arthralgia in children with the MMR vaccine.

• Mild, temporary oculorespiratory syndrome with certain trivalent influenza vaccines used in Canada.

The committee found evidence that favored rejecting the following associations:

• Type 1 diabetes with MMR or with the diphtheria, tetanus, acellular pertussis vaccine (DTaP).

• Autism with MMR.

• Asthma exacerbation, reactive airway disease episodes, and Bell’s palsy with inactivated influenza vaccine.

However, the report stated, "The vast majority of causality conclusions in this report are that the evidence was inadequate to accept or reject a causal relationship. Some might interpret that to mean either of the following statements: Because the committee did not find convincing evidence that the vaccine does cause the adverse event, the vaccine is safe. Or, because the committee did not find convincing evidence that the vaccine does not cause the adverse event, the vaccine is unsafe. Neither of these interpretations is correct. Inadequate to accept or reject means just that – inadequate."

The report represents the best currently available information on these vaccines and any adverse events associated with them, Dr. Barrett reiterated. "From my perspective, the process was incredibly rigorous [and] objective, and included significant debate from a variety of perspectives – that of practicing doctors, public health epidemiologists, basic scientists, and people who understand legal systems. So the rigor of the review process, and the care and detail of the analysis was extraordinary."

The report was funded by the U.S. Department of Health and Human Services. None of the authors reported any financial conflicts.

Vaccines do not cause autism in children who receive them, the Institute of Medicine has reported in an unprecedented review of medical literature.

"Our review found no tangible, credible evidence to support a conclusion that the MMR vaccine causes autism," Dr. Douglas Barrett, a member of the IOM’s review committee, said in an interview.

Although the scientific evidence against the relationship is solid, he said, it may not be enough to change entrenched ideology about the vaccine’s safety for children.

"This won’t preclude people from worrying about it or making a claim about it, but there is just no science behind those worries. But our charge was to look at the science and hard evidence, and that evidence is not there," he said.

© Yarinca/iStockphoto.com

The committee did, however, establish causal links between seven vaccines and 14 other adverse events, including seizures, inflammation of the brain, fainting, and anaphylaxis.

"Many of those findings support vaccine adverse events that are readily apparent, easily identified, or self-limited, transient conditions," said Dr. Barrett, a professor of pediatrics in the division of immunology, infectious disease, and rheumatology at the University of Florida, Gainesville.

The 18-member IOM Committee to Review Adverse Effects of Vaccines was not directed to make practice recommendations regarding vaccine administration. But, Dr. Barrett said, none of its findings is likely to change any current regimen. "However, that is a question for others to decide," he noted.

The report should be "extraordinarily helpful" to practicing physicians who administer vaccines," he said. "They are asked these questions day in and day out by patients relying on their expert opinion about these purported adverse events. This will provide them with today’s best evidence about whether or not there is an association."

The committee examined both epidemiologic and mechanistic evidence to pinpoint true vaccine-related adverse events – a process that highlighted the clinical importance of this interplay. In reviewing the evidence, the committee divided adverse events into four categories: convincingly supported, favoring acceptance, favoring rejection, and inadequate information to accept or reject.

The IOM asked the committee to consider evidence for 79 purported adverse events related to eight vaccines: MMR, varicella, influenza, hepatitis A, hepatitis B, human papillomavirus, meningococcal, and vaccines that contain diphtheria, tetanus or pertussis components.

The evidence convincingly supported the following associations:

• Disseminated Oka varicella zoster virus (VZV) and Oka VZV viral reactivation with varicella vaccine.

• Measles inclusion body encephalitis with MMR vaccine.

• Febrile seizures with MMR vaccine.

• Hypersensitivity and anaphylaxis with MMR, varicella, influenza, hepatitis B, meningococcal, and tetanus toxoid vaccines.

• Syncope and deltoid bursitis with the injection of any vaccine, regardless of antigen.

The committee found evidence that favored acceptance of the following four associations:

• Anaphylaxis and HPV vaccine.

• Transient arthralgia in female adults with the MMR vaccine.

• Transient arthralgia in children with the MMR vaccine.

• Mild, temporary oculorespiratory syndrome with certain trivalent influenza vaccines used in Canada.

The committee found evidence that favored rejecting the following associations:

• Type 1 diabetes with MMR or with the diphtheria, tetanus, acellular pertussis vaccine (DTaP).

• Autism with MMR.

• Asthma exacerbation, reactive airway disease episodes, and Bell’s palsy with inactivated influenza vaccine.

However, the report stated, "The vast majority of causality conclusions in this report are that the evidence was inadequate to accept or reject a causal relationship. Some might interpret that to mean either of the following statements: Because the committee did not find convincing evidence that the vaccine does cause the adverse event, the vaccine is safe. Or, because the committee did not find convincing evidence that the vaccine does not cause the adverse event, the vaccine is unsafe. Neither of these interpretations is correct. Inadequate to accept or reject means just that – inadequate."

The report represents the best currently available information on these vaccines and any adverse events associated with them, Dr. Barrett reiterated. "From my perspective, the process was incredibly rigorous [and] objective, and included significant debate from a variety of perspectives – that of practicing doctors, public health epidemiologists, basic scientists, and people who understand legal systems. So the rigor of the review process, and the care and detail of the analysis was extraordinary."

The report was funded by the U.S. Department of Health and Human Services. None of the authors reported any financial conflicts.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

©Corbis/Fotolia.com

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

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

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

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

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

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

Risks Associated With Nanoparticles

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

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

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

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

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

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

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

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

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

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

Dr. Draelos disclosed financial relationships with numerous pharmaceutical companies.

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

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

©Corbis/Fotolia.com

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

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

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

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

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

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

Risks Associated With Nanoparticles

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

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

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

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

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

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

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

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

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

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

Dr. Draelos disclosed financial relationships with numerous pharmaceutical companies.

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

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

©Corbis/Fotolia.com

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

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

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

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

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

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

Risks Associated With Nanoparticles

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

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

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

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

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

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

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

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

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

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

Dr. Draelos disclosed financial relationships with numerous pharmaceutical companies.

NEW YORK – Children with atopic dermatitis have a high risk of food allergies – although these allergies are not always easy to pinpoint.

"In this population, up to 20% of [those] with mild to moderate atopic dermatitis and 30%-40% of the severe patients will have a true food allergy," that can be confirmed with an open food challenge. Dr. Lawrence F. Eichenfield said at the American Academy of Dermatology’s 2010 meeting.

However, he said, positive skin prick testing – a common form of allergen identification – isn’t a very accurate way to detect the allergies. As a result, parents of children with atopic dermatitis (AD) will frequently state that their child has a food allergy, when, in fact, none exists.

A new national guideline helps clarify that issue, he said. Published in late 2010, "Guidelines for the Diagnosis and Management of Food Allergy in the United States," from the National Institute of Allergy and Infectious Diseases, provides some helpful information for dermatologists trying to make the AD/food allergy connection.

The document defines a food allergy as an adverse health effect arising from a specific immune response that occurs reproducibly on exposure to a given food. Skin prick testing, however, can only identify sensitization to a food, which doesn’t necessarily correlate with a clinical event, said Dr. Eichenfield, a professor of clinical pediatrics and dermatology at the University of California, San Diego.

"It’s very clearly written in the guidelines that an individual can develop allergic sensitization without having clinical symptoms on exposure to the food. Therefore, skin testing is not sufficient to say there is a food allergy."

Nevertheless, a common clinical scenario in the pediatric dermatology office is a parent who claims the child is allergic to a given food – most often eggs, soy, milk, wheat, or peanuts – because of a positive skin test. "What people don’t understand is, these tests are neither very sensitive nor specific," he said.

The specificity of skin prick testing hovers at about 85%, while the sensitivity is around 75%. "That means if we assume a 5% true milk allergy in a group of 1,000 people, skin prick testing will identify 42 of the 50 with a true allergy, miss 8 of those with the allergy, and give a false positive result to 238 people without the allergy," he said. "It’s a problem when you start labeling someone as having an allergy with just a positive test, but no clinical indicator."

The national guidelines stress that both family history and AD are risk factors for food allergy. The report suggests that children younger than 5 years who have moderate to severe AD that is uncontrolled despite optimal treatment, should be tested for allergies to milk, egg, peanut, soy and wheat. A positive, reliable history of a clinical reaction immediately after exposure to a specific food is also grounds for an investigation, according to the report.

Oral food challenge is probably the best way to determine a true food allergy, but can only be carried out in an environment set up to cope with severe reactions – usually an allergist’ s office. The good news is that the common overrepresentation of "food allergies" among children with AD means that many can safely consume foods that have been, literally, taken off the table.

A 2010 retrospective study looked at 125 children with atopic dermatitis, 44 of whom had suspected allergies to a variety of foods. All of them underwent oral food challenges. At baseline, there were 111 reports of food avoidance due to positive skin prick testing – foods included egg, fruit, meat, vegetables, milk, soy, wheat, shellfish, oats, and peanuts (J. Pediatr. 2010;158:578-83).

"Except for wheat, 80% or more of the oral food challenges were negative to the foods being avoided," wrote Dr. David M. Fleisher of the University of Colorado, Denver, and colleagues. This study was funded by National Jewish Health and the authors declared no conflicts. The only positive reactions were for egg, banana, peanut, soy, and wheat.

"Depending on the reason for avoidance, 84%-93% of the foods being avoided were successfully reintroduced into the diet," Dr. Eichenfield said.

The new management guidelines have affected the way he assesses AD patients, Dr. Eichenfield added. "Now I ask about food allergy reactions. If I find anything positive, I take a very detailed history, including the type of reaction, the time course, and the consistency of it after exposure to the food. Many times, just by asking, you will uncover a very significant reaction, like contact dermatitis, urticaria, or even anaphylaxis."

The guidelines note that anaphylaxis can be a real - and life-threatening – complication of food allergy. Parents of children with a proven food allergy should be experts in avoiding the food and in emergency management. "The standard management is to write a prescription for an Epi-Pen and make sure they know how to use it," Dr. Eichenfield said.

He’s also more likely to refer children with moderate to severe AD and persistent flares for testing now. "I am more liberal about using the allergist to evaluate these patients, with the understanding that a positive test may not change the eczema, but with the hope that if there is an avenue that might help, it’s one we want to explore."

Dr. Eichenfield had no financial disclosures.

NEW YORK – Children with atopic dermatitis have a high risk of food allergies – although these allergies are not always easy to pinpoint.

"In this population, up to 20% of [those] with mild to moderate atopic dermatitis and 30%-40% of the severe patients will have a true food allergy," that can be confirmed with an open food challenge. Dr. Lawrence F. Eichenfield said at the American Academy of Dermatology’s 2010 meeting.

However, he said, positive skin prick testing – a common form of allergen identification – isn’t a very accurate way to detect the allergies. As a result, parents of children with atopic dermatitis (AD) will frequently state that their child has a food allergy, when, in fact, none exists.

A new national guideline helps clarify that issue, he said. Published in late 2010, "Guidelines for the Diagnosis and Management of Food Allergy in the United States," from the National Institute of Allergy and Infectious Diseases, provides some helpful information for dermatologists trying to make the AD/food allergy connection.

The document defines a food allergy as an adverse health effect arising from a specific immune response that occurs reproducibly on exposure to a given food. Skin prick testing, however, can only identify sensitization to a food, which doesn’t necessarily correlate with a clinical event, said Dr. Eichenfield, a professor of clinical pediatrics and dermatology at the University of California, San Diego.

"It’s very clearly written in the guidelines that an individual can develop allergic sensitization without having clinical symptoms on exposure to the food. Therefore, skin testing is not sufficient to say there is a food allergy."

Nevertheless, a common clinical scenario in the pediatric dermatology office is a parent who claims the child is allergic to a given food – most often eggs, soy, milk, wheat, or peanuts – because of a positive skin test. "What people don’t understand is, these tests are neither very sensitive nor specific," he said.

The specificity of skin prick testing hovers at about 85%, while the sensitivity is around 75%. "That means if we assume a 5% true milk allergy in a group of 1,000 people, skin prick testing will identify 42 of the 50 with a true allergy, miss 8 of those with the allergy, and give a false positive result to 238 people without the allergy," he said. "It’s a problem when you start labeling someone as having an allergy with just a positive test, but no clinical indicator."

The national guidelines stress that both family history and AD are risk factors for food allergy. The report suggests that children younger than 5 years who have moderate to severe AD that is uncontrolled despite optimal treatment, should be tested for allergies to milk, egg, peanut, soy and wheat. A positive, reliable history of a clinical reaction immediately after exposure to a specific food is also grounds for an investigation, according to the report.

Oral food challenge is probably the best way to determine a true food allergy, but can only be carried out in an environment set up to cope with severe reactions – usually an allergist’ s office. The good news is that the common overrepresentation of "food allergies" among children with AD means that many can safely consume foods that have been, literally, taken off the table.

A 2010 retrospective study looked at 125 children with atopic dermatitis, 44 of whom had suspected allergies to a variety of foods. All of them underwent oral food challenges. At baseline, there were 111 reports of food avoidance due to positive skin prick testing – foods included egg, fruit, meat, vegetables, milk, soy, wheat, shellfish, oats, and peanuts (J. Pediatr. 2010;158:578-83).

"Except for wheat, 80% or more of the oral food challenges were negative to the foods being avoided," wrote Dr. David M. Fleisher of the University of Colorado, Denver, and colleagues. This study was funded by National Jewish Health and the authors declared no conflicts. The only positive reactions were for egg, banana, peanut, soy, and wheat.

"Depending on the reason for avoidance, 84%-93% of the foods being avoided were successfully reintroduced into the diet," Dr. Eichenfield said.

The new management guidelines have affected the way he assesses AD patients, Dr. Eichenfield added. "Now I ask about food allergy reactions. If I find anything positive, I take a very detailed history, including the type of reaction, the time course, and the consistency of it after exposure to the food. Many times, just by asking, you will uncover a very significant reaction, like contact dermatitis, urticaria, or even anaphylaxis."

The guidelines note that anaphylaxis can be a real - and life-threatening – complication of food allergy. Parents of children with a proven food allergy should be experts in avoiding the food and in emergency management. "The standard management is to write a prescription for an Epi-Pen and make sure they know how to use it," Dr. Eichenfield said.

He’s also more likely to refer children with moderate to severe AD and persistent flares for testing now. "I am more liberal about using the allergist to evaluate these patients, with the understanding that a positive test may not change the eczema, but with the hope that if there is an avenue that might help, it’s one we want to explore."

Dr. Eichenfield had no financial disclosures.

NEW YORK – Children with atopic dermatitis have a high risk of food allergies – although these allergies are not always easy to pinpoint.

"In this population, up to 20% of [those] with mild to moderate atopic dermatitis and 30%-40% of the severe patients will have a true food allergy," that can be confirmed with an open food challenge. Dr. Lawrence F. Eichenfield said at the American Academy of Dermatology’s 2010 meeting.

However, he said, positive skin prick testing – a common form of allergen identification – isn’t a very accurate way to detect the allergies. As a result, parents of children with atopic dermatitis (AD) will frequently state that their child has a food allergy, when, in fact, none exists.

A new national guideline helps clarify that issue, he said. Published in late 2010, "Guidelines for the Diagnosis and Management of Food Allergy in the United States," from the National Institute of Allergy and Infectious Diseases, provides some helpful information for dermatologists trying to make the AD/food allergy connection.

The document defines a food allergy as an adverse health effect arising from a specific immune response that occurs reproducibly on exposure to a given food. Skin prick testing, however, can only identify sensitization to a food, which doesn’t necessarily correlate with a clinical event, said Dr. Eichenfield, a professor of clinical pediatrics and dermatology at the University of California, San Diego.

"It’s very clearly written in the guidelines that an individual can develop allergic sensitization without having clinical symptoms on exposure to the food. Therefore, skin testing is not sufficient to say there is a food allergy."

Nevertheless, a common clinical scenario in the pediatric dermatology office is a parent who claims the child is allergic to a given food – most often eggs, soy, milk, wheat, or peanuts – because of a positive skin test. "What people don’t understand is, these tests are neither very sensitive nor specific," he said.

The specificity of skin prick testing hovers at about 85%, while the sensitivity is around 75%. "That means if we assume a 5% true milk allergy in a group of 1,000 people, skin prick testing will identify 42 of the 50 with a true allergy, miss 8 of those with the allergy, and give a false positive result to 238 people without the allergy," he said. "It’s a problem when you start labeling someone as having an allergy with just a positive test, but no clinical indicator."

The national guidelines stress that both family history and AD are risk factors for food allergy. The report suggests that children younger than 5 years who have moderate to severe AD that is uncontrolled despite optimal treatment, should be tested for allergies to milk, egg, peanut, soy and wheat. A positive, reliable history of a clinical reaction immediately after exposure to a specific food is also grounds for an investigation, according to the report.

Oral food challenge is probably the best way to determine a true food allergy, but can only be carried out in an environment set up to cope with severe reactions – usually an allergist’ s office. The good news is that the common overrepresentation of "food allergies" among children with AD means that many can safely consume foods that have been, literally, taken off the table.

A 2010 retrospective study looked at 125 children with atopic dermatitis, 44 of whom had suspected allergies to a variety of foods. All of them underwent oral food challenges. At baseline, there were 111 reports of food avoidance due to positive skin prick testing – foods included egg, fruit, meat, vegetables, milk, soy, wheat, shellfish, oats, and peanuts (J. Pediatr. 2010;158:578-83).

"Except for wheat, 80% or more of the oral food challenges were negative to the foods being avoided," wrote Dr. David M. Fleisher of the University of Colorado, Denver, and colleagues. This study was funded by National Jewish Health and the authors declared no conflicts. The only positive reactions were for egg, banana, peanut, soy, and wheat.

"Depending on the reason for avoidance, 84%-93% of the foods being avoided were successfully reintroduced into the diet," Dr. Eichenfield said.

The new management guidelines have affected the way he assesses AD patients, Dr. Eichenfield added. "Now I ask about food allergy reactions. If I find anything positive, I take a very detailed history, including the type of reaction, the time course, and the consistency of it after exposure to the food. Many times, just by asking, you will uncover a very significant reaction, like contact dermatitis, urticaria, or even anaphylaxis."

The guidelines note that anaphylaxis can be a real - and life-threatening – complication of food allergy. Parents of children with a proven food allergy should be experts in avoiding the food and in emergency management. "The standard management is to write a prescription for an Epi-Pen and make sure they know how to use it," Dr. Eichenfield said.

He’s also more likely to refer children with moderate to severe AD and persistent flares for testing now. "I am more liberal about using the allergist to evaluate these patients, with the understanding that a positive test may not change the eczema, but with the hope that if there is an avenue that might help, it’s one we want to explore."

Dr. Eichenfield had no financial disclosures.

NEW YORK – Children with atopic dermatitis have a high risk of food allergies – although these allergies are not always easy to pinpoint.

"In this population, up to 20% of [those] with mild to moderate atopic dermatitis and 30%-40% of the severe patients will have a true food allergy," that can be confirmed with an open food challenge. Dr. Lawrence F. Eichenfield said at the American Academy of Dermatology’s 2010 meeting.

However, he said, positive skin prick testing – a common form of allergen identification – isn’t a very accurate way to detect the allergies. As a result, parents of children with atopic dermatitis (AD) will frequently state that their child has a food allergy, when, in fact, none exists.

A new national guideline helps clarify that issue, he said. Published in late 2010, "Guidelines for the Diagnosis and Management of Food Allergy in the United States," from the National Institute of Allergy and Infectious Diseases, provides some helpful information for dermatologists trying to make the AD/food allergy connection.

The document defines a food allergy as an adverse health effect arising from a specific immune response that occurs reproducibly on exposure to a given food. Skin prick testing, however, can only identify sensitization to a food, which doesn’t necessarily correlate with a clinical event, said Dr. Eichenfield, a professor of clinical pediatrics and dermatology at the University of California, San Diego.

"It’s very clearly written in the guidelines that an individual can develop allergic sensitization without having clinical symptoms on exposure to the food. Therefore, skin testing is not sufficient to say there is a food allergy."

Nevertheless, a common clinical scenario in the pediatric dermatology office is a parent who claims the child is allergic to a given food – most often eggs, soy, milk, wheat, or peanuts – because of a positive skin test. "What people don’t understand is, these tests are neither very sensitive nor specific," he said.

The specificity of skin prick testing hovers at about 85%, while the sensitivity is around 75%. "That means if we assume a 5% true milk allergy in a group of 1,000 people, skin prick testing will identify 42 of the 50 with a true allergy, miss 8 of those with the allergy, and give a false positive result to 238 people without the allergy," he said. "It’s a problem when you start labeling someone as having an allergy with just a positive test, but no clinical indicator."

The national guidelines stress that both family history and AD are risk factors for food allergy. The report suggests that children younger than 5 years who have moderate to severe AD that is uncontrolled despite optimal treatment, should be tested for allergies to milk, egg, peanut, soy and wheat. A positive, reliable history of a clinical reaction immediately after exposure to a specific food is also grounds for an investigation, according to the report.

Oral food challenge is probably the best way to determine a true food allergy, but can only be carried out in an environment set up to cope with severe reactions – usually an allergist’ s office. The good news is that the common overrepresentation of "food allergies" among children with AD means that many can safely consume foods that have been, literally, taken off the table.

A 2010 retrospective study looked at 125 children with atopic dermatitis, 44 of whom had suspected allergies to a variety of foods. All of them underwent oral food challenges. At baseline, there were 111 reports of food avoidance due to positive skin prick testing – foods included egg, fruit, meat, vegetables, milk, soy, wheat, shellfish, oats, and peanuts (J. Pediatr. 2010;158:578-83).

"Except for wheat, 80% or more of the oral food challenges were negative to the foods being avoided," wrote Dr. David M. Fleisher of the University of Colorado, Denver, and colleagues. This study was funded by National Jewish Health and the authors declared no conflicts. The only positive reactions were for egg, banana, peanut, soy, and wheat.

"Depending on the reason for avoidance, 84%-93% of the foods being avoided were successfully reintroduced into the diet," Dr. Eichenfield said.

The new management guidelines have affected the way he assesses AD patients, Dr. Eichenfield added. "Now I ask about food allergy reactions. If I find anything positive, I take a very detailed history, including the type of reaction, the time course, and the consistency of it after exposure to the food. Many times, just by asking, you will uncover a very significant reaction, like contact dermatitis, urticaria, or even anaphylaxis."

The guidelines note that anaphylaxis can be a real - and life-threatening – complication of food allergy. Parents of children with a proven food allergy should be experts in avoiding the food and in emergency management. "The standard management is to write a prescription for an Epi-Pen and make sure they know how to use it," Dr. Eichenfield said.

He’s also more likely to refer children with moderate to severe AD and persistent flares for testing now. "I am more liberal about using the allergist to evaluate these patients, with the understanding that a positive test may not change the eczema, but with the hope that if there is an avenue that might help, it’s one we want to explore."

Dr. Eichenfield had no financial disclosures.

NEW YORK – Children with atopic dermatitis have a high risk of food allergies – although these allergies are not always easy to pinpoint.

"In this population, up to 20% of [those] with mild to moderate atopic dermatitis and 30%-40% of the severe patients will have a true food allergy," that can be confirmed with an open food challenge. Dr. Lawrence F. Eichenfield said at the American Academy of Dermatology’s 2010 meeting.

However, he said, positive skin prick testing – a common form of allergen identification – isn’t a very accurate way to detect the allergies. As a result, parents of children with atopic dermatitis (AD) will frequently state that their child has a food allergy, when, in fact, none exists.

A new national guideline helps clarify that issue, he said. Published in late 2010, "Guidelines for the Diagnosis and Management of Food Allergy in the United States," from the National Institute of Allergy and Infectious Diseases, provides some helpful information for dermatologists trying to make the AD/food allergy connection.

The document defines a food allergy as an adverse health effect arising from a specific immune response that occurs reproducibly on exposure to a given food. Skin prick testing, however, can only identify sensitization to a food, which doesn’t necessarily correlate with a clinical event, said Dr. Eichenfield, a professor of clinical pediatrics and dermatology at the University of California, San Diego.

"It’s very clearly written in the guidelines that an individual can develop allergic sensitization without having clinical symptoms on exposure to the food. Therefore, skin testing is not sufficient to say there is a food allergy."

Nevertheless, a common clinical scenario in the pediatric dermatology office is a parent who claims the child is allergic to a given food – most often eggs, soy, milk, wheat, or peanuts – because of a positive skin test. "What people don’t understand is, these tests are neither very sensitive nor specific," he said.

The specificity of skin prick testing hovers at about 85%, while the sensitivity is around 75%. "That means if we assume a 5% true milk allergy in a group of 1,000 people, skin prick testing will identify 42 of the 50 with a true allergy, miss 8 of those with the allergy, and give a false positive result to 238 people without the allergy," he said. "It’s a problem when you start labeling someone as having an allergy with just a positive test, but no clinical indicator."

The national guidelines stress that both family history and AD are risk factors for food allergy. The report suggests that children younger than 5 years who have moderate to severe AD that is uncontrolled despite optimal treatment, should be tested for allergies to milk, egg, peanut, soy and wheat. A positive, reliable history of a clinical reaction immediately after exposure to a specific food is also grounds for an investigation, according to the report.

Oral food challenge is probably the best way to determine a true food allergy, but can only be carried out in an environment set up to cope with severe reactions – usually an allergist’ s office. The good news is that the common overrepresentation of "food allergies" among children with AD means that many can safely consume foods that have been, literally, taken off the table.

A 2010 retrospective study looked at 125 children with atopic dermatitis, 44 of whom had suspected allergies to a variety of foods. All of them underwent oral food challenges. At baseline, there were 111 reports of food avoidance due to positive skin prick testing – foods included egg, fruit, meat, vegetables, milk, soy, wheat, shellfish, oats, and peanuts (J. Pediatr. 2010;158:578-83).

"Except for wheat, 80% or more of the oral food challenges were negative to the foods being avoided," wrote Dr. David M. Fleisher of the University of Colorado, Denver, and colleagues. This study was funded by National Jewish Health and the authors declared no conflicts. The only positive reactions were for egg, banana, peanut, soy, and wheat.

"Depending on the reason for avoidance, 84%-93% of the foods being avoided were successfully reintroduced into the diet," Dr. Eichenfield said.

The new management guidelines have affected the way he assesses AD patients, Dr. Eichenfield added. "Now I ask about food allergy reactions. If I find anything positive, I take a very detailed history, including the type of reaction, the time course, and the consistency of it after exposure to the food. Many times, just by asking, you will uncover a very significant reaction, like contact dermatitis, urticaria, or even anaphylaxis."

The guidelines note that anaphylaxis can be a real - and life-threatening – complication of food allergy. Parents of children with a proven food allergy should be experts in avoiding the food and in emergency management. "The standard management is to write a prescription for an Epi-Pen and make sure they know how to use it," Dr. Eichenfield said.

He’s also more likely to refer children with moderate to severe AD and persistent flares for testing now. "I am more liberal about using the allergist to evaluate these patients, with the understanding that a positive test may not change the eczema, but with the hope that if there is an avenue that might help, it’s one we want to explore."

Dr. Eichenfield had no financial disclosures.

NEW YORK – Children with atopic dermatitis have a high risk of food allergies – although these allergies are not always easy to pinpoint.

"In this population, up to 20% of [those] with mild to moderate atopic dermatitis and 30%-40% of the severe patients will have a true food allergy," that can be confirmed with an open food challenge. Dr. Lawrence F. Eichenfield said at the American Academy of Dermatology’s 2010 meeting.

However, he said, positive skin prick testing – a common form of allergen identification – isn’t a very accurate way to detect the allergies. As a result, parents of children with atopic dermatitis (AD) will frequently state that their child has a food allergy, when, in fact, none exists.

A new national guideline helps clarify that issue, he said. Published in late 2010, "Guidelines for the Diagnosis and Management of Food Allergy in the United States," from the National Institute of Allergy and Infectious Diseases, provides some helpful information for dermatologists trying to make the AD/food allergy connection.

The document defines a food allergy as an adverse health effect arising from a specific immune response that occurs reproducibly on exposure to a given food. Skin prick testing, however, can only identify sensitization to a food, which doesn’t necessarily correlate with a clinical event, said Dr. Eichenfield, a professor of clinical pediatrics and dermatology at the University of California, San Diego.

"It’s very clearly written in the guidelines that an individual can develop allergic sensitization without having clinical symptoms on exposure to the food. Therefore, skin testing is not sufficient to say there is a food allergy."

Nevertheless, a common clinical scenario in the pediatric dermatology office is a parent who claims the child is allergic to a given food – most often eggs, soy, milk, wheat, or peanuts – because of a positive skin test. "What people don’t understand is, these tests are neither very sensitive nor specific," he said.

The specificity of skin prick testing hovers at about 85%, while the sensitivity is around 75%. "That means if we assume a 5% true milk allergy in a group of 1,000 people, skin prick testing will identify 42 of the 50 with a true allergy, miss 8 of those with the allergy, and give a false positive result to 238 people without the allergy," he said. "It’s a problem when you start labeling someone as having an allergy with just a positive test, but no clinical indicator."

The national guidelines stress that both family history and AD are risk factors for food allergy. The report suggests that children younger than 5 years who have moderate to severe AD that is uncontrolled despite optimal treatment, should be tested for allergies to milk, egg, peanut, soy and wheat. A positive, reliable history of a clinical reaction immediately after exposure to a specific food is also grounds for an investigation, according to the report.

Oral food challenge is probably the best way to determine a true food allergy, but can only be carried out in an environment set up to cope with severe reactions – usually an allergist’ s office. The good news is that the common overrepresentation of "food allergies" among children with AD means that many can safely consume foods that have been, literally, taken off the table.

A 2010 retrospective study looked at 125 children with atopic dermatitis, 44 of whom had suspected allergies to a variety of foods. All of them underwent oral food challenges. At baseline, there were 111 reports of food avoidance due to positive skin prick testing – foods included egg, fruit, meat, vegetables, milk, soy, wheat, shellfish, oats, and peanuts (J. Pediatr. 2010;158:578-83).

"Except for wheat, 80% or more of the oral food challenges were negative to the foods being avoided," wrote Dr. David M. Fleisher of the University of Colorado, Denver, and colleagues. This study was funded by National Jewish Health and the authors declared no conflicts. The only positive reactions were for egg, banana, peanut, soy, and wheat.

"Depending on the reason for avoidance, 84%-93% of the foods being avoided were successfully reintroduced into the diet," Dr. Eichenfield said.

The new management guidelines have affected the way he assesses AD patients, Dr. Eichenfield added. "Now I ask about food allergy reactions. If I find anything positive, I take a very detailed history, including the type of reaction, the time course, and the consistency of it after exposure to the food. Many times, just by asking, you will uncover a very significant reaction, like contact dermatitis, urticaria, or even anaphylaxis."

The guidelines note that anaphylaxis can be a real - and life-threatening – complication of food allergy. Parents of children with a proven food allergy should be experts in avoiding the food and in emergency management. "The standard management is to write a prescription for an Epi-Pen and make sure they know how to use it," Dr. Eichenfield said.

He’s also more likely to refer children with moderate to severe AD and persistent flares for testing now. "I am more liberal about using the allergist to evaluate these patients, with the understanding that a positive test may not change the eczema, but with the hope that if there is an avenue that might help, it’s one we want to explore."

Dr. Eichenfield had no financial disclosures.