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Minority Correctly Use EpiPen or Metered Dose Inhaler
SAN DIEGO – Only 12% of 91 patients in Texas allergy/immunology clinics knew how to use an epinephrine autoinjector correctly, and only 7% of 41 patients could demonstrate correct use of their metered dose inhaler with a spacer, a small prospective study showed.
That’s not good enough, Dr. Rana S. Bonds said at the annual meeting of the American Academy of Allergy, Asthma, and Immunology. Her team has begun studying interventions to improve correct use of those devices and "will be sharing that data in the near future," she said.
They asked patients to demonstrate the use of an EpiPen or a metered dose inhaler (MDI) and spacer and scored the patients’ adherence to the EpiPen manufacturer’s instructions or published standards for MDI/spacers.
For the EpiPen, 25% of patients missed one of the five steps for correct use, 18% missed two steps, and 19% missed three steps. "It was fairly alarming" to find that 31% got four steps wrong and 8% missed all five steps, said Dr. Bonds of the University of Texas Medical Branch, Galveston. (Percentages total more than 100% because they were rounded.)
The most common mistake with the EpiPen involved the final step. "Once they deployed the epinephrine injection, they didn’t hold it down long enough. They were bouncing it off the thigh or whatever body part they thought they should inject it into," she said.
For the MDI/spacer, 16% of patients performed 1 of 11 steps for use incorrectly, 16% missed 2 steps, 21% missed 3 steps, and 18% missed 4 steps. Another 11% missed 5 steps, 5% missed 6 steps, 11% missed 7 steps, and 3% got all 11 steps wrong, Dr. Bonds and her associates reported. The most common mistake was failing to exhale before triggering the inhaler for inhalation.
The study recruited patients from the university’s main allergy/immunology clinic and its satellite clinics. Trainers are available at each clinic, and patients are supposed to see them before leaving with one of the devices, but the findings raise the question of whether health care providers at the clinics consistently make sure that happens, she said.
Younger patients, males, and patients with a medical background were more likely to show that they could use the EpiPen correctly. Being African American or less educated was associated with a greater likelihood of incorrect use. Correct usage rates differed significantly between some of the clinic sites. Factors that didn’t correlate with correct or incorrect use of the EpiPen included whether a family member also used the device, being prescribed the EpiPen more or less than 1 year ago, and whether patients had ever used the EpiPen (most hadn’t).
The number of patients in the MDI/spacer group was too small to permit risk factors to be analyzed, Dr. Bonds said.
Previously published studies have reported that 22% of food-allergic adolescents could demonstrate correct use of epinephrine and that rates of incorrect inhaler use ranged from 50% to 94%, she said. Other studies have shown that incorrect use reduces the treatment’s clinical efficacy, and that repeated instruction increases the likelihood of correct use.
Dr. Bonds reported having no relevant financial disclosures.
On Twitter @sherryboschert
SAN DIEGO – Only 12% of 91 patients in Texas allergy/immunology clinics knew how to use an epinephrine autoinjector correctly, and only 7% of 41 patients could demonstrate correct use of their metered dose inhaler with a spacer, a small prospective study showed.
That’s not good enough, Dr. Rana S. Bonds said at the annual meeting of the American Academy of Allergy, Asthma, and Immunology. Her team has begun studying interventions to improve correct use of those devices and "will be sharing that data in the near future," she said.
They asked patients to demonstrate the use of an EpiPen or a metered dose inhaler (MDI) and spacer and scored the patients’ adherence to the EpiPen manufacturer’s instructions or published standards for MDI/spacers.
For the EpiPen, 25% of patients missed one of the five steps for correct use, 18% missed two steps, and 19% missed three steps. "It was fairly alarming" to find that 31% got four steps wrong and 8% missed all five steps, said Dr. Bonds of the University of Texas Medical Branch, Galveston. (Percentages total more than 100% because they were rounded.)
The most common mistake with the EpiPen involved the final step. "Once they deployed the epinephrine injection, they didn’t hold it down long enough. They were bouncing it off the thigh or whatever body part they thought they should inject it into," she said.
For the MDI/spacer, 16% of patients performed 1 of 11 steps for use incorrectly, 16% missed 2 steps, 21% missed 3 steps, and 18% missed 4 steps. Another 11% missed 5 steps, 5% missed 6 steps, 11% missed 7 steps, and 3% got all 11 steps wrong, Dr. Bonds and her associates reported. The most common mistake was failing to exhale before triggering the inhaler for inhalation.
The study recruited patients from the university’s main allergy/immunology clinic and its satellite clinics. Trainers are available at each clinic, and patients are supposed to see them before leaving with one of the devices, but the findings raise the question of whether health care providers at the clinics consistently make sure that happens, she said.
Younger patients, males, and patients with a medical background were more likely to show that they could use the EpiPen correctly. Being African American or less educated was associated with a greater likelihood of incorrect use. Correct usage rates differed significantly between some of the clinic sites. Factors that didn’t correlate with correct or incorrect use of the EpiPen included whether a family member also used the device, being prescribed the EpiPen more or less than 1 year ago, and whether patients had ever used the EpiPen (most hadn’t).
The number of patients in the MDI/spacer group was too small to permit risk factors to be analyzed, Dr. Bonds said.
Previously published studies have reported that 22% of food-allergic adolescents could demonstrate correct use of epinephrine and that rates of incorrect inhaler use ranged from 50% to 94%, she said. Other studies have shown that incorrect use reduces the treatment’s clinical efficacy, and that repeated instruction increases the likelihood of correct use.
Dr. Bonds reported having no relevant financial disclosures.
On Twitter @sherryboschert
SAN DIEGO – Only 12% of 91 patients in Texas allergy/immunology clinics knew how to use an epinephrine autoinjector correctly, and only 7% of 41 patients could demonstrate correct use of their metered dose inhaler with a spacer, a small prospective study showed.
That’s not good enough, Dr. Rana S. Bonds said at the annual meeting of the American Academy of Allergy, Asthma, and Immunology. Her team has begun studying interventions to improve correct use of those devices and "will be sharing that data in the near future," she said.
They asked patients to demonstrate the use of an EpiPen or a metered dose inhaler (MDI) and spacer and scored the patients’ adherence to the EpiPen manufacturer’s instructions or published standards for MDI/spacers.
For the EpiPen, 25% of patients missed one of the five steps for correct use, 18% missed two steps, and 19% missed three steps. "It was fairly alarming" to find that 31% got four steps wrong and 8% missed all five steps, said Dr. Bonds of the University of Texas Medical Branch, Galveston. (Percentages total more than 100% because they were rounded.)
The most common mistake with the EpiPen involved the final step. "Once they deployed the epinephrine injection, they didn’t hold it down long enough. They were bouncing it off the thigh or whatever body part they thought they should inject it into," she said.
For the MDI/spacer, 16% of patients performed 1 of 11 steps for use incorrectly, 16% missed 2 steps, 21% missed 3 steps, and 18% missed 4 steps. Another 11% missed 5 steps, 5% missed 6 steps, 11% missed 7 steps, and 3% got all 11 steps wrong, Dr. Bonds and her associates reported. The most common mistake was failing to exhale before triggering the inhaler for inhalation.
The study recruited patients from the university’s main allergy/immunology clinic and its satellite clinics. Trainers are available at each clinic, and patients are supposed to see them before leaving with one of the devices, but the findings raise the question of whether health care providers at the clinics consistently make sure that happens, she said.
Younger patients, males, and patients with a medical background were more likely to show that they could use the EpiPen correctly. Being African American or less educated was associated with a greater likelihood of incorrect use. Correct usage rates differed significantly between some of the clinic sites. Factors that didn’t correlate with correct or incorrect use of the EpiPen included whether a family member also used the device, being prescribed the EpiPen more or less than 1 year ago, and whether patients had ever used the EpiPen (most hadn’t).
The number of patients in the MDI/spacer group was too small to permit risk factors to be analyzed, Dr. Bonds said.
Previously published studies have reported that 22% of food-allergic adolescents could demonstrate correct use of epinephrine and that rates of incorrect inhaler use ranged from 50% to 94%, she said. Other studies have shown that incorrect use reduces the treatment’s clinical efficacy, and that repeated instruction increases the likelihood of correct use.
Dr. Bonds reported having no relevant financial disclosures.
On Twitter @sherryboschert
FDA Approves First Grass-pollen Allergy Pill
Oralair was approved April 1 by the Food and Drug Administration for the treatment of allergic rhinitis; it is the first sublingual allergen extract approved for use in the United States.
Oralair is indicated to treat allergic rhinitis with or without eye inflammation that is induced by certain grass pollens in people aged 10-65 years. The company had proposed that the treatment be approved for patients aged 5 years and older.
The treatment contains a mixture of freeze-dried extracts from the pollens of five grasses: Kentucky Blue Grass, Orchard, Perennial Rye, Sweet Vernal, and Timothy.
Once-daily Oralair is started 4 months prior to the grass-pollen season and continued throughout the season. The first dose is delivered in the doctor’s office, and the remaining doses can be self-administered at home. Manufacturer Greer Laboratories claims that Oralair may reduce grass allergy symptoms for patients within the first allergy season it is taken.
Treatment with a sublingual tablet would open up the treatment options for the approximately 30 million Americans who suffer from allergic rhinitis every year, said Dr. Linda Cox, immediate past president of the American Academy of Allergy Asthma and Immunology and a practicing allergist in Ft. Lauderdale, Fla.
She said that she sees it as a game changer for the treatment of allergic rhinitis.
"What sublingual immunotherapy offers is home treatment and easier access to care because its safety profile is so good," Dr. Cox said in an interview. "That could potentially open up this treatment for the 90% or so of patients who are not receiving anything and are just treating the symptoms."
She added that Oralair treats the underlying causes of allergic rhinitis, not just the symptoms caused by the disease. "It will bring a group of people who are just suffering through their [allergy] seasons and are getting suboptimal control with various products and give them the potential to just knock out their disease," she added.
Approval of Oralair was based on double-blind, placebo-controlled trials in the United States and Europe that enrolled more than 2,500 adults and children. To assess the treatment’s effectiveness, patients reported their symptoms and additional medications needed to cope with their allergy symptoms. During treatment for one grass-pollen season, patients taking Oralair saw a 16%-30% reduction in symptoms and the need for medications, compared with those who received a placebo.
The trials demonstrated that treatment with Oralair before and during allergy season reduced patients’ allergy symptoms and their need for symptom-relieving medication.
The most common adverse events for Oralair, reported in less than 5% of patients, were oral pruritus, throat irritation, ear pruritus, mouth edema, tongue pruritus, cough, and oropharyngeal pain, Greer Laboratories said in an April 1 statement.
Oralair was first approved in Europe in 2008, and is currently approved in 31 countries.
Oralair was approved April 1 by the Food and Drug Administration for the treatment of allergic rhinitis; it is the first sublingual allergen extract approved for use in the United States.
Oralair is indicated to treat allergic rhinitis with or without eye inflammation that is induced by certain grass pollens in people aged 10-65 years. The company had proposed that the treatment be approved for patients aged 5 years and older.
The treatment contains a mixture of freeze-dried extracts from the pollens of five grasses: Kentucky Blue Grass, Orchard, Perennial Rye, Sweet Vernal, and Timothy.
Once-daily Oralair is started 4 months prior to the grass-pollen season and continued throughout the season. The first dose is delivered in the doctor’s office, and the remaining doses can be self-administered at home. Manufacturer Greer Laboratories claims that Oralair may reduce grass allergy symptoms for patients within the first allergy season it is taken.
Treatment with a sublingual tablet would open up the treatment options for the approximately 30 million Americans who suffer from allergic rhinitis every year, said Dr. Linda Cox, immediate past president of the American Academy of Allergy Asthma and Immunology and a practicing allergist in Ft. Lauderdale, Fla.
She said that she sees it as a game changer for the treatment of allergic rhinitis.
"What sublingual immunotherapy offers is home treatment and easier access to care because its safety profile is so good," Dr. Cox said in an interview. "That could potentially open up this treatment for the 90% or so of patients who are not receiving anything and are just treating the symptoms."
She added that Oralair treats the underlying causes of allergic rhinitis, not just the symptoms caused by the disease. "It will bring a group of people who are just suffering through their [allergy] seasons and are getting suboptimal control with various products and give them the potential to just knock out their disease," she added.
Approval of Oralair was based on double-blind, placebo-controlled trials in the United States and Europe that enrolled more than 2,500 adults and children. To assess the treatment’s effectiveness, patients reported their symptoms and additional medications needed to cope with their allergy symptoms. During treatment for one grass-pollen season, patients taking Oralair saw a 16%-30% reduction in symptoms and the need for medications, compared with those who received a placebo.
The trials demonstrated that treatment with Oralair before and during allergy season reduced patients’ allergy symptoms and their need for symptom-relieving medication.
The most common adverse events for Oralair, reported in less than 5% of patients, were oral pruritus, throat irritation, ear pruritus, mouth edema, tongue pruritus, cough, and oropharyngeal pain, Greer Laboratories said in an April 1 statement.
Oralair was first approved in Europe in 2008, and is currently approved in 31 countries.
Oralair was approved April 1 by the Food and Drug Administration for the treatment of allergic rhinitis; it is the first sublingual allergen extract approved for use in the United States.
Oralair is indicated to treat allergic rhinitis with or without eye inflammation that is induced by certain grass pollens in people aged 10-65 years. The company had proposed that the treatment be approved for patients aged 5 years and older.
The treatment contains a mixture of freeze-dried extracts from the pollens of five grasses: Kentucky Blue Grass, Orchard, Perennial Rye, Sweet Vernal, and Timothy.
Once-daily Oralair is started 4 months prior to the grass-pollen season and continued throughout the season. The first dose is delivered in the doctor’s office, and the remaining doses can be self-administered at home. Manufacturer Greer Laboratories claims that Oralair may reduce grass allergy symptoms for patients within the first allergy season it is taken.
Treatment with a sublingual tablet would open up the treatment options for the approximately 30 million Americans who suffer from allergic rhinitis every year, said Dr. Linda Cox, immediate past president of the American Academy of Allergy Asthma and Immunology and a practicing allergist in Ft. Lauderdale, Fla.
She said that she sees it as a game changer for the treatment of allergic rhinitis.
"What sublingual immunotherapy offers is home treatment and easier access to care because its safety profile is so good," Dr. Cox said in an interview. "That could potentially open up this treatment for the 90% or so of patients who are not receiving anything and are just treating the symptoms."
She added that Oralair treats the underlying causes of allergic rhinitis, not just the symptoms caused by the disease. "It will bring a group of people who are just suffering through their [allergy] seasons and are getting suboptimal control with various products and give them the potential to just knock out their disease," she added.
Approval of Oralair was based on double-blind, placebo-controlled trials in the United States and Europe that enrolled more than 2,500 adults and children. To assess the treatment’s effectiveness, patients reported their symptoms and additional medications needed to cope with their allergy symptoms. During treatment for one grass-pollen season, patients taking Oralair saw a 16%-30% reduction in symptoms and the need for medications, compared with those who received a placebo.
The trials demonstrated that treatment with Oralair before and during allergy season reduced patients’ allergy symptoms and their need for symptom-relieving medication.
The most common adverse events for Oralair, reported in less than 5% of patients, were oral pruritus, throat irritation, ear pruritus, mouth edema, tongue pruritus, cough, and oropharyngeal pain, Greer Laboratories said in an April 1 statement.
Oralair was first approved in Europe in 2008, and is currently approved in 31 countries.
Asthma May Increase Risk of Cardiovascular Events
SAN DIEGO – Having asthma appears to significantly increase your risk for cardiovascular events, while having allergic rhinitis appears to protect your risk for such events, results from a large cohort study demonstrated.
Studies of mouse models have suggested that Th1 inflammation "is associated with atherosclerosis and plaque development, while the Th2 or general allergic response seems to be protective against atherosclerosis," Dr. Angelina Crans Yoon said during a press briefing at the annual meeting of the American Academy of Allergy, Asthma, and Immunology. At the same time, results from human studies regarding the association between allergic rhinitis and cardiovascular events are mixed, said Dr. Crans Yoon, a first-year allergy fellow at Kaiser Permanente Los Angeles Medical Center.
In an effort to assess the relationship between cardiovascular disease and allergic rhinitis, she and her associates used the Kaiser Permanente Southern California regional database and ICD-9 codes to compare the incidence of cardiovascular and cerebrovascular events and all-cause mortality in a cohort of 109,229 allergic rhinitis patients and 92,775 asthma patients who were seen between Jan. 1, 1995, and Dec. 31, 2012. The cohorts were matched by age, sex, and ethnicity to reference cohorts and followed for a median of 8 years.
Dr. Crans Yoon reported that patients with allergic rhinitis had significantly lower risk for myocardial infarction (hazard ratio, 0.75), cerebrovascular disease (HR, 0.81), and all-cause mortality (HR, 0.51), yet their risk of all cardiovascular events was equal to that of the control cohort (HR, 0.97). At the same time, patients with asthma had a significantly higher risk of all cardiovascular disease (HR, 1.36), yet no significantly higher risk of cerebrovascular disease (HR, 1.03) or all-cause mortality (HR, 1.00).
The findings "led us to think of more questions," Dr. Crans Yoon said. "Why is there this decreased risk of events in patients with allergic rhinitis? What explains the risk of cardiovascular events in patients with asthma? Is atopy related to these differences? We started some secondary analyses looking at medication use. It looks like if you use any medications for allergic rhinitis or asthma, you have a decreased risk of some of these events, except for long-acting beta-agonists, which is consistent with previous reports. We’re also starting to look at specific IgE data on these patients. It looks like positive IgE testing may be associated with a decreased risk of all these events."
She speculated that asthma physiology may explain why patients with asthma had significantly higher risk of cardiovascular disease but not cerebrovascular disease. "The interesting point is that potentially, atopic asthmatics may not have the same increased risk," she said.
Dr. Crans Yoon said that she had no relevant financial conflicts to disclose.
SAN DIEGO – Having asthma appears to significantly increase your risk for cardiovascular events, while having allergic rhinitis appears to protect your risk for such events, results from a large cohort study demonstrated.
Studies of mouse models have suggested that Th1 inflammation "is associated with atherosclerosis and plaque development, while the Th2 or general allergic response seems to be protective against atherosclerosis," Dr. Angelina Crans Yoon said during a press briefing at the annual meeting of the American Academy of Allergy, Asthma, and Immunology. At the same time, results from human studies regarding the association between allergic rhinitis and cardiovascular events are mixed, said Dr. Crans Yoon, a first-year allergy fellow at Kaiser Permanente Los Angeles Medical Center.
In an effort to assess the relationship between cardiovascular disease and allergic rhinitis, she and her associates used the Kaiser Permanente Southern California regional database and ICD-9 codes to compare the incidence of cardiovascular and cerebrovascular events and all-cause mortality in a cohort of 109,229 allergic rhinitis patients and 92,775 asthma patients who were seen between Jan. 1, 1995, and Dec. 31, 2012. The cohorts were matched by age, sex, and ethnicity to reference cohorts and followed for a median of 8 years.
Dr. Crans Yoon reported that patients with allergic rhinitis had significantly lower risk for myocardial infarction (hazard ratio, 0.75), cerebrovascular disease (HR, 0.81), and all-cause mortality (HR, 0.51), yet their risk of all cardiovascular events was equal to that of the control cohort (HR, 0.97). At the same time, patients with asthma had a significantly higher risk of all cardiovascular disease (HR, 1.36), yet no significantly higher risk of cerebrovascular disease (HR, 1.03) or all-cause mortality (HR, 1.00).
The findings "led us to think of more questions," Dr. Crans Yoon said. "Why is there this decreased risk of events in patients with allergic rhinitis? What explains the risk of cardiovascular events in patients with asthma? Is atopy related to these differences? We started some secondary analyses looking at medication use. It looks like if you use any medications for allergic rhinitis or asthma, you have a decreased risk of some of these events, except for long-acting beta-agonists, which is consistent with previous reports. We’re also starting to look at specific IgE data on these patients. It looks like positive IgE testing may be associated with a decreased risk of all these events."
She speculated that asthma physiology may explain why patients with asthma had significantly higher risk of cardiovascular disease but not cerebrovascular disease. "The interesting point is that potentially, atopic asthmatics may not have the same increased risk," she said.
Dr. Crans Yoon said that she had no relevant financial conflicts to disclose.
SAN DIEGO – Having asthma appears to significantly increase your risk for cardiovascular events, while having allergic rhinitis appears to protect your risk for such events, results from a large cohort study demonstrated.
Studies of mouse models have suggested that Th1 inflammation "is associated with atherosclerosis and plaque development, while the Th2 or general allergic response seems to be protective against atherosclerosis," Dr. Angelina Crans Yoon said during a press briefing at the annual meeting of the American Academy of Allergy, Asthma, and Immunology. At the same time, results from human studies regarding the association between allergic rhinitis and cardiovascular events are mixed, said Dr. Crans Yoon, a first-year allergy fellow at Kaiser Permanente Los Angeles Medical Center.
In an effort to assess the relationship between cardiovascular disease and allergic rhinitis, she and her associates used the Kaiser Permanente Southern California regional database and ICD-9 codes to compare the incidence of cardiovascular and cerebrovascular events and all-cause mortality in a cohort of 109,229 allergic rhinitis patients and 92,775 asthma patients who were seen between Jan. 1, 1995, and Dec. 31, 2012. The cohorts were matched by age, sex, and ethnicity to reference cohorts and followed for a median of 8 years.
Dr. Crans Yoon reported that patients with allergic rhinitis had significantly lower risk for myocardial infarction (hazard ratio, 0.75), cerebrovascular disease (HR, 0.81), and all-cause mortality (HR, 0.51), yet their risk of all cardiovascular events was equal to that of the control cohort (HR, 0.97). At the same time, patients with asthma had a significantly higher risk of all cardiovascular disease (HR, 1.36), yet no significantly higher risk of cerebrovascular disease (HR, 1.03) or all-cause mortality (HR, 1.00).
The findings "led us to think of more questions," Dr. Crans Yoon said. "Why is there this decreased risk of events in patients with allergic rhinitis? What explains the risk of cardiovascular events in patients with asthma? Is atopy related to these differences? We started some secondary analyses looking at medication use. It looks like if you use any medications for allergic rhinitis or asthma, you have a decreased risk of some of these events, except for long-acting beta-agonists, which is consistent with previous reports. We’re also starting to look at specific IgE data on these patients. It looks like positive IgE testing may be associated with a decreased risk of all these events."
She speculated that asthma physiology may explain why patients with asthma had significantly higher risk of cardiovascular disease but not cerebrovascular disease. "The interesting point is that potentially, atopic asthmatics may not have the same increased risk," she said.
Dr. Crans Yoon said that she had no relevant financial conflicts to disclose.
AT THE 2014 AAAAI ANNUAL MEETING
Do Antibiotics Contribute to Pediatric C difficile Infection Rate?
Nearly three-quarters of Clostridium difficile infections in children and teens were community associated, with the highest incidence among 1-year-olds, according to a study published March 3 in Pediatrics.
The 944 pediatric cases analyzed for the study involved 885 children identified in select counties throughout eight states in 2010 and 10 states in 2011 as part of the Centers for Disease Control and Prevention’s Emerging Infections Program. Among those cases, 71% were community associated, 17% were community onset health care facility–associated and 12% were health care facility–onset (Pediatrics 2014 March 3 [doi:10.1542/peds.2013-3049]).
The highest incidence of 66.3 children/100,000 occurred among those aged 12-23 months old, followed by an incidence of 35.7 in children aged 2-3 years, 15.6 for those aged 4-9 years, and 16.6 for children aged 10-17 years.
"The high C. difficile infection incidence we observed among the youngest age group may be related to the finding that children 0-2 years of age have the highest outpatient antibiotic prescribing rate," reported Dr. Joyanna Wendt, a medical officer at the CDC, and her colleagues. Antibiotic use increases risk of C. difficile infection because the medication can change or kill beneficial bacteria that protect against infection.
Among a smaller sample of 84 cases interviewed in the study and reporting diarrhea on the first day of stool collection, 73% (61 cases) reported taking antibiotics within 12 weeks before the diarrhea began. Ear, sinus, and upper respiratory tract infections comprised the most common reasons for antibiotic use.
"Improved antibiotic prescribing is critical to protect the health of our nation’s children," Dr. Tom Frieden, CDC director, said in a prepared statement. "When antibiotics are prescribed incorrectly, our children are needlessly put at risk for health problems, including C. difficile infection and dangerous antibiotic-resistant infections."
Incidence did not differ by sex, but white children had a higher incidence, with 23.9 cases/100,000 children, compared with 17.4 for nonwhite children, "likely reflecting, in part, differences in health care access," the researchers wrote.
This study was supported by the CDC. Coauthor Dr. Dennis N. Gerding is a board member at Merck, Rebiotix, Summit, and Actelion and consults for Roche, Novartis, Sanofi Pasteur, and Cubist; he consults for and holds patents licensed to ViroPharma, which manufactures vancomycin to treat C difficile. No other authors reported disclosures.
Nearly three-quarters of Clostridium difficile infections in children and teens were community associated, with the highest incidence among 1-year-olds, according to a study published March 3 in Pediatrics.
The 944 pediatric cases analyzed for the study involved 885 children identified in select counties throughout eight states in 2010 and 10 states in 2011 as part of the Centers for Disease Control and Prevention’s Emerging Infections Program. Among those cases, 71% were community associated, 17% were community onset health care facility–associated and 12% were health care facility–onset (Pediatrics 2014 March 3 [doi:10.1542/peds.2013-3049]).
The highest incidence of 66.3 children/100,000 occurred among those aged 12-23 months old, followed by an incidence of 35.7 in children aged 2-3 years, 15.6 for those aged 4-9 years, and 16.6 for children aged 10-17 years.
"The high C. difficile infection incidence we observed among the youngest age group may be related to the finding that children 0-2 years of age have the highest outpatient antibiotic prescribing rate," reported Dr. Joyanna Wendt, a medical officer at the CDC, and her colleagues. Antibiotic use increases risk of C. difficile infection because the medication can change or kill beneficial bacteria that protect against infection.
Among a smaller sample of 84 cases interviewed in the study and reporting diarrhea on the first day of stool collection, 73% (61 cases) reported taking antibiotics within 12 weeks before the diarrhea began. Ear, sinus, and upper respiratory tract infections comprised the most common reasons for antibiotic use.
"Improved antibiotic prescribing is critical to protect the health of our nation’s children," Dr. Tom Frieden, CDC director, said in a prepared statement. "When antibiotics are prescribed incorrectly, our children are needlessly put at risk for health problems, including C. difficile infection and dangerous antibiotic-resistant infections."
Incidence did not differ by sex, but white children had a higher incidence, with 23.9 cases/100,000 children, compared with 17.4 for nonwhite children, "likely reflecting, in part, differences in health care access," the researchers wrote.
This study was supported by the CDC. Coauthor Dr. Dennis N. Gerding is a board member at Merck, Rebiotix, Summit, and Actelion and consults for Roche, Novartis, Sanofi Pasteur, and Cubist; he consults for and holds patents licensed to ViroPharma, which manufactures vancomycin to treat C difficile. No other authors reported disclosures.
Nearly three-quarters of Clostridium difficile infections in children and teens were community associated, with the highest incidence among 1-year-olds, according to a study published March 3 in Pediatrics.
The 944 pediatric cases analyzed for the study involved 885 children identified in select counties throughout eight states in 2010 and 10 states in 2011 as part of the Centers for Disease Control and Prevention’s Emerging Infections Program. Among those cases, 71% were community associated, 17% were community onset health care facility–associated and 12% were health care facility–onset (Pediatrics 2014 March 3 [doi:10.1542/peds.2013-3049]).
The highest incidence of 66.3 children/100,000 occurred among those aged 12-23 months old, followed by an incidence of 35.7 in children aged 2-3 years, 15.6 for those aged 4-9 years, and 16.6 for children aged 10-17 years.
"The high C. difficile infection incidence we observed among the youngest age group may be related to the finding that children 0-2 years of age have the highest outpatient antibiotic prescribing rate," reported Dr. Joyanna Wendt, a medical officer at the CDC, and her colleagues. Antibiotic use increases risk of C. difficile infection because the medication can change or kill beneficial bacteria that protect against infection.
Among a smaller sample of 84 cases interviewed in the study and reporting diarrhea on the first day of stool collection, 73% (61 cases) reported taking antibiotics within 12 weeks before the diarrhea began. Ear, sinus, and upper respiratory tract infections comprised the most common reasons for antibiotic use.
"Improved antibiotic prescribing is critical to protect the health of our nation’s children," Dr. Tom Frieden, CDC director, said in a prepared statement. "When antibiotics are prescribed incorrectly, our children are needlessly put at risk for health problems, including C. difficile infection and dangerous antibiotic-resistant infections."
Incidence did not differ by sex, but white children had a higher incidence, with 23.9 cases/100,000 children, compared with 17.4 for nonwhite children, "likely reflecting, in part, differences in health care access," the researchers wrote.
This study was supported by the CDC. Coauthor Dr. Dennis N. Gerding is a board member at Merck, Rebiotix, Summit, and Actelion and consults for Roche, Novartis, Sanofi Pasteur, and Cubist; he consults for and holds patents licensed to ViroPharma, which manufactures vancomycin to treat C difficile. No other authors reported disclosures.
FROM PEDIATRICS
Allergic Rhinitis & Immunotherapy: Hope or Hype
CE/CME No: CR-1403
PROGRAM OVERVIEW
Earn credit by reading this article and successfully completing the posttest. Successful completion is defined as a cumulative score of at least 70% correct.
EDUCATIONAL OBJECTIVES
• Explain the pathophysiology and etiology of allergic rhinitis (AR).
• Describe the prevalence and types of AR.
• List the differential diagnoses for AR.
• Describe the historical and physical examination findings that are typical
of AR.
• Explain the indications for and types of allergy testing.
• Discuss the types of allergy desensitization therapies/immunotherapies.
FACULTY
Randy D. Danielsen is a Professor and Dean of the Arizona School of Health Sciences, A.T. Still University in Mesa, Arizona, and a long-time PA with the Arizona Asthma & Allergy Institute. Linda S. MacConnell is an Assistant Professor in the Department of Physician Assistant Studies at the Arizona School of Health Sciences, A.T. Still University, and a formally trained otolaryngology PA.
The authors have no financial disclosures to report.
ACCREDITATION STATEMENT
Article begins on next page >>
Allergic rhinitis (AR), one of the most familiar complaints seen in primary care, is a common immunologic condition that occurs in genetically predisposed patients. AR is routinely treated through allergen avoidance and pharmacologic therapy. When these measures fail, however, immunologic treatment may be indicated. This review of AR and its treatment focuses on injection and oral immunotherapy.
Congestion; sneezing (particularly paroxysms); itchy nose, palate, and eyes; and runny nose are symptoms characteristic of allergic rhinitis (AR) seen every day in virtually all primary care offices. Patients are plagued not only by their symptoms, but also by AR-related sleep disturbances, resulting in fatigue and daytime sleepiness, irritability, and memory deficits. In children, these sleep disruptions may even cause behavioral disturbances. Depending on the cause, some patients may experience allergic symptoms only with outdoor environmental exposure and subsequent immunoglobulin E (IgE)–mediated responses to otherwise innocuous allergens, while others find that their symptoms are constant, occurring both indoors and out.
Although the prevalence of AR is increasing,1 allergies are certainly nothing new to humankind. In fact, hieroglyphics and Egyptian wall paintings have been discovered depicting a pharaoh dying from anaphylactic shock after receiving a wasp sting.2 In 1565, Leonardo Botallo described AR, calling it “rose catarrh” (mucous or phlegm) or “rose fever,” based on the mistaken idea that the symptoms were caused by rose pollen.2 John Babcock, an English physician, first diagnosed an upper respiratory disease that he called “hay fever” in 1819.
Seventy years later, Charles Blackley identified pollen as a cause of hay fever, documenting his findings in his 1873 book Experimental Researches on the Causes and Nature of Catarrhus Aestivus.2 Dr. Blackley performed the initial documented attempts at allergy desensitization treatments on himself—a willing patient, as he suffered from AR. He placed rye grass pollen onto his nasal mucosa, finding that after 30 minutes the nostril was completely occluded. He continued his experimentation by repeatedly exposing himself to pollen grains via abraded skin. Alas, he never noted any decrease in his symptoms.3
Presently, AR affects more than 55 million people in the United States4—approximately 10% to 30% of the adult population5 and more than 40% of children.6 The rising prevalence of AR is of concern in older adults, who tend to have related comorbidities (eg, chronic sinusitis, asthma, and otitis media). In fact, AR is the fifth most common chronic disease in the US.7
AR and its treatment impose a great economic burden on the health care system, critical in these days of affordable health care. In fact, in 2005 in the US, the overall (direct medical and indirect) cost of AR was $11.2 billion.8 Direct costs derive from office visits, diagnostic testing, and therapeutics. Costs are considerably higher when indirect expenses, including decreased productivity, missed school and missed workdays to care for children, and costs of travel to medical appointments, are included. In the US, approximately 3.5 million workdays and 2 million school days are lost each year due to AR.9 Decreases in productivity cost an estimated $600 per affected employee per year, all of which results in AR being the fifth costliest chronic disease.10,11
On the next page: Pathophysiology and examination >>
PATHOPHYSIOLOGY
AR is an immunologic disorder that occurs in genetically susceptible individuals who produce allergen-specific IgE antibody responses after environmental exposures. The IgE-mediated response causes inflammation of the nasal mucosa. Compared to controls, individuals with AR demonstrate increased amounts of IgE antibodies in the nasal mucosa.11 IgE binds to basophils in the bloodstream and mast cells in tissue. Allergens then attach to IgE on basophils and mast cells, which release histamines, prostaglandins, cytokines, and leukotrienes, with histamine being the most significant mediator in the inflammatory response.
In response to allergy-provoking substances, patients experience immediate- and late-phase symptoms. Symptoms of each stage are similar, but congestion is the hallmark of the late phase. While both phases are clinically important because of their contribution to the patient’s symptoms, most patients experience continued exposure to allergens, resulting in constant, overlapping symptoms.
HISTORY AND PHYSICAL EXAMINATION
Patients with AR relate a history of congestion, excessive mucous production, itchy, watery eyes, bouts of sneezing, and more systemic symptoms, such as headache, malaise, and excessive fatigue. It is important to evaluate the degree and duration of the symptoms, noting patterns and triggers, in an effort to confirm the diagnosis and to help the patient evaluate treatment options.
When taking the patient history, always review the family history, which is often notable for allergies and other atopic diseases. Be sure to ask about medications and recreational drug use; a number of substances have been implicated in the development of rhinitis, including anticholinergic medications, oxymetazoline (when overused), and cocaine. Also, question the patient about self-medication and treatment to determine what may or may not have provided relief. Further questioning may also reveal a history of comorbidities, including contact dermatitis, asthma, eczema, and chronic sinusitis.
The physical examination of the patient with rhinitis begins with observation of the patient’s outward appearance, which may reveal allergic shiners (dark to purplish areas under the eyes), conjunctivitis, an allergic salute (a transverse crease of the nose caused by upward rubbing of an itchy nose), mouth breathing, and a generally tired appearance. The nasal turbinates are swollen and often pale. Mucous secretions are usually thin and clear. Enlarged tonsils and posterior nasal drainage may be visualized. The types of AR are listed in Table 1.
On the next page: Diagnosis and treatment >>
DIAGNOSIS
Most of the clues needed to arrive at a diagnosis are discovered by taking a careful history and completing a physical examination. AR frequently underlies and/or coexists with acute upper respiratory infection (URI) and acute and chronic sinusitis. Differentiating acute URI and acute sinusitis from AR is usually relatively straightforward, based on the symptoms of the illness. The diagnosis of chronic sinusitis is made by radiologic imaging with CT scan.
Distinguishing nonallergic rhinitis (NAR) from AR can be far more difficult, because the symptoms of these conditions are similar and chronic in nature (see Table 2). Empiric treatment for AR may be attempted; however, further testing is often needed to differentiate the two. At this point, clinicians may choose to proceed with specific IgE blood tests. Alternatively, many medical practices are prepared to perform or refer for allergy skin testing.
TREATMENT
Avoidance of known triggers is the cornerstone of allergy treatment. Currently, the most effective pharmaceutical treatment for the majority of AR symptoms is inhaled nasal corticosteroids. Although less effective than corticosteroids, antihistamines—both nasal and oral—are a recommended addition to the regimen if the adverse effects and costs to the patient are tolerable. Other treatments include the leukotriene receptor antagonists, intranasal formulations of cromolyn, and the anticholinergic ipratropium bromide nasal spray, which is effective primarily on watery rhinorrhea. If symptoms are not controlled with medication, allergy immunotherapy (AI), the only known disease-modifying therapy for AR, may be indicated.
On the next page: Allergy testing >>
ALLERGY TESTING
In order to distinguish between AR and NAR and to direct treatment toward specific allergen avoidance and immunotherapy, providers have the choice of ordering in vitro blood IgE testing (to measure the antibodies that mediate an allergic response) or in vivo allergy skin testing (to measure the immune response to allergens that induces an allergic atopic reaction). Allergy testing is not a contemporary concept; the first allergy testing was documented in 1656 when Pierre Borel applied egg to a patient’s skin, which exhibited an allergic reaction.2
Allergy skin testing consists of applying multiple allergens to the skin of the patient’s forearms via tiny pinpricks while watching for immediate hypersensitivity reactions. The test begins with the placement of a drop of histamine to serve as a control. If after 10 minutes of watchful waiting the patient develops a reaction to the histamine (a positive test result), it is appropriate to test for antigens by placing drops of suspected allergen extracts on the skin.
After a period of time (usually 20 to 30 minutes), the area is inspected for allergic reaction. An immediate (early phase) wheal and flare (surrounding erythema) reaction may develop. This positive reaction indicates the presence of a mast cell–bound IgE antibody specific to the tested allergen. The size of the reactions is measured in millimeters, allowing for comparison to the histamine control.
A list of the commonly tested antigens in Arizona, as an example, is shown in Table 3. Antigens vary geographically and even from practice to practice. For up-to-date information on pollen counts by region, visit the American Academy of Allergy Asthma & Immunology Web site (see “Pollen Counts”).
On the next page: Patient selection and allergy immunotherapy >>
Patient Selection
After the clinician has determined that there is a high likelihood that the diagnosis is AR, allergy testing, needed to guide AI, is appropriate. Although not true of specific IgE testing, the accuracy of allergy skin testing results can be adversely affected by several medications. For example, some practitioners may choose to stop first-generation antihistamines two to three days before testing. It is generally accepted that the newer, second-generation antihistamines, which can affect skin-testing results longer, be stopped a week prior to testing.
Patients should be reminded that OTC sleep aids frequently contain antihistamines (particularly diphenhydramine) and that they must be discontinued prior to testing as well. Histamine H2-receptor antagonists such as cimetidine and ranitidine may be stopped a day or two before testing. Although β-blockers are only relatively contraindicated in both allergy testing and AI, many health care providers avoid testing and AI in patients taking oral and/or topical (eye drops) β-blocker therapy. Ultimately, the decision is made by individual health care practices.
In vivo allergy skin testing should not be performed on patients taking tricyclic antidepressants and monoamine oxidase inhibitors. Patients with significant cardiovascular disease should not undergo testing or treatment. Pregnancy is a relative contraindication, and allergy skin testing and AI are done only with obstetrician approval. Most allergists avoid allergy skin testing in pregnant women, however, because use of epinephrine, if required, introduces the risk for preterm labor.12,13 Special consideration should also be given to patients with immune deficiencies.
Setting for Allergy Evaluation and Treatment
Recently, many primary care practices have added allergy evaluation and management to the procedures and treatments they offer; however, evaluations and testing traditionally have been performed by allergy and immunology specialists, many of whom include PAs and NPs on their staff. PAs and NPs frequently manage the practices’ allergy programs. Allergists who are listed as American Board of Allergy and Immunology (ABAI)–certified have successfully passed the ABAI’s certifying examination. Other medical specialists, including otolaryngologists and the primary care specialties, are also well placed to evaluate patients with common allergy symptoms and provide appropriate treatment.
Allergy Immunotherapy
AI has now become more efficacious, safer, and more tolerable for the patient than when it was first introduced in 1911. At that time, Leonard Noon authored a brief article claiming that allergen-specific injections could modify AR. Unfortunately, Noon died at age 36 from tuberculosis, but his work was carried on by his associate, John Freeman. Together, they established the guidelines upon which contemporary AI is based, including the protocol to gradually increase the dose of allergen serum, starting with initial weekly to biweekly injections. They also voiced warnings about the potential for anaphylaxis.14 To this day, immunotherapy is still accomplished by the gradual administration of increasing amounts of the allergen to which the patient is sensitive. This tempers the abnormal immune response to that allergen, easing allergic symptoms.
In patients with IgE-mediated hypersensitivity reactions, confirmed by history, physical examination, and allergy skin testing, immunotherapy can be very effective. The results of immunotherapy may last for years and may even prevent the allergic march, the progression of allergic disease experienced by many patients that frequently begins early in life.15 This includes other allergy-related conditions, such as asthma and eczema (atopic dermatitis), and the acquisition of additional new allergies, including those to foods. AI also has been shown to decrease the frequency of comorbidities such as asthma.5 In addition, AI is used in carefully screened patients who desire to reduce the dosages of medication required to control their symptoms.
In a study published in 1999, Durham and colleagues clarified the questions surrounding the amount of time required for ongoing immunotherapy. They found that the desensitization and tolerance to allergens achieved by AI can last up to three years after a three- to four-year course of therapy. They also found that treatment should not start until an allergic component is identified by allergy skin testing or serum tests for allergen-specific IgE.16
As effective as immunotherapy has been documented to be, it is underused as a therapeutic modality. There are only 2 to 3 million patients receiving subcutaneous immunotherapy out of more than 55 million patients with AR.17
On the next page: Types of allergy immunotherapy >>
Types of AI
There are two categories of allergen desensitization therapy. The most common method is subcutaneous immunotherapy (SCIT), the so-called allergy shots. Less common and still somewhat controversial is sublingual immunotherapy (SLIT). Immunotherapy should be considered for patients who have secondary complications (eg, sinusitis, otitis) or asthma with allergies, or those in whom avoidance measures and medications fail. SCIT or SLIT may be desirable for patients with AR who have difficulty taking regular medications.
Subcutaneous immunotherapy. Currently, SCIT is the most recognized immunotherapy and the only one currently reimbursed by insurance. The procedure involves the subcutaneous injection of increasing doses of therapeutic solutions to which a patient has demonstrated sensitivity. The indications for this treatment are usually inhaled allergens, such as pollens and animal dander. SCIT may also be valuable in patients with asthma and atopic dermatitis.
The most common adverse reaction to allergy injections is a large localized reaction—primarily erythema, pruritus, discomfort, and possibly edema. Severe systemic reactions are extremely rare, with near-fatal to fatal reactions occurring at the rate of only 5.4 per million injections.11 The majority of these rare, albeit serious, complications are caused by higher-than-normal levels of pollen in the environment and dosing errors.11 Because of the uncommon but significant complications, patients undergoing immunotherapy should always receive injections in a medical office equipped with appropriate equipment and staff trained in handling anaphylaxis. It is standard protocol for patients to remain in the office for 30 minutes after administration for observation. Some clinicians prescribe epinephrine injectors (Epi-Pens) for patients to bring to every appointment as a condition for receiving their shot. Because of continuing controversy on this point, others only employ this requirement if the patient has a history of an adverse reaction.
Various protocols exist for the up-dosing of immunotherapy, most of which recommend weekly to twice-weekly injections prior to initiating maintenance therapy. Costs, risks, and benefits must be carefully considered and discussed with the patient prior to initiating immunotherapy.
Many insurance companies reimburse for immunotherapy, with varying copayments. Additionally, the time commitment may be taxing on the patient’s busy schedule. Weekly or biweekly appointments are required initially, and the patient must remain on site for half an hour. Although direct costs of SCIT are relatively easily measured and perhaps compensated, the indirect costs of time spent commuting and at the clinic are less tangible.
Success rates with SCIT may be more than 70% for certain allergens,18 but it is a long-term process with initial improvement often not seen until after six to 12 months of therapy. The benefits of therapy lead not only to reduction and suppression in symptoms (and medication), but also to reduction in comorbidity and lost school or workdays and improvement in quality of life.
Sublingual immunotherapy. Because of the possible safety concerns surrounding SCIT, along with problems relating to patient adherence to weekly office visits, alternative means of achieving allergen desensitization have been implemented. One of these methods, SLIT, has been increasingly supported by clinical evidence, especially in Europe. This therapy consists of applying aqueous allergen extract to the sublingual or oral mucosa, allowing it to be absorbed into the body. Subsequent swallowing of the extract allows the gut to respond with an increase in tolerance. The changes that result from this type of administration appear to be similar to those observed with SCIT.
SLIT has been in use for almost 30 years; the first published controlled study of this therapy was done in 1986 by Scadding and Brostoff.19 The World Allergy Organization recognized the safety and clinical efficacy of SLIT in 2009 after reviewing more than 60 controlled studies.20
A 2010 meta-analysis, reviewing documents from the prior 20 years of research, showed that SLIT decreased medication use and improved symptoms.21 Generally, SLIT was found to be more effective in adults than children. It was not as effective in patients with asthma as in those who were asthma-free. The timing of initiation of SLIT was also an important finding; when SLIT is used for grass pollen allergy, it should be started at least three months before the beginning of grass season.21 For other allergens, SLIT can be started at any time.
Because it is a home-based treatment, SLIT is far more convenient for the patient and therefore has become more popular in the US in the past decade. Its increased safety also contributes to its popularity. Although SLIT is commonly used in many parts of the world, at this writing, medications used in SLIT have not yet been approved by the US FDA. The FDA is currently reviewing two oral tablets for SLIT, and it is expected that its use in the US will increase once an approved product becomes available.22
It should be noted that no studies have directly compared SCIT and SLIT. Careful consultation between clinician and patient can help the patient arrive at the most appropriate modality for his or her condition based on symptomatology and lifestyle needs.
On the next page: Conclusion >>
CONCLUSION
For most patients, AR has little morbidity; however, for some whose rhinitis is moderate to severe, the complications can be a concern. If symptoms are not controlled with avoidance and/or medication, AI may be indicated. It comprises the building up of tolerance to the specific allergens as identified by allergy skin testing or in vitro specific IgE testing. AI, whether SCIT or SLIT, is the only means of altering the abnormal immune system response that underlies AR. Treatment may last as long as three to four years, which provides long-term efficacy of at least three years after cessation of therapy. The long-term prognosis for AR is excellent.
Appreciation is extended to Roxy Irestone, RN, Arizona Asthma & Allergy Institute, for her assistance is gathering factual information for this article.
1. Sibbald B, Rink E, D’Souza M. Is the prevalence of atopy increasing? Br J Gen Pract. 1990;40(337):338-340.
2. History of allergy. Allergy and Asthma Specialists Web site. www.allergyasthmaspecialist.com/allergy-and-asthma-clinic-of-kenosha-sc-education.htm. Accessed February 14, 2014.
3. Blackley CH. Hay Fever: Its Causes, Treatment, and Effective Prevention. London, England: Balliere, Tindall, & Cox; 1880.
4. Settipane RA. Rhinitis: a dose of epidemiological reality. Allergy Asthma Proc. 2003;24(3):147-154.
5. Wallace DV, Dykewicz MS, Bernstein DI, et al. The diagnosis and management of rhinitis: an updated practice parameter. J Allergy Clin Immunol. 2008;122(2 suppl):S1-S84.
6. Wright AL, Holberg CJ, Halonen M, et al. Epidemiology of physician-diagnosed allergic rhinitis in childhood. Pediatrics. 1994;94(6):895 -901.
7. Bernstein JA. Allergic and mixed rhinitis: epidemiology and natural history. Allergy Asthma Proc. 2010;31:365-369.
8. Meltzer EO, Bukstein DA. The economic impact of allergic rhinitis and current guidelines for treatment. Ann Allergy Asthma Immunol. 2011; 106(suppl 2):S12-S16.
9. American Academy of Allergy, Asthma & Immunology. Task force on allergic disorders: promoting best practice: raising the standard of care for patients with allergic disorders. Executive summary report. 1998.
10. Nathan RA. The burden of allergic rhinitis. Allergy Asthma Proc. 2007; 28:3-9.
11. Tran NP, Vickery J, Blaiss MS. Management of rhinitis: allergic and non-allergic. Allergy Asthma Immunol Res. 2011;3:148-156.
12. Disease Summaries: Allergic Diseases and Asthma in Pregnancy. World Allergy Organization. www.worldallergy.org/professional/allergic_
diseases_center/allergy_in_pregnancy/. Accessed February 14, 2014.
13. Simons FE, Ardusso LR, Dimov V, et al. World Allergy Organization Anaphylaxis Guidelines: 2013 update of the evidence base. Int Arch Allergy Immunol. 2013;162:193-204.
14. Noon L. Prophylactic inoculation against hay fever. Lancet. 1911;177:1572-1573.
15. Purello-D’Ambrosio F, Gangemi S, Merendino RA, et al. Prevention of new sensitizations in monosensitized subjects submitted to specific immunotherapy or not: a retrospective study. Clin & Exper Allergy. 2001;31:1295-1302.
16. Durham SR, Walker SM, Varga EM, et al. Long-term clinical efficacy of grass-pollen immunotherapy. N Engl J Med. 1999;341:468-475.
17. Mohapatra SS, Qazi M, Hellermann G. Immunotherapy for allergies and asthma: present and future. Curr Opin Pharmacol. 2010;10:276-288.
18. Calderon MA, Alves B, Jacobson M, et al. Allergen injection immunotherapy for seasonal allergic rhinitis. Cochrane Database Syst Rev. 2007; Iss 1, Art No: CD001936.
19. Scadding GK, Brostoff J. Low dose sublingual therapy in patients with allergic rhinitis due to house dust mite.Clin Allergy. 1986;16:483-491.
20. Canonica GW, Bousquet J, Casale T, et al. Sub-lingual immunotherapy: World Allergy Organization Position Paper 2009. Allergy. 2009;64 suppl 91:1-59.
21. Di Bona D, Plaia A, Scafidi V, et al. Efficacy of sublingual immunotherapy with grass allergens for seasonal allergic rhinitis: a systematic review and meta-analysis. J Allergy Clin Immunol. 2010;126:558-566.
22. Sikora JM, Tankersley MS; ACAAI Immunotherapy and Diagnostics Committee. Perception and practice of sublingual immunotherapy among practicing allergists in the United States: a follow-up survey. Ann Allergy Asthma Immunol. 2013;110:194-197.
CE/CME No: CR-1403
PROGRAM OVERVIEW
Earn credit by reading this article and successfully completing the posttest. Successful completion is defined as a cumulative score of at least 70% correct.
EDUCATIONAL OBJECTIVES
• Explain the pathophysiology and etiology of allergic rhinitis (AR).
• Describe the prevalence and types of AR.
• List the differential diagnoses for AR.
• Describe the historical and physical examination findings that are typical
of AR.
• Explain the indications for and types of allergy testing.
• Discuss the types of allergy desensitization therapies/immunotherapies.
FACULTY
Randy D. Danielsen is a Professor and Dean of the Arizona School of Health Sciences, A.T. Still University in Mesa, Arizona, and a long-time PA with the Arizona Asthma & Allergy Institute. Linda S. MacConnell is an Assistant Professor in the Department of Physician Assistant Studies at the Arizona School of Health Sciences, A.T. Still University, and a formally trained otolaryngology PA.
The authors have no financial disclosures to report.
ACCREDITATION STATEMENT
Article begins on next page >>
Allergic rhinitis (AR), one of the most familiar complaints seen in primary care, is a common immunologic condition that occurs in genetically predisposed patients. AR is routinely treated through allergen avoidance and pharmacologic therapy. When these measures fail, however, immunologic treatment may be indicated. This review of AR and its treatment focuses on injection and oral immunotherapy.
Congestion; sneezing (particularly paroxysms); itchy nose, palate, and eyes; and runny nose are symptoms characteristic of allergic rhinitis (AR) seen every day in virtually all primary care offices. Patients are plagued not only by their symptoms, but also by AR-related sleep disturbances, resulting in fatigue and daytime sleepiness, irritability, and memory deficits. In children, these sleep disruptions may even cause behavioral disturbances. Depending on the cause, some patients may experience allergic symptoms only with outdoor environmental exposure and subsequent immunoglobulin E (IgE)–mediated responses to otherwise innocuous allergens, while others find that their symptoms are constant, occurring both indoors and out.
Although the prevalence of AR is increasing,1 allergies are certainly nothing new to humankind. In fact, hieroglyphics and Egyptian wall paintings have been discovered depicting a pharaoh dying from anaphylactic shock after receiving a wasp sting.2 In 1565, Leonardo Botallo described AR, calling it “rose catarrh” (mucous or phlegm) or “rose fever,” based on the mistaken idea that the symptoms were caused by rose pollen.2 John Babcock, an English physician, first diagnosed an upper respiratory disease that he called “hay fever” in 1819.
Seventy years later, Charles Blackley identified pollen as a cause of hay fever, documenting his findings in his 1873 book Experimental Researches on the Causes and Nature of Catarrhus Aestivus.2 Dr. Blackley performed the initial documented attempts at allergy desensitization treatments on himself—a willing patient, as he suffered from AR. He placed rye grass pollen onto his nasal mucosa, finding that after 30 minutes the nostril was completely occluded. He continued his experimentation by repeatedly exposing himself to pollen grains via abraded skin. Alas, he never noted any decrease in his symptoms.3
Presently, AR affects more than 55 million people in the United States4—approximately 10% to 30% of the adult population5 and more than 40% of children.6 The rising prevalence of AR is of concern in older adults, who tend to have related comorbidities (eg, chronic sinusitis, asthma, and otitis media). In fact, AR is the fifth most common chronic disease in the US.7
AR and its treatment impose a great economic burden on the health care system, critical in these days of affordable health care. In fact, in 2005 in the US, the overall (direct medical and indirect) cost of AR was $11.2 billion.8 Direct costs derive from office visits, diagnostic testing, and therapeutics. Costs are considerably higher when indirect expenses, including decreased productivity, missed school and missed workdays to care for children, and costs of travel to medical appointments, are included. In the US, approximately 3.5 million workdays and 2 million school days are lost each year due to AR.9 Decreases in productivity cost an estimated $600 per affected employee per year, all of which results in AR being the fifth costliest chronic disease.10,11
On the next page: Pathophysiology and examination >>
PATHOPHYSIOLOGY
AR is an immunologic disorder that occurs in genetically susceptible individuals who produce allergen-specific IgE antibody responses after environmental exposures. The IgE-mediated response causes inflammation of the nasal mucosa. Compared to controls, individuals with AR demonstrate increased amounts of IgE antibodies in the nasal mucosa.11 IgE binds to basophils in the bloodstream and mast cells in tissue. Allergens then attach to IgE on basophils and mast cells, which release histamines, prostaglandins, cytokines, and leukotrienes, with histamine being the most significant mediator in the inflammatory response.
In response to allergy-provoking substances, patients experience immediate- and late-phase symptoms. Symptoms of each stage are similar, but congestion is the hallmark of the late phase. While both phases are clinically important because of their contribution to the patient’s symptoms, most patients experience continued exposure to allergens, resulting in constant, overlapping symptoms.
HISTORY AND PHYSICAL EXAMINATION
Patients with AR relate a history of congestion, excessive mucous production, itchy, watery eyes, bouts of sneezing, and more systemic symptoms, such as headache, malaise, and excessive fatigue. It is important to evaluate the degree and duration of the symptoms, noting patterns and triggers, in an effort to confirm the diagnosis and to help the patient evaluate treatment options.
When taking the patient history, always review the family history, which is often notable for allergies and other atopic diseases. Be sure to ask about medications and recreational drug use; a number of substances have been implicated in the development of rhinitis, including anticholinergic medications, oxymetazoline (when overused), and cocaine. Also, question the patient about self-medication and treatment to determine what may or may not have provided relief. Further questioning may also reveal a history of comorbidities, including contact dermatitis, asthma, eczema, and chronic sinusitis.
The physical examination of the patient with rhinitis begins with observation of the patient’s outward appearance, which may reveal allergic shiners (dark to purplish areas under the eyes), conjunctivitis, an allergic salute (a transverse crease of the nose caused by upward rubbing of an itchy nose), mouth breathing, and a generally tired appearance. The nasal turbinates are swollen and often pale. Mucous secretions are usually thin and clear. Enlarged tonsils and posterior nasal drainage may be visualized. The types of AR are listed in Table 1.
On the next page: Diagnosis and treatment >>
DIAGNOSIS
Most of the clues needed to arrive at a diagnosis are discovered by taking a careful history and completing a physical examination. AR frequently underlies and/or coexists with acute upper respiratory infection (URI) and acute and chronic sinusitis. Differentiating acute URI and acute sinusitis from AR is usually relatively straightforward, based on the symptoms of the illness. The diagnosis of chronic sinusitis is made by radiologic imaging with CT scan.
Distinguishing nonallergic rhinitis (NAR) from AR can be far more difficult, because the symptoms of these conditions are similar and chronic in nature (see Table 2). Empiric treatment for AR may be attempted; however, further testing is often needed to differentiate the two. At this point, clinicians may choose to proceed with specific IgE blood tests. Alternatively, many medical practices are prepared to perform or refer for allergy skin testing.
TREATMENT
Avoidance of known triggers is the cornerstone of allergy treatment. Currently, the most effective pharmaceutical treatment for the majority of AR symptoms is inhaled nasal corticosteroids. Although less effective than corticosteroids, antihistamines—both nasal and oral—are a recommended addition to the regimen if the adverse effects and costs to the patient are tolerable. Other treatments include the leukotriene receptor antagonists, intranasal formulations of cromolyn, and the anticholinergic ipratropium bromide nasal spray, which is effective primarily on watery rhinorrhea. If symptoms are not controlled with medication, allergy immunotherapy (AI), the only known disease-modifying therapy for AR, may be indicated.
On the next page: Allergy testing >>
ALLERGY TESTING
In order to distinguish between AR and NAR and to direct treatment toward specific allergen avoidance and immunotherapy, providers have the choice of ordering in vitro blood IgE testing (to measure the antibodies that mediate an allergic response) or in vivo allergy skin testing (to measure the immune response to allergens that induces an allergic atopic reaction). Allergy testing is not a contemporary concept; the first allergy testing was documented in 1656 when Pierre Borel applied egg to a patient’s skin, which exhibited an allergic reaction.2
Allergy skin testing consists of applying multiple allergens to the skin of the patient’s forearms via tiny pinpricks while watching for immediate hypersensitivity reactions. The test begins with the placement of a drop of histamine to serve as a control. If after 10 minutes of watchful waiting the patient develops a reaction to the histamine (a positive test result), it is appropriate to test for antigens by placing drops of suspected allergen extracts on the skin.
After a period of time (usually 20 to 30 minutes), the area is inspected for allergic reaction. An immediate (early phase) wheal and flare (surrounding erythema) reaction may develop. This positive reaction indicates the presence of a mast cell–bound IgE antibody specific to the tested allergen. The size of the reactions is measured in millimeters, allowing for comparison to the histamine control.
A list of the commonly tested antigens in Arizona, as an example, is shown in Table 3. Antigens vary geographically and even from practice to practice. For up-to-date information on pollen counts by region, visit the American Academy of Allergy Asthma & Immunology Web site (see “Pollen Counts”).
On the next page: Patient selection and allergy immunotherapy >>
Patient Selection
After the clinician has determined that there is a high likelihood that the diagnosis is AR, allergy testing, needed to guide AI, is appropriate. Although not true of specific IgE testing, the accuracy of allergy skin testing results can be adversely affected by several medications. For example, some practitioners may choose to stop first-generation antihistamines two to three days before testing. It is generally accepted that the newer, second-generation antihistamines, which can affect skin-testing results longer, be stopped a week prior to testing.
Patients should be reminded that OTC sleep aids frequently contain antihistamines (particularly diphenhydramine) and that they must be discontinued prior to testing as well. Histamine H2-receptor antagonists such as cimetidine and ranitidine may be stopped a day or two before testing. Although β-blockers are only relatively contraindicated in both allergy testing and AI, many health care providers avoid testing and AI in patients taking oral and/or topical (eye drops) β-blocker therapy. Ultimately, the decision is made by individual health care practices.
In vivo allergy skin testing should not be performed on patients taking tricyclic antidepressants and monoamine oxidase inhibitors. Patients with significant cardiovascular disease should not undergo testing or treatment. Pregnancy is a relative contraindication, and allergy skin testing and AI are done only with obstetrician approval. Most allergists avoid allergy skin testing in pregnant women, however, because use of epinephrine, if required, introduces the risk for preterm labor.12,13 Special consideration should also be given to patients with immune deficiencies.
Setting for Allergy Evaluation and Treatment
Recently, many primary care practices have added allergy evaluation and management to the procedures and treatments they offer; however, evaluations and testing traditionally have been performed by allergy and immunology specialists, many of whom include PAs and NPs on their staff. PAs and NPs frequently manage the practices’ allergy programs. Allergists who are listed as American Board of Allergy and Immunology (ABAI)–certified have successfully passed the ABAI’s certifying examination. Other medical specialists, including otolaryngologists and the primary care specialties, are also well placed to evaluate patients with common allergy symptoms and provide appropriate treatment.
Allergy Immunotherapy
AI has now become more efficacious, safer, and more tolerable for the patient than when it was first introduced in 1911. At that time, Leonard Noon authored a brief article claiming that allergen-specific injections could modify AR. Unfortunately, Noon died at age 36 from tuberculosis, but his work was carried on by his associate, John Freeman. Together, they established the guidelines upon which contemporary AI is based, including the protocol to gradually increase the dose of allergen serum, starting with initial weekly to biweekly injections. They also voiced warnings about the potential for anaphylaxis.14 To this day, immunotherapy is still accomplished by the gradual administration of increasing amounts of the allergen to which the patient is sensitive. This tempers the abnormal immune response to that allergen, easing allergic symptoms.
In patients with IgE-mediated hypersensitivity reactions, confirmed by history, physical examination, and allergy skin testing, immunotherapy can be very effective. The results of immunotherapy may last for years and may even prevent the allergic march, the progression of allergic disease experienced by many patients that frequently begins early in life.15 This includes other allergy-related conditions, such as asthma and eczema (atopic dermatitis), and the acquisition of additional new allergies, including those to foods. AI also has been shown to decrease the frequency of comorbidities such as asthma.5 In addition, AI is used in carefully screened patients who desire to reduce the dosages of medication required to control their symptoms.
In a study published in 1999, Durham and colleagues clarified the questions surrounding the amount of time required for ongoing immunotherapy. They found that the desensitization and tolerance to allergens achieved by AI can last up to three years after a three- to four-year course of therapy. They also found that treatment should not start until an allergic component is identified by allergy skin testing or serum tests for allergen-specific IgE.16
As effective as immunotherapy has been documented to be, it is underused as a therapeutic modality. There are only 2 to 3 million patients receiving subcutaneous immunotherapy out of more than 55 million patients with AR.17
On the next page: Types of allergy immunotherapy >>
Types of AI
There are two categories of allergen desensitization therapy. The most common method is subcutaneous immunotherapy (SCIT), the so-called allergy shots. Less common and still somewhat controversial is sublingual immunotherapy (SLIT). Immunotherapy should be considered for patients who have secondary complications (eg, sinusitis, otitis) or asthma with allergies, or those in whom avoidance measures and medications fail. SCIT or SLIT may be desirable for patients with AR who have difficulty taking regular medications.
Subcutaneous immunotherapy. Currently, SCIT is the most recognized immunotherapy and the only one currently reimbursed by insurance. The procedure involves the subcutaneous injection of increasing doses of therapeutic solutions to which a patient has demonstrated sensitivity. The indications for this treatment are usually inhaled allergens, such as pollens and animal dander. SCIT may also be valuable in patients with asthma and atopic dermatitis.
The most common adverse reaction to allergy injections is a large localized reaction—primarily erythema, pruritus, discomfort, and possibly edema. Severe systemic reactions are extremely rare, with near-fatal to fatal reactions occurring at the rate of only 5.4 per million injections.11 The majority of these rare, albeit serious, complications are caused by higher-than-normal levels of pollen in the environment and dosing errors.11 Because of the uncommon but significant complications, patients undergoing immunotherapy should always receive injections in a medical office equipped with appropriate equipment and staff trained in handling anaphylaxis. It is standard protocol for patients to remain in the office for 30 minutes after administration for observation. Some clinicians prescribe epinephrine injectors (Epi-Pens) for patients to bring to every appointment as a condition for receiving their shot. Because of continuing controversy on this point, others only employ this requirement if the patient has a history of an adverse reaction.
Various protocols exist for the up-dosing of immunotherapy, most of which recommend weekly to twice-weekly injections prior to initiating maintenance therapy. Costs, risks, and benefits must be carefully considered and discussed with the patient prior to initiating immunotherapy.
Many insurance companies reimburse for immunotherapy, with varying copayments. Additionally, the time commitment may be taxing on the patient’s busy schedule. Weekly or biweekly appointments are required initially, and the patient must remain on site for half an hour. Although direct costs of SCIT are relatively easily measured and perhaps compensated, the indirect costs of time spent commuting and at the clinic are less tangible.
Success rates with SCIT may be more than 70% for certain allergens,18 but it is a long-term process with initial improvement often not seen until after six to 12 months of therapy. The benefits of therapy lead not only to reduction and suppression in symptoms (and medication), but also to reduction in comorbidity and lost school or workdays and improvement in quality of life.
Sublingual immunotherapy. Because of the possible safety concerns surrounding SCIT, along with problems relating to patient adherence to weekly office visits, alternative means of achieving allergen desensitization have been implemented. One of these methods, SLIT, has been increasingly supported by clinical evidence, especially in Europe. This therapy consists of applying aqueous allergen extract to the sublingual or oral mucosa, allowing it to be absorbed into the body. Subsequent swallowing of the extract allows the gut to respond with an increase in tolerance. The changes that result from this type of administration appear to be similar to those observed with SCIT.
SLIT has been in use for almost 30 years; the first published controlled study of this therapy was done in 1986 by Scadding and Brostoff.19 The World Allergy Organization recognized the safety and clinical efficacy of SLIT in 2009 after reviewing more than 60 controlled studies.20
A 2010 meta-analysis, reviewing documents from the prior 20 years of research, showed that SLIT decreased medication use and improved symptoms.21 Generally, SLIT was found to be more effective in adults than children. It was not as effective in patients with asthma as in those who were asthma-free. The timing of initiation of SLIT was also an important finding; when SLIT is used for grass pollen allergy, it should be started at least three months before the beginning of grass season.21 For other allergens, SLIT can be started at any time.
Because it is a home-based treatment, SLIT is far more convenient for the patient and therefore has become more popular in the US in the past decade. Its increased safety also contributes to its popularity. Although SLIT is commonly used in many parts of the world, at this writing, medications used in SLIT have not yet been approved by the US FDA. The FDA is currently reviewing two oral tablets for SLIT, and it is expected that its use in the US will increase once an approved product becomes available.22
It should be noted that no studies have directly compared SCIT and SLIT. Careful consultation between clinician and patient can help the patient arrive at the most appropriate modality for his or her condition based on symptomatology and lifestyle needs.
On the next page: Conclusion >>
CONCLUSION
For most patients, AR has little morbidity; however, for some whose rhinitis is moderate to severe, the complications can be a concern. If symptoms are not controlled with avoidance and/or medication, AI may be indicated. It comprises the building up of tolerance to the specific allergens as identified by allergy skin testing or in vitro specific IgE testing. AI, whether SCIT or SLIT, is the only means of altering the abnormal immune system response that underlies AR. Treatment may last as long as three to four years, which provides long-term efficacy of at least three years after cessation of therapy. The long-term prognosis for AR is excellent.
Appreciation is extended to Roxy Irestone, RN, Arizona Asthma & Allergy Institute, for her assistance is gathering factual information for this article.
CE/CME No: CR-1403
PROGRAM OVERVIEW
Earn credit by reading this article and successfully completing the posttest. Successful completion is defined as a cumulative score of at least 70% correct.
EDUCATIONAL OBJECTIVES
• Explain the pathophysiology and etiology of allergic rhinitis (AR).
• Describe the prevalence and types of AR.
• List the differential diagnoses for AR.
• Describe the historical and physical examination findings that are typical
of AR.
• Explain the indications for and types of allergy testing.
• Discuss the types of allergy desensitization therapies/immunotherapies.
FACULTY
Randy D. Danielsen is a Professor and Dean of the Arizona School of Health Sciences, A.T. Still University in Mesa, Arizona, and a long-time PA with the Arizona Asthma & Allergy Institute. Linda S. MacConnell is an Assistant Professor in the Department of Physician Assistant Studies at the Arizona School of Health Sciences, A.T. Still University, and a formally trained otolaryngology PA.
The authors have no financial disclosures to report.
ACCREDITATION STATEMENT
Article begins on next page >>
Allergic rhinitis (AR), one of the most familiar complaints seen in primary care, is a common immunologic condition that occurs in genetically predisposed patients. AR is routinely treated through allergen avoidance and pharmacologic therapy. When these measures fail, however, immunologic treatment may be indicated. This review of AR and its treatment focuses on injection and oral immunotherapy.
Congestion; sneezing (particularly paroxysms); itchy nose, palate, and eyes; and runny nose are symptoms characteristic of allergic rhinitis (AR) seen every day in virtually all primary care offices. Patients are plagued not only by their symptoms, but also by AR-related sleep disturbances, resulting in fatigue and daytime sleepiness, irritability, and memory deficits. In children, these sleep disruptions may even cause behavioral disturbances. Depending on the cause, some patients may experience allergic symptoms only with outdoor environmental exposure and subsequent immunoglobulin E (IgE)–mediated responses to otherwise innocuous allergens, while others find that their symptoms are constant, occurring both indoors and out.
Although the prevalence of AR is increasing,1 allergies are certainly nothing new to humankind. In fact, hieroglyphics and Egyptian wall paintings have been discovered depicting a pharaoh dying from anaphylactic shock after receiving a wasp sting.2 In 1565, Leonardo Botallo described AR, calling it “rose catarrh” (mucous or phlegm) or “rose fever,” based on the mistaken idea that the symptoms were caused by rose pollen.2 John Babcock, an English physician, first diagnosed an upper respiratory disease that he called “hay fever” in 1819.
Seventy years later, Charles Blackley identified pollen as a cause of hay fever, documenting his findings in his 1873 book Experimental Researches on the Causes and Nature of Catarrhus Aestivus.2 Dr. Blackley performed the initial documented attempts at allergy desensitization treatments on himself—a willing patient, as he suffered from AR. He placed rye grass pollen onto his nasal mucosa, finding that after 30 minutes the nostril was completely occluded. He continued his experimentation by repeatedly exposing himself to pollen grains via abraded skin. Alas, he never noted any decrease in his symptoms.3
Presently, AR affects more than 55 million people in the United States4—approximately 10% to 30% of the adult population5 and more than 40% of children.6 The rising prevalence of AR is of concern in older adults, who tend to have related comorbidities (eg, chronic sinusitis, asthma, and otitis media). In fact, AR is the fifth most common chronic disease in the US.7
AR and its treatment impose a great economic burden on the health care system, critical in these days of affordable health care. In fact, in 2005 in the US, the overall (direct medical and indirect) cost of AR was $11.2 billion.8 Direct costs derive from office visits, diagnostic testing, and therapeutics. Costs are considerably higher when indirect expenses, including decreased productivity, missed school and missed workdays to care for children, and costs of travel to medical appointments, are included. In the US, approximately 3.5 million workdays and 2 million school days are lost each year due to AR.9 Decreases in productivity cost an estimated $600 per affected employee per year, all of which results in AR being the fifth costliest chronic disease.10,11
On the next page: Pathophysiology and examination >>
PATHOPHYSIOLOGY
AR is an immunologic disorder that occurs in genetically susceptible individuals who produce allergen-specific IgE antibody responses after environmental exposures. The IgE-mediated response causes inflammation of the nasal mucosa. Compared to controls, individuals with AR demonstrate increased amounts of IgE antibodies in the nasal mucosa.11 IgE binds to basophils in the bloodstream and mast cells in tissue. Allergens then attach to IgE on basophils and mast cells, which release histamines, prostaglandins, cytokines, and leukotrienes, with histamine being the most significant mediator in the inflammatory response.
In response to allergy-provoking substances, patients experience immediate- and late-phase symptoms. Symptoms of each stage are similar, but congestion is the hallmark of the late phase. While both phases are clinically important because of their contribution to the patient’s symptoms, most patients experience continued exposure to allergens, resulting in constant, overlapping symptoms.
HISTORY AND PHYSICAL EXAMINATION
Patients with AR relate a history of congestion, excessive mucous production, itchy, watery eyes, bouts of sneezing, and more systemic symptoms, such as headache, malaise, and excessive fatigue. It is important to evaluate the degree and duration of the symptoms, noting patterns and triggers, in an effort to confirm the diagnosis and to help the patient evaluate treatment options.
When taking the patient history, always review the family history, which is often notable for allergies and other atopic diseases. Be sure to ask about medications and recreational drug use; a number of substances have been implicated in the development of rhinitis, including anticholinergic medications, oxymetazoline (when overused), and cocaine. Also, question the patient about self-medication and treatment to determine what may or may not have provided relief. Further questioning may also reveal a history of comorbidities, including contact dermatitis, asthma, eczema, and chronic sinusitis.
The physical examination of the patient with rhinitis begins with observation of the patient’s outward appearance, which may reveal allergic shiners (dark to purplish areas under the eyes), conjunctivitis, an allergic salute (a transverse crease of the nose caused by upward rubbing of an itchy nose), mouth breathing, and a generally tired appearance. The nasal turbinates are swollen and often pale. Mucous secretions are usually thin and clear. Enlarged tonsils and posterior nasal drainage may be visualized. The types of AR are listed in Table 1.
On the next page: Diagnosis and treatment >>
DIAGNOSIS
Most of the clues needed to arrive at a diagnosis are discovered by taking a careful history and completing a physical examination. AR frequently underlies and/or coexists with acute upper respiratory infection (URI) and acute and chronic sinusitis. Differentiating acute URI and acute sinusitis from AR is usually relatively straightforward, based on the symptoms of the illness. The diagnosis of chronic sinusitis is made by radiologic imaging with CT scan.
Distinguishing nonallergic rhinitis (NAR) from AR can be far more difficult, because the symptoms of these conditions are similar and chronic in nature (see Table 2). Empiric treatment for AR may be attempted; however, further testing is often needed to differentiate the two. At this point, clinicians may choose to proceed with specific IgE blood tests. Alternatively, many medical practices are prepared to perform or refer for allergy skin testing.
TREATMENT
Avoidance of known triggers is the cornerstone of allergy treatment. Currently, the most effective pharmaceutical treatment for the majority of AR symptoms is inhaled nasal corticosteroids. Although less effective than corticosteroids, antihistamines—both nasal and oral—are a recommended addition to the regimen if the adverse effects and costs to the patient are tolerable. Other treatments include the leukotriene receptor antagonists, intranasal formulations of cromolyn, and the anticholinergic ipratropium bromide nasal spray, which is effective primarily on watery rhinorrhea. If symptoms are not controlled with medication, allergy immunotherapy (AI), the only known disease-modifying therapy for AR, may be indicated.
On the next page: Allergy testing >>
ALLERGY TESTING
In order to distinguish between AR and NAR and to direct treatment toward specific allergen avoidance and immunotherapy, providers have the choice of ordering in vitro blood IgE testing (to measure the antibodies that mediate an allergic response) or in vivo allergy skin testing (to measure the immune response to allergens that induces an allergic atopic reaction). Allergy testing is not a contemporary concept; the first allergy testing was documented in 1656 when Pierre Borel applied egg to a patient’s skin, which exhibited an allergic reaction.2
Allergy skin testing consists of applying multiple allergens to the skin of the patient’s forearms via tiny pinpricks while watching for immediate hypersensitivity reactions. The test begins with the placement of a drop of histamine to serve as a control. If after 10 minutes of watchful waiting the patient develops a reaction to the histamine (a positive test result), it is appropriate to test for antigens by placing drops of suspected allergen extracts on the skin.
After a period of time (usually 20 to 30 minutes), the area is inspected for allergic reaction. An immediate (early phase) wheal and flare (surrounding erythema) reaction may develop. This positive reaction indicates the presence of a mast cell–bound IgE antibody specific to the tested allergen. The size of the reactions is measured in millimeters, allowing for comparison to the histamine control.
A list of the commonly tested antigens in Arizona, as an example, is shown in Table 3. Antigens vary geographically and even from practice to practice. For up-to-date information on pollen counts by region, visit the American Academy of Allergy Asthma & Immunology Web site (see “Pollen Counts”).
On the next page: Patient selection and allergy immunotherapy >>
Patient Selection
After the clinician has determined that there is a high likelihood that the diagnosis is AR, allergy testing, needed to guide AI, is appropriate. Although not true of specific IgE testing, the accuracy of allergy skin testing results can be adversely affected by several medications. For example, some practitioners may choose to stop first-generation antihistamines two to three days before testing. It is generally accepted that the newer, second-generation antihistamines, which can affect skin-testing results longer, be stopped a week prior to testing.
Patients should be reminded that OTC sleep aids frequently contain antihistamines (particularly diphenhydramine) and that they must be discontinued prior to testing as well. Histamine H2-receptor antagonists such as cimetidine and ranitidine may be stopped a day or two before testing. Although β-blockers are only relatively contraindicated in both allergy testing and AI, many health care providers avoid testing and AI in patients taking oral and/or topical (eye drops) β-blocker therapy. Ultimately, the decision is made by individual health care practices.
In vivo allergy skin testing should not be performed on patients taking tricyclic antidepressants and monoamine oxidase inhibitors. Patients with significant cardiovascular disease should not undergo testing or treatment. Pregnancy is a relative contraindication, and allergy skin testing and AI are done only with obstetrician approval. Most allergists avoid allergy skin testing in pregnant women, however, because use of epinephrine, if required, introduces the risk for preterm labor.12,13 Special consideration should also be given to patients with immune deficiencies.
Setting for Allergy Evaluation and Treatment
Recently, many primary care practices have added allergy evaluation and management to the procedures and treatments they offer; however, evaluations and testing traditionally have been performed by allergy and immunology specialists, many of whom include PAs and NPs on their staff. PAs and NPs frequently manage the practices’ allergy programs. Allergists who are listed as American Board of Allergy and Immunology (ABAI)–certified have successfully passed the ABAI’s certifying examination. Other medical specialists, including otolaryngologists and the primary care specialties, are also well placed to evaluate patients with common allergy symptoms and provide appropriate treatment.
Allergy Immunotherapy
AI has now become more efficacious, safer, and more tolerable for the patient than when it was first introduced in 1911. At that time, Leonard Noon authored a brief article claiming that allergen-specific injections could modify AR. Unfortunately, Noon died at age 36 from tuberculosis, but his work was carried on by his associate, John Freeman. Together, they established the guidelines upon which contemporary AI is based, including the protocol to gradually increase the dose of allergen serum, starting with initial weekly to biweekly injections. They also voiced warnings about the potential for anaphylaxis.14 To this day, immunotherapy is still accomplished by the gradual administration of increasing amounts of the allergen to which the patient is sensitive. This tempers the abnormal immune response to that allergen, easing allergic symptoms.
In patients with IgE-mediated hypersensitivity reactions, confirmed by history, physical examination, and allergy skin testing, immunotherapy can be very effective. The results of immunotherapy may last for years and may even prevent the allergic march, the progression of allergic disease experienced by many patients that frequently begins early in life.15 This includes other allergy-related conditions, such as asthma and eczema (atopic dermatitis), and the acquisition of additional new allergies, including those to foods. AI also has been shown to decrease the frequency of comorbidities such as asthma.5 In addition, AI is used in carefully screened patients who desire to reduce the dosages of medication required to control their symptoms.
In a study published in 1999, Durham and colleagues clarified the questions surrounding the amount of time required for ongoing immunotherapy. They found that the desensitization and tolerance to allergens achieved by AI can last up to three years after a three- to four-year course of therapy. They also found that treatment should not start until an allergic component is identified by allergy skin testing or serum tests for allergen-specific IgE.16
As effective as immunotherapy has been documented to be, it is underused as a therapeutic modality. There are only 2 to 3 million patients receiving subcutaneous immunotherapy out of more than 55 million patients with AR.17
On the next page: Types of allergy immunotherapy >>
Types of AI
There are two categories of allergen desensitization therapy. The most common method is subcutaneous immunotherapy (SCIT), the so-called allergy shots. Less common and still somewhat controversial is sublingual immunotherapy (SLIT). Immunotherapy should be considered for patients who have secondary complications (eg, sinusitis, otitis) or asthma with allergies, or those in whom avoidance measures and medications fail. SCIT or SLIT may be desirable for patients with AR who have difficulty taking regular medications.
Subcutaneous immunotherapy. Currently, SCIT is the most recognized immunotherapy and the only one currently reimbursed by insurance. The procedure involves the subcutaneous injection of increasing doses of therapeutic solutions to which a patient has demonstrated sensitivity. The indications for this treatment are usually inhaled allergens, such as pollens and animal dander. SCIT may also be valuable in patients with asthma and atopic dermatitis.
The most common adverse reaction to allergy injections is a large localized reaction—primarily erythema, pruritus, discomfort, and possibly edema. Severe systemic reactions are extremely rare, with near-fatal to fatal reactions occurring at the rate of only 5.4 per million injections.11 The majority of these rare, albeit serious, complications are caused by higher-than-normal levels of pollen in the environment and dosing errors.11 Because of the uncommon but significant complications, patients undergoing immunotherapy should always receive injections in a medical office equipped with appropriate equipment and staff trained in handling anaphylaxis. It is standard protocol for patients to remain in the office for 30 minutes after administration for observation. Some clinicians prescribe epinephrine injectors (Epi-Pens) for patients to bring to every appointment as a condition for receiving their shot. Because of continuing controversy on this point, others only employ this requirement if the patient has a history of an adverse reaction.
Various protocols exist for the up-dosing of immunotherapy, most of which recommend weekly to twice-weekly injections prior to initiating maintenance therapy. Costs, risks, and benefits must be carefully considered and discussed with the patient prior to initiating immunotherapy.
Many insurance companies reimburse for immunotherapy, with varying copayments. Additionally, the time commitment may be taxing on the patient’s busy schedule. Weekly or biweekly appointments are required initially, and the patient must remain on site for half an hour. Although direct costs of SCIT are relatively easily measured and perhaps compensated, the indirect costs of time spent commuting and at the clinic are less tangible.
Success rates with SCIT may be more than 70% for certain allergens,18 but it is a long-term process with initial improvement often not seen until after six to 12 months of therapy. The benefits of therapy lead not only to reduction and suppression in symptoms (and medication), but also to reduction in comorbidity and lost school or workdays and improvement in quality of life.
Sublingual immunotherapy. Because of the possible safety concerns surrounding SCIT, along with problems relating to patient adherence to weekly office visits, alternative means of achieving allergen desensitization have been implemented. One of these methods, SLIT, has been increasingly supported by clinical evidence, especially in Europe. This therapy consists of applying aqueous allergen extract to the sublingual or oral mucosa, allowing it to be absorbed into the body. Subsequent swallowing of the extract allows the gut to respond with an increase in tolerance. The changes that result from this type of administration appear to be similar to those observed with SCIT.
SLIT has been in use for almost 30 years; the first published controlled study of this therapy was done in 1986 by Scadding and Brostoff.19 The World Allergy Organization recognized the safety and clinical efficacy of SLIT in 2009 after reviewing more than 60 controlled studies.20
A 2010 meta-analysis, reviewing documents from the prior 20 years of research, showed that SLIT decreased medication use and improved symptoms.21 Generally, SLIT was found to be more effective in adults than children. It was not as effective in patients with asthma as in those who were asthma-free. The timing of initiation of SLIT was also an important finding; when SLIT is used for grass pollen allergy, it should be started at least three months before the beginning of grass season.21 For other allergens, SLIT can be started at any time.
Because it is a home-based treatment, SLIT is far more convenient for the patient and therefore has become more popular in the US in the past decade. Its increased safety also contributes to its popularity. Although SLIT is commonly used in many parts of the world, at this writing, medications used in SLIT have not yet been approved by the US FDA. The FDA is currently reviewing two oral tablets for SLIT, and it is expected that its use in the US will increase once an approved product becomes available.22
It should be noted that no studies have directly compared SCIT and SLIT. Careful consultation between clinician and patient can help the patient arrive at the most appropriate modality for his or her condition based on symptomatology and lifestyle needs.
On the next page: Conclusion >>
CONCLUSION
For most patients, AR has little morbidity; however, for some whose rhinitis is moderate to severe, the complications can be a concern. If symptoms are not controlled with avoidance and/or medication, AI may be indicated. It comprises the building up of tolerance to the specific allergens as identified by allergy skin testing or in vitro specific IgE testing. AI, whether SCIT or SLIT, is the only means of altering the abnormal immune system response that underlies AR. Treatment may last as long as three to four years, which provides long-term efficacy of at least three years after cessation of therapy. The long-term prognosis for AR is excellent.
Appreciation is extended to Roxy Irestone, RN, Arizona Asthma & Allergy Institute, for her assistance is gathering factual information for this article.
1. Sibbald B, Rink E, D’Souza M. Is the prevalence of atopy increasing? Br J Gen Pract. 1990;40(337):338-340.
2. History of allergy. Allergy and Asthma Specialists Web site. www.allergyasthmaspecialist.com/allergy-and-asthma-clinic-of-kenosha-sc-education.htm. Accessed February 14, 2014.
3. Blackley CH. Hay Fever: Its Causes, Treatment, and Effective Prevention. London, England: Balliere, Tindall, & Cox; 1880.
4. Settipane RA. Rhinitis: a dose of epidemiological reality. Allergy Asthma Proc. 2003;24(3):147-154.
5. Wallace DV, Dykewicz MS, Bernstein DI, et al. The diagnosis and management of rhinitis: an updated practice parameter. J Allergy Clin Immunol. 2008;122(2 suppl):S1-S84.
6. Wright AL, Holberg CJ, Halonen M, et al. Epidemiology of physician-diagnosed allergic rhinitis in childhood. Pediatrics. 1994;94(6):895 -901.
7. Bernstein JA. Allergic and mixed rhinitis: epidemiology and natural history. Allergy Asthma Proc. 2010;31:365-369.
8. Meltzer EO, Bukstein DA. The economic impact of allergic rhinitis and current guidelines for treatment. Ann Allergy Asthma Immunol. 2011; 106(suppl 2):S12-S16.
9. American Academy of Allergy, Asthma & Immunology. Task force on allergic disorders: promoting best practice: raising the standard of care for patients with allergic disorders. Executive summary report. 1998.
10. Nathan RA. The burden of allergic rhinitis. Allergy Asthma Proc. 2007; 28:3-9.
11. Tran NP, Vickery J, Blaiss MS. Management of rhinitis: allergic and non-allergic. Allergy Asthma Immunol Res. 2011;3:148-156.
12. Disease Summaries: Allergic Diseases and Asthma in Pregnancy. World Allergy Organization. www.worldallergy.org/professional/allergic_
diseases_center/allergy_in_pregnancy/. Accessed February 14, 2014.
13. Simons FE, Ardusso LR, Dimov V, et al. World Allergy Organization Anaphylaxis Guidelines: 2013 update of the evidence base. Int Arch Allergy Immunol. 2013;162:193-204.
14. Noon L. Prophylactic inoculation against hay fever. Lancet. 1911;177:1572-1573.
15. Purello-D’Ambrosio F, Gangemi S, Merendino RA, et al. Prevention of new sensitizations in monosensitized subjects submitted to specific immunotherapy or not: a retrospective study. Clin & Exper Allergy. 2001;31:1295-1302.
16. Durham SR, Walker SM, Varga EM, et al. Long-term clinical efficacy of grass-pollen immunotherapy. N Engl J Med. 1999;341:468-475.
17. Mohapatra SS, Qazi M, Hellermann G. Immunotherapy for allergies and asthma: present and future. Curr Opin Pharmacol. 2010;10:276-288.
18. Calderon MA, Alves B, Jacobson M, et al. Allergen injection immunotherapy for seasonal allergic rhinitis. Cochrane Database Syst Rev. 2007; Iss 1, Art No: CD001936.
19. Scadding GK, Brostoff J. Low dose sublingual therapy in patients with allergic rhinitis due to house dust mite.Clin Allergy. 1986;16:483-491.
20. Canonica GW, Bousquet J, Casale T, et al. Sub-lingual immunotherapy: World Allergy Organization Position Paper 2009. Allergy. 2009;64 suppl 91:1-59.
21. Di Bona D, Plaia A, Scafidi V, et al. Efficacy of sublingual immunotherapy with grass allergens for seasonal allergic rhinitis: a systematic review and meta-analysis. J Allergy Clin Immunol. 2010;126:558-566.
22. Sikora JM, Tankersley MS; ACAAI Immunotherapy and Diagnostics Committee. Perception and practice of sublingual immunotherapy among practicing allergists in the United States: a follow-up survey. Ann Allergy Asthma Immunol. 2013;110:194-197.
1. Sibbald B, Rink E, D’Souza M. Is the prevalence of atopy increasing? Br J Gen Pract. 1990;40(337):338-340.
2. History of allergy. Allergy and Asthma Specialists Web site. www.allergyasthmaspecialist.com/allergy-and-asthma-clinic-of-kenosha-sc-education.htm. Accessed February 14, 2014.
3. Blackley CH. Hay Fever: Its Causes, Treatment, and Effective Prevention. London, England: Balliere, Tindall, & Cox; 1880.
4. Settipane RA. Rhinitis: a dose of epidemiological reality. Allergy Asthma Proc. 2003;24(3):147-154.
5. Wallace DV, Dykewicz MS, Bernstein DI, et al. The diagnosis and management of rhinitis: an updated practice parameter. J Allergy Clin Immunol. 2008;122(2 suppl):S1-S84.
6. Wright AL, Holberg CJ, Halonen M, et al. Epidemiology of physician-diagnosed allergic rhinitis in childhood. Pediatrics. 1994;94(6):895 -901.
7. Bernstein JA. Allergic and mixed rhinitis: epidemiology and natural history. Allergy Asthma Proc. 2010;31:365-369.
8. Meltzer EO, Bukstein DA. The economic impact of allergic rhinitis and current guidelines for treatment. Ann Allergy Asthma Immunol. 2011; 106(suppl 2):S12-S16.
9. American Academy of Allergy, Asthma & Immunology. Task force on allergic disorders: promoting best practice: raising the standard of care for patients with allergic disorders. Executive summary report. 1998.
10. Nathan RA. The burden of allergic rhinitis. Allergy Asthma Proc. 2007; 28:3-9.
11. Tran NP, Vickery J, Blaiss MS. Management of rhinitis: allergic and non-allergic. Allergy Asthma Immunol Res. 2011;3:148-156.
12. Disease Summaries: Allergic Diseases and Asthma in Pregnancy. World Allergy Organization. www.worldallergy.org/professional/allergic_
diseases_center/allergy_in_pregnancy/. Accessed February 14, 2014.
13. Simons FE, Ardusso LR, Dimov V, et al. World Allergy Organization Anaphylaxis Guidelines: 2013 update of the evidence base. Int Arch Allergy Immunol. 2013;162:193-204.
14. Noon L. Prophylactic inoculation against hay fever. Lancet. 1911;177:1572-1573.
15. Purello-D’Ambrosio F, Gangemi S, Merendino RA, et al. Prevention of new sensitizations in monosensitized subjects submitted to specific immunotherapy or not: a retrospective study. Clin & Exper Allergy. 2001;31:1295-1302.
16. Durham SR, Walker SM, Varga EM, et al. Long-term clinical efficacy of grass-pollen immunotherapy. N Engl J Med. 1999;341:468-475.
17. Mohapatra SS, Qazi M, Hellermann G. Immunotherapy for allergies and asthma: present and future. Curr Opin Pharmacol. 2010;10:276-288.
18. Calderon MA, Alves B, Jacobson M, et al. Allergen injection immunotherapy for seasonal allergic rhinitis. Cochrane Database Syst Rev. 2007; Iss 1, Art No: CD001936.
19. Scadding GK, Brostoff J. Low dose sublingual therapy in patients with allergic rhinitis due to house dust mite.Clin Allergy. 1986;16:483-491.
20. Canonica GW, Bousquet J, Casale T, et al. Sub-lingual immunotherapy: World Allergy Organization Position Paper 2009. Allergy. 2009;64 suppl 91:1-59.
21. Di Bona D, Plaia A, Scafidi V, et al. Efficacy of sublingual immunotherapy with grass allergens for seasonal allergic rhinitis: a systematic review and meta-analysis. J Allergy Clin Immunol. 2010;126:558-566.
22. Sikora JM, Tankersley MS; ACAAI Immunotherapy and Diagnostics Committee. Perception and practice of sublingual immunotherapy among practicing allergists in the United States: a follow-up survey. Ann Allergy Asthma Immunol. 2013;110:194-197.
Myasthenia gravis
To the Editor: Dr. Li and colleagues provide a well-written article about what is generally believed regarding myasthenia gravis (MG). However, like most reviews, it perpetuates the myths surrounding current medical practice, resulting in delays in diagnosis, treatment initiation, and insurance approval and reimbursement, and therefore increased morbidity and mortality. Stricter statistical and editorial review is needed and what is known and unknown clearly stated. Patients, in particular those of us who are physicians ourselves, recognize that this is no academic quibble.
Myasthenia gravis was a clinical diagnosis until blood tests began to pick up antibodies. If the blood tests have to be positive to diagnose MG, then everyone diagnosed with MG will have positive blood tests. If the muscle studies have to show particular abnormalities to diagnose MG, then everyone diagnosed with MG will have those abnormalities. It makes doctors more comfortable to have these evidences of their understanding verified, but it does not help any of the patients who do not meet the testing criteria but have the clinical findings.
We know, in contrast to what was thought a number of years ago, that there are “seronegative” patients with clinical evidence of myasthenia who are antibody-positive. For those who are MuSK-positive, their problem is now well described, and although it affects a different part of the neuromuscular junction, it remains under the MG umbrella. We also know there are other antibodies, for which we have no commercial tests, in patients with symptoms of MG who respond to treatment for autoimmune problems. This article is relatively dismissive of the clinical validity of those antibodies, and certainly a degree of skepticism is a good thing as long as the patients remain diagnosed and treated.
It is of more than academic interest that these misconceptions and prejudices be recognized. At the very least, editorial boards should insist that statistics in papers reflect the diagnostic skills of the authors. If over 95% of an author’s diagnosed patients are seropositive, then one can suspect there is heavy reliance on blood studies for diagnosis, and rejection of those who do not meet those criteria. The statistics should read “over 95% of patients we diagnose with MG have positive blood studies” rather than “over 95% of patients with MG have positive blood studies.” Dismissing a significant portion of a patient population will also affect treatment statistics, which then should read that “for those who meet this criteria, —% will respond to…”
If patients meet clinical criteria for the diagnosis of MG and a large percentage do not have positive serology, then more research needs to be done into their particular autoimmune problems, and better testing may become commercially viable. Recognizing the problem will lead to better clinical diagnosis and treatment, and strict diagnostic criteria would permit their inclusion in studies. For many of us this would create a more open and questioning atmosphere as to our understanding of the spectrum of autoimmune myasthenia and the ability and willingness to diagnose and treat “seronegative” autoimmune myasthenia when we see it.
To the Editor: Dr. Li and colleagues provide a well-written article about what is generally believed regarding myasthenia gravis (MG). However, like most reviews, it perpetuates the myths surrounding current medical practice, resulting in delays in diagnosis, treatment initiation, and insurance approval and reimbursement, and therefore increased morbidity and mortality. Stricter statistical and editorial review is needed and what is known and unknown clearly stated. Patients, in particular those of us who are physicians ourselves, recognize that this is no academic quibble.
Myasthenia gravis was a clinical diagnosis until blood tests began to pick up antibodies. If the blood tests have to be positive to diagnose MG, then everyone diagnosed with MG will have positive blood tests. If the muscle studies have to show particular abnormalities to diagnose MG, then everyone diagnosed with MG will have those abnormalities. It makes doctors more comfortable to have these evidences of their understanding verified, but it does not help any of the patients who do not meet the testing criteria but have the clinical findings.
We know, in contrast to what was thought a number of years ago, that there are “seronegative” patients with clinical evidence of myasthenia who are antibody-positive. For those who are MuSK-positive, their problem is now well described, and although it affects a different part of the neuromuscular junction, it remains under the MG umbrella. We also know there are other antibodies, for which we have no commercial tests, in patients with symptoms of MG who respond to treatment for autoimmune problems. This article is relatively dismissive of the clinical validity of those antibodies, and certainly a degree of skepticism is a good thing as long as the patients remain diagnosed and treated.
It is of more than academic interest that these misconceptions and prejudices be recognized. At the very least, editorial boards should insist that statistics in papers reflect the diagnostic skills of the authors. If over 95% of an author’s diagnosed patients are seropositive, then one can suspect there is heavy reliance on blood studies for diagnosis, and rejection of those who do not meet those criteria. The statistics should read “over 95% of patients we diagnose with MG have positive blood studies” rather than “over 95% of patients with MG have positive blood studies.” Dismissing a significant portion of a patient population will also affect treatment statistics, which then should read that “for those who meet this criteria, —% will respond to…”
If patients meet clinical criteria for the diagnosis of MG and a large percentage do not have positive serology, then more research needs to be done into their particular autoimmune problems, and better testing may become commercially viable. Recognizing the problem will lead to better clinical diagnosis and treatment, and strict diagnostic criteria would permit their inclusion in studies. For many of us this would create a more open and questioning atmosphere as to our understanding of the spectrum of autoimmune myasthenia and the ability and willingness to diagnose and treat “seronegative” autoimmune myasthenia when we see it.
To the Editor: Dr. Li and colleagues provide a well-written article about what is generally believed regarding myasthenia gravis (MG). However, like most reviews, it perpetuates the myths surrounding current medical practice, resulting in delays in diagnosis, treatment initiation, and insurance approval and reimbursement, and therefore increased morbidity and mortality. Stricter statistical and editorial review is needed and what is known and unknown clearly stated. Patients, in particular those of us who are physicians ourselves, recognize that this is no academic quibble.
Myasthenia gravis was a clinical diagnosis until blood tests began to pick up antibodies. If the blood tests have to be positive to diagnose MG, then everyone diagnosed with MG will have positive blood tests. If the muscle studies have to show particular abnormalities to diagnose MG, then everyone diagnosed with MG will have those abnormalities. It makes doctors more comfortable to have these evidences of their understanding verified, but it does not help any of the patients who do not meet the testing criteria but have the clinical findings.
We know, in contrast to what was thought a number of years ago, that there are “seronegative” patients with clinical evidence of myasthenia who are antibody-positive. For those who are MuSK-positive, their problem is now well described, and although it affects a different part of the neuromuscular junction, it remains under the MG umbrella. We also know there are other antibodies, for which we have no commercial tests, in patients with symptoms of MG who respond to treatment for autoimmune problems. This article is relatively dismissive of the clinical validity of those antibodies, and certainly a degree of skepticism is a good thing as long as the patients remain diagnosed and treated.
It is of more than academic interest that these misconceptions and prejudices be recognized. At the very least, editorial boards should insist that statistics in papers reflect the diagnostic skills of the authors. If over 95% of an author’s diagnosed patients are seropositive, then one can suspect there is heavy reliance on blood studies for diagnosis, and rejection of those who do not meet those criteria. The statistics should read “over 95% of patients we diagnose with MG have positive blood studies” rather than “over 95% of patients with MG have positive blood studies.” Dismissing a significant portion of a patient population will also affect treatment statistics, which then should read that “for those who meet this criteria, —% will respond to…”
If patients meet clinical criteria for the diagnosis of MG and a large percentage do not have positive serology, then more research needs to be done into their particular autoimmune problems, and better testing may become commercially viable. Recognizing the problem will lead to better clinical diagnosis and treatment, and strict diagnostic criteria would permit their inclusion in studies. For many of us this would create a more open and questioning atmosphere as to our understanding of the spectrum of autoimmune myasthenia and the ability and willingness to diagnose and treat “seronegative” autoimmune myasthenia when we see it.
In reply: Myasthenia gravis
In Reply: We appreciate Dr. Keiter’s comments. We agree that myasthenia gravis, like most medical disorders, rests on clinical diagnosis. We have patients we treat for myasthenia gravis in the absence of the typical serological confirmation. A very few of these patients with restricted oculobulbar symptoms may also have normal single-fiber EMG studies. In this situation, the decision to treat an individual for myasthenia gravis must rest on the physician’s clinical judgment, but also on the patient’s understanding that the condition does not have the diagnostic support often seen. The decision to treat with medications that have potential severe side effects requires the patient’s understanding of the context in which the diagnosis is being made and the specific treatment is being suggested.
In Reply: We appreciate Dr. Keiter’s comments. We agree that myasthenia gravis, like most medical disorders, rests on clinical diagnosis. We have patients we treat for myasthenia gravis in the absence of the typical serological confirmation. A very few of these patients with restricted oculobulbar symptoms may also have normal single-fiber EMG studies. In this situation, the decision to treat an individual for myasthenia gravis must rest on the physician’s clinical judgment, but also on the patient’s understanding that the condition does not have the diagnostic support often seen. The decision to treat with medications that have potential severe side effects requires the patient’s understanding of the context in which the diagnosis is being made and the specific treatment is being suggested.
In Reply: We appreciate Dr. Keiter’s comments. We agree that myasthenia gravis, like most medical disorders, rests on clinical diagnosis. We have patients we treat for myasthenia gravis in the absence of the typical serological confirmation. A very few of these patients with restricted oculobulbar symptoms may also have normal single-fiber EMG studies. In this situation, the decision to treat an individual for myasthenia gravis must rest on the physician’s clinical judgment, but also on the patient’s understanding that the condition does not have the diagnostic support often seen. The decision to treat with medications that have potential severe side effects requires the patient’s understanding of the context in which the diagnosis is being made and the specific treatment is being suggested.
Drug Combo Effective in Resistant Hepatitis C
A combined regimen of daclatasvir and sofosbuvir achieved sustained virologic response rates greater than 90% in an industry-sponsored trial involving patients with chronic HCV, according to study published online Jan. 16 in the New England Journal of Medicine.
The once-daily oral treatment was effective against HCV type 1 among patients with any viral subtype, as well as among patients who had failed to respond to or had developed resistance to protease inhibitors. The latter group currently has no other treatment options. It also was effective against HCV types 2 and 3, said Dr. Mark S. Sulkowski of Johns Hopkins University, Baltimore, and his associates ((N. Engl. J. Med. 2014 Jan. 16;370:211-21).
In particular, the daclatasvir-sofosbuvir combination was very effective in patients "with characteristics that were previously associated with a poor response to treatment – HCV genotypes 1a and 3, the non-CC IL28B genotype, and black race," the investigators noted.
Dr. Sulkowski and his colleagues assessed the combination therapy in an open-label study involving 211 adults treated during a 17-month period at 18 medical centers across the United States.
Initially, 44 previously untreated patients with HCV 1 infection and 44 patients with HCV 2 or 3 were randomly assigned to receive daclatasvir plus sofosbuvir, with or without concurrent ribavirin, for 24 weeks. Then the study was expanded to include another 123 patients with HCV 1 infection: 82 who were previously untreated were randomly assigned to receive the combination therapy, with or without ribavirin, for 12 weeks; and the remaining 41 who had failed on telaprevir or boceprevir plus peginterferon alfa-ribavirin were assigned to receive the combination therapy, with or without ribavirin, for 24 weeks.
The primary efficacy endpoint was a sustained virologic response (defined as an HCV RNA level of less than 25 IU/mL) at week 12 after the end of treatment.
That rate was 98% (164 of 167 patients) among those who had HCV 1 infection. Of the three patients in that group classified as not having a sustained virologic response at week 12, two missed their assessment visit at 12 weeks but showed a sustained virologic response at 24 weeks, and the third was lost to follow-up.
The rate of sustained virologic response was 91% (40 of 44 patients) among those who had HCV 2 or 3 infection. Individually, the rate was 92% in patients with HCV 2 and 89% among those with HCV 3, the investigators said.
The high rates of sustained virologic response were consistent across all subgroups of patients, including 129 of the 132 (98%) who had genotype 1a; 57 of the 61 (93%) who had genotype IL28B; 25 of the 26 (96%) who were black; 9 of the 10 (90%) who were of "other" race/ethnicity; 85 of the 90 (94%) who received concurrent ribavirin; 119 of the 121 (98%) who did not receive ribavirin; and 40 of the 41 (98%) who had failed on or developed resistance to protease inhibitors.
"This represents proof of concept that a sustained virologic response can be achieved in patients in whom previous treatment with telaprevir or boceprevir had failed, including patients who have persistent HCV variants with resistance to protease inhibitors," Dr. Sulkowski and his associates said.
Two patients discontinued treatment because of adverse events. One patient developed fibromyalgia, and another had a stroke. Both had shown a sustained virologic response to the combination therapy. The most common adverse events were fatigue, headache, and nausea. The most common grade 3 or 4 laboratory abnormalities were low phosphorous levels and elevated glucose levels.
The study was supported by Bristol-Myers Squibb and Pharmasset (now Gilead). Dr. Sulkowski reported financial ties to Bristol-Myers Squibb and Gilead, in addition to other pharmaceutical companies. His associates reported ties to numerous industry sources.
A combined regimen of daclatasvir and sofosbuvir achieved sustained virologic response rates greater than 90% in an industry-sponsored trial involving patients with chronic HCV, according to study published online Jan. 16 in the New England Journal of Medicine.
The once-daily oral treatment was effective against HCV type 1 among patients with any viral subtype, as well as among patients who had failed to respond to or had developed resistance to protease inhibitors. The latter group currently has no other treatment options. It also was effective against HCV types 2 and 3, said Dr. Mark S. Sulkowski of Johns Hopkins University, Baltimore, and his associates ((N. Engl. J. Med. 2014 Jan. 16;370:211-21).
In particular, the daclatasvir-sofosbuvir combination was very effective in patients "with characteristics that were previously associated with a poor response to treatment – HCV genotypes 1a and 3, the non-CC IL28B genotype, and black race," the investigators noted.
Dr. Sulkowski and his colleagues assessed the combination therapy in an open-label study involving 211 adults treated during a 17-month period at 18 medical centers across the United States.
Initially, 44 previously untreated patients with HCV 1 infection and 44 patients with HCV 2 or 3 were randomly assigned to receive daclatasvir plus sofosbuvir, with or without concurrent ribavirin, for 24 weeks. Then the study was expanded to include another 123 patients with HCV 1 infection: 82 who were previously untreated were randomly assigned to receive the combination therapy, with or without ribavirin, for 12 weeks; and the remaining 41 who had failed on telaprevir or boceprevir plus peginterferon alfa-ribavirin were assigned to receive the combination therapy, with or without ribavirin, for 24 weeks.
The primary efficacy endpoint was a sustained virologic response (defined as an HCV RNA level of less than 25 IU/mL) at week 12 after the end of treatment.
That rate was 98% (164 of 167 patients) among those who had HCV 1 infection. Of the three patients in that group classified as not having a sustained virologic response at week 12, two missed their assessment visit at 12 weeks but showed a sustained virologic response at 24 weeks, and the third was lost to follow-up.
The rate of sustained virologic response was 91% (40 of 44 patients) among those who had HCV 2 or 3 infection. Individually, the rate was 92% in patients with HCV 2 and 89% among those with HCV 3, the investigators said.
The high rates of sustained virologic response were consistent across all subgroups of patients, including 129 of the 132 (98%) who had genotype 1a; 57 of the 61 (93%) who had genotype IL28B; 25 of the 26 (96%) who were black; 9 of the 10 (90%) who were of "other" race/ethnicity; 85 of the 90 (94%) who received concurrent ribavirin; 119 of the 121 (98%) who did not receive ribavirin; and 40 of the 41 (98%) who had failed on or developed resistance to protease inhibitors.
"This represents proof of concept that a sustained virologic response can be achieved in patients in whom previous treatment with telaprevir or boceprevir had failed, including patients who have persistent HCV variants with resistance to protease inhibitors," Dr. Sulkowski and his associates said.
Two patients discontinued treatment because of adverse events. One patient developed fibromyalgia, and another had a stroke. Both had shown a sustained virologic response to the combination therapy. The most common adverse events were fatigue, headache, and nausea. The most common grade 3 or 4 laboratory abnormalities were low phosphorous levels and elevated glucose levels.
The study was supported by Bristol-Myers Squibb and Pharmasset (now Gilead). Dr. Sulkowski reported financial ties to Bristol-Myers Squibb and Gilead, in addition to other pharmaceutical companies. His associates reported ties to numerous industry sources.
A combined regimen of daclatasvir and sofosbuvir achieved sustained virologic response rates greater than 90% in an industry-sponsored trial involving patients with chronic HCV, according to study published online Jan. 16 in the New England Journal of Medicine.
The once-daily oral treatment was effective against HCV type 1 among patients with any viral subtype, as well as among patients who had failed to respond to or had developed resistance to protease inhibitors. The latter group currently has no other treatment options. It also was effective against HCV types 2 and 3, said Dr. Mark S. Sulkowski of Johns Hopkins University, Baltimore, and his associates ((N. Engl. J. Med. 2014 Jan. 16;370:211-21).
In particular, the daclatasvir-sofosbuvir combination was very effective in patients "with characteristics that were previously associated with a poor response to treatment – HCV genotypes 1a and 3, the non-CC IL28B genotype, and black race," the investigators noted.
Dr. Sulkowski and his colleagues assessed the combination therapy in an open-label study involving 211 adults treated during a 17-month period at 18 medical centers across the United States.
Initially, 44 previously untreated patients with HCV 1 infection and 44 patients with HCV 2 or 3 were randomly assigned to receive daclatasvir plus sofosbuvir, with or without concurrent ribavirin, for 24 weeks. Then the study was expanded to include another 123 patients with HCV 1 infection: 82 who were previously untreated were randomly assigned to receive the combination therapy, with or without ribavirin, for 12 weeks; and the remaining 41 who had failed on telaprevir or boceprevir plus peginterferon alfa-ribavirin were assigned to receive the combination therapy, with or without ribavirin, for 24 weeks.
The primary efficacy endpoint was a sustained virologic response (defined as an HCV RNA level of less than 25 IU/mL) at week 12 after the end of treatment.
That rate was 98% (164 of 167 patients) among those who had HCV 1 infection. Of the three patients in that group classified as not having a sustained virologic response at week 12, two missed their assessment visit at 12 weeks but showed a sustained virologic response at 24 weeks, and the third was lost to follow-up.
The rate of sustained virologic response was 91% (40 of 44 patients) among those who had HCV 2 or 3 infection. Individually, the rate was 92% in patients with HCV 2 and 89% among those with HCV 3, the investigators said.
The high rates of sustained virologic response were consistent across all subgroups of patients, including 129 of the 132 (98%) who had genotype 1a; 57 of the 61 (93%) who had genotype IL28B; 25 of the 26 (96%) who were black; 9 of the 10 (90%) who were of "other" race/ethnicity; 85 of the 90 (94%) who received concurrent ribavirin; 119 of the 121 (98%) who did not receive ribavirin; and 40 of the 41 (98%) who had failed on or developed resistance to protease inhibitors.
"This represents proof of concept that a sustained virologic response can be achieved in patients in whom previous treatment with telaprevir or boceprevir had failed, including patients who have persistent HCV variants with resistance to protease inhibitors," Dr. Sulkowski and his associates said.
Two patients discontinued treatment because of adverse events. One patient developed fibromyalgia, and another had a stroke. Both had shown a sustained virologic response to the combination therapy. The most common adverse events were fatigue, headache, and nausea. The most common grade 3 or 4 laboratory abnormalities were low phosphorous levels and elevated glucose levels.
The study was supported by Bristol-Myers Squibb and Pharmasset (now Gilead). Dr. Sulkowski reported financial ties to Bristol-Myers Squibb and Gilead, in addition to other pharmaceutical companies. His associates reported ties to numerous industry sources.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
The Art and Science of Detecting Allergic Contact Dermatitis
WOODINVILLE, WASH. – Identifying the culprit in allergic contact dermatitis often requires careful sleuthing and tailored patch testing, according to Dr. James G. Marks Jr.
Dr. Marks reviewed the current options for patch testing trays, described several cases of allergic contact dermatitis, and shared pointers for diagnosis and management at the annual Coastal Dermatology Symposium.
Allergen-screening series
Dermatologists can now choose from a variety of standard screening trays for patch testing, said Dr. Marks, professor and chair of the department of dermatology, Pennsylvania State University, Hershey. The TRUE test (the only one approved by the Food and Drug Administration) contains 35 antigens.
However, dermatologists can supplement and customize these screening trays to create a system specific to their practice and geographic area. Dr. Marks said he uses a customized tray with 100 antigens.
"The important point is there is no universal standard screening tray, so pick what works for you," he said.
"Those of you who use the TRUE test, great; as you know in the last year you have had another panel [added], so you get more screening antigens," he said. "It makes sense intuitively, and it’s proven by publications of the North American [Contact Dermatitis] Group and others that the more antigens you test with, the more positives you get and the more relevant reactions you can get," he explained.
"Then create your own," Dr. Marks advised. "So if you use the TRUE test, maybe supplement ... with a few more allergens."
Alpha-methylene-gamma-butyrolactone
Florists may come in contact with alpha-methylene-gamma-butyrolactone through handling Alstroemeria (also known as Peruvian lily), a flower popular because of its long-lasting blooms.
The compound is found in the sap that leaks out from cut stems; thus, the presentation is typically finger dermatitis, Dr. Marks said at the meeting, which was presented by the Caribbean Dermatology Symposium.
"It is the most common cause of allergic contact dermatitis in florists. So if you see florists, this is the allergen until proven otherwise," he said.
The compound is also found in the white epidermis of tulips, in which case it is known as tuliposide A. About half of tulip bulb sorters are allergic to it.
"You either patch test with parts of the Alstroemeria plant or get the allergen alpha-methylene-gamma-butyrolactone" commercially, Dr. Marks said. "I test everyone to alpha-methylene-gamma-butyrolactone, even though it’s a small subset. That’s one of my 100 [antigens]."
Methylisothiazolinone
"Methylisothiazolinone has become a very important and hot allergen," Dr. Marks commented. This allergen is increasingly used in personal care products and requires a special approach to patch testing. It is found in many wet wipes, use of which can produce, for example, perioral dermatitis.
The standard combination test antigen, applied at 100 parts per million, contains 3 parts methylchloroisothiazolinone (MCI) and 1 part methylisothiazolinone (MI), he noted. Thus, "you are really only patch testing to 25 parts per million of MI."
"The recommended concentration of patch test to MI is a bit in flux," said Dr. Marks; the North American group currently uses 2,000 parts per million but is considering halving that number, he noted.
"You can see how you can miss patients who are allergic to MI if you only patch test to MCI/MI," he commented. "So those of you who are using the TRUE test, you are going to miss patients who are allergic to MI."
"The important point is you’ve got to test both – MCI/MI and MI alone. ... You should supplement what you are patch testing with MI, certainly at least at 1,000 parts per million, if not at 2,000," Dr. Marks advised.
"The Cosmetic Ingredient Review, which sets limits for [MI] in the U.S., is going to be reevaluating, and I’m sure will be having lower limits in leave-on and rinse-off products," he noted.
Rubber accelerators
Surgeons may develop particularly problematic allergic contact dermatitis as a reaction to the rubber accelerators used in the manufacturing of many surgical gloves, Dr. Marks noted.
He described the case of a surgeon who developed severe hand dermatitis and eventually a generalized dermatitis. "In this case, if you used the TRUE test, you would make the diagnosis; he was positive to thiuram and carba mix."
Allergen avoidance entailed finding an alternative, rubber-free surgical glove, the Derma Prene Ultra glove (manufactured by Ansell), which is made of neoprene. Also, the surgeon switched to vinyl exam gloves for outpatient care.
"There may be other surgical gloves ...," Dr. Marks acknowledged. "But be sure and keep this some place because some time in the future when you have your surgeon friend with hand dermatitis, you can recommend that glove after you patch test them and prove that they are rubber-accelerator positive."
Cocamidopropyl betaine contaminants
Patients may develop allergic contact dermatitis after using shampoos and bath gels containing cocamidopropyl betaine, a surfactant.
In fact, they are actually reacting to a contaminant or impurity generated in the manufacturing process, either 3-dimethylaminopropylamine or amidoamine, according to Dr. Marks.
"So if you have pure cocamidopropyl betaine, there will be no allergy," he noted. But if you test for "cocamidopropyl betaine, and what you are patch testing with is from, say, Chemotechnique or Allergeaze, it’s going to have presumably the contaminants or the impurities in it, 3-dimethylaminopropylamine and amidoamine."
Treatment entails careful reading of labels on personal care products and avoidance of those containing cocamidopropyl betaine.
Acrylates
Don’t rule out acrylates – either acrylic or methacrylic acid – monomers that are polymerized with heat or light to form solid plastics that can cause reactions.
"The monomers are both irritants and allergens, so you need the right concentration to patch test to," Dr. Marks noted. "They are found in all sorts of things – adhesives, inks, artificial nails, dental resins, bone cement, and plastics."
Presentations may vary widely, including, for example, finger dermatitis in patients who have sculptured nails, and gum stomatitis in patients who have undergone procedures involving dental resin, said Dr. Marks.
"If you have workers or patients who have exposure to acrylates, you need more extensive screening," Dr. Marks advised, noting that his acrylate patch test series contains six compounds.
"No one is a screen for all of them," he commented. "Some [experts] feel that ethyl acrylate is the best screen; certainly, for sculptured nails it’s good." Others in his series include methyl methacrylate (found in bone cement) and ethyl cyanoacrylate (found in Super Glue adhesive).
Glyceryl thioglycolate
Allergy to glyceryl thioglycolate, found in acid permanent waves, can manifest as hand dermatitis in hairdressers and as dermatitis of the face, neck, and ears in their clients.
"If you see hairdressers [in your practice], you should consider strongly having this antigen as part of your [patch test] armamentarium," Dr. Marks recommended.
Alkaline perms, by contrast, do not contain glyceryl thioglycolate and thus provide a simple solution. "You can cure that hairdresser, and she or he can continue to do perms just by switching from an acid to an alkaline perm," he explained.
Dr. Marks said he had no relevant financial disclosures.
WOODINVILLE, WASH. – Identifying the culprit in allergic contact dermatitis often requires careful sleuthing and tailored patch testing, according to Dr. James G. Marks Jr.
Dr. Marks reviewed the current options for patch testing trays, described several cases of allergic contact dermatitis, and shared pointers for diagnosis and management at the annual Coastal Dermatology Symposium.
Allergen-screening series
Dermatologists can now choose from a variety of standard screening trays for patch testing, said Dr. Marks, professor and chair of the department of dermatology, Pennsylvania State University, Hershey. The TRUE test (the only one approved by the Food and Drug Administration) contains 35 antigens.
However, dermatologists can supplement and customize these screening trays to create a system specific to their practice and geographic area. Dr. Marks said he uses a customized tray with 100 antigens.
"The important point is there is no universal standard screening tray, so pick what works for you," he said.
"Those of you who use the TRUE test, great; as you know in the last year you have had another panel [added], so you get more screening antigens," he said. "It makes sense intuitively, and it’s proven by publications of the North American [Contact Dermatitis] Group and others that the more antigens you test with, the more positives you get and the more relevant reactions you can get," he explained.
"Then create your own," Dr. Marks advised. "So if you use the TRUE test, maybe supplement ... with a few more allergens."
Alpha-methylene-gamma-butyrolactone
Florists may come in contact with alpha-methylene-gamma-butyrolactone through handling Alstroemeria (also known as Peruvian lily), a flower popular because of its long-lasting blooms.
The compound is found in the sap that leaks out from cut stems; thus, the presentation is typically finger dermatitis, Dr. Marks said at the meeting, which was presented by the Caribbean Dermatology Symposium.
"It is the most common cause of allergic contact dermatitis in florists. So if you see florists, this is the allergen until proven otherwise," he said.
The compound is also found in the white epidermis of tulips, in which case it is known as tuliposide A. About half of tulip bulb sorters are allergic to it.
"You either patch test with parts of the Alstroemeria plant or get the allergen alpha-methylene-gamma-butyrolactone" commercially, Dr. Marks said. "I test everyone to alpha-methylene-gamma-butyrolactone, even though it’s a small subset. That’s one of my 100 [antigens]."
Methylisothiazolinone
"Methylisothiazolinone has become a very important and hot allergen," Dr. Marks commented. This allergen is increasingly used in personal care products and requires a special approach to patch testing. It is found in many wet wipes, use of which can produce, for example, perioral dermatitis.
The standard combination test antigen, applied at 100 parts per million, contains 3 parts methylchloroisothiazolinone (MCI) and 1 part methylisothiazolinone (MI), he noted. Thus, "you are really only patch testing to 25 parts per million of MI."
"The recommended concentration of patch test to MI is a bit in flux," said Dr. Marks; the North American group currently uses 2,000 parts per million but is considering halving that number, he noted.
"You can see how you can miss patients who are allergic to MI if you only patch test to MCI/MI," he commented. "So those of you who are using the TRUE test, you are going to miss patients who are allergic to MI."
"The important point is you’ve got to test both – MCI/MI and MI alone. ... You should supplement what you are patch testing with MI, certainly at least at 1,000 parts per million, if not at 2,000," Dr. Marks advised.
"The Cosmetic Ingredient Review, which sets limits for [MI] in the U.S., is going to be reevaluating, and I’m sure will be having lower limits in leave-on and rinse-off products," he noted.
Rubber accelerators
Surgeons may develop particularly problematic allergic contact dermatitis as a reaction to the rubber accelerators used in the manufacturing of many surgical gloves, Dr. Marks noted.
He described the case of a surgeon who developed severe hand dermatitis and eventually a generalized dermatitis. "In this case, if you used the TRUE test, you would make the diagnosis; he was positive to thiuram and carba mix."
Allergen avoidance entailed finding an alternative, rubber-free surgical glove, the Derma Prene Ultra glove (manufactured by Ansell), which is made of neoprene. Also, the surgeon switched to vinyl exam gloves for outpatient care.
"There may be other surgical gloves ...," Dr. Marks acknowledged. "But be sure and keep this some place because some time in the future when you have your surgeon friend with hand dermatitis, you can recommend that glove after you patch test them and prove that they are rubber-accelerator positive."
Cocamidopropyl betaine contaminants
Patients may develop allergic contact dermatitis after using shampoos and bath gels containing cocamidopropyl betaine, a surfactant.
In fact, they are actually reacting to a contaminant or impurity generated in the manufacturing process, either 3-dimethylaminopropylamine or amidoamine, according to Dr. Marks.
"So if you have pure cocamidopropyl betaine, there will be no allergy," he noted. But if you test for "cocamidopropyl betaine, and what you are patch testing with is from, say, Chemotechnique or Allergeaze, it’s going to have presumably the contaminants or the impurities in it, 3-dimethylaminopropylamine and amidoamine."
Treatment entails careful reading of labels on personal care products and avoidance of those containing cocamidopropyl betaine.
Acrylates
Don’t rule out acrylates – either acrylic or methacrylic acid – monomers that are polymerized with heat or light to form solid plastics that can cause reactions.
"The monomers are both irritants and allergens, so you need the right concentration to patch test to," Dr. Marks noted. "They are found in all sorts of things – adhesives, inks, artificial nails, dental resins, bone cement, and plastics."
Presentations may vary widely, including, for example, finger dermatitis in patients who have sculptured nails, and gum stomatitis in patients who have undergone procedures involving dental resin, said Dr. Marks.
"If you have workers or patients who have exposure to acrylates, you need more extensive screening," Dr. Marks advised, noting that his acrylate patch test series contains six compounds.
"No one is a screen for all of them," he commented. "Some [experts] feel that ethyl acrylate is the best screen; certainly, for sculptured nails it’s good." Others in his series include methyl methacrylate (found in bone cement) and ethyl cyanoacrylate (found in Super Glue adhesive).
Glyceryl thioglycolate
Allergy to glyceryl thioglycolate, found in acid permanent waves, can manifest as hand dermatitis in hairdressers and as dermatitis of the face, neck, and ears in their clients.
"If you see hairdressers [in your practice], you should consider strongly having this antigen as part of your [patch test] armamentarium," Dr. Marks recommended.
Alkaline perms, by contrast, do not contain glyceryl thioglycolate and thus provide a simple solution. "You can cure that hairdresser, and she or he can continue to do perms just by switching from an acid to an alkaline perm," he explained.
Dr. Marks said he had no relevant financial disclosures.
WOODINVILLE, WASH. – Identifying the culprit in allergic contact dermatitis often requires careful sleuthing and tailored patch testing, according to Dr. James G. Marks Jr.
Dr. Marks reviewed the current options for patch testing trays, described several cases of allergic contact dermatitis, and shared pointers for diagnosis and management at the annual Coastal Dermatology Symposium.
Allergen-screening series
Dermatologists can now choose from a variety of standard screening trays for patch testing, said Dr. Marks, professor and chair of the department of dermatology, Pennsylvania State University, Hershey. The TRUE test (the only one approved by the Food and Drug Administration) contains 35 antigens.
However, dermatologists can supplement and customize these screening trays to create a system specific to their practice and geographic area. Dr. Marks said he uses a customized tray with 100 antigens.
"The important point is there is no universal standard screening tray, so pick what works for you," he said.
"Those of you who use the TRUE test, great; as you know in the last year you have had another panel [added], so you get more screening antigens," he said. "It makes sense intuitively, and it’s proven by publications of the North American [Contact Dermatitis] Group and others that the more antigens you test with, the more positives you get and the more relevant reactions you can get," he explained.
"Then create your own," Dr. Marks advised. "So if you use the TRUE test, maybe supplement ... with a few more allergens."
Alpha-methylene-gamma-butyrolactone
Florists may come in contact with alpha-methylene-gamma-butyrolactone through handling Alstroemeria (also known as Peruvian lily), a flower popular because of its long-lasting blooms.
The compound is found in the sap that leaks out from cut stems; thus, the presentation is typically finger dermatitis, Dr. Marks said at the meeting, which was presented by the Caribbean Dermatology Symposium.
"It is the most common cause of allergic contact dermatitis in florists. So if you see florists, this is the allergen until proven otherwise," he said.
The compound is also found in the white epidermis of tulips, in which case it is known as tuliposide A. About half of tulip bulb sorters are allergic to it.
"You either patch test with parts of the Alstroemeria plant or get the allergen alpha-methylene-gamma-butyrolactone" commercially, Dr. Marks said. "I test everyone to alpha-methylene-gamma-butyrolactone, even though it’s a small subset. That’s one of my 100 [antigens]."
Methylisothiazolinone
"Methylisothiazolinone has become a very important and hot allergen," Dr. Marks commented. This allergen is increasingly used in personal care products and requires a special approach to patch testing. It is found in many wet wipes, use of which can produce, for example, perioral dermatitis.
The standard combination test antigen, applied at 100 parts per million, contains 3 parts methylchloroisothiazolinone (MCI) and 1 part methylisothiazolinone (MI), he noted. Thus, "you are really only patch testing to 25 parts per million of MI."
"The recommended concentration of patch test to MI is a bit in flux," said Dr. Marks; the North American group currently uses 2,000 parts per million but is considering halving that number, he noted.
"You can see how you can miss patients who are allergic to MI if you only patch test to MCI/MI," he commented. "So those of you who are using the TRUE test, you are going to miss patients who are allergic to MI."
"The important point is you’ve got to test both – MCI/MI and MI alone. ... You should supplement what you are patch testing with MI, certainly at least at 1,000 parts per million, if not at 2,000," Dr. Marks advised.
"The Cosmetic Ingredient Review, which sets limits for [MI] in the U.S., is going to be reevaluating, and I’m sure will be having lower limits in leave-on and rinse-off products," he noted.
Rubber accelerators
Surgeons may develop particularly problematic allergic contact dermatitis as a reaction to the rubber accelerators used in the manufacturing of many surgical gloves, Dr. Marks noted.
He described the case of a surgeon who developed severe hand dermatitis and eventually a generalized dermatitis. "In this case, if you used the TRUE test, you would make the diagnosis; he was positive to thiuram and carba mix."
Allergen avoidance entailed finding an alternative, rubber-free surgical glove, the Derma Prene Ultra glove (manufactured by Ansell), which is made of neoprene. Also, the surgeon switched to vinyl exam gloves for outpatient care.
"There may be other surgical gloves ...," Dr. Marks acknowledged. "But be sure and keep this some place because some time in the future when you have your surgeon friend with hand dermatitis, you can recommend that glove after you patch test them and prove that they are rubber-accelerator positive."
Cocamidopropyl betaine contaminants
Patients may develop allergic contact dermatitis after using shampoos and bath gels containing cocamidopropyl betaine, a surfactant.
In fact, they are actually reacting to a contaminant or impurity generated in the manufacturing process, either 3-dimethylaminopropylamine or amidoamine, according to Dr. Marks.
"So if you have pure cocamidopropyl betaine, there will be no allergy," he noted. But if you test for "cocamidopropyl betaine, and what you are patch testing with is from, say, Chemotechnique or Allergeaze, it’s going to have presumably the contaminants or the impurities in it, 3-dimethylaminopropylamine and amidoamine."
Treatment entails careful reading of labels on personal care products and avoidance of those containing cocamidopropyl betaine.
Acrylates
Don’t rule out acrylates – either acrylic or methacrylic acid – monomers that are polymerized with heat or light to form solid plastics that can cause reactions.
"The monomers are both irritants and allergens, so you need the right concentration to patch test to," Dr. Marks noted. "They are found in all sorts of things – adhesives, inks, artificial nails, dental resins, bone cement, and plastics."
Presentations may vary widely, including, for example, finger dermatitis in patients who have sculptured nails, and gum stomatitis in patients who have undergone procedures involving dental resin, said Dr. Marks.
"If you have workers or patients who have exposure to acrylates, you need more extensive screening," Dr. Marks advised, noting that his acrylate patch test series contains six compounds.
"No one is a screen for all of them," he commented. "Some [experts] feel that ethyl acrylate is the best screen; certainly, for sculptured nails it’s good." Others in his series include methyl methacrylate (found in bone cement) and ethyl cyanoacrylate (found in Super Glue adhesive).
Glyceryl thioglycolate
Allergy to glyceryl thioglycolate, found in acid permanent waves, can manifest as hand dermatitis in hairdressers and as dermatitis of the face, neck, and ears in their clients.
"If you see hairdressers [in your practice], you should consider strongly having this antigen as part of your [patch test] armamentarium," Dr. Marks recommended.
Alkaline perms, by contrast, do not contain glyceryl thioglycolate and thus provide a simple solution. "You can cure that hairdresser, and she or he can continue to do perms just by switching from an acid to an alkaline perm," he explained.
Dr. Marks said he had no relevant financial disclosures.
AT THE COASTAL DERMATOLOGY SYMPOSIUM
Clinician Recommendation Key to HPV Vaccine Coverage
Better vaccine coverage of adolescents against HPV infection hinges on clinicians and other health care professionals both recommending the vaccine and educating patients and parents about its importance, according to a report published online Nov. 25 in JAMA Pediatrics.
In a review of the extensive literature concerning barriers to HPV vaccination among patients aged 11-17 years, health care professionals’ failure to recommend the vaccine was found to be a leading obstacle to more widespread coverage, said Dawn M. Holman of the division of cancer prevention and control, Centers for Disease Control and Prevention, Atlanta, and her associates.
The most recent data from the National Immunization Survey indicates that only 53% of adolescent girls in the United States have received at least one dose of the HPV vaccine series, only 35% have completed all three doses in the series, and only 8% of adolescent boys in the United States have initiated the HPV vaccine series. By comparison, coverage for the meningococcal conjugate vaccine is approximately 70% and coverage for the tetanus, diphtheria, and acellular pertussis vaccine is 78% in the same age group.
Ms. Holman and her associates performed a systematic review of the literature and found 55 studies published in 2009-2012 that addressed obstacles to HPV vaccination in this age group.
In ten articles that addressed barriers to HPV vaccination among health care professionals, researchers found that while most physicians support HPV vaccination and offer it to their patients, many tend not to offer it to the youngest adolescents or to boys. Many also offer HPV vaccination only according to their own perception of the patient’s risk of contracting the virus. And many do not appear to understand the importance of giving the HPV vaccine well before adolescents become sexually active.
Health care professionals also tend not to provide detailed information to either patients or their parents regarding the risks and benefits of HPV vaccination, or they emphasize the fact that it is optional – both of which come across to patients and parents as a less-than-ringing endorsement. Some health care professionals reported that HPV vaccination is under the parents’ control rather than theirs, and many cited the cost of the HPV vaccine, and the lack or lateness of insurance reimbursement, as a significant obstacle.
In contrast, concerns about the safety and efficacy of the HPV vaccine were rarely cited as contributing to poor coverage (JAMA Pediatrics 2013 Nov. 25 [doi:10.1001/jamapediatrics.2013.2752]).
A total of 64% of the reviewed articles involved barriers to vaccination among parents. Not having a physician recommendation and not getting enough information about the HPV vaccine from health care providers were the chief obstacles to greater coverage in this group. Certain religious affiliations also were associated with opposition to the HPV vaccine.
In contrast, costs and lack of access were cited infrequently. Few parents reported concerns about vaccine safety or efficacy, and few reported concern that the vaccination might affect their child’s sexual behavior.
"Providing adequate, clear, and accessible information to parents about HPV infection, vaccine safety, adverse effects, and the appropriate age for vaccination may be one way health care professionals can reduce concerns and misconceptions about the vaccine," Ms. Holman and her colleagues noted.
Other strategies to improve HPV vaccination coverage include educating health care professionals and the public in general about the importance of vaccinating adolescent males, and ensuring that underserved populations are informed about and given access to the vaccine, they added.
Better vaccine coverage of adolescents against HPV infection hinges on clinicians and other health care professionals both recommending the vaccine and educating patients and parents about its importance, according to a report published online Nov. 25 in JAMA Pediatrics.
In a review of the extensive literature concerning barriers to HPV vaccination among patients aged 11-17 years, health care professionals’ failure to recommend the vaccine was found to be a leading obstacle to more widespread coverage, said Dawn M. Holman of the division of cancer prevention and control, Centers for Disease Control and Prevention, Atlanta, and her associates.
The most recent data from the National Immunization Survey indicates that only 53% of adolescent girls in the United States have received at least one dose of the HPV vaccine series, only 35% have completed all three doses in the series, and only 8% of adolescent boys in the United States have initiated the HPV vaccine series. By comparison, coverage for the meningococcal conjugate vaccine is approximately 70% and coverage for the tetanus, diphtheria, and acellular pertussis vaccine is 78% in the same age group.
Ms. Holman and her associates performed a systematic review of the literature and found 55 studies published in 2009-2012 that addressed obstacles to HPV vaccination in this age group.
In ten articles that addressed barriers to HPV vaccination among health care professionals, researchers found that while most physicians support HPV vaccination and offer it to their patients, many tend not to offer it to the youngest adolescents or to boys. Many also offer HPV vaccination only according to their own perception of the patient’s risk of contracting the virus. And many do not appear to understand the importance of giving the HPV vaccine well before adolescents become sexually active.
Health care professionals also tend not to provide detailed information to either patients or their parents regarding the risks and benefits of HPV vaccination, or they emphasize the fact that it is optional – both of which come across to patients and parents as a less-than-ringing endorsement. Some health care professionals reported that HPV vaccination is under the parents’ control rather than theirs, and many cited the cost of the HPV vaccine, and the lack or lateness of insurance reimbursement, as a significant obstacle.
In contrast, concerns about the safety and efficacy of the HPV vaccine were rarely cited as contributing to poor coverage (JAMA Pediatrics 2013 Nov. 25 [doi:10.1001/jamapediatrics.2013.2752]).
A total of 64% of the reviewed articles involved barriers to vaccination among parents. Not having a physician recommendation and not getting enough information about the HPV vaccine from health care providers were the chief obstacles to greater coverage in this group. Certain religious affiliations also were associated with opposition to the HPV vaccine.
In contrast, costs and lack of access were cited infrequently. Few parents reported concerns about vaccine safety or efficacy, and few reported concern that the vaccination might affect their child’s sexual behavior.
"Providing adequate, clear, and accessible information to parents about HPV infection, vaccine safety, adverse effects, and the appropriate age for vaccination may be one way health care professionals can reduce concerns and misconceptions about the vaccine," Ms. Holman and her colleagues noted.
Other strategies to improve HPV vaccination coverage include educating health care professionals and the public in general about the importance of vaccinating adolescent males, and ensuring that underserved populations are informed about and given access to the vaccine, they added.
Better vaccine coverage of adolescents against HPV infection hinges on clinicians and other health care professionals both recommending the vaccine and educating patients and parents about its importance, according to a report published online Nov. 25 in JAMA Pediatrics.
In a review of the extensive literature concerning barriers to HPV vaccination among patients aged 11-17 years, health care professionals’ failure to recommend the vaccine was found to be a leading obstacle to more widespread coverage, said Dawn M. Holman of the division of cancer prevention and control, Centers for Disease Control and Prevention, Atlanta, and her associates.
The most recent data from the National Immunization Survey indicates that only 53% of adolescent girls in the United States have received at least one dose of the HPV vaccine series, only 35% have completed all three doses in the series, and only 8% of adolescent boys in the United States have initiated the HPV vaccine series. By comparison, coverage for the meningococcal conjugate vaccine is approximately 70% and coverage for the tetanus, diphtheria, and acellular pertussis vaccine is 78% in the same age group.
Ms. Holman and her associates performed a systematic review of the literature and found 55 studies published in 2009-2012 that addressed obstacles to HPV vaccination in this age group.
In ten articles that addressed barriers to HPV vaccination among health care professionals, researchers found that while most physicians support HPV vaccination and offer it to their patients, many tend not to offer it to the youngest adolescents or to boys. Many also offer HPV vaccination only according to their own perception of the patient’s risk of contracting the virus. And many do not appear to understand the importance of giving the HPV vaccine well before adolescents become sexually active.
Health care professionals also tend not to provide detailed information to either patients or their parents regarding the risks and benefits of HPV vaccination, or they emphasize the fact that it is optional – both of which come across to patients and parents as a less-than-ringing endorsement. Some health care professionals reported that HPV vaccination is under the parents’ control rather than theirs, and many cited the cost of the HPV vaccine, and the lack or lateness of insurance reimbursement, as a significant obstacle.
In contrast, concerns about the safety and efficacy of the HPV vaccine were rarely cited as contributing to poor coverage (JAMA Pediatrics 2013 Nov. 25 [doi:10.1001/jamapediatrics.2013.2752]).
A total of 64% of the reviewed articles involved barriers to vaccination among parents. Not having a physician recommendation and not getting enough information about the HPV vaccine from health care providers were the chief obstacles to greater coverage in this group. Certain religious affiliations also were associated with opposition to the HPV vaccine.
In contrast, costs and lack of access were cited infrequently. Few parents reported concerns about vaccine safety or efficacy, and few reported concern that the vaccination might affect their child’s sexual behavior.
"Providing adequate, clear, and accessible information to parents about HPV infection, vaccine safety, adverse effects, and the appropriate age for vaccination may be one way health care professionals can reduce concerns and misconceptions about the vaccine," Ms. Holman and her colleagues noted.
Other strategies to improve HPV vaccination coverage include educating health care professionals and the public in general about the importance of vaccinating adolescent males, and ensuring that underserved populations are informed about and given access to the vaccine, they added.
FROM JAMA PEDIATRICS
