Atopic Dermatitis

Patients with atopic dermatitis are at an increased risk of Staphylococcus aureus colonization of both their lesional and nonlesional skin, as well as their nose, compared with healthy controls, according to a report in the British Journal of Dermatology.

Dr. J.E.E. Totté of the department of dermatology at the Erasmus MC University Medical Centre, Rotterdam, and associates conducted a systematic literature review and meta-analysis to derive pooled estimates of the prevalence and odds of colonization with S. aureus in patients with atopic dermatitis. They focused on original, human experimental, and observational studies including patients of any age with a confirmed diagnosis of atopic dermatitis (Br J Dermatol. 2016 Mar 19. doi: 10.1111/bjd.14566).

Dr. Totté and colleagues identified a total of 4,909 articles, of which 95 were found to meet the study inclusion criteria. All of the included studies were observational, with 30 comparing atopic dermatitis patients with healthy controls.

Almost three-quarters (70%) of patients had S. aureus colonization of lesional skin, while 39% had colonization of nonlesional skin, based on 81 studies including 5,231 patients and 30 studies including 1,496 patients, respectively. Nasal colonization was found in 62% of patients, based on analysis of 43 studies including 2,476 patients.

S. aureus colonization is an important factor in the pathogenesis of atopic dermatitis and should lead to evaluations of targeted antistaphylococcal therapy for the skin and nose, the investigators advised.

The authors reported that the department of dermatology of the Erasmus MC University Medical Centre Rotterdam received an unrestricted grant from Micreos Human Health. Two coauthors disclosed ties to industry sources.

Patients with atopic dermatitis are at an increased risk of Staphylococcus aureus colonization of both their lesional and nonlesional skin, as well as their nose, compared with healthy controls, according to a report in the British Journal of Dermatology.

Dr. J.E.E. Totté of the department of dermatology at the Erasmus MC University Medical Centre, Rotterdam, and associates conducted a systematic literature review and meta-analysis to derive pooled estimates of the prevalence and odds of colonization with S. aureus in patients with atopic dermatitis. They focused on original, human experimental, and observational studies including patients of any age with a confirmed diagnosis of atopic dermatitis (Br J Dermatol. 2016 Mar 19. doi: 10.1111/bjd.14566).

Dr. Totté and colleagues identified a total of 4,909 articles, of which 95 were found to meet the study inclusion criteria. All of the included studies were observational, with 30 comparing atopic dermatitis patients with healthy controls.

Almost three-quarters (70%) of patients had S. aureus colonization of lesional skin, while 39% had colonization of nonlesional skin, based on 81 studies including 5,231 patients and 30 studies including 1,496 patients, respectively. Nasal colonization was found in 62% of patients, based on analysis of 43 studies including 2,476 patients.

S. aureus colonization is an important factor in the pathogenesis of atopic dermatitis and should lead to evaluations of targeted antistaphylococcal therapy for the skin and nose, the investigators advised.

The authors reported that the department of dermatology of the Erasmus MC University Medical Centre Rotterdam received an unrestricted grant from Micreos Human Health. Two coauthors disclosed ties to industry sources.

Patients with atopic dermatitis are at an increased risk of Staphylococcus aureus colonization of both their lesional and nonlesional skin, as well as their nose, compared with healthy controls, according to a report in the British Journal of Dermatology.

Dr. J.E.E. Totté of the department of dermatology at the Erasmus MC University Medical Centre, Rotterdam, and associates conducted a systematic literature review and meta-analysis to derive pooled estimates of the prevalence and odds of colonization with S. aureus in patients with atopic dermatitis. They focused on original, human experimental, and observational studies including patients of any age with a confirmed diagnosis of atopic dermatitis (Br J Dermatol. 2016 Mar 19. doi: 10.1111/bjd.14566).

Dr. Totté and colleagues identified a total of 4,909 articles, of which 95 were found to meet the study inclusion criteria. All of the included studies were observational, with 30 comparing atopic dermatitis patients with healthy controls.

Almost three-quarters (70%) of patients had S. aureus colonization of lesional skin, while 39% had colonization of nonlesional skin, based on 81 studies including 5,231 patients and 30 studies including 1,496 patients, respectively. Nasal colonization was found in 62% of patients, based on analysis of 43 studies including 2,476 patients.

S. aureus colonization is an important factor in the pathogenesis of atopic dermatitis and should lead to evaluations of targeted antistaphylococcal therapy for the skin and nose, the investigators advised.

The authors reported that the department of dermatology of the Erasmus MC University Medical Centre Rotterdam received an unrestricted grant from Micreos Human Health. Two coauthors disclosed ties to industry sources.

Atopic dermatitis (AD), or eczema, is the leading dermatologic diagnosis worldwide and is vexing to patients due to the itchiness of the rash. It is the leading cause of skin disease burden worldwide with a prevalence of 229,761,000 reported cases in 2010, presenting largely in preadolescence but also persisting through adulthood.¹ Using the children’s life quality index, it has been demonstrated that AD has a greater impact on health-related quality of life than renal disease and cystic fibrosis.² The overall burden of AD includes stress on the patient and his/her family as well as financial burdens that have been estimated to be similar to that of type 1 diabetes mellitus.³

Epidemiology of AD

The worldwide prevalence of AD varies by country and age group surveyed, with a higher prevalence in wealthy developed nations (eg, the United States) compared to poorer developing nations.⁴ Efforts to identify prevalence data for AD in the United States have been approached through a variety of strategies. A group in Oregon estimated the prevalence of AD in children aged 5 to 9 years to be 17.2% via a survey of parents (N=1465) and 11.8% with doctor-diagnosed eczema. In the same study, the question “Has a doctor ever said that your child has eczema?” was found to have a 91.3% predictive correlation.⁵ Analysis of the 2003 National Survey of Children’s Health demonstrated the overall US prevalence of pediatric AD to be 10.7% in 102,353 children 17 years or younger, with a range of 8.7% to 18.1% by region.⁶

In its evaluation of the worldwide prevalence of AD, the International Study of Asthma and Allergies in Childhood ranked the United States 17th.^7,8 The prevalence of AD in developed countries such as the United States is fluid and is expected to increase if the trends from the last 20 years remain true. In an assessment of the National Health Interview Survey data from 1997 to 2011 based on responses to the question, “During the past 12 months, has your child had eczema or any kind of skin allergy?”, the Centers for Disease Control and Prevention identified an increase in the prevalence of AD in patients aged 0 to 17 years from 7.4% in 1997-1999 to 12.5% in 2009-2011.⁹ Rising prevalence seems to be paired with rising incidence in the total number of severe intractable cases, reduced clearance at the approach of grade school, or cases persisting into adulthood.

Racial Disparity in AD

Racial disparity worldwide and migration are thought to contribute to the prevalence of and therapeutic need for AD. For example, in the United Kingdom, the prevalence of AD in London-born Afro-Caribbean children versus white children (total cross-section, N=693 [junior school children]) was 16.3% and 8.7%, respectively.¹⁰ In the United States, black children were more likely to have AD than white children (odds ratio, 1.7).⁶ Asian and black children also were more likely to present to a physician for treatment of AD than white children.^6,10-13

Definition and Diagnostic Considerations

According to Hanifin,¹⁴ “Eczema represents a family of inflammatory skin conditions characterized by pruritic, papulovesicular, sometimes weeping dermatitis. All demonstrate the histological hallmark of spongiosis, which helps to distinguish the eczemas from papulosquamous diseases such as psoriasis.”¹⁴ Atopic dermatitis is a variant of eczema; however, most laymen identify eczema and AD as being one and the same.

The Hanifin and Rajka¹⁵ criteria are the major diagnostic criteria for AD but are difficult to use in clinical practice. Three of the following 4 major criteria are needed for diagnosis: (1) pruritus, which is present universally; (2) typical morphology and distribution; (3) chronic or chronically relapsing dermatitis; and (4) personal and/or family history of atopy. Additionally, 3 of the following 23 minor criteria are needed for diagnosis: xerosis; ichthyosis vulgaris, palmar hyperlinearity, or keratosis pilaris; positive skin prick test; elevated serum IgE level; early age of onset; tendency toward cutaneous infections or impaired cell-mediated immunity; tendency toward nonspecific hand or foot dermatitis; nipple eczema; cheilitis; recurrent conjunctivitis; Dennie-Morgan fold (infraorbital fold); keratoconus; anterior subcapsular cataracts; orbital darkening; facial pallor or facial erythema; pityriasis alba; anterior neck folds; itching when sweating; intolerance to wool and lipid solvents; perifollicular accentuation; skin reactions from ingested foods or by food contact; environmental or emotional factors; and lesional/nonlesional white dermographism or delayed blanch.^15-17

More pragmatic streamlined diagnostic criteria were established by Eichenfield et al.¹⁸ According to these guidelines, essential features for AD include pruritus and eczema. Important features seen in most cases and adding support to the diagnosis include early age of onset, atopy, and xerosis.¹⁸ In clinical practice, diagnosis is often made based on a pruritic relapsing condition in typical locations including the face, neck, and extensor surfaces in infants and children.

Age Considerations

Diagnosis of AD is made by 5 years of age in 85% to 90% of children who will develop the disease and by age 1 year in 60% to 65%.^6,19,20 Atopic dermatitis will persist into adulthood in up to one-third of children.^21,22 Infantile AD is characterized by erythematous, oozing, excoriated plaques on the cheeks (sparing the nose), scalp, trunk, and extensor surfaces. Pruritus is always seen in AD and can be a source of morbidity.^16-18 Seborrheic dermatitis may complicate or overlap with AD in infancy.²²

By 2 years of age, most children who are going to develop AD begin to show disease signs of childhood AD characterized by flexural lesions and lesions on the neck and in the postauricular area with sparing of the diaper area.²³ Adult AD often presents as eczema of the hands and/or feet. Hand eczema in adulthood is correlated with a prior history of childhood hand eczema and/or childhood AD as well as wet work and caring for small children.²⁴ Children with skin of color may manifest with follicular eczema as their primary disease phenotype. Facial and eyelid dermatitis are more common in Asian females, infants, and teenagers.^12,25 Other disease phenotypes that are common in patients with skin of color include lichenoid AD and postinflammatory hypopigmentation.¹²

Pathogenesis of AD

There are 2 theories on the pathogenesis of AD known as the inside-out and outside-in hypotheses.²⁶ The inside-out hypothesis suggests that allergic triggering leads to a weakened skin barrier that furthers allergen introduction and presentation, while the outside-in hypothesis suggests that the skin barrier is weakened in AD and allows for the presentation of allergens. Both theories have validity and biologic basis, and both may in fact be true in certain individuals.²⁶

The Skin Barrier: An Overview

The skin barrier is a complex set of factors present and functional at birth that seal the keratinocytes and the interkeratinocyte space so that the skin can perform key processes and functions including retention of fluid, exclusion of allergens, protection from UV light and solvents, and prevention of pathogen entry (eg, infections).^27-29 The superficial stratum corneum or the cornified envelope consists of keratinocytes with intercellular stripes of hydrophobic and hydrophilic substances formed by various intercellular lipids, largely ceramides, cholesterol, and free fatty acids.^30,31 Keratinocytes are the first responders to a variety of environmental insults with the production of IL-18, RANTES (regulated on activation, normal T-expressed, and presumably secreted), granulocyte-macrophage colony-stimulating factor, and thymic stromal lymphopoietin. These inflammatory substances produce acute and chronic inflammation, mast cell reactivity, and T-cell activation.¹⁴ Corneodesmosins link the keratinocytes. Peptidases released will cleave the corneodesmosins and allow normal desquamation or shedding of surface skin, which is replaced by division of stem cells in the basal layer.²⁹

The stratum granulosum is the layer beneath the stratum corneum that co-contributes to barrier activity. The stratum granulosum is absent or reduced histologically in ichthyosis vulgaris,³² a form of skin dryness linked to filaggrin mutations and AD. Filaggrin breakdown creates natural moisturizing factor, a series of hygroscopic compounds that attract water into the skin.³³ Histidine, a filaggrin breakdown product, is used by urocanic acid to process UV light insults.³⁴ Filaggrin also contributes to other barrier functions including pH and stratum corneum cohesion as well as paracellular permeability of the stratum corneum. Tight junctions in the stratum granulosum include claudin-1 and claudin-6 and provide another barrier feature.²⁹

The skin barrier is composed of lipids and keratinocytes. Ceramides, which represent one type of lipids, are reduced in AD, causing alteration in the lamellar pattern³⁵ and increased transepidermal water loss. Furthermore, the stratum corneum is thickened in AD, possibly in response to trauma, and hydration is reduced.³⁶ Filaggrin (chromosome arm 1q21.3) is formed from the 400-kDa⁺ precursor profilaggrin through dephosphorylation and cleavage, and it performs an essential function in the skin barrier through its differential cleavage and breakdown as well as release of natural moisturizing factor and other compounds.³⁷ Filaggrin mutations are linked to AD and ichthyosis vulgaris; however, barrier defects as evidenced by transepidermal water loss in the absence of filaggrin mutation are sufficient to allow for sensitization to allergens through the skin.²⁹ Filaggrin mutations have been associated with AD development and vary in prevalence worldwide. In the United Kingdom, a prevalence study of filaggrin mutations in patients aged 7 to 9 years (N=792) demonstrated an 18.4% carrier rate in AD patients versus 12.9% in controls.³⁴ A similar study in Sweden (N=3301) showed carrier rates of 13.5% versus 6.5%, respectively.³⁸ Although filaggrin mutations are lower in black patients,³⁹ ceramide content may be reduced in this population, demonstrating that a variety of skin barrier defects can result in AD. Carriers of filaggrin mutations are more likely to have eczema on skin exposed to environmental factors (eg, face, hands).⁴⁰

Barrier Defects Contributing to AD

The breakdown of the stratum corneum allows for antigen presentation to Langerhans cells, the dendritic antigen-presenting cells of the skin. Breaks in the stratum corneum may occur from scratching. These macroscopic breaks are large, whereas the breaks that otherwise occur due to barrier breakdown may be more microscopic in nature. Scratching causes aggravation of the helper T cell (T_H2) response.²⁹ For example, it allows the dendritic ends of Langerhans cells to be exposed to antigens. The dendritic ends capture allergens through IgE (may be elevated in AD²⁹), which is bound to the high-affinity FCER1 receptors on Langerhans cells. Rather than causing a type I hypersensitivity reaction, these Langerhans cells are activated and move to the lymph nodes where they present antigen and initiate a cascade of proinflammatory activity. This T_H2 cascade includes release of cytokines such as IL-2, IL-4, IL-8, IL-10, tumor necrosis factor α, and IFN-γ.^26,29

Transepidermal water loss and barrier dysfunction contribute to disease activity and facilitate food/environmental allergen sensitization by allowing increased penetration of allergens through the skin to be presented by Langerhans cells to T_H1 cells (sensitization phase). The Langerhans cells can reach their dendritic ends through tight junctions and into the stratum corneum, allowing them to reach surface allergens when the barrier is impaired. Ultimate expansion to systemic allergy (effector phase) occurs when dendritic cells move to draining lymph nodes, causing antigen presentation to CD4 and/or CD8 cells. Langerhans cells and dendritic cell sensitization through the weakened skin is believed to be the basis or role of barrier disruption as a trigger of atopic diseases, including AD and food and environmental allergies.

Many different forms of barrier disruption can cause a T_H2 response in AD. The T_H2 response triggers a constellation of proinflammatory activities including release of IL-4, associated with eosinophilia and elevated IgE levels, the latter being minor criterion in the diagnosis of AD.¹⁵ One mechanism by which the T_H2 response is elicited may be the release of molecules such as danger-associated molecule patterns that may elicit recruitment of other inflammatory cells. Helper T cell (T_H2) activity also can worsen barrier defects through IL-4 and IL-13 release, which can reduce filaggrin expression,^29,41 and can aggravate barrier dysfunction in AD.

Inflammatory activation in AD also may involve inflammatory dendritic epidermal cells (IDECs). The IDECs can be tolerogenic or immunogenic mature phenotypes. The IDECs activate helper T cells (T_H1), which may contribute to long-term AD activity.

Conclusion

Atopic dermatitis is a common skin condition worldwide and is characterized by the hallmark of pruritus and features that include a typical pattern, history of atopy (personal or family), and usually xerosis and early disease onset. Barrier dysfunction and immune dysregulation are prominent in AD, both of which aggravate the other and may encourage increased development of allergies and other forms of atopy over time.

Atopic dermatitis (AD), or eczema, is the leading dermatologic diagnosis worldwide and is vexing to patients due to the itchiness of the rash. It is the leading cause of skin disease burden worldwide with a prevalence of 229,761,000 reported cases in 2010, presenting largely in preadolescence but also persisting through adulthood.¹ Using the children’s life quality index, it has been demonstrated that AD has a greater impact on health-related quality of life than renal disease and cystic fibrosis.² The overall burden of AD includes stress on the patient and his/her family as well as financial burdens that have been estimated to be similar to that of type 1 diabetes mellitus.³

Epidemiology of AD

The worldwide prevalence of AD varies by country and age group surveyed, with a higher prevalence in wealthy developed nations (eg, the United States) compared to poorer developing nations.⁴ Efforts to identify prevalence data for AD in the United States have been approached through a variety of strategies. A group in Oregon estimated the prevalence of AD in children aged 5 to 9 years to be 17.2% via a survey of parents (N=1465) and 11.8% with doctor-diagnosed eczema. In the same study, the question “Has a doctor ever said that your child has eczema?” was found to have a 91.3% predictive correlation.⁵ Analysis of the 2003 National Survey of Children’s Health demonstrated the overall US prevalence of pediatric AD to be 10.7% in 102,353 children 17 years or younger, with a range of 8.7% to 18.1% by region.⁶

In its evaluation of the worldwide prevalence of AD, the International Study of Asthma and Allergies in Childhood ranked the United States 17th.^7,8 The prevalence of AD in developed countries such as the United States is fluid and is expected to increase if the trends from the last 20 years remain true. In an assessment of the National Health Interview Survey data from 1997 to 2011 based on responses to the question, “During the past 12 months, has your child had eczema or any kind of skin allergy?”, the Centers for Disease Control and Prevention identified an increase in the prevalence of AD in patients aged 0 to 17 years from 7.4% in 1997-1999 to 12.5% in 2009-2011.⁹ Rising prevalence seems to be paired with rising incidence in the total number of severe intractable cases, reduced clearance at the approach of grade school, or cases persisting into adulthood.

Racial Disparity in AD

Racial disparity worldwide and migration are thought to contribute to the prevalence of and therapeutic need for AD. For example, in the United Kingdom, the prevalence of AD in London-born Afro-Caribbean children versus white children (total cross-section, N=693 [junior school children]) was 16.3% and 8.7%, respectively.¹⁰ In the United States, black children were more likely to have AD than white children (odds ratio, 1.7).⁶ Asian and black children also were more likely to present to a physician for treatment of AD than white children.^6,10-13

Definition and Diagnostic Considerations

According to Hanifin,¹⁴ “Eczema represents a family of inflammatory skin conditions characterized by pruritic, papulovesicular, sometimes weeping dermatitis. All demonstrate the histological hallmark of spongiosis, which helps to distinguish the eczemas from papulosquamous diseases such as psoriasis.”¹⁴ Atopic dermatitis is a variant of eczema; however, most laymen identify eczema and AD as being one and the same.

The Hanifin and Rajka¹⁵ criteria are the major diagnostic criteria for AD but are difficult to use in clinical practice. Three of the following 4 major criteria are needed for diagnosis: (1) pruritus, which is present universally; (2) typical morphology and distribution; (3) chronic or chronically relapsing dermatitis; and (4) personal and/or family history of atopy. Additionally, 3 of the following 23 minor criteria are needed for diagnosis: xerosis; ichthyosis vulgaris, palmar hyperlinearity, or keratosis pilaris; positive skin prick test; elevated serum IgE level; early age of onset; tendency toward cutaneous infections or impaired cell-mediated immunity; tendency toward nonspecific hand or foot dermatitis; nipple eczema; cheilitis; recurrent conjunctivitis; Dennie-Morgan fold (infraorbital fold); keratoconus; anterior subcapsular cataracts; orbital darkening; facial pallor or facial erythema; pityriasis alba; anterior neck folds; itching when sweating; intolerance to wool and lipid solvents; perifollicular accentuation; skin reactions from ingested foods or by food contact; environmental or emotional factors; and lesional/nonlesional white dermographism or delayed blanch.^15-17

More pragmatic streamlined diagnostic criteria were established by Eichenfield et al.¹⁸ According to these guidelines, essential features for AD include pruritus and eczema. Important features seen in most cases and adding support to the diagnosis include early age of onset, atopy, and xerosis.¹⁸ In clinical practice, diagnosis is often made based on a pruritic relapsing condition in typical locations including the face, neck, and extensor surfaces in infants and children.

Age Considerations

Diagnosis of AD is made by 5 years of age in 85% to 90% of children who will develop the disease and by age 1 year in 60% to 65%.^6,19,20 Atopic dermatitis will persist into adulthood in up to one-third of children.^21,22 Infantile AD is characterized by erythematous, oozing, excoriated plaques on the cheeks (sparing the nose), scalp, trunk, and extensor surfaces. Pruritus is always seen in AD and can be a source of morbidity.^16-18 Seborrheic dermatitis may complicate or overlap with AD in infancy.²²

By 2 years of age, most children who are going to develop AD begin to show disease signs of childhood AD characterized by flexural lesions and lesions on the neck and in the postauricular area with sparing of the diaper area.²³ Adult AD often presents as eczema of the hands and/or feet. Hand eczema in adulthood is correlated with a prior history of childhood hand eczema and/or childhood AD as well as wet work and caring for small children.²⁴ Children with skin of color may manifest with follicular eczema as their primary disease phenotype. Facial and eyelid dermatitis are more common in Asian females, infants, and teenagers.^12,25 Other disease phenotypes that are common in patients with skin of color include lichenoid AD and postinflammatory hypopigmentation.¹²

Pathogenesis of AD

There are 2 theories on the pathogenesis of AD known as the inside-out and outside-in hypotheses.²⁶ The inside-out hypothesis suggests that allergic triggering leads to a weakened skin barrier that furthers allergen introduction and presentation, while the outside-in hypothesis suggests that the skin barrier is weakened in AD and allows for the presentation of allergens. Both theories have validity and biologic basis, and both may in fact be true in certain individuals.²⁶

The Skin Barrier: An Overview

The skin barrier is a complex set of factors present and functional at birth that seal the keratinocytes and the interkeratinocyte space so that the skin can perform key processes and functions including retention of fluid, exclusion of allergens, protection from UV light and solvents, and prevention of pathogen entry (eg, infections).^27-29 The superficial stratum corneum or the cornified envelope consists of keratinocytes with intercellular stripes of hydrophobic and hydrophilic substances formed by various intercellular lipids, largely ceramides, cholesterol, and free fatty acids.^30,31 Keratinocytes are the first responders to a variety of environmental insults with the production of IL-18, RANTES (regulated on activation, normal T-expressed, and presumably secreted), granulocyte-macrophage colony-stimulating factor, and thymic stromal lymphopoietin. These inflammatory substances produce acute and chronic inflammation, mast cell reactivity, and T-cell activation.¹⁴ Corneodesmosins link the keratinocytes. Peptidases released will cleave the corneodesmosins and allow normal desquamation or shedding of surface skin, which is replaced by division of stem cells in the basal layer.²⁹

The stratum granulosum is the layer beneath the stratum corneum that co-contributes to barrier activity. The stratum granulosum is absent or reduced histologically in ichthyosis vulgaris,³² a form of skin dryness linked to filaggrin mutations and AD. Filaggrin breakdown creates natural moisturizing factor, a series of hygroscopic compounds that attract water into the skin.³³ Histidine, a filaggrin breakdown product, is used by urocanic acid to process UV light insults.³⁴ Filaggrin also contributes to other barrier functions including pH and stratum corneum cohesion as well as paracellular permeability of the stratum corneum. Tight junctions in the stratum granulosum include claudin-1 and claudin-6 and provide another barrier feature.²⁹

The skin barrier is composed of lipids and keratinocytes. Ceramides, which represent one type of lipids, are reduced in AD, causing alteration in the lamellar pattern³⁵ and increased transepidermal water loss. Furthermore, the stratum corneum is thickened in AD, possibly in response to trauma, and hydration is reduced.³⁶ Filaggrin (chromosome arm 1q21.3) is formed from the 400-kDa⁺ precursor profilaggrin through dephosphorylation and cleavage, and it performs an essential function in the skin barrier through its differential cleavage and breakdown as well as release of natural moisturizing factor and other compounds.³⁷ Filaggrin mutations are linked to AD and ichthyosis vulgaris; however, barrier defects as evidenced by transepidermal water loss in the absence of filaggrin mutation are sufficient to allow for sensitization to allergens through the skin.²⁹ Filaggrin mutations have been associated with AD development and vary in prevalence worldwide. In the United Kingdom, a prevalence study of filaggrin mutations in patients aged 7 to 9 years (N=792) demonstrated an 18.4% carrier rate in AD patients versus 12.9% in controls.³⁴ A similar study in Sweden (N=3301) showed carrier rates of 13.5% versus 6.5%, respectively.³⁸ Although filaggrin mutations are lower in black patients,³⁹ ceramide content may be reduced in this population, demonstrating that a variety of skin barrier defects can result in AD. Carriers of filaggrin mutations are more likely to have eczema on skin exposed to environmental factors (eg, face, hands).⁴⁰

Barrier Defects Contributing to AD

The breakdown of the stratum corneum allows for antigen presentation to Langerhans cells, the dendritic antigen-presenting cells of the skin. Breaks in the stratum corneum may occur from scratching. These macroscopic breaks are large, whereas the breaks that otherwise occur due to barrier breakdown may be more microscopic in nature. Scratching causes aggravation of the helper T cell (T_H2) response.²⁹ For example, it allows the dendritic ends of Langerhans cells to be exposed to antigens. The dendritic ends capture allergens through IgE (may be elevated in AD²⁹), which is bound to the high-affinity FCER1 receptors on Langerhans cells. Rather than causing a type I hypersensitivity reaction, these Langerhans cells are activated and move to the lymph nodes where they present antigen and initiate a cascade of proinflammatory activity. This T_H2 cascade includes release of cytokines such as IL-2, IL-4, IL-8, IL-10, tumor necrosis factor α, and IFN-γ.^26,29

Transepidermal water loss and barrier dysfunction contribute to disease activity and facilitate food/environmental allergen sensitization by allowing increased penetration of allergens through the skin to be presented by Langerhans cells to T_H1 cells (sensitization phase). The Langerhans cells can reach their dendritic ends through tight junctions and into the stratum corneum, allowing them to reach surface allergens when the barrier is impaired. Ultimate expansion to systemic allergy (effector phase) occurs when dendritic cells move to draining lymph nodes, causing antigen presentation to CD4 and/or CD8 cells. Langerhans cells and dendritic cell sensitization through the weakened skin is believed to be the basis or role of barrier disruption as a trigger of atopic diseases, including AD and food and environmental allergies.

Many different forms of barrier disruption can cause a T_H2 response in AD. The T_H2 response triggers a constellation of proinflammatory activities including release of IL-4, associated with eosinophilia and elevated IgE levels, the latter being minor criterion in the diagnosis of AD.¹⁵ One mechanism by which the T_H2 response is elicited may be the release of molecules such as danger-associated molecule patterns that may elicit recruitment of other inflammatory cells. Helper T cell (T_H2) activity also can worsen barrier defects through IL-4 and IL-13 release, which can reduce filaggrin expression,^29,41 and can aggravate barrier dysfunction in AD.

Inflammatory activation in AD also may involve inflammatory dendritic epidermal cells (IDECs). The IDECs can be tolerogenic or immunogenic mature phenotypes. The IDECs activate helper T cells (T_H1), which may contribute to long-term AD activity.

Conclusion

Atopic dermatitis is a common skin condition worldwide and is characterized by the hallmark of pruritus and features that include a typical pattern, history of atopy (personal or family), and usually xerosis and early disease onset. Barrier dysfunction and immune dysregulation are prominent in AD, both of which aggravate the other and may encourage increased development of allergies and other forms of atopy over time.

Atopic dermatitis (AD), or eczema, is the leading dermatologic diagnosis worldwide and is vexing to patients due to the itchiness of the rash. It is the leading cause of skin disease burden worldwide with a prevalence of 229,761,000 reported cases in 2010, presenting largely in preadolescence but also persisting through adulthood.¹ Using the children’s life quality index, it has been demonstrated that AD has a greater impact on health-related quality of life than renal disease and cystic fibrosis.² The overall burden of AD includes stress on the patient and his/her family as well as financial burdens that have been estimated to be similar to that of type 1 diabetes mellitus.³

Epidemiology of AD

The worldwide prevalence of AD varies by country and age group surveyed, with a higher prevalence in wealthy developed nations (eg, the United States) compared to poorer developing nations.⁴ Efforts to identify prevalence data for AD in the United States have been approached through a variety of strategies. A group in Oregon estimated the prevalence of AD in children aged 5 to 9 years to be 17.2% via a survey of parents (N=1465) and 11.8% with doctor-diagnosed eczema. In the same study, the question “Has a doctor ever said that your child has eczema?” was found to have a 91.3% predictive correlation.⁵ Analysis of the 2003 National Survey of Children’s Health demonstrated the overall US prevalence of pediatric AD to be 10.7% in 102,353 children 17 years or younger, with a range of 8.7% to 18.1% by region.⁶

In its evaluation of the worldwide prevalence of AD, the International Study of Asthma and Allergies in Childhood ranked the United States 17th.^7,8 The prevalence of AD in developed countries such as the United States is fluid and is expected to increase if the trends from the last 20 years remain true. In an assessment of the National Health Interview Survey data from 1997 to 2011 based on responses to the question, “During the past 12 months, has your child had eczema or any kind of skin allergy?”, the Centers for Disease Control and Prevention identified an increase in the prevalence of AD in patients aged 0 to 17 years from 7.4% in 1997-1999 to 12.5% in 2009-2011.⁹ Rising prevalence seems to be paired with rising incidence in the total number of severe intractable cases, reduced clearance at the approach of grade school, or cases persisting into adulthood.

Racial Disparity in AD

Racial disparity worldwide and migration are thought to contribute to the prevalence of and therapeutic need for AD. For example, in the United Kingdom, the prevalence of AD in London-born Afro-Caribbean children versus white children (total cross-section, N=693 [junior school children]) was 16.3% and 8.7%, respectively.¹⁰ In the United States, black children were more likely to have AD than white children (odds ratio, 1.7).⁶ Asian and black children also were more likely to present to a physician for treatment of AD than white children.^6,10-13

Definition and Diagnostic Considerations

According to Hanifin,¹⁴ “Eczema represents a family of inflammatory skin conditions characterized by pruritic, papulovesicular, sometimes weeping dermatitis. All demonstrate the histological hallmark of spongiosis, which helps to distinguish the eczemas from papulosquamous diseases such as psoriasis.”¹⁴ Atopic dermatitis is a variant of eczema; however, most laymen identify eczema and AD as being one and the same.

The Hanifin and Rajka¹⁵ criteria are the major diagnostic criteria for AD but are difficult to use in clinical practice. Three of the following 4 major criteria are needed for diagnosis: (1) pruritus, which is present universally; (2) typical morphology and distribution; (3) chronic or chronically relapsing dermatitis; and (4) personal and/or family history of atopy. Additionally, 3 of the following 23 minor criteria are needed for diagnosis: xerosis; ichthyosis vulgaris, palmar hyperlinearity, or keratosis pilaris; positive skin prick test; elevated serum IgE level; early age of onset; tendency toward cutaneous infections or impaired cell-mediated immunity; tendency toward nonspecific hand or foot dermatitis; nipple eczema; cheilitis; recurrent conjunctivitis; Dennie-Morgan fold (infraorbital fold); keratoconus; anterior subcapsular cataracts; orbital darkening; facial pallor or facial erythema; pityriasis alba; anterior neck folds; itching when sweating; intolerance to wool and lipid solvents; perifollicular accentuation; skin reactions from ingested foods or by food contact; environmental or emotional factors; and lesional/nonlesional white dermographism or delayed blanch.^15-17

More pragmatic streamlined diagnostic criteria were established by Eichenfield et al.¹⁸ According to these guidelines, essential features for AD include pruritus and eczema. Important features seen in most cases and adding support to the diagnosis include early age of onset, atopy, and xerosis.¹⁸ In clinical practice, diagnosis is often made based on a pruritic relapsing condition in typical locations including the face, neck, and extensor surfaces in infants and children.

Age Considerations

Diagnosis of AD is made by 5 years of age in 85% to 90% of children who will develop the disease and by age 1 year in 60% to 65%.^6,19,20 Atopic dermatitis will persist into adulthood in up to one-third of children.^21,22 Infantile AD is characterized by erythematous, oozing, excoriated plaques on the cheeks (sparing the nose), scalp, trunk, and extensor surfaces. Pruritus is always seen in AD and can be a source of morbidity.^16-18 Seborrheic dermatitis may complicate or overlap with AD in infancy.²²

By 2 years of age, most children who are going to develop AD begin to show disease signs of childhood AD characterized by flexural lesions and lesions on the neck and in the postauricular area with sparing of the diaper area.²³ Adult AD often presents as eczema of the hands and/or feet. Hand eczema in adulthood is correlated with a prior history of childhood hand eczema and/or childhood AD as well as wet work and caring for small children.²⁴ Children with skin of color may manifest with follicular eczema as their primary disease phenotype. Facial and eyelid dermatitis are more common in Asian females, infants, and teenagers.^12,25 Other disease phenotypes that are common in patients with skin of color include lichenoid AD and postinflammatory hypopigmentation.¹²

Pathogenesis of AD

There are 2 theories on the pathogenesis of AD known as the inside-out and outside-in hypotheses.²⁶ The inside-out hypothesis suggests that allergic triggering leads to a weakened skin barrier that furthers allergen introduction and presentation, while the outside-in hypothesis suggests that the skin barrier is weakened in AD and allows for the presentation of allergens. Both theories have validity and biologic basis, and both may in fact be true in certain individuals.²⁶

The Skin Barrier: An Overview

The skin barrier is a complex set of factors present and functional at birth that seal the keratinocytes and the interkeratinocyte space so that the skin can perform key processes and functions including retention of fluid, exclusion of allergens, protection from UV light and solvents, and prevention of pathogen entry (eg, infections).^27-29 The superficial stratum corneum or the cornified envelope consists of keratinocytes with intercellular stripes of hydrophobic and hydrophilic substances formed by various intercellular lipids, largely ceramides, cholesterol, and free fatty acids.^30,31 Keratinocytes are the first responders to a variety of environmental insults with the production of IL-18, RANTES (regulated on activation, normal T-expressed, and presumably secreted), granulocyte-macrophage colony-stimulating factor, and thymic stromal lymphopoietin. These inflammatory substances produce acute and chronic inflammation, mast cell reactivity, and T-cell activation.¹⁴ Corneodesmosins link the keratinocytes. Peptidases released will cleave the corneodesmosins and allow normal desquamation or shedding of surface skin, which is replaced by division of stem cells in the basal layer.²⁹

The stratum granulosum is the layer beneath the stratum corneum that co-contributes to barrier activity. The stratum granulosum is absent or reduced histologically in ichthyosis vulgaris,³² a form of skin dryness linked to filaggrin mutations and AD. Filaggrin breakdown creates natural moisturizing factor, a series of hygroscopic compounds that attract water into the skin.³³ Histidine, a filaggrin breakdown product, is used by urocanic acid to process UV light insults.³⁴ Filaggrin also contributes to other barrier functions including pH and stratum corneum cohesion as well as paracellular permeability of the stratum corneum. Tight junctions in the stratum granulosum include claudin-1 and claudin-6 and provide another barrier feature.²⁹

The skin barrier is composed of lipids and keratinocytes. Ceramides, which represent one type of lipids, are reduced in AD, causing alteration in the lamellar pattern³⁵ and increased transepidermal water loss. Furthermore, the stratum corneum is thickened in AD, possibly in response to trauma, and hydration is reduced.³⁶ Filaggrin (chromosome arm 1q21.3) is formed from the 400-kDa⁺ precursor profilaggrin through dephosphorylation and cleavage, and it performs an essential function in the skin barrier through its differential cleavage and breakdown as well as release of natural moisturizing factor and other compounds.³⁷ Filaggrin mutations are linked to AD and ichthyosis vulgaris; however, barrier defects as evidenced by transepidermal water loss in the absence of filaggrin mutation are sufficient to allow for sensitization to allergens through the skin.²⁹ Filaggrin mutations have been associated with AD development and vary in prevalence worldwide. In the United Kingdom, a prevalence study of filaggrin mutations in patients aged 7 to 9 years (N=792) demonstrated an 18.4% carrier rate in AD patients versus 12.9% in controls.³⁴ A similar study in Sweden (N=3301) showed carrier rates of 13.5% versus 6.5%, respectively.³⁸ Although filaggrin mutations are lower in black patients,³⁹ ceramide content may be reduced in this population, demonstrating that a variety of skin barrier defects can result in AD. Carriers of filaggrin mutations are more likely to have eczema on skin exposed to environmental factors (eg, face, hands).⁴⁰

Barrier Defects Contributing to AD

The breakdown of the stratum corneum allows for antigen presentation to Langerhans cells, the dendritic antigen-presenting cells of the skin. Breaks in the stratum corneum may occur from scratching. These macroscopic breaks are large, whereas the breaks that otherwise occur due to barrier breakdown may be more microscopic in nature. Scratching causes aggravation of the helper T cell (T_H2) response.²⁹ For example, it allows the dendritic ends of Langerhans cells to be exposed to antigens. The dendritic ends capture allergens through IgE (may be elevated in AD²⁹), which is bound to the high-affinity FCER1 receptors on Langerhans cells. Rather than causing a type I hypersensitivity reaction, these Langerhans cells are activated and move to the lymph nodes where they present antigen and initiate a cascade of proinflammatory activity. This T_H2 cascade includes release of cytokines such as IL-2, IL-4, IL-8, IL-10, tumor necrosis factor α, and IFN-γ.^26,29

Transepidermal water loss and barrier dysfunction contribute to disease activity and facilitate food/environmental allergen sensitization by allowing increased penetration of allergens through the skin to be presented by Langerhans cells to T_H1 cells (sensitization phase). The Langerhans cells can reach their dendritic ends through tight junctions and into the stratum corneum, allowing them to reach surface allergens when the barrier is impaired. Ultimate expansion to systemic allergy (effector phase) occurs when dendritic cells move to draining lymph nodes, causing antigen presentation to CD4 and/or CD8 cells. Langerhans cells and dendritic cell sensitization through the weakened skin is believed to be the basis or role of barrier disruption as a trigger of atopic diseases, including AD and food and environmental allergies.

Many different forms of barrier disruption can cause a T_H2 response in AD. The T_H2 response triggers a constellation of proinflammatory activities including release of IL-4, associated with eosinophilia and elevated IgE levels, the latter being minor criterion in the diagnosis of AD.¹⁵ One mechanism by which the T_H2 response is elicited may be the release of molecules such as danger-associated molecule patterns that may elicit recruitment of other inflammatory cells. Helper T cell (T_H2) activity also can worsen barrier defects through IL-4 and IL-13 release, which can reduce filaggrin expression,^29,41 and can aggravate barrier dysfunction in AD.

Inflammatory activation in AD also may involve inflammatory dendritic epidermal cells (IDECs). The IDECs can be tolerogenic or immunogenic mature phenotypes. The IDECs activate helper T cells (T_H1), which may contribute to long-term AD activity.

Conclusion

Atopic dermatitis is a common skin condition worldwide and is characterized by the hallmark of pruritus and features that include a typical pattern, history of atopy (personal or family), and usually xerosis and early disease onset. Barrier dysfunction and immune dysregulation are prominent in AD, both of which aggravate the other and may encourage increased development of allergies and other forms of atopy over time.

LOS ANGELES – Children who pass oral food challenges to baked egg and milk with wheat flour are at risk for reacting to baked goods made with nonwheat flours, according to a review of more than 200 pediatric food challenges at National Jewish Health in Denver.

The children were already known to be sensitive to egg and milk, and some were being challenged to see if exposure therapy was helping. Unbeknown to the pediatric food allergy team, a kitchen worker at National Jewish had started making muffins with rice flour, thinking it would be safer.

During the month of muffins with rice flour, the failure rate for baked egg challenge muffins rose from 28% (33/120) to 58% (11/19) with rice flour. Failure to baked milk muffins rose from 14% (9/66) to 36% (5/14) (J Allergy Clin Immunol. 2016 Feb. doi: 10.1016/j.jaci.2015.12.579).

Adjusting for age, gender, and atopic dermatitis, children were more than five times more likely to fail baked eggs without wheat (odds ratio, 5.4; P = .002), and more than four times more likely to fail baked milk (OR, 4.06; P = .05).

Given that the phenomenon hasn’t been reported before, “This was very surprising to us,” said study investigator Dr. Bruce Lanser, director of the pediatric food allergy program at National Jewish. “You have to warn parents that if children pass a baked challenge with wheat, they have to continue to eat their baked milk and egg with wheat. Gluten-free products are not going to have the same effect.

“If somebody is avoiding wheat because it causes a bit of redness and itchiness, you have to clear that wheat allergy” before moving to baked egg and milk, Dr. Lanser added.

There’s also concern that “kids will go home after passing a wheat muffin challenge, eat something that’s gluten-free, and have a reaction,” he noted. Wheat-free baked goods might also not build tolerance as well, although that’s not clear from the study, Dr. Lanser said at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

Wheat seems to have something unique that alters the allergic properties of egg and milk proteins to help children outgrow their sensitivities. “Rice doesn’t have the same effect,” he observed, and it’s not known if any other grains do. Dr. Lanser said he is interested in looking into rye, barley, oats, and other alternatives.

The mean age of the children in the study was 6 years, and most children had multiple food allergies. Sensitization was confirmed by skin tests and specific IgE.

Meanwhile, there’s a new rule in the National Jewish kitchen: Unless a child has true celiac disease, “always make [challenge] muffins with wheat,” Dr. Lanser said.

There was no industry funding for the work, and the investigators had no disclosures.

aotto@frontlinemedcom.com

LOS ANGELES – Children who pass oral food challenges to baked egg and milk with wheat flour are at risk for reacting to baked goods made with nonwheat flours, according to a review of more than 200 pediatric food challenges at National Jewish Health in Denver.

The children were already known to be sensitive to egg and milk, and some were being challenged to see if exposure therapy was helping. Unbeknown to the pediatric food allergy team, a kitchen worker at National Jewish had started making muffins with rice flour, thinking it would be safer.

During the month of muffins with rice flour, the failure rate for baked egg challenge muffins rose from 28% (33/120) to 58% (11/19) with rice flour. Failure to baked milk muffins rose from 14% (9/66) to 36% (5/14) (J Allergy Clin Immunol. 2016 Feb. doi: 10.1016/j.jaci.2015.12.579).

Adjusting for age, gender, and atopic dermatitis, children were more than five times more likely to fail baked eggs without wheat (odds ratio, 5.4; P = .002), and more than four times more likely to fail baked milk (OR, 4.06; P = .05).

Given that the phenomenon hasn’t been reported before, “This was very surprising to us,” said study investigator Dr. Bruce Lanser, director of the pediatric food allergy program at National Jewish. “You have to warn parents that if children pass a baked challenge with wheat, they have to continue to eat their baked milk and egg with wheat. Gluten-free products are not going to have the same effect.

“If somebody is avoiding wheat because it causes a bit of redness and itchiness, you have to clear that wheat allergy” before moving to baked egg and milk, Dr. Lanser added.

There’s also concern that “kids will go home after passing a wheat muffin challenge, eat something that’s gluten-free, and have a reaction,” he noted. Wheat-free baked goods might also not build tolerance as well, although that’s not clear from the study, Dr. Lanser said at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

Wheat seems to have something unique that alters the allergic properties of egg and milk proteins to help children outgrow their sensitivities. “Rice doesn’t have the same effect,” he observed, and it’s not known if any other grains do. Dr. Lanser said he is interested in looking into rye, barley, oats, and other alternatives.

The mean age of the children in the study was 6 years, and most children had multiple food allergies. Sensitization was confirmed by skin tests and specific IgE.

Meanwhile, there’s a new rule in the National Jewish kitchen: Unless a child has true celiac disease, “always make [challenge] muffins with wheat,” Dr. Lanser said.

There was no industry funding for the work, and the investigators had no disclosures.

aotto@frontlinemedcom.com

LOS ANGELES – Children who pass oral food challenges to baked egg and milk with wheat flour are at risk for reacting to baked goods made with nonwheat flours, according to a review of more than 200 pediatric food challenges at National Jewish Health in Denver.

The children were already known to be sensitive to egg and milk, and some were being challenged to see if exposure therapy was helping. Unbeknown to the pediatric food allergy team, a kitchen worker at National Jewish had started making muffins with rice flour, thinking it would be safer.

During the month of muffins with rice flour, the failure rate for baked egg challenge muffins rose from 28% (33/120) to 58% (11/19) with rice flour. Failure to baked milk muffins rose from 14% (9/66) to 36% (5/14) (J Allergy Clin Immunol. 2016 Feb. doi: 10.1016/j.jaci.2015.12.579).

Adjusting for age, gender, and atopic dermatitis, children were more than five times more likely to fail baked eggs without wheat (odds ratio, 5.4; P = .002), and more than four times more likely to fail baked milk (OR, 4.06; P = .05).

Given that the phenomenon hasn’t been reported before, “This was very surprising to us,” said study investigator Dr. Bruce Lanser, director of the pediatric food allergy program at National Jewish. “You have to warn parents that if children pass a baked challenge with wheat, they have to continue to eat their baked milk and egg with wheat. Gluten-free products are not going to have the same effect.

“If somebody is avoiding wheat because it causes a bit of redness and itchiness, you have to clear that wheat allergy” before moving to baked egg and milk, Dr. Lanser added.

There’s also concern that “kids will go home after passing a wheat muffin challenge, eat something that’s gluten-free, and have a reaction,” he noted. Wheat-free baked goods might also not build tolerance as well, although that’s not clear from the study, Dr. Lanser said at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

Wheat seems to have something unique that alters the allergic properties of egg and milk proteins to help children outgrow their sensitivities. “Rice doesn’t have the same effect,” he observed, and it’s not known if any other grains do. Dr. Lanser said he is interested in looking into rye, barley, oats, and other alternatives.

The mean age of the children in the study was 6 years, and most children had multiple food allergies. Sensitization was confirmed by skin tests and specific IgE.

Meanwhile, there’s a new rule in the National Jewish kitchen: Unless a child has true celiac disease, “always make [challenge] muffins with wheat,” Dr. Lanser said.

There was no industry funding for the work, and the investigators had no disclosures.

aotto@frontlinemedcom.com

Neonates with the highest transepidermal water loss at birth, likely mediated through an impaired epidermal barrier, show significantly elevated chymotrypsinlike protease activity and reduced levels of filaggrin-derived natural moisturizing factors, which may predispose them to the development of atopic dermatitis, according to a report published online in the British Journal of Dermatology.

John Chittock of the University of Sheffield, England, and his colleagues assessed the biophysical, biologic, and functional properties of the developing neonatal stratum corneum (SC) from birth to 4 weeks of age in 115 healthy, full-term (at least 37 weeks’ gestation) neonates from the OBSERVE (Oil in Baby Skincare) randomized study birth cohort recruited at Saint Mary’s Hospital, Central Manchester NHS Foundation Trust, between September 2013 and June 2014.

For comparative purposes, an unrelated cohort of 20 adults with healthy skin was recruited from the local community between January and April 2015 (Br J Dermatol. 2016 Mar 19. doi: 10.1111/bjd.14568).

The researchers found that the biophysical properties of the neonatal SC are transitional from birth. For example, overall transepidermal water loss (TEWL) increased significantly during the first 4 weeks of infant life. Compared with adult skin, the newborn infant SC was found to be drier and more alkaline. In addition, levels of superficial chymotrypsinlike protease activity at birth did not differ between newborns and adults, while levels of filaggrin-derived natural moisturizing factors (NMF) were significantly lower at birth than in adulthood.

The increased chymotrypsinlike protease activity and NMF at 4 weeks of age exceeded levels found in healthy adults, rather than reaching their mature state. Compared with adult skin, the skin of infants is functionally immature, with undeveloped mechanisms of desquamation and differentiation, the investigators noted.

Further analysis revealed a correlation between TEWL and both superficial chymotrypsinlike protease activity and filaggrin-derived NMF at birth.

To explore that link, the researchers stratified the neonatal cohort according to TEWL percentile. The neonates in the 76th-100th percentile, the highest TEWL at birth, showed significantly elevated chymotrypsinlike protease activity and reduced levels of filaggrin-derived NMF, compared with neonates in lower percentiles. Therefore, those neonates are at highest risk for developing atopic dermatitis, the study authors said.

The findings indicate a need for infant skin care regimens that protect and support normal barrier development from birth, the researchers noted. They also suggested that clinical strategies targeting the early mechanisms of barrier breakdown could act as preventive measures in neonates at increased risk of developing atopic dermatitis.

The research was funded jointly by the University of Sheffield and a doctoral research fellowship supported by the National Institute for Health Research. The authors declared no conflicts of interest.

Neonates with the highest transepidermal water loss at birth, likely mediated through an impaired epidermal barrier, show significantly elevated chymotrypsinlike protease activity and reduced levels of filaggrin-derived natural moisturizing factors, which may predispose them to the development of atopic dermatitis, according to a report published online in the British Journal of Dermatology.

John Chittock of the University of Sheffield, England, and his colleagues assessed the biophysical, biologic, and functional properties of the developing neonatal stratum corneum (SC) from birth to 4 weeks of age in 115 healthy, full-term (at least 37 weeks’ gestation) neonates from the OBSERVE (Oil in Baby Skincare) randomized study birth cohort recruited at Saint Mary’s Hospital, Central Manchester NHS Foundation Trust, between September 2013 and June 2014.

For comparative purposes, an unrelated cohort of 20 adults with healthy skin was recruited from the local community between January and April 2015 (Br J Dermatol. 2016 Mar 19. doi: 10.1111/bjd.14568).

The researchers found that the biophysical properties of the neonatal SC are transitional from birth. For example, overall transepidermal water loss (TEWL) increased significantly during the first 4 weeks of infant life. Compared with adult skin, the newborn infant SC was found to be drier and more alkaline. In addition, levels of superficial chymotrypsinlike protease activity at birth did not differ between newborns and adults, while levels of filaggrin-derived natural moisturizing factors (NMF) were significantly lower at birth than in adulthood.

The increased chymotrypsinlike protease activity and NMF at 4 weeks of age exceeded levels found in healthy adults, rather than reaching their mature state. Compared with adult skin, the skin of infants is functionally immature, with undeveloped mechanisms of desquamation and differentiation, the investigators noted.

Further analysis revealed a correlation between TEWL and both superficial chymotrypsinlike protease activity and filaggrin-derived NMF at birth.

To explore that link, the researchers stratified the neonatal cohort according to TEWL percentile. The neonates in the 76th-100th percentile, the highest TEWL at birth, showed significantly elevated chymotrypsinlike protease activity and reduced levels of filaggrin-derived NMF, compared with neonates in lower percentiles. Therefore, those neonates are at highest risk for developing atopic dermatitis, the study authors said.

The findings indicate a need for infant skin care regimens that protect and support normal barrier development from birth, the researchers noted. They also suggested that clinical strategies targeting the early mechanisms of barrier breakdown could act as preventive measures in neonates at increased risk of developing atopic dermatitis.

The research was funded jointly by the University of Sheffield and a doctoral research fellowship supported by the National Institute for Health Research. The authors declared no conflicts of interest.

Neonates with the highest transepidermal water loss at birth, likely mediated through an impaired epidermal barrier, show significantly elevated chymotrypsinlike protease activity and reduced levels of filaggrin-derived natural moisturizing factors, which may predispose them to the development of atopic dermatitis, according to a report published online in the British Journal of Dermatology.

John Chittock of the University of Sheffield, England, and his colleagues assessed the biophysical, biologic, and functional properties of the developing neonatal stratum corneum (SC) from birth to 4 weeks of age in 115 healthy, full-term (at least 37 weeks’ gestation) neonates from the OBSERVE (Oil in Baby Skincare) randomized study birth cohort recruited at Saint Mary’s Hospital, Central Manchester NHS Foundation Trust, between September 2013 and June 2014.

For comparative purposes, an unrelated cohort of 20 adults with healthy skin was recruited from the local community between January and April 2015 (Br J Dermatol. 2016 Mar 19. doi: 10.1111/bjd.14568).

The researchers found that the biophysical properties of the neonatal SC are transitional from birth. For example, overall transepidermal water loss (TEWL) increased significantly during the first 4 weeks of infant life. Compared with adult skin, the newborn infant SC was found to be drier and more alkaline. In addition, levels of superficial chymotrypsinlike protease activity at birth did not differ between newborns and adults, while levels of filaggrin-derived natural moisturizing factors (NMF) were significantly lower at birth than in adulthood.

The increased chymotrypsinlike protease activity and NMF at 4 weeks of age exceeded levels found in healthy adults, rather than reaching their mature state. Compared with adult skin, the skin of infants is functionally immature, with undeveloped mechanisms of desquamation and differentiation, the investigators noted.

Further analysis revealed a correlation between TEWL and both superficial chymotrypsinlike protease activity and filaggrin-derived NMF at birth.

To explore that link, the researchers stratified the neonatal cohort according to TEWL percentile. The neonates in the 76th-100th percentile, the highest TEWL at birth, showed significantly elevated chymotrypsinlike protease activity and reduced levels of filaggrin-derived NMF, compared with neonates in lower percentiles. Therefore, those neonates are at highest risk for developing atopic dermatitis, the study authors said.

The findings indicate a need for infant skin care regimens that protect and support normal barrier development from birth, the researchers noted. They also suggested that clinical strategies targeting the early mechanisms of barrier breakdown could act as preventive measures in neonates at increased risk of developing atopic dermatitis.

The research was funded jointly by the University of Sheffield and a doctoral research fellowship supported by the National Institute for Health Research. The authors declared no conflicts of interest.

Treatment with dupilumab resulted in significant clinical improvements in adults with inadequately controlled moderate to-severe atopic dermatitis, in two phase III studies evaluating the biologic agent, according to Regeneron and Sanofi.

The phase III results of the two 16-week studies, SOLO 1 and SOLO 2, in nearly 1,400 adults with baseline Investigator’s Global Assessment (IGA) scores of 3 (moderate disease) or 4 (severe), were announced by Regeneron and Sanofi. The companies are codeveloping dupilumab, which inhibits signaling of interleukin-4 and IL-13, “two key cytokines required for the T helper 2 (Th2) immune response,” according to Regeneron.

©James Heilman, MD/Wikimedia Commons/CC BY-SA 3.0

In the studies, patients were randomized to treatment with 300 mg subcutaneously of dupilumab once a week or every 2 weeks (after a 600-mg loading dose) or placebo, for 16 weeks.

At 16 weeks, significantly more of those in the two treatment groups achieved clearing or near clearing of skin lesions – a primary endpoint – compared with placebo: In SOLO 1 and SOLO 2, respectively, an IGA score of 0 (clear) or 1 (almost clear) was achieved by 37% and 36% of those treated with 300 mg weekly, and 38% and 36% of those treated every 2 weeks, compared with 10% and 8.5% of those on placebo (P less than .0001).

Improvement from baseline in the Eczema Area and Severity Index (EASI) score in the SOLO 1 and SOLO 2 studies, respectively, were 72% and 69% of those treated with 300 mg weekly and 72% and 67% of those treated every 2 weeks, compared with 38% and 31% of those on placebo (P less than .0001).

The rates of adverse events ranged from 65% to 73% for those on dupilumab, and from 65% to 72% for those on placebo. The rates of serious adverse events were 1%-3% among those on dupilumab and 5%-6% for placebo; serious and severe infections were more common among those on placebo. Compared with placebo, injection site reactions were higher among those on dupilumab (10%-20% vs. 7%-8%). Conjunctivitis was more common among dupilumab-treated patients (7%-12% vs. 2% for placebo). One patient stopped treatment because of conjunctivitis.

The phase III results, which were announced in an April 1 press release, will be presented at a future medical meeting, and the companies plan to file for approval with the Food and Drug Administration in the third quarter of 2016.

emechcatie@frontlinemedcom.com

Treatment with dupilumab resulted in significant clinical improvements in adults with inadequately controlled moderate to-severe atopic dermatitis, in two phase III studies evaluating the biologic agent, according to Regeneron and Sanofi.

The phase III results of the two 16-week studies, SOLO 1 and SOLO 2, in nearly 1,400 adults with baseline Investigator’s Global Assessment (IGA) scores of 3 (moderate disease) or 4 (severe), were announced by Regeneron and Sanofi. The companies are codeveloping dupilumab, which inhibits signaling of interleukin-4 and IL-13, “two key cytokines required for the T helper 2 (Th2) immune response,” according to Regeneron.

©James Heilman, MD/Wikimedia Commons/CC BY-SA 3.0

In the studies, patients were randomized to treatment with 300 mg subcutaneously of dupilumab once a week or every 2 weeks (after a 600-mg loading dose) or placebo, for 16 weeks.

At 16 weeks, significantly more of those in the two treatment groups achieved clearing or near clearing of skin lesions – a primary endpoint – compared with placebo: In SOLO 1 and SOLO 2, respectively, an IGA score of 0 (clear) or 1 (almost clear) was achieved by 37% and 36% of those treated with 300 mg weekly, and 38% and 36% of those treated every 2 weeks, compared with 10% and 8.5% of those on placebo (P less than .0001).

Improvement from baseline in the Eczema Area and Severity Index (EASI) score in the SOLO 1 and SOLO 2 studies, respectively, were 72% and 69% of those treated with 300 mg weekly and 72% and 67% of those treated every 2 weeks, compared with 38% and 31% of those on placebo (P less than .0001).

The rates of adverse events ranged from 65% to 73% for those on dupilumab, and from 65% to 72% for those on placebo. The rates of serious adverse events were 1%-3% among those on dupilumab and 5%-6% for placebo; serious and severe infections were more common among those on placebo. Compared with placebo, injection site reactions were higher among those on dupilumab (10%-20% vs. 7%-8%). Conjunctivitis was more common among dupilumab-treated patients (7%-12% vs. 2% for placebo). One patient stopped treatment because of conjunctivitis.

The phase III results, which were announced in an April 1 press release, will be presented at a future medical meeting, and the companies plan to file for approval with the Food and Drug Administration in the third quarter of 2016.

emechcatie@frontlinemedcom.com

Treatment with dupilumab resulted in significant clinical improvements in adults with inadequately controlled moderate to-severe atopic dermatitis, in two phase III studies evaluating the biologic agent, according to Regeneron and Sanofi.

The phase III results of the two 16-week studies, SOLO 1 and SOLO 2, in nearly 1,400 adults with baseline Investigator’s Global Assessment (IGA) scores of 3 (moderate disease) or 4 (severe), were announced by Regeneron and Sanofi. The companies are codeveloping dupilumab, which inhibits signaling of interleukin-4 and IL-13, “two key cytokines required for the T helper 2 (Th2) immune response,” according to Regeneron.

©James Heilman, MD/Wikimedia Commons/CC BY-SA 3.0

In the studies, patients were randomized to treatment with 300 mg subcutaneously of dupilumab once a week or every 2 weeks (after a 600-mg loading dose) or placebo, for 16 weeks.

At 16 weeks, significantly more of those in the two treatment groups achieved clearing or near clearing of skin lesions – a primary endpoint – compared with placebo: In SOLO 1 and SOLO 2, respectively, an IGA score of 0 (clear) or 1 (almost clear) was achieved by 37% and 36% of those treated with 300 mg weekly, and 38% and 36% of those treated every 2 weeks, compared with 10% and 8.5% of those on placebo (P less than .0001).

Improvement from baseline in the Eczema Area and Severity Index (EASI) score in the SOLO 1 and SOLO 2 studies, respectively, were 72% and 69% of those treated with 300 mg weekly and 72% and 67% of those treated every 2 weeks, compared with 38% and 31% of those on placebo (P less than .0001).

The rates of adverse events ranged from 65% to 73% for those on dupilumab, and from 65% to 72% for those on placebo. The rates of serious adverse events were 1%-3% among those on dupilumab and 5%-6% for placebo; serious and severe infections were more common among those on placebo. Compared with placebo, injection site reactions were higher among those on dupilumab (10%-20% vs. 7%-8%). Conjunctivitis was more common among dupilumab-treated patients (7%-12% vs. 2% for placebo). One patient stopped treatment because of conjunctivitis.

The phase III results, which were announced in an April 1 press release, will be presented at a future medical meeting, and the companies plan to file for approval with the Food and Drug Administration in the third quarter of 2016.

emechcatie@frontlinemedcom.com

WAIKOLOA, HAWAII – The list of nonatopic comorbid conditions associated with atopic dermatitis is rapidly expanding.

Just in the past year, published studies have linked pediatric atopic dermatitis to increased risks of obesity, high blood pressure, headaches, anemia, and speech disorders. Meanwhile, adult atopic dermatitis was reported to be associated with increased rates of fracture and cardiovascular disease. And in the dermatologic arena, a link between atopic dermatitis, vitiligo, and alopecia areata was identified, Dr. Lawrence F. Eichenfield noted at the Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation.

Actually, these reported associations published in 2015-2016 might best be termed “emerging comorbidities,” as they are first reports and thus need confirmation, said Dr. Eichenfield, professor of dermatology and pediatrics at the University of California, San Diego, and chief of pediatric and adolescent dermatology at Rady Children’s Hospital San Diego.

Much of this work on emerging comorbidities has been done by dermatologist Dr. Jonathan I. Silverberg of Northwestern University, Chicago, and various coinvestigators. They have been prolific.

For example, in a multivariate logistic regression analysis of 207,007 children and adolescents included in the cross-sectional 1997-2013 U.S. National Health Interview Survey, Dr. Silverberg and coinvestigators found that eczema was independently associated with a 1.83-fold increased odds of anemia. They bolstered this observation with an analysis of more than 30,000 children and adolescents in the 1992-2012 National Health and Nutrition Examination Survey (NHANES) in which they found that current eczema was associated with a 1.93-fold increased odds of anemia, particularly microcytic anemia. The underlying mechanism is unknown; however, the investigators noted that chronic inflammation and systemic immunosuppressant drugs have been shown to be associated with anemia (JAMA Pediatr. 2016;170[1]:29-34).

Dr. Silverberg also found in a multivariate logistic regression analysis of data on more than 400,000 pediatric participants in the National Survey of Children’s Health and the National Health Interview Survey that mild and severe eczema were independently associated with 1.79-fold and 2.72-fold, respectively, increased odds of headaches (J Allergy Clin Immunol. 2016 Feb;137[2]:492-9).

Using these same two data sources, with multivariate analysis adjusted for potential confounders, the investigators found that eczema was associated with a 1.81-fold increased risk of speech disorder (J Pediatr. 2016 Jan;168:185-92).

In a case-control study involving 132 children and adolescents with current moderate to severe atopic dermatitis and 143 healthy controls, Dr. Silverberg and coinvestigators found in a logistic regression analysis that atopic dermatitis was independently associated with a doubled risk of having a systolic blood pressure in the 90th percentile or higher – as well as 3.92-fold increased odds of central obesity, as defined by a waist circumference in the 85th percentile or higher (JAMA Dermatol. 2015 Feb;151[2]:144-52).

In a systematic review and meta-analysis of 16 published vitiligo studies and 17 published studies of alopecia areata, Dr. Silverberg and medical student Girish C. Mohan found that patients with vitiligo or alopecia areata were respectively 7.8 and 2.6 times more likely to have atopic dermatitis than controls without those disorders (JAMA Dermatol. 2015 May;151[5]:522-8).

In a logistic regression analysis of data on 34,500 adults with a history of eczema within the prior year who participated in the 2012 National Health Interview Survey, Drs. Nitin Garg and Dr. Silverberg concluded that the results suggested that adult atopic dermatitis is a previously unrecognized risk factor for fracture and other bone or joint injuries causing limitation. Adults with atopic dermatitis were at a 1.67-fold increased risk for such injuries in an analysis controlling for sociodemographics, other forms of atopic disease, and psychiatric and behavioral disorders (JAMA Dermatol. 2015 Jan;151[1]:33-41).

In another large cross-sectional study, Dr. Silverberg found that adults with atopic dermatitis had significantly higher odds of a history of acute MI, coronary artery disease, heart failure, and stroke (Allergy. 2015 Oct;70[10]:1300-8).

Dr. Eichenfield said that while he would like to see these hot-off-the-presses 2015-2016 findings on nonatopic comorbidities backed up by confirmatory studies in other populations, the evidence is stronger for an association between pediatric atopic dermatitis and several mental health disorders. The initial reports came mainly from Europe, but were then supported by a large study by Dr. Eric L. Simpson and coinvestigators at Oregon Health and Science University, Portland.

In their analysis of data on nearly 93,000 noninstitutionalized children and adolescents included in the 2007 National Survey of Children’s Health, the investigators found after controlling for potential confounders that atopic dermatitis was associated with a 1.87-fold increased risk of having attention-deficit/hyperactivity disorder, a 3-fold increased risk of diagnosed autism, an adjusted 1.81-fold increase in depression, and 1.87-fold increased odds of conduct disorder. The Oregon group found a clear dose-dependent relationship between the reported severity of the skin disease and the likelihood of those mental health disorders (J Allergy Clin Immunol. 2013 Feb;131[2]:428-33).

The hope is that emerging strategies to prevent atopic dermatitis or aggressively treat it early on will reduce the risk of many of these comorbid conditions, Dr. Eichenfield said.

SDEF and this news organization are owned by the same parent company.

bjancin@frontlinemedcom.com

WAIKOLOA, HAWAII – The list of nonatopic comorbid conditions associated with atopic dermatitis is rapidly expanding.

Just in the past year, published studies have linked pediatric atopic dermatitis to increased risks of obesity, high blood pressure, headaches, anemia, and speech disorders. Meanwhile, adult atopic dermatitis was reported to be associated with increased rates of fracture and cardiovascular disease. And in the dermatologic arena, a link between atopic dermatitis, vitiligo, and alopecia areata was identified, Dr. Lawrence F. Eichenfield noted at the Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation.

Actually, these reported associations published in 2015-2016 might best be termed “emerging comorbidities,” as they are first reports and thus need confirmation, said Dr. Eichenfield, professor of dermatology and pediatrics at the University of California, San Diego, and chief of pediatric and adolescent dermatology at Rady Children’s Hospital San Diego.

Much of this work on emerging comorbidities has been done by dermatologist Dr. Jonathan I. Silverberg of Northwestern University, Chicago, and various coinvestigators. They have been prolific.

For example, in a multivariate logistic regression analysis of 207,007 children and adolescents included in the cross-sectional 1997-2013 U.S. National Health Interview Survey, Dr. Silverberg and coinvestigators found that eczema was independently associated with a 1.83-fold increased odds of anemia. They bolstered this observation with an analysis of more than 30,000 children and adolescents in the 1992-2012 National Health and Nutrition Examination Survey (NHANES) in which they found that current eczema was associated with a 1.93-fold increased odds of anemia, particularly microcytic anemia. The underlying mechanism is unknown; however, the investigators noted that chronic inflammation and systemic immunosuppressant drugs have been shown to be associated with anemia (JAMA Pediatr. 2016;170[1]:29-34).

Dr. Silverberg also found in a multivariate logistic regression analysis of data on more than 400,000 pediatric participants in the National Survey of Children’s Health and the National Health Interview Survey that mild and severe eczema were independently associated with 1.79-fold and 2.72-fold, respectively, increased odds of headaches (J Allergy Clin Immunol. 2016 Feb;137[2]:492-9).

Using these same two data sources, with multivariate analysis adjusted for potential confounders, the investigators found that eczema was associated with a 1.81-fold increased risk of speech disorder (J Pediatr. 2016 Jan;168:185-92).

In a case-control study involving 132 children and adolescents with current moderate to severe atopic dermatitis and 143 healthy controls, Dr. Silverberg and coinvestigators found in a logistic regression analysis that atopic dermatitis was independently associated with a doubled risk of having a systolic blood pressure in the 90th percentile or higher – as well as 3.92-fold increased odds of central obesity, as defined by a waist circumference in the 85th percentile or higher (JAMA Dermatol. 2015 Feb;151[2]:144-52).

In a systematic review and meta-analysis of 16 published vitiligo studies and 17 published studies of alopecia areata, Dr. Silverberg and medical student Girish C. Mohan found that patients with vitiligo or alopecia areata were respectively 7.8 and 2.6 times more likely to have atopic dermatitis than controls without those disorders (JAMA Dermatol. 2015 May;151[5]:522-8).

In a logistic regression analysis of data on 34,500 adults with a history of eczema within the prior year who participated in the 2012 National Health Interview Survey, Drs. Nitin Garg and Dr. Silverberg concluded that the results suggested that adult atopic dermatitis is a previously unrecognized risk factor for fracture and other bone or joint injuries causing limitation. Adults with atopic dermatitis were at a 1.67-fold increased risk for such injuries in an analysis controlling for sociodemographics, other forms of atopic disease, and psychiatric and behavioral disorders (JAMA Dermatol. 2015 Jan;151[1]:33-41).

In another large cross-sectional study, Dr. Silverberg found that adults with atopic dermatitis had significantly higher odds of a history of acute MI, coronary artery disease, heart failure, and stroke (Allergy. 2015 Oct;70[10]:1300-8).

Dr. Eichenfield said that while he would like to see these hot-off-the-presses 2015-2016 findings on nonatopic comorbidities backed up by confirmatory studies in other populations, the evidence is stronger for an association between pediatric atopic dermatitis and several mental health disorders. The initial reports came mainly from Europe, but were then supported by a large study by Dr. Eric L. Simpson and coinvestigators at Oregon Health and Science University, Portland.

In their analysis of data on nearly 93,000 noninstitutionalized children and adolescents included in the 2007 National Survey of Children’s Health, the investigators found after controlling for potential confounders that atopic dermatitis was associated with a 1.87-fold increased risk of having attention-deficit/hyperactivity disorder, a 3-fold increased risk of diagnosed autism, an adjusted 1.81-fold increase in depression, and 1.87-fold increased odds of conduct disorder. The Oregon group found a clear dose-dependent relationship between the reported severity of the skin disease and the likelihood of those mental health disorders (J Allergy Clin Immunol. 2013 Feb;131[2]:428-33).

The hope is that emerging strategies to prevent atopic dermatitis or aggressively treat it early on will reduce the risk of many of these comorbid conditions, Dr. Eichenfield said.

SDEF and this news organization are owned by the same parent company.

bjancin@frontlinemedcom.com

WAIKOLOA, HAWAII – The list of nonatopic comorbid conditions associated with atopic dermatitis is rapidly expanding.

Just in the past year, published studies have linked pediatric atopic dermatitis to increased risks of obesity, high blood pressure, headaches, anemia, and speech disorders. Meanwhile, adult atopic dermatitis was reported to be associated with increased rates of fracture and cardiovascular disease. And in the dermatologic arena, a link between atopic dermatitis, vitiligo, and alopecia areata was identified, Dr. Lawrence F. Eichenfield noted at the Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation.

Actually, these reported associations published in 2015-2016 might best be termed “emerging comorbidities,” as they are first reports and thus need confirmation, said Dr. Eichenfield, professor of dermatology and pediatrics at the University of California, San Diego, and chief of pediatric and adolescent dermatology at Rady Children’s Hospital San Diego.

Much of this work on emerging comorbidities has been done by dermatologist Dr. Jonathan I. Silverberg of Northwestern University, Chicago, and various coinvestigators. They have been prolific.

For example, in a multivariate logistic regression analysis of 207,007 children and adolescents included in the cross-sectional 1997-2013 U.S. National Health Interview Survey, Dr. Silverberg and coinvestigators found that eczema was independently associated with a 1.83-fold increased odds of anemia. They bolstered this observation with an analysis of more than 30,000 children and adolescents in the 1992-2012 National Health and Nutrition Examination Survey (NHANES) in which they found that current eczema was associated with a 1.93-fold increased odds of anemia, particularly microcytic anemia. The underlying mechanism is unknown; however, the investigators noted that chronic inflammation and systemic immunosuppressant drugs have been shown to be associated with anemia (JAMA Pediatr. 2016;170[1]:29-34).

Dr. Silverberg also found in a multivariate logistic regression analysis of data on more than 400,000 pediatric participants in the National Survey of Children’s Health and the National Health Interview Survey that mild and severe eczema were independently associated with 1.79-fold and 2.72-fold, respectively, increased odds of headaches (J Allergy Clin Immunol. 2016 Feb;137[2]:492-9).

Using these same two data sources, with multivariate analysis adjusted for potential confounders, the investigators found that eczema was associated with a 1.81-fold increased risk of speech disorder (J Pediatr. 2016 Jan;168:185-92).

In a case-control study involving 132 children and adolescents with current moderate to severe atopic dermatitis and 143 healthy controls, Dr. Silverberg and coinvestigators found in a logistic regression analysis that atopic dermatitis was independently associated with a doubled risk of having a systolic blood pressure in the 90th percentile or higher – as well as 3.92-fold increased odds of central obesity, as defined by a waist circumference in the 85th percentile or higher (JAMA Dermatol. 2015 Feb;151[2]:144-52).

In a systematic review and meta-analysis of 16 published vitiligo studies and 17 published studies of alopecia areata, Dr. Silverberg and medical student Girish C. Mohan found that patients with vitiligo or alopecia areata were respectively 7.8 and 2.6 times more likely to have atopic dermatitis than controls without those disorders (JAMA Dermatol. 2015 May;151[5]:522-8).

In a logistic regression analysis of data on 34,500 adults with a history of eczema within the prior year who participated in the 2012 National Health Interview Survey, Drs. Nitin Garg and Dr. Silverberg concluded that the results suggested that adult atopic dermatitis is a previously unrecognized risk factor for fracture and other bone or joint injuries causing limitation. Adults with atopic dermatitis were at a 1.67-fold increased risk for such injuries in an analysis controlling for sociodemographics, other forms of atopic disease, and psychiatric and behavioral disorders (JAMA Dermatol. 2015 Jan;151[1]:33-41).

In another large cross-sectional study, Dr. Silverberg found that adults with atopic dermatitis had significantly higher odds of a history of acute MI, coronary artery disease, heart failure, and stroke (Allergy. 2015 Oct;70[10]:1300-8).

Dr. Eichenfield said that while he would like to see these hot-off-the-presses 2015-2016 findings on nonatopic comorbidities backed up by confirmatory studies in other populations, the evidence is stronger for an association between pediatric atopic dermatitis and several mental health disorders. The initial reports came mainly from Europe, but were then supported by a large study by Dr. Eric L. Simpson and coinvestigators at Oregon Health and Science University, Portland.

In their analysis of data on nearly 93,000 noninstitutionalized children and adolescents included in the 2007 National Survey of Children’s Health, the investigators found after controlling for potential confounders that atopic dermatitis was associated with a 1.87-fold increased risk of having attention-deficit/hyperactivity disorder, a 3-fold increased risk of diagnosed autism, an adjusted 1.81-fold increase in depression, and 1.87-fold increased odds of conduct disorder. The Oregon group found a clear dose-dependent relationship between the reported severity of the skin disease and the likelihood of those mental health disorders (J Allergy Clin Immunol. 2013 Feb;131[2]:428-33).

The hope is that emerging strategies to prevent atopic dermatitis or aggressively treat it early on will reduce the risk of many of these comorbid conditions, Dr. Eichenfield said.

SDEF and this news organization are owned by the same parent company.

bjancin@frontlinemedcom.com

LOS ANGELES – Evidence is building for the hypothesis that impairments in the skin’s microbiome promote Staphylococcus aureus colonization and drive atopic dermatitis, Dr. Donald Y.M. Leung said at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

The link between the bacteria and atopic dermatitis has long been discussed, but its role in pathogenesis still needs definition, he said.

“We’ve never been able to look at the total bacterial composition of the skin, but now with next-generation sequencing it’s finally possible to look at all the phylla and species. Other investigators have shown that during flares of atopic dermatitis there’s a reduction in bacterial diversity and an increase in staph, with S. aureus being particularly abundant. Then, post-flare, you see see a drop in S. aureus; this clearly suggests (it’s) important,” according to Dr. Leung, head of the division of pediatric allergy and immunology at National Jewish Health in Denver and professor of pediatrics at the University of Colorado.

Staphylococcus aureus is known to secrete virulence factors including cytotoxins, superantigens, lipases, and proteases that activate inflammatory cells and can cause significant skin barrier dysfunction.

The discovery that filaggrin mutations result in structural abnormalities in the skin barrier and are associated with sharply increased rates of atopic dermatitis and peanut allergy have strengthened the association, but filaggrin can’t be the whole story. Mutations in filaggrin are largely confined to individuals of Northern European ancestry; African Americans don’t have filaggrin mutations.

Yet atopic dermatitis is a global phenomenon. Further, a skin barrier defect is not enough to cause atopic dermatitis, Dr. Leung said. But such a defect, whether caused by a filaggrin mutation or something else, allows S. aureus to attach to and colonize the skin. Staph overgrowth or infection then activates an inflammatory cell cascade involving natural killer T cells, mast cells, cytokines, and Langerhans cells. That’s why the most effective treatments for atopic dermatitis address both the need to rebuild the skin barrier as well as the counterproductive immune response, he added.

Elsewhere at the AAAAI meeting, Dr. Andrea L. Jones, of National Jewish Health, presented an analysis of 718 children and adolescents with atopic dermatitis, all of whom had been cultured for S. aureus, in that institution’s database. Methicillin-resistant S. aureus (MRSA) was found in 19%; 57% were positive for methicillin-sensitive S. aureus (MSSA) and 23% lacked S. aureus. Of note, the prevalence of peanut allergy was highest at 78% in the group with MRSA; the prevalence was 39% in those with MSSA and 4% in those without S. aureus.

The prevalence of allergies to wheat, egg, milk, or soybeans in the youths with atopic dermatitis was unrelated to MRSA colonization.

“Our hypothesis – although we need to do a prospective study – is that staph colonization may lead to barrier dysfunction and thus allow environmental allergens to invade through the skin. Interestingly enough, people who weren’t colonized by staph had a very low level of sensitization to peanut,” said Dr. Leung, who was the senior investigator in the study.

Dr. Leung was a coauthor on another study that points to a potential new avenue of treatment in atopic dermatitis. Presented by investigators at the University of California, San Diego, at a recent meeting of the Society for Investigative Dermatology, the study showed that atopic dermatitis is marked by a defect in the commensal skin bacteria which normally keep S. aureus in check.

In that study, the amount of S. aureus growing on a defined area of lesional skin of atopic dermatitis patients was nearly 10-fold greater than that on nonlesional skin and the skin of controls without atopic dermatitis.

Commensal bacteria on lesional skin may possess markedly reduced antimicrobial activity. The NIH-sponsored Atopic Dermatitis Research Network plans to conduct clinical trials to see if transplanting beneficial commensal bacteria will reduce staph colonization in atopic dermatitis patients and thereby result in therapeutic benefit, Dr. Leung noted.

He reported serving on scientific advisory boards for more than half a dozen pharmaceutical companies and receiving numerous research grants from the NIH.

bjancin@frontlinemedcom.com

LOS ANGELES – Evidence is building for the hypothesis that impairments in the skin’s microbiome promote Staphylococcus aureus colonization and drive atopic dermatitis, Dr. Donald Y.M. Leung said at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

The link between the bacteria and atopic dermatitis has long been discussed, but its role in pathogenesis still needs definition, he said.

“We’ve never been able to look at the total bacterial composition of the skin, but now with next-generation sequencing it’s finally possible to look at all the phylla and species. Other investigators have shown that during flares of atopic dermatitis there’s a reduction in bacterial diversity and an increase in staph, with S. aureus being particularly abundant. Then, post-flare, you see see a drop in S. aureus; this clearly suggests (it’s) important,” according to Dr. Leung, head of the division of pediatric allergy and immunology at National Jewish Health in Denver and professor of pediatrics at the University of Colorado.

Staphylococcus aureus is known to secrete virulence factors including cytotoxins, superantigens, lipases, and proteases that activate inflammatory cells and can cause significant skin barrier dysfunction.

The discovery that filaggrin mutations result in structural abnormalities in the skin barrier and are associated with sharply increased rates of atopic dermatitis and peanut allergy have strengthened the association, but filaggrin can’t be the whole story. Mutations in filaggrin are largely confined to individuals of Northern European ancestry; African Americans don’t have filaggrin mutations.

Yet atopic dermatitis is a global phenomenon. Further, a skin barrier defect is not enough to cause atopic dermatitis, Dr. Leung said. But such a defect, whether caused by a filaggrin mutation or something else, allows S. aureus to attach to and colonize the skin. Staph overgrowth or infection then activates an inflammatory cell cascade involving natural killer T cells, mast cells, cytokines, and Langerhans cells. That’s why the most effective treatments for atopic dermatitis address both the need to rebuild the skin barrier as well as the counterproductive immune response, he added.

Elsewhere at the AAAAI meeting, Dr. Andrea L. Jones, of National Jewish Health, presented an analysis of 718 children and adolescents with atopic dermatitis, all of whom had been cultured for S. aureus, in that institution’s database. Methicillin-resistant S. aureus (MRSA) was found in 19%; 57% were positive for methicillin-sensitive S. aureus (MSSA) and 23% lacked S. aureus. Of note, the prevalence of peanut allergy was highest at 78% in the group with MRSA; the prevalence was 39% in those with MSSA and 4% in those without S. aureus.

The prevalence of allergies to wheat, egg, milk, or soybeans in the youths with atopic dermatitis was unrelated to MRSA colonization.

“Our hypothesis – although we need to do a prospective study – is that staph colonization may lead to barrier dysfunction and thus allow environmental allergens to invade through the skin. Interestingly enough, people who weren’t colonized by staph had a very low level of sensitization to peanut,” said Dr. Leung, who was the senior investigator in the study.

Dr. Leung was a coauthor on another study that points to a potential new avenue of treatment in atopic dermatitis. Presented by investigators at the University of California, San Diego, at a recent meeting of the Society for Investigative Dermatology, the study showed that atopic dermatitis is marked by a defect in the commensal skin bacteria which normally keep S. aureus in check.

In that study, the amount of S. aureus growing on a defined area of lesional skin of atopic dermatitis patients was nearly 10-fold greater than that on nonlesional skin and the skin of controls without atopic dermatitis.

Commensal bacteria on lesional skin may possess markedly reduced antimicrobial activity. The NIH-sponsored Atopic Dermatitis Research Network plans to conduct clinical trials to see if transplanting beneficial commensal bacteria will reduce staph colonization in atopic dermatitis patients and thereby result in therapeutic benefit, Dr. Leung noted.

He reported serving on scientific advisory boards for more than half a dozen pharmaceutical companies and receiving numerous research grants from the NIH.

bjancin@frontlinemedcom.com

LOS ANGELES – Evidence is building for the hypothesis that impairments in the skin’s microbiome promote Staphylococcus aureus colonization and drive atopic dermatitis, Dr. Donald Y.M. Leung said at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

The link between the bacteria and atopic dermatitis has long been discussed, but its role in pathogenesis still needs definition, he said.

“We’ve never been able to look at the total bacterial composition of the skin, but now with next-generation sequencing it’s finally possible to look at all the phylla and species. Other investigators have shown that during flares of atopic dermatitis there’s a reduction in bacterial diversity and an increase in staph, with S. aureus being particularly abundant. Then, post-flare, you see see a drop in S. aureus; this clearly suggests (it’s) important,” according to Dr. Leung, head of the division of pediatric allergy and immunology at National Jewish Health in Denver and professor of pediatrics at the University of Colorado.

Staphylococcus aureus is known to secrete virulence factors including cytotoxins, superantigens, lipases, and proteases that activate inflammatory cells and can cause significant skin barrier dysfunction.

The discovery that filaggrin mutations result in structural abnormalities in the skin barrier and are associated with sharply increased rates of atopic dermatitis and peanut allergy have strengthened the association, but filaggrin can’t be the whole story. Mutations in filaggrin are largely confined to individuals of Northern European ancestry; African Americans don’t have filaggrin mutations.

Yet atopic dermatitis is a global phenomenon. Further, a skin barrier defect is not enough to cause atopic dermatitis, Dr. Leung said. But such a defect, whether caused by a filaggrin mutation or something else, allows S. aureus to attach to and colonize the skin. Staph overgrowth or infection then activates an inflammatory cell cascade involving natural killer T cells, mast cells, cytokines, and Langerhans cells. That’s why the most effective treatments for atopic dermatitis address both the need to rebuild the skin barrier as well as the counterproductive immune response, he added.

Elsewhere at the AAAAI meeting, Dr. Andrea L. Jones, of National Jewish Health, presented an analysis of 718 children and adolescents with atopic dermatitis, all of whom had been cultured for S. aureus, in that institution’s database. Methicillin-resistant S. aureus (MRSA) was found in 19%; 57% were positive for methicillin-sensitive S. aureus (MSSA) and 23% lacked S. aureus. Of note, the prevalence of peanut allergy was highest at 78% in the group with MRSA; the prevalence was 39% in those with MSSA and 4% in those without S. aureus.

The prevalence of allergies to wheat, egg, milk, or soybeans in the youths with atopic dermatitis was unrelated to MRSA colonization.

“Our hypothesis – although we need to do a prospective study – is that staph colonization may lead to barrier dysfunction and thus allow environmental allergens to invade through the skin. Interestingly enough, people who weren’t colonized by staph had a very low level of sensitization to peanut,” said Dr. Leung, who was the senior investigator in the study.

Dr. Leung was a coauthor on another study that points to a potential new avenue of treatment in atopic dermatitis. Presented by investigators at the University of California, San Diego, at a recent meeting of the Society for Investigative Dermatology, the study showed that atopic dermatitis is marked by a defect in the commensal skin bacteria which normally keep S. aureus in check.

In that study, the amount of S. aureus growing on a defined area of lesional skin of atopic dermatitis patients was nearly 10-fold greater than that on nonlesional skin and the skin of controls without atopic dermatitis.

Commensal bacteria on lesional skin may possess markedly reduced antimicrobial activity. The NIH-sponsored Atopic Dermatitis Research Network plans to conduct clinical trials to see if transplanting beneficial commensal bacteria will reduce staph colonization in atopic dermatitis patients and thereby result in therapeutic benefit, Dr. Leung noted.

He reported serving on scientific advisory boards for more than half a dozen pharmaceutical companies and receiving numerous research grants from the NIH.

bjancin@frontlinemedcom.com

Although psoriasis was once at the forefront of therapeutic advancements in dermatology, atopic dermatitis (AD) is now taking center stage with several new treatments in the pipeline. Dr. Emma Guttman-Yassky provides an overview of the future of AD treatment, which includes new topical and systemic agents that currently are moving forward in advanced clinical trials or are close to registration. She also discusses strategies for improving disease management in AD patients, noting that prevention and education of both patients and their caregivers are key to effective treatment.

Although psoriasis was once at the forefront of therapeutic advancements in dermatology, atopic dermatitis (AD) is now taking center stage with several new treatments in the pipeline. Dr. Emma Guttman-Yassky provides an overview of the future of AD treatment, which includes new topical and systemic agents that currently are moving forward in advanced clinical trials or are close to registration. She also discusses strategies for improving disease management in AD patients, noting that prevention and education of both patients and their caregivers are key to effective treatment.

Although psoriasis was once at the forefront of therapeutic advancements in dermatology, atopic dermatitis (AD) is now taking center stage with several new treatments in the pipeline. Dr. Emma Guttman-Yassky provides an overview of the future of AD treatment, which includes new topical and systemic agents that currently are moving forward in advanced clinical trials or are close to registration. She also discusses strategies for improving disease management in AD patients, noting that prevention and education of both patients and their caregivers are key to effective treatment.

WASHINGTON – Nemolizumab, an anti-interleukin-31 receptor A monoclonal antibody, was shown to rapidly and consistently improve pruritus, dermatitis, and sleep disturbance in patients with previously uncontrolled moderate-to-severe atopic dermatitis in a phase II, randomized, double-blind, placebo-controlled trial.

“The patients notice that the itch is gone very quickly, sometimes within days, even before their dermatitis starts to heal,” said Dr. Jon M. Hanifin, one of the treatment’s investigators. “It’s very exciting.”

jancin

Dr. Hanifin, a researcher at Oregon Health & Science University, Portland, made his comments while presenting the data during the late-breaking clinical research session at this year’s annual meeting of the American Academy of Dermatology.

The novel treatment, currently known as CIM331 (Chugai) targets elevated levels of interleukin-31, a cytokine that has been implicated in the pathophysiology of atopic dermatitis (AD) and pruritus.

The multicenter, multi-dose study assigned 264 patients, primarily in their mid-30s, with moderate-to-severe AD, uncontrolled by topical treatments, to either placebo or 0.1 mg/kg, 0.5 mg/kg, or 2.0 mg/kg CIM331 every 4 weeks. The study completion rate was 82%.

Using a visual analog scale of 0 to 10, with 10 characterized as “the worst imaginable,” at week 12, patients in the three study groups reported −41.5%, −61.2%, and −60.5% reductions in pruritus vs. −20.1% for placebo (P less than .01 for all).

The “significant reductions” in itch began as early as week 1, particularly in the group treated with the 2-mg/kg dose. Dr. Hanifin said that the patients had a very high mean pruritis score, and some had as much as half of their body surface area affected by AD.

Rescue medications such as topical corticosteroids were not permitted until after at least 1 month of treatment. Patients given rescue therapies were required to have both itch and dermatitis. “This was kind of a tough thing to get through, but [patients] did okay,” Dr. Hanifin said.

Patients treated with the 0.5-mg/kg dose showed the most improvement from baseline in Eczema Area and Severity Index scores at week 12 at −44.6%, compared with −20.9% for placebo. Across the study arms, the proportion of static Investigator’s Global Assessment of 1 or less was 20.9% vs. 4.7% for placebo. Additionally, Dr. Hanifin said sleep latency in the study groups was improved by half and there was an increase in total overall sleep time.

CIM331 was well tolerated, with the most common adverse events being exacerbation of AD and nasopharyngitis. “The risk of immune suppression seemed to be low,” Dr. Hanifin said.

wmcknight@frontlinemedcom.com

On Twitter @whitneymcknight

WASHINGTON – Nemolizumab, an anti-interleukin-31 receptor A monoclonal antibody, was shown to rapidly and consistently improve pruritus, dermatitis, and sleep disturbance in patients with previously uncontrolled moderate-to-severe atopic dermatitis in a phase II, randomized, double-blind, placebo-controlled trial.

“The patients notice that the itch is gone very quickly, sometimes within days, even before their dermatitis starts to heal,” said Dr. Jon M. Hanifin, one of the treatment’s investigators. “It’s very exciting.”

jancin

Dr. Hanifin, a researcher at Oregon Health & Science University, Portland, made his comments while presenting the data during the late-breaking clinical research session at this year’s annual meeting of the American Academy of Dermatology.

The novel treatment, currently known as CIM331 (Chugai) targets elevated levels of interleukin-31, a cytokine that has been implicated in the pathophysiology of atopic dermatitis (AD) and pruritus.

The multicenter, multi-dose study assigned 264 patients, primarily in their mid-30s, with moderate-to-severe AD, uncontrolled by topical treatments, to either placebo or 0.1 mg/kg, 0.5 mg/kg, or 2.0 mg/kg CIM331 every 4 weeks. The study completion rate was 82%.

Using a visual analog scale of 0 to 10, with 10 characterized as “the worst imaginable,” at week 12, patients in the three study groups reported −41.5%, −61.2%, and −60.5% reductions in pruritus vs. −20.1% for placebo (P less than .01 for all).

The “significant reductions” in itch began as early as week 1, particularly in the group treated with the 2-mg/kg dose. Dr. Hanifin said that the patients had a very high mean pruritis score, and some had as much as half of their body surface area affected by AD.

Rescue medications such as topical corticosteroids were not permitted until after at least 1 month of treatment. Patients given rescue therapies were required to have both itch and dermatitis. “This was kind of a tough thing to get through, but [patients] did okay,” Dr. Hanifin said.

Patients treated with the 0.5-mg/kg dose showed the most improvement from baseline in Eczema Area and Severity Index scores at week 12 at −44.6%, compared with −20.9% for placebo. Across the study arms, the proportion of static Investigator’s Global Assessment of 1 or less was 20.9% vs. 4.7% for placebo. Additionally, Dr. Hanifin said sleep latency in the study groups was improved by half and there was an increase in total overall sleep time.

CIM331 was well tolerated, with the most common adverse events being exacerbation of AD and nasopharyngitis. “The risk of immune suppression seemed to be low,” Dr. Hanifin said.

wmcknight@frontlinemedcom.com

On Twitter @whitneymcknight

WASHINGTON – Nemolizumab, an anti-interleukin-31 receptor A monoclonal antibody, was shown to rapidly and consistently improve pruritus, dermatitis, and sleep disturbance in patients with previously uncontrolled moderate-to-severe atopic dermatitis in a phase II, randomized, double-blind, placebo-controlled trial.

“The patients notice that the itch is gone very quickly, sometimes within days, even before their dermatitis starts to heal,” said Dr. Jon M. Hanifin, one of the treatment’s investigators. “It’s very exciting.”

jancin

Dr. Hanifin, a researcher at Oregon Health & Science University, Portland, made his comments while presenting the data during the late-breaking clinical research session at this year’s annual meeting of the American Academy of Dermatology.

The novel treatment, currently known as CIM331 (Chugai) targets elevated levels of interleukin-31, a cytokine that has been implicated in the pathophysiology of atopic dermatitis (AD) and pruritus.

The multicenter, multi-dose study assigned 264 patients, primarily in their mid-30s, with moderate-to-severe AD, uncontrolled by topical treatments, to either placebo or 0.1 mg/kg, 0.5 mg/kg, or 2.0 mg/kg CIM331 every 4 weeks. The study completion rate was 82%.

Using a visual analog scale of 0 to 10, with 10 characterized as “the worst imaginable,” at week 12, patients in the three study groups reported −41.5%, −61.2%, and −60.5% reductions in pruritus vs. −20.1% for placebo (P less than .01 for all).

The “significant reductions” in itch began as early as week 1, particularly in the group treated with the 2-mg/kg dose. Dr. Hanifin said that the patients had a very high mean pruritis score, and some had as much as half of their body surface area affected by AD.

Rescue medications such as topical corticosteroids were not permitted until after at least 1 month of treatment. Patients given rescue therapies were required to have both itch and dermatitis. “This was kind of a tough thing to get through, but [patients] did okay,” Dr. Hanifin said.

Patients treated with the 0.5-mg/kg dose showed the most improvement from baseline in Eczema Area and Severity Index scores at week 12 at −44.6%, compared with −20.9% for placebo. Across the study arms, the proportion of static Investigator’s Global Assessment of 1 or less was 20.9% vs. 4.7% for placebo. Additionally, Dr. Hanifin said sleep latency in the study groups was improved by half and there was an increase in total overall sleep time.

CIM331 was well tolerated, with the most common adverse events being exacerbation of AD and nasopharyngitis. “The risk of immune suppression seemed to be low,” Dr. Hanifin said.

wmcknight@frontlinemedcom.com

On Twitter @whitneymcknight

LOS ANGELES – Among infants at risk for allergic disease, egg introduction at 4 months cuts the risk of egg sensitization at 12 months by about half, according a randomized, placebo-controlled, double blind trial from Australia.

“This is what we hoped to find.” Introducing egg early “is certainly safe, and it may promote tolerance,” said senior investigator Dr. Dianne Campbell, professor and chair of pediatric allergy and clinical immunology at the Children’s Hospital at Westmead, which is affiliated with the University of Sydney.

Four-month-old children were randomized to 350 mg of pasteurized raw whole egg powder or – as a control – rice powder sprinkled once daily on their weaning food until month 8, at which time parents in both groups were encouraged to add eggs to their children’s diets. At least one of each child’s parents had a history of atopic disease, including asthma, eczema, hay fever, or food allergy. Even so, all of the infants had negative (less than 2 mm) skin prick tests (SPTs) at baseline. Compliance by parent diary was 89% in the rice and 81% in the egg groups.

At 12 months, SPTs were positive (3 mm or more) for whole egg in 25 of 122 (20%) children in the rice group, but only 13 of 122 (11%) in the egg group (odds ratio, 0.46; 95% confidence interval, 0.22-0.95; P = .03). Whole egg IgG4 and IgG4/IgE ratios to egg, ovalbumin, and ovomucoid were also higher in the egg group, indicating developing tolerance (P less than .0001 for each).

About 10% of the children originally in the egg group broke out in hives after their first few doses, and were withdrawn from the study. “This intervention may not be for everybody. There will be individuals who react” and it’s impossible, at this point, to predict who they will be. “We cannot prevent allergy in everyone,” said lead investigator Dr. John Tan, a pediatric immunologist at the hospital.

Overall, however, early introduction was safe. There was no anaphylaxis in the trial, and no cardiovascular or respiratory complications. Rates of eczema and peanut allergy were similar at 12 months between the two groups, meaning that early egg introduction did not increase the risk of atopy.

The findings echo results from several recent pediatric egg allergy studies, as well as findings from recent peanut trials. Slowly, it’s becoming clear that delaying the introduction of at least some allergenic foods – a common practice for years – doesn’t prevent allergies and may, in fact, promote them.

Despite those findings, there remains “a big disconnect between the [new] research and what we [still] recommend” in Australia, the United States, and elsewhere. Delaying food introductions was medical “dogma for 20 years, from highly esteemed societies,” and it corresponded with a marked increase in food allergies, but “it’s very hard to turn these things around,” Dr. Campbell said at the American Academy of Allergy, Asthma, and Immunology annual meeting.

The Australian government is reworking its infant feeding guidelines to incorporate the new evidence. “Our revised guidelines will say that there’s strong evidence for peanut and moderate evidence for egg” in favor of early introduction in children who are not sensitized by 4 or so months old, she said.

The trial was powered to detect differences in SPT, not actual egg allergies, which were diagnosed in 13 children (11%) in the rice group and eight (7%) in the egg group; the difference was not statistically significant. “Not all kids who are sensitized will be allergic,” she noted.

The study groups were well matched; there were about equal numbers of boys and girls in each, and, in both groups, about 15% of children were exposed to second hand smoke at home and almost all were breastfed.

The work was funded by the Australian government, among others. The investigators have no disclosures.

aotto@frontlinemedcom.com

LOS ANGELES – Among infants at risk for allergic disease, egg introduction at 4 months cuts the risk of egg sensitization at 12 months by about half, according a randomized, placebo-controlled, double blind trial from Australia.

“This is what we hoped to find.” Introducing egg early “is certainly safe, and it may promote tolerance,” said senior investigator Dr. Dianne Campbell, professor and chair of pediatric allergy and clinical immunology at the Children’s Hospital at Westmead, which is affiliated with the University of Sydney.

Four-month-old children were randomized to 350 mg of pasteurized raw whole egg powder or – as a control – rice powder sprinkled once daily on their weaning food until month 8, at which time parents in both groups were encouraged to add eggs to their children’s diets. At least one of each child’s parents had a history of atopic disease, including asthma, eczema, hay fever, or food allergy. Even so, all of the infants had negative (less than 2 mm) skin prick tests (SPTs) at baseline. Compliance by parent diary was 89% in the rice and 81% in the egg groups.

At 12 months, SPTs were positive (3 mm or more) for whole egg in 25 of 122 (20%) children in the rice group, but only 13 of 122 (11%) in the egg group (odds ratio, 0.46; 95% confidence interval, 0.22-0.95; P = .03). Whole egg IgG4 and IgG4/IgE ratios to egg, ovalbumin, and ovomucoid were also higher in the egg group, indicating developing tolerance (P less than .0001 for each).

About 10% of the children originally in the egg group broke out in hives after their first few doses, and were withdrawn from the study. “This intervention may not be for everybody. There will be individuals who react” and it’s impossible, at this point, to predict who they will be. “We cannot prevent allergy in everyone,” said lead investigator Dr. John Tan, a pediatric immunologist at the hospital.

Overall, however, early introduction was safe. There was no anaphylaxis in the trial, and no cardiovascular or respiratory complications. Rates of eczema and peanut allergy were similar at 12 months between the two groups, meaning that early egg introduction did not increase the risk of atopy.

The findings echo results from several recent pediatric egg allergy studies, as well as findings from recent peanut trials. Slowly, it’s becoming clear that delaying the introduction of at least some allergenic foods – a common practice for years – doesn’t prevent allergies and may, in fact, promote them.

Despite those findings, there remains “a big disconnect between the [new] research and what we [still] recommend” in Australia, the United States, and elsewhere. Delaying food introductions was medical “dogma for 20 years, from highly esteemed societies,” and it corresponded with a marked increase in food allergies, but “it’s very hard to turn these things around,” Dr. Campbell said at the American Academy of Allergy, Asthma, and Immunology annual meeting.

The Australian government is reworking its infant feeding guidelines to incorporate the new evidence. “Our revised guidelines will say that there’s strong evidence for peanut and moderate evidence for egg” in favor of early introduction in children who are not sensitized by 4 or so months old, she said.

The trial was powered to detect differences in SPT, not actual egg allergies, which were diagnosed in 13 children (11%) in the rice group and eight (7%) in the egg group; the difference was not statistically significant. “Not all kids who are sensitized will be allergic,” she noted.

The study groups were well matched; there were about equal numbers of boys and girls in each, and, in both groups, about 15% of children were exposed to second hand smoke at home and almost all were breastfed.

The work was funded by the Australian government, among others. The investigators have no disclosures.

aotto@frontlinemedcom.com

LOS ANGELES – Among infants at risk for allergic disease, egg introduction at 4 months cuts the risk of egg sensitization at 12 months by about half, according a randomized, placebo-controlled, double blind trial from Australia.

“This is what we hoped to find.” Introducing egg early “is certainly safe, and it may promote tolerance,” said senior investigator Dr. Dianne Campbell, professor and chair of pediatric allergy and clinical immunology at the Children’s Hospital at Westmead, which is affiliated with the University of Sydney.

Four-month-old children were randomized to 350 mg of pasteurized raw whole egg powder or – as a control – rice powder sprinkled once daily on their weaning food until month 8, at which time parents in both groups were encouraged to add eggs to their children’s diets. At least one of each child’s parents had a history of atopic disease, including asthma, eczema, hay fever, or food allergy. Even so, all of the infants had negative (less than 2 mm) skin prick tests (SPTs) at baseline. Compliance by parent diary was 89% in the rice and 81% in the egg groups.

At 12 months, SPTs were positive (3 mm or more) for whole egg in 25 of 122 (20%) children in the rice group, but only 13 of 122 (11%) in the egg group (odds ratio, 0.46; 95% confidence interval, 0.22-0.95; P = .03). Whole egg IgG4 and IgG4/IgE ratios to egg, ovalbumin, and ovomucoid were also higher in the egg group, indicating developing tolerance (P less than .0001 for each).

About 10% of the children originally in the egg group broke out in hives after their first few doses, and were withdrawn from the study. “This intervention may not be for everybody. There will be individuals who react” and it’s impossible, at this point, to predict who they will be. “We cannot prevent allergy in everyone,” said lead investigator Dr. John Tan, a pediatric immunologist at the hospital.

Overall, however, early introduction was safe. There was no anaphylaxis in the trial, and no cardiovascular or respiratory complications. Rates of eczema and peanut allergy were similar at 12 months between the two groups, meaning that early egg introduction did not increase the risk of atopy.

The findings echo results from several recent pediatric egg allergy studies, as well as findings from recent peanut trials. Slowly, it’s becoming clear that delaying the introduction of at least some allergenic foods – a common practice for years – doesn’t prevent allergies and may, in fact, promote them.

Despite those findings, there remains “a big disconnect between the [new] research and what we [still] recommend” in Australia, the United States, and elsewhere. Delaying food introductions was medical “dogma for 20 years, from highly esteemed societies,” and it corresponded with a marked increase in food allergies, but “it’s very hard to turn these things around,” Dr. Campbell said at the American Academy of Allergy, Asthma, and Immunology annual meeting.

The Australian government is reworking its infant feeding guidelines to incorporate the new evidence. “Our revised guidelines will say that there’s strong evidence for peanut and moderate evidence for egg” in favor of early introduction in children who are not sensitized by 4 or so months old, she said.

The trial was powered to detect differences in SPT, not actual egg allergies, which were diagnosed in 13 children (11%) in the rice group and eight (7%) in the egg group; the difference was not statistically significant. “Not all kids who are sensitized will be allergic,” she noted.

The study groups were well matched; there were about equal numbers of boys and girls in each, and, in both groups, about 15% of children were exposed to second hand smoke at home and almost all were breastfed.

The work was funded by the Australian government, among others. The investigators have no disclosures.

aotto@frontlinemedcom.com