Atopic Dermatitis

Martin Steinhoff, MD, PhD, Ferda Cevikbas, PhD, Akihiko Ikoma, MD, PhD, and Timothy G. Berger, MD

Pruritus (itch) is a major symptom in many dermatologic as well as systemic diseases and has a dramatic impact on the quality of life in these patients. The symptom of itch has to be treated on the basis of its pathophysiology and its underlying disease. In daily practice, a “quick” diagnosis of the underlying disease is often difficult, although a rapid relief of the itch is desired. We often treat patients on the basis of the symptomatology. A rational therapeutic ladder for a symptomatic therapy is useful until the final diagnosis has been confirmed. There are probably many subtypes of pruritus, just as there are many diseases that cause itch. The pathophysiology in many subtypes of pruritus is still poorly understood, hindering a rapid and targeted treatment strategy. An extensive diagnostic workup is often required to determine the final cause(s) of the itch. Thus, in daily life, physicians often start with a more or less rational therapeutic strategy to combat the debilitating itch. We present possible therapeutic ladders that form the basis for effective therapeutic itch strategies in various diseases. On the basis of our current knowledge about the different  pathophysiologies of itch, on clinical trials or case reports, and our own clinical experience, we aim to present therapeutic ladders for the rapid as well as long-term management of itch. Finally, we summarize current exciting developments of experimental strategies in itch research and in clinical development for itch therapy.

*For a PDF of the full article, click on the link to the left of this introduction.

Martin Steinhoff, MD, PhD, Ferda Cevikbas, PhD, Akihiko Ikoma, MD, PhD, and Timothy G. Berger, MD

Pruritus (itch) is a major symptom in many dermatologic as well as systemic diseases and has a dramatic impact on the quality of life in these patients. The symptom of itch has to be treated on the basis of its pathophysiology and its underlying disease. In daily practice, a “quick” diagnosis of the underlying disease is often difficult, although a rapid relief of the itch is desired. We often treat patients on the basis of the symptomatology. A rational therapeutic ladder for a symptomatic therapy is useful until the final diagnosis has been confirmed. There are probably many subtypes of pruritus, just as there are many diseases that cause itch. The pathophysiology in many subtypes of pruritus is still poorly understood, hindering a rapid and targeted treatment strategy. An extensive diagnostic workup is often required to determine the final cause(s) of the itch. Thus, in daily life, physicians often start with a more or less rational therapeutic strategy to combat the debilitating itch. We present possible therapeutic ladders that form the basis for effective therapeutic itch strategies in various diseases. On the basis of our current knowledge about the different  pathophysiologies of itch, on clinical trials or case reports, and our own clinical experience, we aim to present therapeutic ladders for the rapid as well as long-term management of itch. Finally, we summarize current exciting developments of experimental strategies in itch research and in clinical development for itch therapy.

*For a PDF of the full article, click on the link to the left of this introduction.

Martin Steinhoff, MD, PhD, Ferda Cevikbas, PhD, Akihiko Ikoma, MD, PhD, and Timothy G. Berger, MD

Pruritus (itch) is a major symptom in many dermatologic as well as systemic diseases and has a dramatic impact on the quality of life in these patients. The symptom of itch has to be treated on the basis of its pathophysiology and its underlying disease. In daily practice, a “quick” diagnosis of the underlying disease is often difficult, although a rapid relief of the itch is desired. We often treat patients on the basis of the symptomatology. A rational therapeutic ladder for a symptomatic therapy is useful until the final diagnosis has been confirmed. There are probably many subtypes of pruritus, just as there are many diseases that cause itch. The pathophysiology in many subtypes of pruritus is still poorly understood, hindering a rapid and targeted treatment strategy. An extensive diagnostic workup is often required to determine the final cause(s) of the itch. Thus, in daily life, physicians often start with a more or less rational therapeutic strategy to combat the debilitating itch. We present possible therapeutic ladders that form the basis for effective therapeutic itch strategies in various diseases. On the basis of our current knowledge about the different  pathophysiologies of itch, on clinical trials or case reports, and our own clinical experience, we aim to present therapeutic ladders for the rapid as well as long-term management of itch. Finally, we summarize current exciting developments of experimental strategies in itch research and in clinical development for itch therapy.

*For a PDF of the full article, click on the link to the left of this introduction.

Food allergy is defined as an immune-mediated adverse health reaction that occurs reproducibly on exposure to a given food. More than 12 million people in the United States have food allergies, which account for 30,000 emergency department visits and more than 100 deaths annually.

Food allergy (FA) is estimated to affect approximately 5% of children, teens, and adults. Specifically, peanut allergy occurs in approximately 0.6% of people, seafood allergy in 0.2%-0.5%, and milk and egg allergy in approximately 2%. Children with FA have an increased likelihood of asthma, atopic dermatitis, and respiratory allergies. Typically, FA is a reaction to a protein in the food that causes the body’s immune system to identify it as harmful. An allergen-specific, IgE-mediated FA requires both the presence of clinical symptoms and sensitization on exposure to a given food item.

Risk Factors

Patients with a medical history of asthma, atopic dermatitis, eosinophilic esophagitis, and exercise-induced anaphylaxis have an increased associated risk for FA. Symptoms often manifest within the first 2 years of life but can occur at any time.

Clinical Manifestations

The clinical manifestations of FA can involve multiple organ systems:

– Gastrointestinal: The most common gastrointestinal reaction is vomiting from an immediate GI hypersensitivity to a given food.

– Cutaneous: The most common cutaneous manifestations include hives during acute urticaria. Soft-tissue swelling from angioedema occurs less commonly. Atopic dermatitis and allergic contact dermatitis can be exacerbated.

– Respiratory: Respiratory reactions are rare but can occur in conjunction with other systemic manifestations.

Diagnosis

A diagnosis of FA should be considered in patients who present with an allergic reaction shortly after eating; in addition, FA may be considered in children with moderate to severe atopic dermatitis. A careful history usually provides the clues that a reaction may be allergic in nature, and physical exam may or may not show the manifestations of an allergic reaction at the time of the evaluation.

By Dr. Neil S.Skolnik and Dr. Sona M. Garg

Parent and patient reports should be confirmed with further testing, as 50%-90% of presumed FAs turn out to be untrue. Confirmation may involve oral food challenge tests or tests of allergic sensitization. The panel recommends oral food challenge as the most accurate test, and it should be considered when diagnosing FA.

Skin prick tests (SPTs) can be helpful, as they are sensitive both for FA and have high negative predictive value. SPTs, however, have low specificity and are prone to false positive results, with many people who do not manifest FA still having a positive reaction to a food.

Allergen-specific serum IgE is helpful in identifying foods that provoke IgE-mediated FA, and it has similar accuracy to SPTs. Food elimination diets can help diagnose non-IgE-mediated FA when symptoms resolve and do not recur on exclusion of a given food. All other tests suffer from lack of specificity and may cause patients to make substantial efforts to avoid foods that may pose no danger. Intradermal tests, measurement of total serum IgE, and atopy patch tests are not recommended.

Natural History

Most children with FA will eventually tolerate milk, egg, soy, and wheat, though fewer will eventually be able to tolerate tree nuts and peanuts. Resolution of FAs in children often occurs during the teenage years. The higher the level of serum IgE, the less likely it is that the FA will resolve. A decrease in IgE levels often is associated with the ability to tolerate the food. FAs that begin in adulthood often do not resolve.

Treatment

Allergen avoidance is the mainstay of prevention and treatment. The challenge is deciding whether potentially cross-reactive foods also need to be avoided.

Patients and families need to learn how to accurately read food labels. By law, eight major food allergens (milk, egg, peanut, tree nuts, soy, wheat, fish, and crustacean shellfish) that are responsible for more than 90% of serious adverse food-induced reactions must be included on food labels when appropriate.

Currently, there are no medications recommended for prevention of IgE-mediated food allergies.

When a patient has a FA reaction, antihistamines on an as-needed basis are the recommended treatment. In severe cases, such as anaphylaxis, patients should be treated immediately with an intramuscular dose of epinephrine. Secondary treatment will depend on the patient’s response and can involve hemodynamic support and/or adjunctive treatment with albuterol, diphenhydramine, H₂-blockers, and corticosteroids.

Vaccination

A National Institute of Allergy and Infectious Diseases expert panel recommended that children with egg allergies receive the measles/mumps/rubella and varicella (MMRV) vaccines even if they have had a severe allergic reaction to eggs. There is insufficient evidence regarding influenza vaccination of patients with a history of severe egg allergy. Yellow fever and rabies vaccines should not be administered to patients with severe egg allergies.

The Bottom Line

Food allergies are common and can be suspected by history and confirmed through food allergy testing. The mainstay of treatment for mild reactions is as-needed antihistamines, and the treatment for anaphylaxis is an intramuscular dose of epinephrine. MMRV can still be administered to children with severe egg allergies.

References

Guidelines for the Diagnosis and Management of Food Allergy in the United States: Report of the NIAID-Sponsored Expert Panel. J. Allergy Clin. Immunol. 2010;126[6 suppl]:S1-S58.

Dr. Garg is chief resident in the family medicine residency program at Abington (Pa.) Memorial Hospital. Dr. Skolnik is an associate director of the family medicine residency program at Abington Memorial Hospital.

Food allergy is defined as an immune-mediated adverse health reaction that occurs reproducibly on exposure to a given food. More than 12 million people in the United States have food allergies, which account for 30,000 emergency department visits and more than 100 deaths annually.

Food allergy (FA) is estimated to affect approximately 5% of children, teens, and adults. Specifically, peanut allergy occurs in approximately 0.6% of people, seafood allergy in 0.2%-0.5%, and milk and egg allergy in approximately 2%. Children with FA have an increased likelihood of asthma, atopic dermatitis, and respiratory allergies. Typically, FA is a reaction to a protein in the food that causes the body’s immune system to identify it as harmful. An allergen-specific, IgE-mediated FA requires both the presence of clinical symptoms and sensitization on exposure to a given food item.

Risk Factors

Patients with a medical history of asthma, atopic dermatitis, eosinophilic esophagitis, and exercise-induced anaphylaxis have an increased associated risk for FA. Symptoms often manifest within the first 2 years of life but can occur at any time.

Clinical Manifestations

The clinical manifestations of FA can involve multiple organ systems:

– Gastrointestinal: The most common gastrointestinal reaction is vomiting from an immediate GI hypersensitivity to a given food.

– Cutaneous: The most common cutaneous manifestations include hives during acute urticaria. Soft-tissue swelling from angioedema occurs less commonly. Atopic dermatitis and allergic contact dermatitis can be exacerbated.

– Respiratory: Respiratory reactions are rare but can occur in conjunction with other systemic manifestations.

Diagnosis

A diagnosis of FA should be considered in patients who present with an allergic reaction shortly after eating; in addition, FA may be considered in children with moderate to severe atopic dermatitis. A careful history usually provides the clues that a reaction may be allergic in nature, and physical exam may or may not show the manifestations of an allergic reaction at the time of the evaluation.

By Dr. Neil S.Skolnik and Dr. Sona M. Garg

Parent and patient reports should be confirmed with further testing, as 50%-90% of presumed FAs turn out to be untrue. Confirmation may involve oral food challenge tests or tests of allergic sensitization. The panel recommends oral food challenge as the most accurate test, and it should be considered when diagnosing FA.

Skin prick tests (SPTs) can be helpful, as they are sensitive both for FA and have high negative predictive value. SPTs, however, have low specificity and are prone to false positive results, with many people who do not manifest FA still having a positive reaction to a food.

Allergen-specific serum IgE is helpful in identifying foods that provoke IgE-mediated FA, and it has similar accuracy to SPTs. Food elimination diets can help diagnose non-IgE-mediated FA when symptoms resolve and do not recur on exclusion of a given food. All other tests suffer from lack of specificity and may cause patients to make substantial efforts to avoid foods that may pose no danger. Intradermal tests, measurement of total serum IgE, and atopy patch tests are not recommended.

Natural History

Most children with FA will eventually tolerate milk, egg, soy, and wheat, though fewer will eventually be able to tolerate tree nuts and peanuts. Resolution of FAs in children often occurs during the teenage years. The higher the level of serum IgE, the less likely it is that the FA will resolve. A decrease in IgE levels often is associated with the ability to tolerate the food. FAs that begin in adulthood often do not resolve.

Treatment

Allergen avoidance is the mainstay of prevention and treatment. The challenge is deciding whether potentially cross-reactive foods also need to be avoided.

Patients and families need to learn how to accurately read food labels. By law, eight major food allergens (milk, egg, peanut, tree nuts, soy, wheat, fish, and crustacean shellfish) that are responsible for more than 90% of serious adverse food-induced reactions must be included on food labels when appropriate.

Currently, there are no medications recommended for prevention of IgE-mediated food allergies.

When a patient has a FA reaction, antihistamines on an as-needed basis are the recommended treatment. In severe cases, such as anaphylaxis, patients should be treated immediately with an intramuscular dose of epinephrine. Secondary treatment will depend on the patient’s response and can involve hemodynamic support and/or adjunctive treatment with albuterol, diphenhydramine, H₂-blockers, and corticosteroids.

Vaccination

A National Institute of Allergy and Infectious Diseases expert panel recommended that children with egg allergies receive the measles/mumps/rubella and varicella (MMRV) vaccines even if they have had a severe allergic reaction to eggs. There is insufficient evidence regarding influenza vaccination of patients with a history of severe egg allergy. Yellow fever and rabies vaccines should not be administered to patients with severe egg allergies.

The Bottom Line

Food allergies are common and can be suspected by history and confirmed through food allergy testing. The mainstay of treatment for mild reactions is as-needed antihistamines, and the treatment for anaphylaxis is an intramuscular dose of epinephrine. MMRV can still be administered to children with severe egg allergies.

References

Guidelines for the Diagnosis and Management of Food Allergy in the United States: Report of the NIAID-Sponsored Expert Panel. J. Allergy Clin. Immunol. 2010;126[6 suppl]:S1-S58.

Dr. Garg is chief resident in the family medicine residency program at Abington (Pa.) Memorial Hospital. Dr. Skolnik is an associate director of the family medicine residency program at Abington Memorial Hospital.

Food allergy is defined as an immune-mediated adverse health reaction that occurs reproducibly on exposure to a given food. More than 12 million people in the United States have food allergies, which account for 30,000 emergency department visits and more than 100 deaths annually.

Food allergy (FA) is estimated to affect approximately 5% of children, teens, and adults. Specifically, peanut allergy occurs in approximately 0.6% of people, seafood allergy in 0.2%-0.5%, and milk and egg allergy in approximately 2%. Children with FA have an increased likelihood of asthma, atopic dermatitis, and respiratory allergies. Typically, FA is a reaction to a protein in the food that causes the body’s immune system to identify it as harmful. An allergen-specific, IgE-mediated FA requires both the presence of clinical symptoms and sensitization on exposure to a given food item.

Risk Factors

Patients with a medical history of asthma, atopic dermatitis, eosinophilic esophagitis, and exercise-induced anaphylaxis have an increased associated risk for FA. Symptoms often manifest within the first 2 years of life but can occur at any time.

Clinical Manifestations

The clinical manifestations of FA can involve multiple organ systems:

– Gastrointestinal: The most common gastrointestinal reaction is vomiting from an immediate GI hypersensitivity to a given food.

– Cutaneous: The most common cutaneous manifestations include hives during acute urticaria. Soft-tissue swelling from angioedema occurs less commonly. Atopic dermatitis and allergic contact dermatitis can be exacerbated.

– Respiratory: Respiratory reactions are rare but can occur in conjunction with other systemic manifestations.

Diagnosis

A diagnosis of FA should be considered in patients who present with an allergic reaction shortly after eating; in addition, FA may be considered in children with moderate to severe atopic dermatitis. A careful history usually provides the clues that a reaction may be allergic in nature, and physical exam may or may not show the manifestations of an allergic reaction at the time of the evaluation.

By Dr. Neil S.Skolnik and Dr. Sona M. Garg

Parent and patient reports should be confirmed with further testing, as 50%-90% of presumed FAs turn out to be untrue. Confirmation may involve oral food challenge tests or tests of allergic sensitization. The panel recommends oral food challenge as the most accurate test, and it should be considered when diagnosing FA.

Skin prick tests (SPTs) can be helpful, as they are sensitive both for FA and have high negative predictive value. SPTs, however, have low specificity and are prone to false positive results, with many people who do not manifest FA still having a positive reaction to a food.

Allergen-specific serum IgE is helpful in identifying foods that provoke IgE-mediated FA, and it has similar accuracy to SPTs. Food elimination diets can help diagnose non-IgE-mediated FA when symptoms resolve and do not recur on exclusion of a given food. All other tests suffer from lack of specificity and may cause patients to make substantial efforts to avoid foods that may pose no danger. Intradermal tests, measurement of total serum IgE, and atopy patch tests are not recommended.

Natural History

Most children with FA will eventually tolerate milk, egg, soy, and wheat, though fewer will eventually be able to tolerate tree nuts and peanuts. Resolution of FAs in children often occurs during the teenage years. The higher the level of serum IgE, the less likely it is that the FA will resolve. A decrease in IgE levels often is associated with the ability to tolerate the food. FAs that begin in adulthood often do not resolve.

Treatment

Allergen avoidance is the mainstay of prevention and treatment. The challenge is deciding whether potentially cross-reactive foods also need to be avoided.

Patients and families need to learn how to accurately read food labels. By law, eight major food allergens (milk, egg, peanut, tree nuts, soy, wheat, fish, and crustacean shellfish) that are responsible for more than 90% of serious adverse food-induced reactions must be included on food labels when appropriate.

Currently, there are no medications recommended for prevention of IgE-mediated food allergies.

When a patient has a FA reaction, antihistamines on an as-needed basis are the recommended treatment. In severe cases, such as anaphylaxis, patients should be treated immediately with an intramuscular dose of epinephrine. Secondary treatment will depend on the patient’s response and can involve hemodynamic support and/or adjunctive treatment with albuterol, diphenhydramine, H₂-blockers, and corticosteroids.

Vaccination

A National Institute of Allergy and Infectious Diseases expert panel recommended that children with egg allergies receive the measles/mumps/rubella and varicella (MMRV) vaccines even if they have had a severe allergic reaction to eggs. There is insufficient evidence regarding influenza vaccination of patients with a history of severe egg allergy. Yellow fever and rabies vaccines should not be administered to patients with severe egg allergies.

The Bottom Line

Food allergies are common and can be suspected by history and confirmed through food allergy testing. The mainstay of treatment for mild reactions is as-needed antihistamines, and the treatment for anaphylaxis is an intramuscular dose of epinephrine. MMRV can still be administered to children with severe egg allergies.

References

Guidelines for the Diagnosis and Management of Food Allergy in the United States: Report of the NIAID-Sponsored Expert Panel. J. Allergy Clin. Immunol. 2010;126[6 suppl]:S1-S58.

Dr. Garg is chief resident in the family medicine residency program at Abington (Pa.) Memorial Hospital. Dr. Skolnik is an associate director of the family medicine residency program at Abington Memorial Hospital.

SAN FRANCISCO – Some lots of tetanus toxoid, reduced diphtheria toxoid, acellular pertussis vaccine may contain milk protein, which puts milk-allergic children at risk for reactions, according to Dr. Hugh A. Sampson, professor of pediatrics, allergy and immunology and dean for translational biomedical sciences at the Mount Sinai School of Medicine, New York.

Seven milk-allergic children in his practice had severe anaphylactic reactions to either primary or booster shots of the Tdap vaccine (Sanofi Pasteur's Adacel) that were given between September 2007 and March 2010.

"We were struck by the fact that just in our practice we had seven patients with milk allergy who reacted. You wouldn't anticipate that kind of number from one single practice. We believe it is due to contamination of milk protein in this vaccine," Dr. Sampson said at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

The five boys and two girls (median age, 11 years; range, 5-17 years) had prior allergic reactions to cow's milk, including five severe reactions and four reactions to trace exposures. One was diagnosed with milk allergy based on serologic testing.

Dr. Sampson and his colleagues suspect it was milk protein in the vaccine after testing two vials from two lots by inhibition-ELISA. One vial "clearly had milk protein in it" (30 ng/mL). "The other did not," he said.

Bacterial growth media that are used to produce the vaccine contain casamino acids, according to Adacel labeling. These are derived from the milk protein casein.

As "with any process, there can be some variation, lots that for some reason seem to be higher in milk protein. Apparently, there were enough lots that we had seven children end up with anaphylactic reactions," Dr. Sampson said.

He and his colleagues confirmed that two patients received shots from the same vaccine lot, but the vials used on the children were not available for testing.

Even so, "we certainly have circumstantial evidence that there is the possibility of sufficient milk protein in certain lots" that could potentially – if given to a person who is highly milk allergic – cause a reaction, he said.

The problem must be "uncommon or it would have shown up before," and there are no reports yet in the literature, said Dr. Robert A. Wood, a professor of pediatrics and chief of the division of allergy and immunology at Johns Hopkins Children’s Center in Baltimore.

The children all had elevated, milk-specific IgE levels (most over 100 kUA/L) within 2 years of their reactions.

Each had symptoms consistent with anaphylaxis promptly after getting the shot, including wheezing and urticaria in five; sneezing, nasal congestion, and angioedema in three; and repetitive cough in two.

Five were treated with antihistamines, three with epinephrine, three with inhaled beta-agonists, and two with corticosteroids.

Dr. Sampson and his colleagues are continuing to test additional vaccine lots for milk protein.

"There used to be a tremendous variation in the amount of egg protein in flu vaccine, and I think that's why, in egg-allergic children receiving flu shots, some of them had bad reactions [and] some of them did not. It just depended on the content of the egg protein in the lot," he said.

"I think, with the Tdap vaccine, we are seeing basically the same thing. There are lots that for some reason seem to be higher in milk protein," he said.

Dr. Sampson is a consultant for Genentech and holds shares in Herbal Springs LLC. Dr. Wood said he had no relevant financial disclosures.

SAN FRANCISCO – Some lots of tetanus toxoid, reduced diphtheria toxoid, acellular pertussis vaccine may contain milk protein, which puts milk-allergic children at risk for reactions, according to Dr. Hugh A. Sampson, professor of pediatrics, allergy and immunology and dean for translational biomedical sciences at the Mount Sinai School of Medicine, New York.

Seven milk-allergic children in his practice had severe anaphylactic reactions to either primary or booster shots of the Tdap vaccine (Sanofi Pasteur's Adacel) that were given between September 2007 and March 2010.

"We were struck by the fact that just in our practice we had seven patients with milk allergy who reacted. You wouldn't anticipate that kind of number from one single practice. We believe it is due to contamination of milk protein in this vaccine," Dr. Sampson said at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

The five boys and two girls (median age, 11 years; range, 5-17 years) had prior allergic reactions to cow's milk, including five severe reactions and four reactions to trace exposures. One was diagnosed with milk allergy based on serologic testing.

Dr. Sampson and his colleagues suspect it was milk protein in the vaccine after testing two vials from two lots by inhibition-ELISA. One vial "clearly had milk protein in it" (30 ng/mL). "The other did not," he said.

Bacterial growth media that are used to produce the vaccine contain casamino acids, according to Adacel labeling. These are derived from the milk protein casein.

As "with any process, there can be some variation, lots that for some reason seem to be higher in milk protein. Apparently, there were enough lots that we had seven children end up with anaphylactic reactions," Dr. Sampson said.

He and his colleagues confirmed that two patients received shots from the same vaccine lot, but the vials used on the children were not available for testing.

Even so, "we certainly have circumstantial evidence that there is the possibility of sufficient milk protein in certain lots" that could potentially – if given to a person who is highly milk allergic – cause a reaction, he said.

The problem must be "uncommon or it would have shown up before," and there are no reports yet in the literature, said Dr. Robert A. Wood, a professor of pediatrics and chief of the division of allergy and immunology at Johns Hopkins Children’s Center in Baltimore.

The children all had elevated, milk-specific IgE levels (most over 100 kUA/L) within 2 years of their reactions.

Each had symptoms consistent with anaphylaxis promptly after getting the shot, including wheezing and urticaria in five; sneezing, nasal congestion, and angioedema in three; and repetitive cough in two.

Five were treated with antihistamines, three with epinephrine, three with inhaled beta-agonists, and two with corticosteroids.

Dr. Sampson and his colleagues are continuing to test additional vaccine lots for milk protein.

"There used to be a tremendous variation in the amount of egg protein in flu vaccine, and I think that's why, in egg-allergic children receiving flu shots, some of them had bad reactions [and] some of them did not. It just depended on the content of the egg protein in the lot," he said.

"I think, with the Tdap vaccine, we are seeing basically the same thing. There are lots that for some reason seem to be higher in milk protein," he said.

Dr. Sampson is a consultant for Genentech and holds shares in Herbal Springs LLC. Dr. Wood said he had no relevant financial disclosures.

SAN FRANCISCO – Some lots of tetanus toxoid, reduced diphtheria toxoid, acellular pertussis vaccine may contain milk protein, which puts milk-allergic children at risk for reactions, according to Dr. Hugh A. Sampson, professor of pediatrics, allergy and immunology and dean for translational biomedical sciences at the Mount Sinai School of Medicine, New York.

Seven milk-allergic children in his practice had severe anaphylactic reactions to either primary or booster shots of the Tdap vaccine (Sanofi Pasteur's Adacel) that were given between September 2007 and March 2010.

"We were struck by the fact that just in our practice we had seven patients with milk allergy who reacted. You wouldn't anticipate that kind of number from one single practice. We believe it is due to contamination of milk protein in this vaccine," Dr. Sampson said at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

The five boys and two girls (median age, 11 years; range, 5-17 years) had prior allergic reactions to cow's milk, including five severe reactions and four reactions to trace exposures. One was diagnosed with milk allergy based on serologic testing.

Dr. Sampson and his colleagues suspect it was milk protein in the vaccine after testing two vials from two lots by inhibition-ELISA. One vial "clearly had milk protein in it" (30 ng/mL). "The other did not," he said.

Bacterial growth media that are used to produce the vaccine contain casamino acids, according to Adacel labeling. These are derived from the milk protein casein.

As "with any process, there can be some variation, lots that for some reason seem to be higher in milk protein. Apparently, there were enough lots that we had seven children end up with anaphylactic reactions," Dr. Sampson said.

He and his colleagues confirmed that two patients received shots from the same vaccine lot, but the vials used on the children were not available for testing.

Even so, "we certainly have circumstantial evidence that there is the possibility of sufficient milk protein in certain lots" that could potentially – if given to a person who is highly milk allergic – cause a reaction, he said.

The problem must be "uncommon or it would have shown up before," and there are no reports yet in the literature, said Dr. Robert A. Wood, a professor of pediatrics and chief of the division of allergy and immunology at Johns Hopkins Children’s Center in Baltimore.

The children all had elevated, milk-specific IgE levels (most over 100 kUA/L) within 2 years of their reactions.

Each had symptoms consistent with anaphylaxis promptly after getting the shot, including wheezing and urticaria in five; sneezing, nasal congestion, and angioedema in three; and repetitive cough in two.

Five were treated with antihistamines, three with epinephrine, three with inhaled beta-agonists, and two with corticosteroids.

Dr. Sampson and his colleagues are continuing to test additional vaccine lots for milk protein.

"There used to be a tremendous variation in the amount of egg protein in flu vaccine, and I think that's why, in egg-allergic children receiving flu shots, some of them had bad reactions [and] some of them did not. It just depended on the content of the egg protein in the lot," he said.

"I think, with the Tdap vaccine, we are seeing basically the same thing. There are lots that for some reason seem to be higher in milk protein," he said.

Dr. Sampson is a consultant for Genentech and holds shares in Herbal Springs LLC. Dr. Wood said he had no relevant financial disclosures.

SAN FRANCISCO – A 9-mm wheal after skin prick testing provided a 95% positive predictive value for egg or peanut allergy in an analysis of data from 5,000 12-month-old infants recruited from the general population.

The current clinical practice of diagnosing peanut or egg allergy in infants who develop wheals larger than 8 mm from skin prick testing is appropriate in the general population, Lyle Gurrin, Ph.D., and his associates reported at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

Infants with a wheal of any size after a skin prick test were invited for a diagnostic oral food challenge unless they had a convincing reaction in the previous month.

The analysis included 181 infants who underwent peanut challenges, 310 with egg challenges, and 71 with sesame challenges. None of the wheal sizes after sesame challenges reached a 95% positive predictive value for allergy, said Dr. Gurrin of the University of Melbourne.

Previous studies have suggested skin-prick-test wheal sizes provide a 95% likelihood of food allergy if the wheal is 8 mm or larger for egg allergy and 7 mm or larger for peanut allergy. Most of those were small studies of high-risk patients drawn from clinics, not the general population. The studies included a broad range of ages and relied on a history of ingestion reaction rather than performing a formal food challenge.

The current analysis used data from the larger HealthNuts study, a population-based study of Australian 1-year-old infants that was conducted to identify the prevalence of food allergy and modifiable risk factors. Investigators recruited parents and infants at childhood immunization sessions, and 2,848 (73%) agreed to participate. Skin prick tests showed sensitization (a wheal of 1 mm or larger) to peanut in 9%, to raw egg white in 16%, and to sesame in 3% (J. Allergy Clin. Immunol. 2011;127:668-676.e2).

Oral food challenges in these sensitized patients proved that 3% of the entire cohort was allergic to peanut, 9% was allergic to raw egg 1%, and had sesame allergy. Of the infants with raw egg allergy, 80% were able to tolerate baked egg. Some infants were allergic to more than one food. Overall, more than 10% of the cohort had challenge-proven IgE-mediated allergy to one of the common allergenic foods of childhood.

Further analysis of wheal-size thresholds for diagnosis will stratify the findings by the presence or absence of eczema, a family history of allergy, and the ingestion/reaction history, Dr. Gurrin said.

A positive oral food challenge was defined as three or more concurrent, noncontact urticaria lasting at least 5 minutes, vomiting, periorbital angioedema, or anaphylaxis occurring within 2 hours of ingesting the test food.

No patients were excluded from the HealthNuts study due to severe eczema, said one of Dr. Gurrin’s study associates, Dr. Katrina Allen, also of the university.

Less than 1% of infants in the study were dark skinned, but demographic factors did not differ significantly between infants who were excluded from the study and those who were enrolled, she said during the question-and-answer session after Dr. Gurrin's presentation.

The demographic characteristics of infants in the HealthNuts study were similar to population data from the Perinatal Data Collection Unit, but the mothers of HealthNuts infants tended to be older than in the general population.

A brief questionnaire completed by parents who declined to participate in the HealthNuts study suggested that nonparticipating infants were less likely to have a family history of allergy and more likely to already be eating and tolerating peanuts.

The study was funded by the Australian National Health and Medical Research Council, the Ilhan Food Allergy Foundation, AnaphylaxiStop, the U.S. Department of Defense, and the Australian Egg Corp. Dr. Gurrin and Dr. Allen said they had no relevant financial disclosures.

SAN FRANCISCO – A 9-mm wheal after skin prick testing provided a 95% positive predictive value for egg or peanut allergy in an analysis of data from 5,000 12-month-old infants recruited from the general population.

The current clinical practice of diagnosing peanut or egg allergy in infants who develop wheals larger than 8 mm from skin prick testing is appropriate in the general population, Lyle Gurrin, Ph.D., and his associates reported at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

Infants with a wheal of any size after a skin prick test were invited for a diagnostic oral food challenge unless they had a convincing reaction in the previous month.

The analysis included 181 infants who underwent peanut challenges, 310 with egg challenges, and 71 with sesame challenges. None of the wheal sizes after sesame challenges reached a 95% positive predictive value for allergy, said Dr. Gurrin of the University of Melbourne.

Previous studies have suggested skin-prick-test wheal sizes provide a 95% likelihood of food allergy if the wheal is 8 mm or larger for egg allergy and 7 mm or larger for peanut allergy. Most of those were small studies of high-risk patients drawn from clinics, not the general population. The studies included a broad range of ages and relied on a history of ingestion reaction rather than performing a formal food challenge.

The current analysis used data from the larger HealthNuts study, a population-based study of Australian 1-year-old infants that was conducted to identify the prevalence of food allergy and modifiable risk factors. Investigators recruited parents and infants at childhood immunization sessions, and 2,848 (73%) agreed to participate. Skin prick tests showed sensitization (a wheal of 1 mm or larger) to peanut in 9%, to raw egg white in 16%, and to sesame in 3% (J. Allergy Clin. Immunol. 2011;127:668-676.e2).

Oral food challenges in these sensitized patients proved that 3% of the entire cohort was allergic to peanut, 9% was allergic to raw egg 1%, and had sesame allergy. Of the infants with raw egg allergy, 80% were able to tolerate baked egg. Some infants were allergic to more than one food. Overall, more than 10% of the cohort had challenge-proven IgE-mediated allergy to one of the common allergenic foods of childhood.

Further analysis of wheal-size thresholds for diagnosis will stratify the findings by the presence or absence of eczema, a family history of allergy, and the ingestion/reaction history, Dr. Gurrin said.

A positive oral food challenge was defined as three or more concurrent, noncontact urticaria lasting at least 5 minutes, vomiting, periorbital angioedema, or anaphylaxis occurring within 2 hours of ingesting the test food.

No patients were excluded from the HealthNuts study due to severe eczema, said one of Dr. Gurrin’s study associates, Dr. Katrina Allen, also of the university.

Less than 1% of infants in the study were dark skinned, but demographic factors did not differ significantly between infants who were excluded from the study and those who were enrolled, she said during the question-and-answer session after Dr. Gurrin's presentation.

The demographic characteristics of infants in the HealthNuts study were similar to population data from the Perinatal Data Collection Unit, but the mothers of HealthNuts infants tended to be older than in the general population.

A brief questionnaire completed by parents who declined to participate in the HealthNuts study suggested that nonparticipating infants were less likely to have a family history of allergy and more likely to already be eating and tolerating peanuts.

The study was funded by the Australian National Health and Medical Research Council, the Ilhan Food Allergy Foundation, AnaphylaxiStop, the U.S. Department of Defense, and the Australian Egg Corp. Dr. Gurrin and Dr. Allen said they had no relevant financial disclosures.

SAN FRANCISCO – A 9-mm wheal after skin prick testing provided a 95% positive predictive value for egg or peanut allergy in an analysis of data from 5,000 12-month-old infants recruited from the general population.

The current clinical practice of diagnosing peanut or egg allergy in infants who develop wheals larger than 8 mm from skin prick testing is appropriate in the general population, Lyle Gurrin, Ph.D., and his associates reported at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

Infants with a wheal of any size after a skin prick test were invited for a diagnostic oral food challenge unless they had a convincing reaction in the previous month.

The analysis included 181 infants who underwent peanut challenges, 310 with egg challenges, and 71 with sesame challenges. None of the wheal sizes after sesame challenges reached a 95% positive predictive value for allergy, said Dr. Gurrin of the University of Melbourne.

Previous studies have suggested skin-prick-test wheal sizes provide a 95% likelihood of food allergy if the wheal is 8 mm or larger for egg allergy and 7 mm or larger for peanut allergy. Most of those were small studies of high-risk patients drawn from clinics, not the general population. The studies included a broad range of ages and relied on a history of ingestion reaction rather than performing a formal food challenge.

The current analysis used data from the larger HealthNuts study, a population-based study of Australian 1-year-old infants that was conducted to identify the prevalence of food allergy and modifiable risk factors. Investigators recruited parents and infants at childhood immunization sessions, and 2,848 (73%) agreed to participate. Skin prick tests showed sensitization (a wheal of 1 mm or larger) to peanut in 9%, to raw egg white in 16%, and to sesame in 3% (J. Allergy Clin. Immunol. 2011;127:668-676.e2).

Oral food challenges in these sensitized patients proved that 3% of the entire cohort was allergic to peanut, 9% was allergic to raw egg 1%, and had sesame allergy. Of the infants with raw egg allergy, 80% were able to tolerate baked egg. Some infants were allergic to more than one food. Overall, more than 10% of the cohort had challenge-proven IgE-mediated allergy to one of the common allergenic foods of childhood.

Further analysis of wheal-size thresholds for diagnosis will stratify the findings by the presence or absence of eczema, a family history of allergy, and the ingestion/reaction history, Dr. Gurrin said.

A positive oral food challenge was defined as three or more concurrent, noncontact urticaria lasting at least 5 minutes, vomiting, periorbital angioedema, or anaphylaxis occurring within 2 hours of ingesting the test food.

No patients were excluded from the HealthNuts study due to severe eczema, said one of Dr. Gurrin’s study associates, Dr. Katrina Allen, also of the university.

Less than 1% of infants in the study were dark skinned, but demographic factors did not differ significantly between infants who were excluded from the study and those who were enrolled, she said during the question-and-answer session after Dr. Gurrin's presentation.

The demographic characteristics of infants in the HealthNuts study were similar to population data from the Perinatal Data Collection Unit, but the mothers of HealthNuts infants tended to be older than in the general population.

A brief questionnaire completed by parents who declined to participate in the HealthNuts study suggested that nonparticipating infants were less likely to have a family history of allergy and more likely to already be eating and tolerating peanuts.

The study was funded by the Australian National Health and Medical Research Council, the Ilhan Food Allergy Foundation, AnaphylaxiStop, the U.S. Department of Defense, and the Australian Egg Corp. Dr. Gurrin and Dr. Allen said they had no relevant financial disclosures.

SAN FRANCISCO – Oral immunotherapy bested sublingual immunotherapy for pediatric milk allergies in the first head-to-head comparison of the two desensitization techniques.

"The results are quite striking in that we found that both groups had significant increases in the amount of milk they could tolerate, but the oral immunotherapy group had a far greater increase," said senior investigator Dr. Robert A. Wood, professor of pediatrics and chief of the division of allergy and immunology at Johns Hopkins Children’s Center, Baltimore, Md.

However, oral therapy – in which powdered milk extract is put in food and taken as a daily treatment – had more frequent adverse events.

Twelve girls and eighteen boys aged 6-17 years participated in the trial. At baseline, they reacted to less than half a teaspoon of milk and had a median baseline milk-IgE of 37.8 kUa/L, with a range 1.1-572 kUa/L.

Ten randomized to sublingual therapy were gradually escalated to maintenance doses of 7 mg of milk extract per day placed under their tongues, held for a few minutes, then swallowed.

Ten children in the oral group were gradually escalated to daily maintenance doses of 1,000 mg, ten others to 2,000 mg.

One girl dropped out because she had a severe eczema flair, but the others reached the maintenance dose and completed milk challenges.

After 3 months of maintenance, children in the sublingual group tolerated a median of 940 mg of milk – a little less than an ounce – with a range of 40-8,140 mg.

Children in the 1,000 mg oral group tolerated a median of 6,140 mg with a range of 2,540-8,140 mg. Those in the 2,000 mg group tolerated 8,140 mg of milk with a range of 4,140-8,140 mg. The findings were statistically significant.

Six children in the sublingual group repeated the challenge at 14 months; one tolerated 8,000 mg, but the rest tolerated less than 1,000 mg and were switched to oral therapy, Dr. Wood said.

Skin prick tests decreased and milk-IgG4 increased in all the groups. Milk-IgE decreased only after oral immunotherapy. Milk-IgE or milk-IgG4 did not predict food challenge outcomes.

Side effects were similar between the sublingual and oral groups, but more severe in the oral groups. Antihistamines were needed with only about 1% of the sublingual doses, but with 18% of the oral doses. Epinephrine was used twice during sublingual therapy but four times during oral therapy.

Oral therapy’s greater side effects didn’t surprise coinvestigator Dr. Wesley Burks, chief of the division of pediatric allergy and immunology at Duke University Medical Center, Durham, N.C.

"In general, oral has more side effects." In immunotherapy trials, "about 15% of children cannot tolerate the procedure at all. They have too many [gastrointestinal] symptoms," he said.

Although promising, Dr. Wood noted the results are preliminary.

His study, as well as immunotherapy trials for peanuts and other allergens, have "very small numbers where we are trying to figure out the right doses and right way to do it. We are hopeful in the next few years we will be comfortable enough with the approach to be able to do some larger studies," he said.

Dr. Wood said he had no relevant financial disclosures. Dr. Burks disclosed that he is a consultant for Actogenix, Dannon, Intelliject, McNeil Nutritionals, Novartis, Schering-Plough (now part of Merck), and Nutricia. He is a minority stockholder in Allertein Therapeutics and Mast Cell Pharmaceuticals Inc. 

SAN FRANCISCO – Oral immunotherapy bested sublingual immunotherapy for pediatric milk allergies in the first head-to-head comparison of the two desensitization techniques.

"The results are quite striking in that we found that both groups had significant increases in the amount of milk they could tolerate, but the oral immunotherapy group had a far greater increase," said senior investigator Dr. Robert A. Wood, professor of pediatrics and chief of the division of allergy and immunology at Johns Hopkins Children’s Center, Baltimore, Md.

However, oral therapy – in which powdered milk extract is put in food and taken as a daily treatment – had more frequent adverse events.

Twelve girls and eighteen boys aged 6-17 years participated in the trial. At baseline, they reacted to less than half a teaspoon of milk and had a median baseline milk-IgE of 37.8 kUa/L, with a range 1.1-572 kUa/L.

Ten randomized to sublingual therapy were gradually escalated to maintenance doses of 7 mg of milk extract per day placed under their tongues, held for a few minutes, then swallowed.

Ten children in the oral group were gradually escalated to daily maintenance doses of 1,000 mg, ten others to 2,000 mg.

One girl dropped out because she had a severe eczema flair, but the others reached the maintenance dose and completed milk challenges.

After 3 months of maintenance, children in the sublingual group tolerated a median of 940 mg of milk – a little less than an ounce – with a range of 40-8,140 mg.

Children in the 1,000 mg oral group tolerated a median of 6,140 mg with a range of 2,540-8,140 mg. Those in the 2,000 mg group tolerated 8,140 mg of milk with a range of 4,140-8,140 mg. The findings were statistically significant.

Six children in the sublingual group repeated the challenge at 14 months; one tolerated 8,000 mg, but the rest tolerated less than 1,000 mg and were switched to oral therapy, Dr. Wood said.

Skin prick tests decreased and milk-IgG4 increased in all the groups. Milk-IgE decreased only after oral immunotherapy. Milk-IgE or milk-IgG4 did not predict food challenge outcomes.

Side effects were similar between the sublingual and oral groups, but more severe in the oral groups. Antihistamines were needed with only about 1% of the sublingual doses, but with 18% of the oral doses. Epinephrine was used twice during sublingual therapy but four times during oral therapy.

Oral therapy’s greater side effects didn’t surprise coinvestigator Dr. Wesley Burks, chief of the division of pediatric allergy and immunology at Duke University Medical Center, Durham, N.C.

"In general, oral has more side effects." In immunotherapy trials, "about 15% of children cannot tolerate the procedure at all. They have too many [gastrointestinal] symptoms," he said.

Although promising, Dr. Wood noted the results are preliminary.

His study, as well as immunotherapy trials for peanuts and other allergens, have "very small numbers where we are trying to figure out the right doses and right way to do it. We are hopeful in the next few years we will be comfortable enough with the approach to be able to do some larger studies," he said.

Dr. Wood said he had no relevant financial disclosures. Dr. Burks disclosed that he is a consultant for Actogenix, Dannon, Intelliject, McNeil Nutritionals, Novartis, Schering-Plough (now part of Merck), and Nutricia. He is a minority stockholder in Allertein Therapeutics and Mast Cell Pharmaceuticals Inc. 

SAN FRANCISCO – Oral immunotherapy bested sublingual immunotherapy for pediatric milk allergies in the first head-to-head comparison of the two desensitization techniques.

"The results are quite striking in that we found that both groups had significant increases in the amount of milk they could tolerate, but the oral immunotherapy group had a far greater increase," said senior investigator Dr. Robert A. Wood, professor of pediatrics and chief of the division of allergy and immunology at Johns Hopkins Children’s Center, Baltimore, Md.

However, oral therapy – in which powdered milk extract is put in food and taken as a daily treatment – had more frequent adverse events.

Twelve girls and eighteen boys aged 6-17 years participated in the trial. At baseline, they reacted to less than half a teaspoon of milk and had a median baseline milk-IgE of 37.8 kUa/L, with a range 1.1-572 kUa/L.

Ten randomized to sublingual therapy were gradually escalated to maintenance doses of 7 mg of milk extract per day placed under their tongues, held for a few minutes, then swallowed.

Ten children in the oral group were gradually escalated to daily maintenance doses of 1,000 mg, ten others to 2,000 mg.

One girl dropped out because she had a severe eczema flair, but the others reached the maintenance dose and completed milk challenges.

After 3 months of maintenance, children in the sublingual group tolerated a median of 940 mg of milk – a little less than an ounce – with a range of 40-8,140 mg.

Children in the 1,000 mg oral group tolerated a median of 6,140 mg with a range of 2,540-8,140 mg. Those in the 2,000 mg group tolerated 8,140 mg of milk with a range of 4,140-8,140 mg. The findings were statistically significant.

Six children in the sublingual group repeated the challenge at 14 months; one tolerated 8,000 mg, but the rest tolerated less than 1,000 mg and were switched to oral therapy, Dr. Wood said.

Skin prick tests decreased and milk-IgG4 increased in all the groups. Milk-IgE decreased only after oral immunotherapy. Milk-IgE or milk-IgG4 did not predict food challenge outcomes.

Side effects were similar between the sublingual and oral groups, but more severe in the oral groups. Antihistamines were needed with only about 1% of the sublingual doses, but with 18% of the oral doses. Epinephrine was used twice during sublingual therapy but four times during oral therapy.

Oral therapy’s greater side effects didn’t surprise coinvestigator Dr. Wesley Burks, chief of the division of pediatric allergy and immunology at Duke University Medical Center, Durham, N.C.

"In general, oral has more side effects." In immunotherapy trials, "about 15% of children cannot tolerate the procedure at all. They have too many [gastrointestinal] symptoms," he said.

Although promising, Dr. Wood noted the results are preliminary.

His study, as well as immunotherapy trials for peanuts and other allergens, have "very small numbers where we are trying to figure out the right doses and right way to do it. We are hopeful in the next few years we will be comfortable enough with the approach to be able to do some larger studies," he said.

Dr. Wood said he had no relevant financial disclosures. Dr. Burks disclosed that he is a consultant for Actogenix, Dannon, Intelliject, McNeil Nutritionals, Novartis, Schering-Plough (now part of Merck), and Nutricia. He is a minority stockholder in Allertein Therapeutics and Mast Cell Pharmaceuticals Inc. 

SAN FRANCISCO – Sublingual immunotherapy desensitized 11 children to peanut allergies in a double-blind, placebo-controlled trial.

When challenged with peanut after a year of treatment, they tolerated a median of 1,710 mg (about seven peanuts), while 7 children in the placebo arm tolerated a median of 85 mg (about one-fifth of a peanut), a 20-fold difference (P = .011).

Photo credit: © mates/Fotolia.com

The results were so impressive that the interim analysis was cut short to switch placebo children to active therapy, said senior investigator Dr. Wesley Burks, professor of pediatrics and chief of the division of pediatric allergy and immunology at Duke University Medical Center, Durham, N.C.

But however promising these results, and those of other immunotherapy trials, Dr. Burks cautioned that additional efficacy and safety verification are needed.

In some immunotherapy trials, children who seemed to tolerate gradual exposure and desensitization to their particular allergens had unexpected anaphylactic reactions, especially if they came down with a viral illness. A significant proportion of children also can't tolerate oral immunotherapy, he said.

Those points are often missed in news reports that suggest immunotherapy cures food allergies. Until more is known, immunotherapy "is not the right thing to do right now. We don’t put people on immunotherapy unless it’s in a study," he said.

Children in the trial were aged 1- to 11-years-old and had histories of peanut reactions plus elevated peanut IgE levels.

Treated children were dose escalated over a period of 6 months to a total of 2,000 mcg of peanut protein daily, then maintenance dosed for the next 6 months. The peanut extract was placed under their tongues, held for a couple minutes, then swallowed; 2,500-mg peanut challenges came at the 1-year mark.

Although the median was 1,710 mg, "there was a pretty wide range in how much [treated children] tolerated," Dr. Burks said, with some able to handle the entire 2,500 mg, others only 200 mg.

Peanut-specific IgE increased over the first 4 months of treatment (P = .002), then steadily decreased over the remaining 8 months (P = .003). Peanut-specific IgG4 increased over the entire year of therapy (P = .014).

"Their skin-prick tests [also] went down in the first 6 months [of treatment] and stayed down" versus placebo, Dr. Burks said. Treated children had wheal sizes significantly smaller than children in the placebo group (P = .020).

The findings "suggest a significant change in the allergic response," Dr. Burks concluded.

Dosing side effects were mostly oropharyngeal and seldom required treatment.

Children in the placebo group were switched to sublingual therapy following the peanut challenges. After a year of treatment, five of the seven now tolerate 2,500 mg of peanut, with the other two tolerating between 1,500 and 2,000 mg, Dr. Burks said.

Dr. Burks disclosed that he is a consultant for Actogenix, Dannon, Intelliject, McNeil Nutritionals, Novartis, Schering-Plough (now a part of Merck), and Nutricia. He is a minority stockholder in Allertein Therapeutics and Mast Cell Pharmaceuticals.

SAN FRANCISCO – Sublingual immunotherapy desensitized 11 children to peanut allergies in a double-blind, placebo-controlled trial.

When challenged with peanut after a year of treatment, they tolerated a median of 1,710 mg (about seven peanuts), while 7 children in the placebo arm tolerated a median of 85 mg (about one-fifth of a peanut), a 20-fold difference (P = .011).

Photo credit: © mates/Fotolia.com

The results were so impressive that the interim analysis was cut short to switch placebo children to active therapy, said senior investigator Dr. Wesley Burks, professor of pediatrics and chief of the division of pediatric allergy and immunology at Duke University Medical Center, Durham, N.C.

But however promising these results, and those of other immunotherapy trials, Dr. Burks cautioned that additional efficacy and safety verification are needed.

In some immunotherapy trials, children who seemed to tolerate gradual exposure and desensitization to their particular allergens had unexpected anaphylactic reactions, especially if they came down with a viral illness. A significant proportion of children also can't tolerate oral immunotherapy, he said.

Those points are often missed in news reports that suggest immunotherapy cures food allergies. Until more is known, immunotherapy "is not the right thing to do right now. We don’t put people on immunotherapy unless it’s in a study," he said.

Children in the trial were aged 1- to 11-years-old and had histories of peanut reactions plus elevated peanut IgE levels.

Treated children were dose escalated over a period of 6 months to a total of 2,000 mcg of peanut protein daily, then maintenance dosed for the next 6 months. The peanut extract was placed under their tongues, held for a couple minutes, then swallowed; 2,500-mg peanut challenges came at the 1-year mark.

Although the median was 1,710 mg, "there was a pretty wide range in how much [treated children] tolerated," Dr. Burks said, with some able to handle the entire 2,500 mg, others only 200 mg.

Peanut-specific IgE increased over the first 4 months of treatment (P = .002), then steadily decreased over the remaining 8 months (P = .003). Peanut-specific IgG4 increased over the entire year of therapy (P = .014).

"Their skin-prick tests [also] went down in the first 6 months [of treatment] and stayed down" versus placebo, Dr. Burks said. Treated children had wheal sizes significantly smaller than children in the placebo group (P = .020).

The findings "suggest a significant change in the allergic response," Dr. Burks concluded.

Dosing side effects were mostly oropharyngeal and seldom required treatment.

Children in the placebo group were switched to sublingual therapy following the peanut challenges. After a year of treatment, five of the seven now tolerate 2,500 mg of peanut, with the other two tolerating between 1,500 and 2,000 mg, Dr. Burks said.

Dr. Burks disclosed that he is a consultant for Actogenix, Dannon, Intelliject, McNeil Nutritionals, Novartis, Schering-Plough (now a part of Merck), and Nutricia. He is a minority stockholder in Allertein Therapeutics and Mast Cell Pharmaceuticals.

SAN FRANCISCO – Sublingual immunotherapy desensitized 11 children to peanut allergies in a double-blind, placebo-controlled trial.

When challenged with peanut after a year of treatment, they tolerated a median of 1,710 mg (about seven peanuts), while 7 children in the placebo arm tolerated a median of 85 mg (about one-fifth of a peanut), a 20-fold difference (P = .011).

Photo credit: © mates/Fotolia.com

The results were so impressive that the interim analysis was cut short to switch placebo children to active therapy, said senior investigator Dr. Wesley Burks, professor of pediatrics and chief of the division of pediatric allergy and immunology at Duke University Medical Center, Durham, N.C.

But however promising these results, and those of other immunotherapy trials, Dr. Burks cautioned that additional efficacy and safety verification are needed.

In some immunotherapy trials, children who seemed to tolerate gradual exposure and desensitization to their particular allergens had unexpected anaphylactic reactions, especially if they came down with a viral illness. A significant proportion of children also can't tolerate oral immunotherapy, he said.

Those points are often missed in news reports that suggest immunotherapy cures food allergies. Until more is known, immunotherapy "is not the right thing to do right now. We don’t put people on immunotherapy unless it’s in a study," he said.

Children in the trial were aged 1- to 11-years-old and had histories of peanut reactions plus elevated peanut IgE levels.

Treated children were dose escalated over a period of 6 months to a total of 2,000 mcg of peanut protein daily, then maintenance dosed for the next 6 months. The peanut extract was placed under their tongues, held for a couple minutes, then swallowed; 2,500-mg peanut challenges came at the 1-year mark.

Although the median was 1,710 mg, "there was a pretty wide range in how much [treated children] tolerated," Dr. Burks said, with some able to handle the entire 2,500 mg, others only 200 mg.

Peanut-specific IgE increased over the first 4 months of treatment (P = .002), then steadily decreased over the remaining 8 months (P = .003). Peanut-specific IgG4 increased over the entire year of therapy (P = .014).

"Their skin-prick tests [also] went down in the first 6 months [of treatment] and stayed down" versus placebo, Dr. Burks said. Treated children had wheal sizes significantly smaller than children in the placebo group (P = .020).

The findings "suggest a significant change in the allergic response," Dr. Burks concluded.

Dosing side effects were mostly oropharyngeal and seldom required treatment.

Children in the placebo group were switched to sublingual therapy following the peanut challenges. After a year of treatment, five of the seven now tolerate 2,500 mg of peanut, with the other two tolerating between 1,500 and 2,000 mg, Dr. Burks said.

Dr. Burks disclosed that he is a consultant for Actogenix, Dannon, Intelliject, McNeil Nutritionals, Novartis, Schering-Plough (now a part of Merck), and Nutricia. He is a minority stockholder in Allertein Therapeutics and Mast Cell Pharmaceuticals.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

SAN FRANCISCO – Baseline milk-IgE level and skin-prick wheal size do a good job of predicting if a child will outgrow a milk allergy, but variation in eczema severity does not, two studies have shown.

"If you have a low milk-specific IgE, less than 2 on the ImmunoCAP test, about [65%] of babies outgrow their allergy" by 30 months. "If you look at those with higher numbers, greater than 10, only 7% of those babies outgrow their allergy," said lead investigator Dr. Robert A. Wood, professor of pediatrics and chief of the division of allergy and immunology at Johns Hopkins Children’s Center, Baltimore.

In the eczema study, "what we found was that the more severe the eczema you had when you came into the study, the less chance of outgrowing your milk allergy," but reduction in eczema severity did not correlate with milk allergy resolution, said Dr. Wood, also an investigator on the second trial.

Being able to predict resolution is important not only to reassure parents and guide treatment, but also because immunotherapy desensitization techniques being developed by Dr. Wood and others may be widely available in 5 or 10 years.

"If we have a marker that says this child can do it on their own by the time they are 2½, that’s great. If we have a marker that says this child will have a lifetime milk allergy, and maybe [immunotherapy] will be most effective if we initiate it early, that will be an incredibly important piece of information," he said at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

Populations for both studies were drawn from the Consortium of Food Allergy Research (CoFAR) cohort, a National Institutes of Health–funded project with more than 500 children.

In the first study, 89 (36.5%) of 244 milk-allergic infants aged 3-15 months tolerated milk by month 30. The median age of resolution was 2 years.

Those who outgrew their allergy started the trial with a median baseline milk-IgE of 0.72 kU/L; those who did not started with a median of 6.99 kU/L. Only 14.2% of infants who entered the trial with IgE values at or above 5 kU/L resolved their allergy by month 30.

Also associated with resolution was a median baseline milk skin-prick wheal size of 5.0 mm. The median size of those who remained allergic was 9.25 mm (P = less than .001).

"You could really tell a mother with [a] 9-month old baby based on IgE and skin test that [there is a] possibility of outgrowing" the allergy within 30 months. Both are "very useful predictors," Dr. Wood said.

In the eczema study, 27 (46%) of 59 infants aged 3-15 months with mild eczema resolved their milk allergies within 2 years, while only 41 (25%) of 165 with moderate to severe eczema outgrew their allergy (P = .004).

However, in a finding that may surprise some allergists, just 12 (19%) of 62 children enrolled with moderate to severe eczema outgrew their allergy even though their eczema improved to none or mild; among 66 children whose eczema didn’t improve, 21 (32%) outgrew their allergy (P = .11).

"We saw kids whose eczema got a lot better who stayed allergic, and other kids whose eczema stayed severe who managed to outgrow their allergies," Dr. Wood said.

That’s surprising because "there’s just sort of an assumption that many allergists [have] that as atopic dermatitis [gets better, children] are more likely to outgrow their food allergy. What this study showed was there wasn’t that direct line," he said.

Dr. Wood and his colleagues also looked at egg allergy; 13 (39%) of 33 children with no or mild eczema at enrollment outgrew their egg allergy within 2 years, compared with 19 (21%) of 89 enrolled with moderate to severe eczema (P = .047).

About a quarter resolved their egg allergies whether their eczema improved or not, but the finding wasn’t statistically significant.

Dr. Wood said he had no relevant financial disclosures.

SAN FRANCISCO – Baseline milk-IgE level and skin-prick wheal size do a good job of predicting if a child will outgrow a milk allergy, but variation in eczema severity does not, two studies have shown.

"If you have a low milk-specific IgE, less than 2 on the ImmunoCAP test, about [65%] of babies outgrow their allergy" by 30 months. "If you look at those with higher numbers, greater than 10, only 7% of those babies outgrow their allergy," said lead investigator Dr. Robert A. Wood, professor of pediatrics and chief of the division of allergy and immunology at Johns Hopkins Children’s Center, Baltimore.

In the eczema study, "what we found was that the more severe the eczema you had when you came into the study, the less chance of outgrowing your milk allergy," but reduction in eczema severity did not correlate with milk allergy resolution, said Dr. Wood, also an investigator on the second trial.

Being able to predict resolution is important not only to reassure parents and guide treatment, but also because immunotherapy desensitization techniques being developed by Dr. Wood and others may be widely available in 5 or 10 years.

"If we have a marker that says this child can do it on their own by the time they are 2½, that’s great. If we have a marker that says this child will have a lifetime milk allergy, and maybe [immunotherapy] will be most effective if we initiate it early, that will be an incredibly important piece of information," he said at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

Populations for both studies were drawn from the Consortium of Food Allergy Research (CoFAR) cohort, a National Institutes of Health–funded project with more than 500 children.

In the first study, 89 (36.5%) of 244 milk-allergic infants aged 3-15 months tolerated milk by month 30. The median age of resolution was 2 years.

Those who outgrew their allergy started the trial with a median baseline milk-IgE of 0.72 kU/L; those who did not started with a median of 6.99 kU/L. Only 14.2% of infants who entered the trial with IgE values at or above 5 kU/L resolved their allergy by month 30.

Also associated with resolution was a median baseline milk skin-prick wheal size of 5.0 mm. The median size of those who remained allergic was 9.25 mm (P = less than .001).

"You could really tell a mother with [a] 9-month old baby based on IgE and skin test that [there is a] possibility of outgrowing" the allergy within 30 months. Both are "very useful predictors," Dr. Wood said.

In the eczema study, 27 (46%) of 59 infants aged 3-15 months with mild eczema resolved their milk allergies within 2 years, while only 41 (25%) of 165 with moderate to severe eczema outgrew their allergy (P = .004).

However, in a finding that may surprise some allergists, just 12 (19%) of 62 children enrolled with moderate to severe eczema outgrew their allergy even though their eczema improved to none or mild; among 66 children whose eczema didn’t improve, 21 (32%) outgrew their allergy (P = .11).

"We saw kids whose eczema got a lot better who stayed allergic, and other kids whose eczema stayed severe who managed to outgrow their allergies," Dr. Wood said.

That’s surprising because "there’s just sort of an assumption that many allergists [have] that as atopic dermatitis [gets better, children] are more likely to outgrow their food allergy. What this study showed was there wasn’t that direct line," he said.

Dr. Wood and his colleagues also looked at egg allergy; 13 (39%) of 33 children with no or mild eczema at enrollment outgrew their egg allergy within 2 years, compared with 19 (21%) of 89 enrolled with moderate to severe eczema (P = .047).

About a quarter resolved their egg allergies whether their eczema improved or not, but the finding wasn’t statistically significant.

Dr. Wood said he had no relevant financial disclosures.

SAN FRANCISCO – Baseline milk-IgE level and skin-prick wheal size do a good job of predicting if a child will outgrow a milk allergy, but variation in eczema severity does not, two studies have shown.

"If you have a low milk-specific IgE, less than 2 on the ImmunoCAP test, about [65%] of babies outgrow their allergy" by 30 months. "If you look at those with higher numbers, greater than 10, only 7% of those babies outgrow their allergy," said lead investigator Dr. Robert A. Wood, professor of pediatrics and chief of the division of allergy and immunology at Johns Hopkins Children’s Center, Baltimore.

In the eczema study, "what we found was that the more severe the eczema you had when you came into the study, the less chance of outgrowing your milk allergy," but reduction in eczema severity did not correlate with milk allergy resolution, said Dr. Wood, also an investigator on the second trial.

Being able to predict resolution is important not only to reassure parents and guide treatment, but also because immunotherapy desensitization techniques being developed by Dr. Wood and others may be widely available in 5 or 10 years.

"If we have a marker that says this child can do it on their own by the time they are 2½, that’s great. If we have a marker that says this child will have a lifetime milk allergy, and maybe [immunotherapy] will be most effective if we initiate it early, that will be an incredibly important piece of information," he said at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

Populations for both studies were drawn from the Consortium of Food Allergy Research (CoFAR) cohort, a National Institutes of Health–funded project with more than 500 children.

In the first study, 89 (36.5%) of 244 milk-allergic infants aged 3-15 months tolerated milk by month 30. The median age of resolution was 2 years.

Those who outgrew their allergy started the trial with a median baseline milk-IgE of 0.72 kU/L; those who did not started with a median of 6.99 kU/L. Only 14.2% of infants who entered the trial with IgE values at or above 5 kU/L resolved their allergy by month 30.

Also associated with resolution was a median baseline milk skin-prick wheal size of 5.0 mm. The median size of those who remained allergic was 9.25 mm (P = less than .001).

"You could really tell a mother with [a] 9-month old baby based on IgE and skin test that [there is a] possibility of outgrowing" the allergy within 30 months. Both are "very useful predictors," Dr. Wood said.

In the eczema study, 27 (46%) of 59 infants aged 3-15 months with mild eczema resolved their milk allergies within 2 years, while only 41 (25%) of 165 with moderate to severe eczema outgrew their allergy (P = .004).

However, in a finding that may surprise some allergists, just 12 (19%) of 62 children enrolled with moderate to severe eczema outgrew their allergy even though their eczema improved to none or mild; among 66 children whose eczema didn’t improve, 21 (32%) outgrew their allergy (P = .11).

"We saw kids whose eczema got a lot better who stayed allergic, and other kids whose eczema stayed severe who managed to outgrow their allergies," Dr. Wood said.

That’s surprising because "there’s just sort of an assumption that many allergists [have] that as atopic dermatitis [gets better, children] are more likely to outgrow their food allergy. What this study showed was there wasn’t that direct line," he said.

Dr. Wood and his colleagues also looked at egg allergy; 13 (39%) of 33 children with no or mild eczema at enrollment outgrew their egg allergy within 2 years, compared with 19 (21%) of 89 enrolled with moderate to severe eczema (P = .047).

About a quarter resolved their egg allergies whether their eczema improved or not, but the finding wasn’t statistically significant.

Dr. Wood said he had no relevant financial disclosures.

Despite being the most common pattern of scarring hair loss among African American women, central centrifugal cicatricial alopecia is still poorly understood, according to a report published online April 11 in Archives of Dermatology.

The etiology of and risk factors for the disorder have not been established. And although African American women commonly present with the condition, the exact prevalence remains unknown, said Dr. Angela Kyei and her associates at the Cleveland Clinic Institute of Dermatology and Plastic Surgery.

Photo credit: Dr. Valerie Callender

Central centrifugal cicatricial alopecia (CCCA) – previously known as hot comb alopecia or follicular degeneration syndrome – is a scarring hair loss centered on the vertex of the scalp and spreading peripherally, which is described almost exclusively in African American women. In the late 1960s it was linked to the use of hot combs, but since then almost every method of hair grooming in this population has been associated, albeit weakly, with the disorder. Few studies have examined other possible etiologies, such as immunologic, dermatologic, or genetic factors.

"Given the lack of epidemiologic data, the main goal of [our] study was to elucidate environmental as well as medical risk factors that may be associated with CCCA," the researchers wrote.

They administered questionnaires to 326 African American women attending two churches and a health fair in the Cleveland area. Sixteen of the women ended up being excluded from the analysis.

The questionnaires asked detailed information about family history of male- and female-pattern hair loss; personal medical history, including bacterial and fungal skin infections, autoimmune conditions, and hormonal dysregulation; and hair grooming methods used. The study subjects also underwent a scalp examination that included the grading of hair loss.

A total of 86 of the 310 women (28%) were judged to have central hair loss. Of these, 52 women – 17% of the total study population – had CCCA.

It appeared that hair grooming practices that cause traction, such as weaves and braids, may contribute to the development of CCCA, as women with the most severe central hair loss used these styles more frequently than did those without hair loss. "This has some clinical bearing because traction can clinically produce folliculitis of the scalp, which can cause scarring if this inflammation is prolonged," noted Dr. Kyei and her colleagues (Arch. Dermatol. 2011 April 11 [doi:10.1001/archdermatol.2011.66]).

After paying hundreds of dollars for such hair styling, women often maintain weaves and braids for weeks to months, so any reactive inflammation usually is prolonged, the investigators added.

However, "the relationship between chemical relaxer use and the development of CCCA continues to be murky," they noted. These products clearly weaken the hair shaft, which can cause breakage, but that does not necessarily lead to CCCA. "The fact that most African Americans use chemical relaxers in combination with braiding and other hair grooming practices makes it even more difficult to tease out a relationship," Dr. Kyei and her associates added.

It is difficult to find subjects who do not use chemical relaxers for comparison, since most African Americans begin the practice in childhood. In this study, 91% of the women reported using chemical relaxers, and began doing so at an average age of 10 years.

Nevertheless, "we feel that it is not unreasonable to assume that the scalp may absorb some of the caustic chemicals found in relaxers, which in time leads to damage of the scalp in the form of scarring," they wrote.

Although the prevalence of bacterial skin infections in these study subjects was only 11%, there was a significant elevation among women with CCCA, compared with women who did not have CCCA. The rate of acne also was elevated in affected subjects, but not to a significant degree. Thus, the researchers said that their study "demonstrates that inflammation in the form of bacterial infection and acne may also be contributing to the development of CCCA, a finding consistent with the histopathologic characteristics of this disease," which show a lymphocytic perifollicular infiltrate in its early stages.

In contrast, there was no such association with fungal infections of the scalp, ringworm, or vaginal yeast infections, which was "surprising given how prone this population is to fungal infection," they added.

"One of the most surprising findings ... was the overrepresentation of type 2 [diabetes mellitus] in those with CCCA," the authors noted. Again, the prevalence of type 2 diabetes was low, at 8%, but it was significantly elevated in women with CCCA, compared with those without CCCA.

"These are important data that need further study because CCCA may be a marker of metabolic dysfunction and, when present, can prompt clinicians to do further testing for diabetes mellitus," Dr. Kyei and her colleagues wrote.

Only 9% of the study subjects had thyroid abnormalities, and three-fourths of them had no or minimal hair loss.

A history of male-pattern baldness in the maternal grandfather was found to be a risk factor for CCCA, which suggests that genetics may play a role.

Hormonal dysregulation did not appear to be associated with development of CCCA. Neither were scarring disorders, since only 6% of the subjects reported a history of keloids, and the rate was no higher in women with CCCA than in those without CCCA.

Similarly, there were relatively high prevalences of seborrheic dermatitis (24%), eczema (13%), and contact dermatitis from chemical relaxers (9%), as would be expected in an African American population. However, these conditions were unrelated to CCCA.

This study was supported in part by the North American Hair Research Society and Procter & Gamble. No financial conflicts of interest were reported.

Despite being the most common pattern of scarring hair loss among African American women, central centrifugal cicatricial alopecia is still poorly understood, according to a report published online April 11 in Archives of Dermatology.

The etiology of and risk factors for the disorder have not been established. And although African American women commonly present with the condition, the exact prevalence remains unknown, said Dr. Angela Kyei and her associates at the Cleveland Clinic Institute of Dermatology and Plastic Surgery.

Photo credit: Dr. Valerie Callender

Central centrifugal cicatricial alopecia (CCCA) – previously known as hot comb alopecia or follicular degeneration syndrome – is a scarring hair loss centered on the vertex of the scalp and spreading peripherally, which is described almost exclusively in African American women. In the late 1960s it was linked to the use of hot combs, but since then almost every method of hair grooming in this population has been associated, albeit weakly, with the disorder. Few studies have examined other possible etiologies, such as immunologic, dermatologic, or genetic factors.

"Given the lack of epidemiologic data, the main goal of [our] study was to elucidate environmental as well as medical risk factors that may be associated with CCCA," the researchers wrote.

They administered questionnaires to 326 African American women attending two churches and a health fair in the Cleveland area. Sixteen of the women ended up being excluded from the analysis.

The questionnaires asked detailed information about family history of male- and female-pattern hair loss; personal medical history, including bacterial and fungal skin infections, autoimmune conditions, and hormonal dysregulation; and hair grooming methods used. The study subjects also underwent a scalp examination that included the grading of hair loss.

A total of 86 of the 310 women (28%) were judged to have central hair loss. Of these, 52 women – 17% of the total study population – had CCCA.

It appeared that hair grooming practices that cause traction, such as weaves and braids, may contribute to the development of CCCA, as women with the most severe central hair loss used these styles more frequently than did those without hair loss. "This has some clinical bearing because traction can clinically produce folliculitis of the scalp, which can cause scarring if this inflammation is prolonged," noted Dr. Kyei and her colleagues (Arch. Dermatol. 2011 April 11 [doi:10.1001/archdermatol.2011.66]).

After paying hundreds of dollars for such hair styling, women often maintain weaves and braids for weeks to months, so any reactive inflammation usually is prolonged, the investigators added.

However, "the relationship between chemical relaxer use and the development of CCCA continues to be murky," they noted. These products clearly weaken the hair shaft, which can cause breakage, but that does not necessarily lead to CCCA. "The fact that most African Americans use chemical relaxers in combination with braiding and other hair grooming practices makes it even more difficult to tease out a relationship," Dr. Kyei and her associates added.

It is difficult to find subjects who do not use chemical relaxers for comparison, since most African Americans begin the practice in childhood. In this study, 91% of the women reported using chemical relaxers, and began doing so at an average age of 10 years.

Nevertheless, "we feel that it is not unreasonable to assume that the scalp may absorb some of the caustic chemicals found in relaxers, which in time leads to damage of the scalp in the form of scarring," they wrote.

Although the prevalence of bacterial skin infections in these study subjects was only 11%, there was a significant elevation among women with CCCA, compared with women who did not have CCCA. The rate of acne also was elevated in affected subjects, but not to a significant degree. Thus, the researchers said that their study "demonstrates that inflammation in the form of bacterial infection and acne may also be contributing to the development of CCCA, a finding consistent with the histopathologic characteristics of this disease," which show a lymphocytic perifollicular infiltrate in its early stages.

In contrast, there was no such association with fungal infections of the scalp, ringworm, or vaginal yeast infections, which was "surprising given how prone this population is to fungal infection," they added.

"One of the most surprising findings ... was the overrepresentation of type 2 [diabetes mellitus] in those with CCCA," the authors noted. Again, the prevalence of type 2 diabetes was low, at 8%, but it was significantly elevated in women with CCCA, compared with those without CCCA.

"These are important data that need further study because CCCA may be a marker of metabolic dysfunction and, when present, can prompt clinicians to do further testing for diabetes mellitus," Dr. Kyei and her colleagues wrote.

Only 9% of the study subjects had thyroid abnormalities, and three-fourths of them had no or minimal hair loss.

A history of male-pattern baldness in the maternal grandfather was found to be a risk factor for CCCA, which suggests that genetics may play a role.

Hormonal dysregulation did not appear to be associated with development of CCCA. Neither were scarring disorders, since only 6% of the subjects reported a history of keloids, and the rate was no higher in women with CCCA than in those without CCCA.

Similarly, there were relatively high prevalences of seborrheic dermatitis (24%), eczema (13%), and contact dermatitis from chemical relaxers (9%), as would be expected in an African American population. However, these conditions were unrelated to CCCA.

This study was supported in part by the North American Hair Research Society and Procter & Gamble. No financial conflicts of interest were reported.

Despite being the most common pattern of scarring hair loss among African American women, central centrifugal cicatricial alopecia is still poorly understood, according to a report published online April 11 in Archives of Dermatology.

The etiology of and risk factors for the disorder have not been established. And although African American women commonly present with the condition, the exact prevalence remains unknown, said Dr. Angela Kyei and her associates at the Cleveland Clinic Institute of Dermatology and Plastic Surgery.

Photo credit: Dr. Valerie Callender

Central centrifugal cicatricial alopecia (CCCA) – previously known as hot comb alopecia or follicular degeneration syndrome – is a scarring hair loss centered on the vertex of the scalp and spreading peripherally, which is described almost exclusively in African American women. In the late 1960s it was linked to the use of hot combs, but since then almost every method of hair grooming in this population has been associated, albeit weakly, with the disorder. Few studies have examined other possible etiologies, such as immunologic, dermatologic, or genetic factors.

"Given the lack of epidemiologic data, the main goal of [our] study was to elucidate environmental as well as medical risk factors that may be associated with CCCA," the researchers wrote.

They administered questionnaires to 326 African American women attending two churches and a health fair in the Cleveland area. Sixteen of the women ended up being excluded from the analysis.

The questionnaires asked detailed information about family history of male- and female-pattern hair loss; personal medical history, including bacterial and fungal skin infections, autoimmune conditions, and hormonal dysregulation; and hair grooming methods used. The study subjects also underwent a scalp examination that included the grading of hair loss.

A total of 86 of the 310 women (28%) were judged to have central hair loss. Of these, 52 women – 17% of the total study population – had CCCA.

It appeared that hair grooming practices that cause traction, such as weaves and braids, may contribute to the development of CCCA, as women with the most severe central hair loss used these styles more frequently than did those without hair loss. "This has some clinical bearing because traction can clinically produce folliculitis of the scalp, which can cause scarring if this inflammation is prolonged," noted Dr. Kyei and her colleagues (Arch. Dermatol. 2011 April 11 [doi:10.1001/archdermatol.2011.66]).

After paying hundreds of dollars for such hair styling, women often maintain weaves and braids for weeks to months, so any reactive inflammation usually is prolonged, the investigators added.

However, "the relationship between chemical relaxer use and the development of CCCA continues to be murky," they noted. These products clearly weaken the hair shaft, which can cause breakage, but that does not necessarily lead to CCCA. "The fact that most African Americans use chemical relaxers in combination with braiding and other hair grooming practices makes it even more difficult to tease out a relationship," Dr. Kyei and her associates added.

It is difficult to find subjects who do not use chemical relaxers for comparison, since most African Americans begin the practice in childhood. In this study, 91% of the women reported using chemical relaxers, and began doing so at an average age of 10 years.

Nevertheless, "we feel that it is not unreasonable to assume that the scalp may absorb some of the caustic chemicals found in relaxers, which in time leads to damage of the scalp in the form of scarring," they wrote.

Although the prevalence of bacterial skin infections in these study subjects was only 11%, there was a significant elevation among women with CCCA, compared with women who did not have CCCA. The rate of acne also was elevated in affected subjects, but not to a significant degree. Thus, the researchers said that their study "demonstrates that inflammation in the form of bacterial infection and acne may also be contributing to the development of CCCA, a finding consistent with the histopathologic characteristics of this disease," which show a lymphocytic perifollicular infiltrate in its early stages.

In contrast, there was no such association with fungal infections of the scalp, ringworm, or vaginal yeast infections, which was "surprising given how prone this population is to fungal infection," they added.

"One of the most surprising findings ... was the overrepresentation of type 2 [diabetes mellitus] in those with CCCA," the authors noted. Again, the prevalence of type 2 diabetes was low, at 8%, but it was significantly elevated in women with CCCA, compared with those without CCCA.

"These are important data that need further study because CCCA may be a marker of metabolic dysfunction and, when present, can prompt clinicians to do further testing for diabetes mellitus," Dr. Kyei and her colleagues wrote.

Only 9% of the study subjects had thyroid abnormalities, and three-fourths of them had no or minimal hair loss.

A history of male-pattern baldness in the maternal grandfather was found to be a risk factor for CCCA, which suggests that genetics may play a role.

Hormonal dysregulation did not appear to be associated with development of CCCA. Neither were scarring disorders, since only 6% of the subjects reported a history of keloids, and the rate was no higher in women with CCCA than in those without CCCA.

Similarly, there were relatively high prevalences of seborrheic dermatitis (24%), eczema (13%), and contact dermatitis from chemical relaxers (9%), as would be expected in an African American population. However, these conditions were unrelated to CCCA.

This study was supported in part by the North American Hair Research Society and Procter & Gamble. No financial conflicts of interest were reported.

Subacute atopic dermatitis of the vulva has been described by Dr. Albert Altchek, which he said "has never been described before."

Atopic dermatitis is a clinical diagnosis, according to Dr. Altchek, clinical professor of obstetrics and gynecology at Mount Sinai School of Medicine, New York. "There's no corresponding biopsy."

His findings are based on his observations of a large number of the same girls over a long period of time at three separate clinics as well as his continuing private office consultation, which he presented at the 15th Annual Postgraduate CME Course on Pediatric, Adolescent, and Young Adult Gynecology held at New York's Mount Sinai Hospital. He also has written a chapter on the topic in "Pediatric, Adolescent, & Young Adult Gynecology" (Oxford: Wiley-Blackwell, 2009), edited by Dr. Altchek and Dr. Liane Deligdisch.

The symptoms include recurrent itching, redness, fissures, and vulva dysuria. Diagnosis of vulvar atopic dermatitis includes gathering a family history of allergies, asthma, hay fever; looking at the past history of the patient; and conducting a physical examination starting from the head, said Dr. Altchek.

Atopic dermatitis fissures are symmetrical and narrow, and look as if they were "made with an artist with a scalpel," he said. The hymen is intact. In early stages, vulvar atopic dermatitis' most pronounced part is bilateral symmetrical fissures between labia minora and majora. Sometimes the fissures are deep and may cause bleeding. In addition, there is a midline sagittal perineal fourchette to the anterior anus at 12 o'clock, where there is usually a papule. The latter is the result of an anterior anal fissure with red inflamed edges. When red and present for a long time, there is severe permanent swelling simulating a hemorrhoid. In more severe cases there is a fissure anterior to clitoris.

In younger girls, the fissures may cause a sudden jump up from sitting because of pain, which is at times misdiagnosed as a neurologic condition.

The condition is sometimes confused with sexual molestation or lichen sclerosis. In sexual molestation cases there may be general signs of trauma and any vulvar fissures are irregular, with lacerations in addition to the history. "Lichen sclerosis of the vulva has coarse, wide irregular fissures in the same areas. With slight trauma the labia and vulva have transient dark blue subcutaneous blood boils," said Dr. Altchek, also an attending ob.gyn. at Lenox Hill Hospital in New York. Lichen sclerosis has a specific biopsy finding, which vulvar atopic dermatitis does not.

Patients with vulvar atopic dermatitis also have the condition on other parts of their body, including behind the ears, in axilla, elbows, or behind the knees, highlighting the importance of whole body exam.

The condition is managed by avoiding things that could irritate the vulva, including wet bathing suits, hot water, perfume, and certain clothing such as leotards and tights. Otherwise, treatment is individualized to reduce irritation and symptoms, Dr. Altchek said.

The condition is most common among prepubertal and young pubertal girls, it may or may not disappear at puberty, and it is less common in adults, said Dr. Altchek.

"Basically, my message is 'wake up, world.' This is how you diagnose [vulvar atopic dermatitis], which has never been described before," said Dr. Altchek.

Dr. Altchek said he had no relevant financial disclosures.

Subacute atopic dermatitis of the vulva has been described by Dr. Albert Altchek, which he said "has never been described before."

Atopic dermatitis is a clinical diagnosis, according to Dr. Altchek, clinical professor of obstetrics and gynecology at Mount Sinai School of Medicine, New York. "There's no corresponding biopsy."

His findings are based on his observations of a large number of the same girls over a long period of time at three separate clinics as well as his continuing private office consultation, which he presented at the 15th Annual Postgraduate CME Course on Pediatric, Adolescent, and Young Adult Gynecology held at New York's Mount Sinai Hospital. He also has written a chapter on the topic in "Pediatric, Adolescent, & Young Adult Gynecology" (Oxford: Wiley-Blackwell, 2009), edited by Dr. Altchek and Dr. Liane Deligdisch.

The symptoms include recurrent itching, redness, fissures, and vulva dysuria. Diagnosis of vulvar atopic dermatitis includes gathering a family history of allergies, asthma, hay fever; looking at the past history of the patient; and conducting a physical examination starting from the head, said Dr. Altchek.

Atopic dermatitis fissures are symmetrical and narrow, and look as if they were "made with an artist with a scalpel," he said. The hymen is intact. In early stages, vulvar atopic dermatitis' most pronounced part is bilateral symmetrical fissures between labia minora and majora. Sometimes the fissures are deep and may cause bleeding. In addition, there is a midline sagittal perineal fourchette to the anterior anus at 12 o'clock, where there is usually a papule. The latter is the result of an anterior anal fissure with red inflamed edges. When red and present for a long time, there is severe permanent swelling simulating a hemorrhoid. In more severe cases there is a fissure anterior to clitoris.

In younger girls, the fissures may cause a sudden jump up from sitting because of pain, which is at times misdiagnosed as a neurologic condition.

The condition is sometimes confused with sexual molestation or lichen sclerosis. In sexual molestation cases there may be general signs of trauma and any vulvar fissures are irregular, with lacerations in addition to the history. "Lichen sclerosis of the vulva has coarse, wide irregular fissures in the same areas. With slight trauma the labia and vulva have transient dark blue subcutaneous blood boils," said Dr. Altchek, also an attending ob.gyn. at Lenox Hill Hospital in New York. Lichen sclerosis has a specific biopsy finding, which vulvar atopic dermatitis does not.

Patients with vulvar atopic dermatitis also have the condition on other parts of their body, including behind the ears, in axilla, elbows, or behind the knees, highlighting the importance of whole body exam.

The condition is managed by avoiding things that could irritate the vulva, including wet bathing suits, hot water, perfume, and certain clothing such as leotards and tights. Otherwise, treatment is individualized to reduce irritation and symptoms, Dr. Altchek said.

The condition is most common among prepubertal and young pubertal girls, it may or may not disappear at puberty, and it is less common in adults, said Dr. Altchek.

"Basically, my message is 'wake up, world.' This is how you diagnose [vulvar atopic dermatitis], which has never been described before," said Dr. Altchek.

Dr. Altchek said he had no relevant financial disclosures.

Subacute atopic dermatitis of the vulva has been described by Dr. Albert Altchek, which he said "has never been described before."

Atopic dermatitis is a clinical diagnosis, according to Dr. Altchek, clinical professor of obstetrics and gynecology at Mount Sinai School of Medicine, New York. "There's no corresponding biopsy."

His findings are based on his observations of a large number of the same girls over a long period of time at three separate clinics as well as his continuing private office consultation, which he presented at the 15th Annual Postgraduate CME Course on Pediatric, Adolescent, and Young Adult Gynecology held at New York's Mount Sinai Hospital. He also has written a chapter on the topic in "Pediatric, Adolescent, & Young Adult Gynecology" (Oxford: Wiley-Blackwell, 2009), edited by Dr. Altchek and Dr. Liane Deligdisch.

The symptoms include recurrent itching, redness, fissures, and vulva dysuria. Diagnosis of vulvar atopic dermatitis includes gathering a family history of allergies, asthma, hay fever; looking at the past history of the patient; and conducting a physical examination starting from the head, said Dr. Altchek.

Atopic dermatitis fissures are symmetrical and narrow, and look as if they were "made with an artist with a scalpel," he said. The hymen is intact. In early stages, vulvar atopic dermatitis' most pronounced part is bilateral symmetrical fissures between labia minora and majora. Sometimes the fissures are deep and may cause bleeding. In addition, there is a midline sagittal perineal fourchette to the anterior anus at 12 o'clock, where there is usually a papule. The latter is the result of an anterior anal fissure with red inflamed edges. When red and present for a long time, there is severe permanent swelling simulating a hemorrhoid. In more severe cases there is a fissure anterior to clitoris.

In younger girls, the fissures may cause a sudden jump up from sitting because of pain, which is at times misdiagnosed as a neurologic condition.

The condition is sometimes confused with sexual molestation or lichen sclerosis. In sexual molestation cases there may be general signs of trauma and any vulvar fissures are irregular, with lacerations in addition to the history. "Lichen sclerosis of the vulva has coarse, wide irregular fissures in the same areas. With slight trauma the labia and vulva have transient dark blue subcutaneous blood boils," said Dr. Altchek, also an attending ob.gyn. at Lenox Hill Hospital in New York. Lichen sclerosis has a specific biopsy finding, which vulvar atopic dermatitis does not.

Patients with vulvar atopic dermatitis also have the condition on other parts of their body, including behind the ears, in axilla, elbows, or behind the knees, highlighting the importance of whole body exam.

The condition is managed by avoiding things that could irritate the vulva, including wet bathing suits, hot water, perfume, and certain clothing such as leotards and tights. Otherwise, treatment is individualized to reduce irritation and symptoms, Dr. Altchek said.

The condition is most common among prepubertal and young pubertal girls, it may or may not disappear at puberty, and it is less common in adults, said Dr. Altchek.

"Basically, my message is 'wake up, world.' This is how you diagnose [vulvar atopic dermatitis], which has never been described before," said Dr. Altchek.

Dr. Altchek said he had no relevant financial disclosures.