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.

The US Food and Drug Administration (FDA) has proposed 2 new rules to protect consumers from health risks associated with indoor tanning by banning use of indoor tanning devices by minors and imposing safety measures.

The first proposed rule restricts the use of indoor tanning devices to adults 18 years and older. It also requires indoor tanning facilities to inform adult users about the health risks of indoor tanning and obtain a signed risk acknowledgement from consumers before their first tanning session and every 6 months thereafter.

“Exposure to UV radiation from indoor tanning is a preventable cause of skin cancer,” explained Markham C. Luke, MD, PhD, deputy office director for the Office of Device Evaluation at the FDA’s Center for Devices and Radiological Health. “The FDA is committed to protecting public health by informing consumers of the risks of indoor tanning.”

The second proposed rule addresses performance standards, requiring manufacturers and indoor tanning facilities to take measures to improve the overall safety of tanning devices. Key changes would include:

• Make consumer warnings more prominent and easier to read on tanning devices.

• Require an easily accessible emergency shutoff switch (or panic button) on all tanning devices.

• Add requirements to limit the amount of light allowed through protective eyewear to protect the eyes.

• Improve labeling on replacement bulbs to ensure tanning facility operators use the proper bulbs to reduce risk for accidental burns.

• Prohibit tanning facilities from making dangerous device modifications (eg, installing stronger bulbs) without recertifying and reidentifying the device with the FDA.

The FDA reports that more than 1 million minors use indoor tanning facilities each year. According to the American Academy of Dermatology, consumers younger than 35 years who use indoor tanning facilities are 59% more likely to develop melanoma than those who have never tanned indoors. Because the effects of UV exposure are cumulative and add up over the course of one’s lifetime, minors who use indoor tanning devices are at an increased risk for developing melanoma and nonmelanoma skin cancers later in life.

In 2014 the FDA began requiring tanning devices to be labeled with a visible warning stating that individuals younger than 18 years should not use them. Additionally, several states have already passed laws prohibiting minors from indoor tanning; in Connecticut, New Jersey, New York, and Pennsylvania, tanning devices are banned in individuals younger than 17 years.

Dermatologists are in the position to discuss the health risks of indoor tanning with all patients regardless of age. Patients should be reminded that failure to wear appropriate protective eyewear can lead to short-term and long-term eye injury and that long exposures can lead to burning that may not be recognized until it is too late. It also is important to warn patients that tanning while using certain medications or cosmetics may cause increased sensitivity to UV radiation. Patients can be referred to the FDA website for more consumer updates about indoor tanning and the proposed rules.

The US Food and Drug Administration (FDA) has proposed 2 new rules to protect consumers from health risks associated with indoor tanning by banning use of indoor tanning devices by minors and imposing safety measures.

The first proposed rule restricts the use of indoor tanning devices to adults 18 years and older. It also requires indoor tanning facilities to inform adult users about the health risks of indoor tanning and obtain a signed risk acknowledgement from consumers before their first tanning session and every 6 months thereafter.

“Exposure to UV radiation from indoor tanning is a preventable cause of skin cancer,” explained Markham C. Luke, MD, PhD, deputy office director for the Office of Device Evaluation at the FDA’s Center for Devices and Radiological Health. “The FDA is committed to protecting public health by informing consumers of the risks of indoor tanning.”

The second proposed rule addresses performance standards, requiring manufacturers and indoor tanning facilities to take measures to improve the overall safety of tanning devices. Key changes would include:

• Make consumer warnings more prominent and easier to read on tanning devices.

• Require an easily accessible emergency shutoff switch (or panic button) on all tanning devices.

• Add requirements to limit the amount of light allowed through protective eyewear to protect the eyes.

• Improve labeling on replacement bulbs to ensure tanning facility operators use the proper bulbs to reduce risk for accidental burns.

• Prohibit tanning facilities from making dangerous device modifications (eg, installing stronger bulbs) without recertifying and reidentifying the device with the FDA.

The FDA reports that more than 1 million minors use indoor tanning facilities each year. According to the American Academy of Dermatology, consumers younger than 35 years who use indoor tanning facilities are 59% more likely to develop melanoma than those who have never tanned indoors. Because the effects of UV exposure are cumulative and add up over the course of one’s lifetime, minors who use indoor tanning devices are at an increased risk for developing melanoma and nonmelanoma skin cancers later in life.

In 2014 the FDA began requiring tanning devices to be labeled with a visible warning stating that individuals younger than 18 years should not use them. Additionally, several states have already passed laws prohibiting minors from indoor tanning; in Connecticut, New Jersey, New York, and Pennsylvania, tanning devices are banned in individuals younger than 17 years.

Dermatologists are in the position to discuss the health risks of indoor tanning with all patients regardless of age. Patients should be reminded that failure to wear appropriate protective eyewear can lead to short-term and long-term eye injury and that long exposures can lead to burning that may not be recognized until it is too late. It also is important to warn patients that tanning while using certain medications or cosmetics may cause increased sensitivity to UV radiation. Patients can be referred to the FDA website for more consumer updates about indoor tanning and the proposed rules.

The US Food and Drug Administration (FDA) has proposed 2 new rules to protect consumers from health risks associated with indoor tanning by banning use of indoor tanning devices by minors and imposing safety measures.

The first proposed rule restricts the use of indoor tanning devices to adults 18 years and older. It also requires indoor tanning facilities to inform adult users about the health risks of indoor tanning and obtain a signed risk acknowledgement from consumers before their first tanning session and every 6 months thereafter.

“Exposure to UV radiation from indoor tanning is a preventable cause of skin cancer,” explained Markham C. Luke, MD, PhD, deputy office director for the Office of Device Evaluation at the FDA’s Center for Devices and Radiological Health. “The FDA is committed to protecting public health by informing consumers of the risks of indoor tanning.”

The second proposed rule addresses performance standards, requiring manufacturers and indoor tanning facilities to take measures to improve the overall safety of tanning devices. Key changes would include:

• Make consumer warnings more prominent and easier to read on tanning devices.

• Require an easily accessible emergency shutoff switch (or panic button) on all tanning devices.

• Add requirements to limit the amount of light allowed through protective eyewear to protect the eyes.

• Improve labeling on replacement bulbs to ensure tanning facility operators use the proper bulbs to reduce risk for accidental burns.

• Prohibit tanning facilities from making dangerous device modifications (eg, installing stronger bulbs) without recertifying and reidentifying the device with the FDA.

The FDA reports that more than 1 million minors use indoor tanning facilities each year. According to the American Academy of Dermatology, consumers younger than 35 years who use indoor tanning facilities are 59% more likely to develop melanoma than those who have never tanned indoors. Because the effects of UV exposure are cumulative and add up over the course of one’s lifetime, minors who use indoor tanning devices are at an increased risk for developing melanoma and nonmelanoma skin cancers later in life.

In 2014 the FDA began requiring tanning devices to be labeled with a visible warning stating that individuals younger than 18 years should not use them. Additionally, several states have already passed laws prohibiting minors from indoor tanning; in Connecticut, New Jersey, New York, and Pennsylvania, tanning devices are banned in individuals younger than 17 years.

Dermatologists are in the position to discuss the health risks of indoor tanning with all patients regardless of age. Patients should be reminded that failure to wear appropriate protective eyewear can lead to short-term and long-term eye injury and that long exposures can lead to burning that may not be recognized until it is too late. It also is important to warn patients that tanning while using certain medications or cosmetics may cause increased sensitivity to UV radiation. Patients can be referred to the FDA website for more consumer updates about indoor tanning and the proposed rules.

I drive a 10-year-old pickup truck. The air conditioner no longer works – not a real problem here in Maine. It has hand-operated roll down windows ... a real plus should I back too far down the boat ramp and find myself in the cold waters of the Atlantic. If I ever decide to lock it, I will need to use a real key. But the pile of mismatched work gloves and rusty garden tools stashed behind the front seat hasn’t seemed to attract any burglars. Its dented body sits on a new frame, thanks to a generous recall from the manufacturer.

It’s a four-wheel drive, handy in the winter. But what I really like about it is that my old truck has a standard manual transmission. I still have that boyish enthusiasm for shifting gears. I can imagine myself driving a low-slung sports car or operating some gargantuan piece of heavy machinery.

Driving a stick shift vehicle demands a level of engagement and concentration several levels above that of simply aiming a car equipped with an automatic transmission. While I am sure some have tried, shifting gears is a serious deterrent to texting at the wheel.

The fact that our three children learned to drive on a standard shift station wagon is a tribute to their parents’ ability to tolerate repeated whiplash injuries. But it also may be one of the reasons that they survived those deadly middle teenage years. Nichole Morris, a researcher at the Human FIRST Laboratory of the University of Minnesota has said, “If you are going to have an early, untimely death, the most dangerous 2 years of your life are between 16 and 17, and the reason for that is driving” (“Teenage Drivers? Be Very Afraid,” by Bruce Feiler, New York Times, March 19, 2016). Six teenagers a day die from motor vehicle accident–related injuries, according to the Centers for Disease Control and Prevention. There are more deaths from motor vehicle accidents in this age group than from suicides, cancer, and other accidents.

©Thinkstock.com

An unfortunate combination of perceived invincibility and inexperience in an environment richly decorated with distractions makes those first years behind the wheel so dangerous. Charlie Klauer, a researcher at Virginia Tech’s Transportation Institute, believes that one in four teenagers will be involved in a motor vehicle crash in his or her first 6 months of driving. My personal experience supports her observation. Luckily, my daughter’s first accident was a low speed rear-ender into a giant pickup truck that sustained no obvious damage.

Given these frightening statistics, it is surprising that any parents would ever allow their teenage children to start on the path toward a driver’s license. As physicians committed to the health and safety of children, why haven’t pediatricians done more to prevent this tragic loss of life? The honest answer is simply that the motor vehicle is too tightly woven into our culture. We have tried, but we could probably do more.

Technological advances such as self-braking cars that are spinning off from the development of autonomous vehicles may save a few teenage drivers. But, watching your 17-year-old child take the wheel for the first time will continue to be an anxiety-provoking experience for the foreseeable future. We can help by reminding parents that the driving is a privilege that can easily be revoked. We must continue to urge parents to create and enforce rules about the use of cell phones behind the wheel. Many states have enacted laws that restrict teenage drivers from driving with other teens in the car, a well-known and often fatal distraction. But parents must be reminded that they are the first line of enforcement.

Enduring those neck-snapping sessions that are unavoidable when your child is learning to drive a standard shift vehicle was a sacrifice my wife and I made gladly. Manual transmissions aren’t coming back. But there are still plenty of sacrifices for today’s parents to make if they want their children to survive those deadly midteen years.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics including “How to Say No to Your Toddler.”

I drive a 10-year-old pickup truck. The air conditioner no longer works – not a real problem here in Maine. It has hand-operated roll down windows ... a real plus should I back too far down the boat ramp and find myself in the cold waters of the Atlantic. If I ever decide to lock it, I will need to use a real key. But the pile of mismatched work gloves and rusty garden tools stashed behind the front seat hasn’t seemed to attract any burglars. Its dented body sits on a new frame, thanks to a generous recall from the manufacturer.

It’s a four-wheel drive, handy in the winter. But what I really like about it is that my old truck has a standard manual transmission. I still have that boyish enthusiasm for shifting gears. I can imagine myself driving a low-slung sports car or operating some gargantuan piece of heavy machinery.

Driving a stick shift vehicle demands a level of engagement and concentration several levels above that of simply aiming a car equipped with an automatic transmission. While I am sure some have tried, shifting gears is a serious deterrent to texting at the wheel.

The fact that our three children learned to drive on a standard shift station wagon is a tribute to their parents’ ability to tolerate repeated whiplash injuries. But it also may be one of the reasons that they survived those deadly middle teenage years. Nichole Morris, a researcher at the Human FIRST Laboratory of the University of Minnesota has said, “If you are going to have an early, untimely death, the most dangerous 2 years of your life are between 16 and 17, and the reason for that is driving” (“Teenage Drivers? Be Very Afraid,” by Bruce Feiler, New York Times, March 19, 2016). Six teenagers a day die from motor vehicle accident–related injuries, according to the Centers for Disease Control and Prevention. There are more deaths from motor vehicle accidents in this age group than from suicides, cancer, and other accidents.

©Thinkstock.com

An unfortunate combination of perceived invincibility and inexperience in an environment richly decorated with distractions makes those first years behind the wheel so dangerous. Charlie Klauer, a researcher at Virginia Tech’s Transportation Institute, believes that one in four teenagers will be involved in a motor vehicle crash in his or her first 6 months of driving. My personal experience supports her observation. Luckily, my daughter’s first accident was a low speed rear-ender into a giant pickup truck that sustained no obvious damage.

Given these frightening statistics, it is surprising that any parents would ever allow their teenage children to start on the path toward a driver’s license. As physicians committed to the health and safety of children, why haven’t pediatricians done more to prevent this tragic loss of life? The honest answer is simply that the motor vehicle is too tightly woven into our culture. We have tried, but we could probably do more.

Technological advances such as self-braking cars that are spinning off from the development of autonomous vehicles may save a few teenage drivers. But, watching your 17-year-old child take the wheel for the first time will continue to be an anxiety-provoking experience for the foreseeable future. We can help by reminding parents that the driving is a privilege that can easily be revoked. We must continue to urge parents to create and enforce rules about the use of cell phones behind the wheel. Many states have enacted laws that restrict teenage drivers from driving with other teens in the car, a well-known and often fatal distraction. But parents must be reminded that they are the first line of enforcement.

Enduring those neck-snapping sessions that are unavoidable when your child is learning to drive a standard shift vehicle was a sacrifice my wife and I made gladly. Manual transmissions aren’t coming back. But there are still plenty of sacrifices for today’s parents to make if they want their children to survive those deadly midteen years.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics including “How to Say No to Your Toddler.”

I drive a 10-year-old pickup truck. The air conditioner no longer works – not a real problem here in Maine. It has hand-operated roll down windows ... a real plus should I back too far down the boat ramp and find myself in the cold waters of the Atlantic. If I ever decide to lock it, I will need to use a real key. But the pile of mismatched work gloves and rusty garden tools stashed behind the front seat hasn’t seemed to attract any burglars. Its dented body sits on a new frame, thanks to a generous recall from the manufacturer.

It’s a four-wheel drive, handy in the winter. But what I really like about it is that my old truck has a standard manual transmission. I still have that boyish enthusiasm for shifting gears. I can imagine myself driving a low-slung sports car or operating some gargantuan piece of heavy machinery.

Driving a stick shift vehicle demands a level of engagement and concentration several levels above that of simply aiming a car equipped with an automatic transmission. While I am sure some have tried, shifting gears is a serious deterrent to texting at the wheel.

The fact that our three children learned to drive on a standard shift station wagon is a tribute to their parents’ ability to tolerate repeated whiplash injuries. But it also may be one of the reasons that they survived those deadly middle teenage years. Nichole Morris, a researcher at the Human FIRST Laboratory of the University of Minnesota has said, “If you are going to have an early, untimely death, the most dangerous 2 years of your life are between 16 and 17, and the reason for that is driving” (“Teenage Drivers? Be Very Afraid,” by Bruce Feiler, New York Times, March 19, 2016). Six teenagers a day die from motor vehicle accident–related injuries, according to the Centers for Disease Control and Prevention. There are more deaths from motor vehicle accidents in this age group than from suicides, cancer, and other accidents.

©Thinkstock.com

An unfortunate combination of perceived invincibility and inexperience in an environment richly decorated with distractions makes those first years behind the wheel so dangerous. Charlie Klauer, a researcher at Virginia Tech’s Transportation Institute, believes that one in four teenagers will be involved in a motor vehicle crash in his or her first 6 months of driving. My personal experience supports her observation. Luckily, my daughter’s first accident was a low speed rear-ender into a giant pickup truck that sustained no obvious damage.

Given these frightening statistics, it is surprising that any parents would ever allow their teenage children to start on the path toward a driver’s license. As physicians committed to the health and safety of children, why haven’t pediatricians done more to prevent this tragic loss of life? The honest answer is simply that the motor vehicle is too tightly woven into our culture. We have tried, but we could probably do more.

Technological advances such as self-braking cars that are spinning off from the development of autonomous vehicles may save a few teenage drivers. But, watching your 17-year-old child take the wheel for the first time will continue to be an anxiety-provoking experience for the foreseeable future. We can help by reminding parents that the driving is a privilege that can easily be revoked. We must continue to urge parents to create and enforce rules about the use of cell phones behind the wheel. Many states have enacted laws that restrict teenage drivers from driving with other teens in the car, a well-known and often fatal distraction. But parents must be reminded that they are the first line of enforcement.

Enduring those neck-snapping sessions that are unavoidable when your child is learning to drive a standard shift vehicle was a sacrifice my wife and I made gladly. Manual transmissions aren’t coming back. But there are still plenty of sacrifices for today’s parents to make if they want their children to survive those deadly midteen years.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics including “How to Say No to Your Toddler.”

Hollywood, FLA. – Although patients and physicians should always be partners in medical decision making, guiding patients into making medically sound choices may involve a lot of listening and empathy, often followed by a little friendly persuasion, suggests an expert in health care decision making,

“Even when you get to a situation where the clinical practice guideline would point toward shared decision making, we’ve got to do shared decision making right or the guideline just doesn’t do the work for us. We clinicians have to know how to partner with our patients to make decisions when their values matter,” said Dr. Peter A Ubel, professor of business, public policy, and medicine at Duke University, Durham, N.H.

Dr. Ubel discussed how to understand and use patient preferences in cancer treatment decisions at the annual conference of the National Comprehensive Cancer Network.

In the case of early-stage prostate cancer, for example, treatment options include surveillance or active treatment with surgery or radiation, but the risk/benefit trade-offs require careful discussion.

“The different approaches have different pros and cons: If you get active treatment, there’s a pretty good chance you’ll experience incontinence or erectile dysfunction, whereas if you undergo surveillance you won’t experience those as side effects of the surveillance strategy, but you will live with a cancer inside your body, the accompanying anxiety, and wondering every 6 months whether it has advanced,” Dr. Ubel said.

“The question is how do we go figure out which treatment is best for which patient?” he added.

What doctors say not always what patients hear

To examine how decisions are made, Dr. Ubel and his colleagues conducted a study in which patients scheduled for biopsy for suspicion of prostate cancer were approached at the time of their clinic visits and asked to participate in a study about prostate cancer decision making. Patients were given a booklet aimed at the seventh-grade reading level describing prostate cancer and its treatment, and were asked, once they had finished, what course of therapy they might pursue if the diagnosis turned out to be positive, and why. They also were asked if it was important to them to maintain natural sexual function.

The encounter between the patients and their urologists at the time of diagnosis were audio recorded, so that investigators could see whether physicians recommend specific treatments and why.

“One of the things that really jumped out in this study was just how much language, how much explanation urologists use to help patients understand their diagnosis,” Dr. Ubel said.

In one encounter, the urologist explained to the patient that 3 out of 12 biopsy cores had less than 30% cancer involvement, suggesting moderately low-risk disease, but then went on to talk about Gleason scores, tumor grades and patterns, and risk categories.

“When a patient just finds out he has prostate cancer, it’s a tough time to put a whole bunch of information in front of him for him to absorb and make a decision,” Dr. Ubel said. Patients need time to absorb the shock of a cancer diagnosis first – even a diagnosis of an early, easily treated cancer – and information overload may actually reduce their ability to comprehend their choices or retain the information, he added. The urologist in this scenario is making a very earnest effort to tell the patient that he doesn’t have the kind of cancer that’s ever going to kill him, or that it is highly unlikely to cause any problems for the next 10-15 years, and there is ample time to decide how to treat it.

“But the doctor kind of forgets that the patient doesn’t speak medicalese, and the doctor feels like you really have to give them thorough informed consent, after all. So you need to inform the heck out of patients with all of the medical detail you believe is necessary to understand the decision, instead of the translation of the medical detail into terms the patient can understand,” he said.

An important part of shared decision making, therefore, is to make sure that patients can understand their alternatives, but not to overwhelm them with detail, because they may give up and ask the physician, “What do you think I should do?” which can introduce physician bias that may not always lead to the right choice for that patient.

“I actually morally don’t recommend that. I think instead we should give the right amount of information at the right time so they can actually get engaged in the choice,” Dr. Ubel said.

Discussion informs choices

The investigators looked at how prediagnosis education materials and discussions with urologists shaped patient decisions about treatment choice. Patients were called before their appointments to ensure that they had read the booklet, and then just before the appointment were asked which way they were leaning if the diagnosis turned out to be positive.

The investigators found that of 44 patients who expressed a preference for active surveillance before the appointment, 55% actually went on to receive active treatment. Among 119 patients with no expressed preference for surveillance or active therapy, 46% went on to treatment, and of 118 expressing previsit preference only for active surveillance, 54% went on to receive it.

“The leaning that they had before seeing the doctor had no influence on what treatment they got,” Dr. Ubel said. Instead, physicians’ recommendations had a strong influence on treatment choice. Recommendations are an essential part of the discussion, “but I don’t think we often do them well,” he said.

Ask patients to think out loud about what they have read or have been told, and ask them to repeat in their own words what they heard the doctor say, Dr. Ubel suggested. It’s incumbent on the physician to try to understand the patient’s preferences, and say something like, “I’m the expert on medical facts, but you’re the expert on you,” or “What sounds good and bad to you about that treatment alternative?”

Finally, physicians need to make recommendations based on patient preferences, he said.

For example, in one recorded encounter, the physician asked the patient, “Are you the kind of person where the idea of just watching your PSA is that unsettling to you?” When the patient replied “Yeah, I think I would be,” the physician was able to make an informed recommendation, saying “then I don’t think you’d be a good candidate for surveillance.”

“This doctor did not just make a recommendation; he tried to find out something about the patient first, and that’s critical to giving good advice,” Dr. Ubel said.

Hollywood, FLA. – Although patients and physicians should always be partners in medical decision making, guiding patients into making medically sound choices may involve a lot of listening and empathy, often followed by a little friendly persuasion, suggests an expert in health care decision making,

“Even when you get to a situation where the clinical practice guideline would point toward shared decision making, we’ve got to do shared decision making right or the guideline just doesn’t do the work for us. We clinicians have to know how to partner with our patients to make decisions when their values matter,” said Dr. Peter A Ubel, professor of business, public policy, and medicine at Duke University, Durham, N.H.

Dr. Ubel discussed how to understand and use patient preferences in cancer treatment decisions at the annual conference of the National Comprehensive Cancer Network.

In the case of early-stage prostate cancer, for example, treatment options include surveillance or active treatment with surgery or radiation, but the risk/benefit trade-offs require careful discussion.

“The different approaches have different pros and cons: If you get active treatment, there’s a pretty good chance you’ll experience incontinence or erectile dysfunction, whereas if you undergo surveillance you won’t experience those as side effects of the surveillance strategy, but you will live with a cancer inside your body, the accompanying anxiety, and wondering every 6 months whether it has advanced,” Dr. Ubel said.

“The question is how do we go figure out which treatment is best for which patient?” he added.

What doctors say not always what patients hear

To examine how decisions are made, Dr. Ubel and his colleagues conducted a study in which patients scheduled for biopsy for suspicion of prostate cancer were approached at the time of their clinic visits and asked to participate in a study about prostate cancer decision making. Patients were given a booklet aimed at the seventh-grade reading level describing prostate cancer and its treatment, and were asked, once they had finished, what course of therapy they might pursue if the diagnosis turned out to be positive, and why. They also were asked if it was important to them to maintain natural sexual function.

The encounter between the patients and their urologists at the time of diagnosis were audio recorded, so that investigators could see whether physicians recommend specific treatments and why.

“One of the things that really jumped out in this study was just how much language, how much explanation urologists use to help patients understand their diagnosis,” Dr. Ubel said.

In one encounter, the urologist explained to the patient that 3 out of 12 biopsy cores had less than 30% cancer involvement, suggesting moderately low-risk disease, but then went on to talk about Gleason scores, tumor grades and patterns, and risk categories.

“When a patient just finds out he has prostate cancer, it’s a tough time to put a whole bunch of information in front of him for him to absorb and make a decision,” Dr. Ubel said. Patients need time to absorb the shock of a cancer diagnosis first – even a diagnosis of an early, easily treated cancer – and information overload may actually reduce their ability to comprehend their choices or retain the information, he added. The urologist in this scenario is making a very earnest effort to tell the patient that he doesn’t have the kind of cancer that’s ever going to kill him, or that it is highly unlikely to cause any problems for the next 10-15 years, and there is ample time to decide how to treat it.

“But the doctor kind of forgets that the patient doesn’t speak medicalese, and the doctor feels like you really have to give them thorough informed consent, after all. So you need to inform the heck out of patients with all of the medical detail you believe is necessary to understand the decision, instead of the translation of the medical detail into terms the patient can understand,” he said.

An important part of shared decision making, therefore, is to make sure that patients can understand their alternatives, but not to overwhelm them with detail, because they may give up and ask the physician, “What do you think I should do?” which can introduce physician bias that may not always lead to the right choice for that patient.

“I actually morally don’t recommend that. I think instead we should give the right amount of information at the right time so they can actually get engaged in the choice,” Dr. Ubel said.

Discussion informs choices

The investigators looked at how prediagnosis education materials and discussions with urologists shaped patient decisions about treatment choice. Patients were called before their appointments to ensure that they had read the booklet, and then just before the appointment were asked which way they were leaning if the diagnosis turned out to be positive.

The investigators found that of 44 patients who expressed a preference for active surveillance before the appointment, 55% actually went on to receive active treatment. Among 119 patients with no expressed preference for surveillance or active therapy, 46% went on to treatment, and of 118 expressing previsit preference only for active surveillance, 54% went on to receive it.

“The leaning that they had before seeing the doctor had no influence on what treatment they got,” Dr. Ubel said. Instead, physicians’ recommendations had a strong influence on treatment choice. Recommendations are an essential part of the discussion, “but I don’t think we often do them well,” he said.

Ask patients to think out loud about what they have read or have been told, and ask them to repeat in their own words what they heard the doctor say, Dr. Ubel suggested. It’s incumbent on the physician to try to understand the patient’s preferences, and say something like, “I’m the expert on medical facts, but you’re the expert on you,” or “What sounds good and bad to you about that treatment alternative?”

Finally, physicians need to make recommendations based on patient preferences, he said.

For example, in one recorded encounter, the physician asked the patient, “Are you the kind of person where the idea of just watching your PSA is that unsettling to you?” When the patient replied “Yeah, I think I would be,” the physician was able to make an informed recommendation, saying “then I don’t think you’d be a good candidate for surveillance.”

“This doctor did not just make a recommendation; he tried to find out something about the patient first, and that’s critical to giving good advice,” Dr. Ubel said.

Hollywood, FLA. – Although patients and physicians should always be partners in medical decision making, guiding patients into making medically sound choices may involve a lot of listening and empathy, often followed by a little friendly persuasion, suggests an expert in health care decision making,

“Even when you get to a situation where the clinical practice guideline would point toward shared decision making, we’ve got to do shared decision making right or the guideline just doesn’t do the work for us. We clinicians have to know how to partner with our patients to make decisions when their values matter,” said Dr. Peter A Ubel, professor of business, public policy, and medicine at Duke University, Durham, N.H.

Dr. Ubel discussed how to understand and use patient preferences in cancer treatment decisions at the annual conference of the National Comprehensive Cancer Network.

In the case of early-stage prostate cancer, for example, treatment options include surveillance or active treatment with surgery or radiation, but the risk/benefit trade-offs require careful discussion.

“The different approaches have different pros and cons: If you get active treatment, there’s a pretty good chance you’ll experience incontinence or erectile dysfunction, whereas if you undergo surveillance you won’t experience those as side effects of the surveillance strategy, but you will live with a cancer inside your body, the accompanying anxiety, and wondering every 6 months whether it has advanced,” Dr. Ubel said.

“The question is how do we go figure out which treatment is best for which patient?” he added.

What doctors say not always what patients hear

To examine how decisions are made, Dr. Ubel and his colleagues conducted a study in which patients scheduled for biopsy for suspicion of prostate cancer were approached at the time of their clinic visits and asked to participate in a study about prostate cancer decision making. Patients were given a booklet aimed at the seventh-grade reading level describing prostate cancer and its treatment, and were asked, once they had finished, what course of therapy they might pursue if the diagnosis turned out to be positive, and why. They also were asked if it was important to them to maintain natural sexual function.

The encounter between the patients and their urologists at the time of diagnosis were audio recorded, so that investigators could see whether physicians recommend specific treatments and why.

“One of the things that really jumped out in this study was just how much language, how much explanation urologists use to help patients understand their diagnosis,” Dr. Ubel said.

In one encounter, the urologist explained to the patient that 3 out of 12 biopsy cores had less than 30% cancer involvement, suggesting moderately low-risk disease, but then went on to talk about Gleason scores, tumor grades and patterns, and risk categories.

“When a patient just finds out he has prostate cancer, it’s a tough time to put a whole bunch of information in front of him for him to absorb and make a decision,” Dr. Ubel said. Patients need time to absorb the shock of a cancer diagnosis first – even a diagnosis of an early, easily treated cancer – and information overload may actually reduce their ability to comprehend their choices or retain the information, he added. The urologist in this scenario is making a very earnest effort to tell the patient that he doesn’t have the kind of cancer that’s ever going to kill him, or that it is highly unlikely to cause any problems for the next 10-15 years, and there is ample time to decide how to treat it.

“But the doctor kind of forgets that the patient doesn’t speak medicalese, and the doctor feels like you really have to give them thorough informed consent, after all. So you need to inform the heck out of patients with all of the medical detail you believe is necessary to understand the decision, instead of the translation of the medical detail into terms the patient can understand,” he said.

An important part of shared decision making, therefore, is to make sure that patients can understand their alternatives, but not to overwhelm them with detail, because they may give up and ask the physician, “What do you think I should do?” which can introduce physician bias that may not always lead to the right choice for that patient.

“I actually morally don’t recommend that. I think instead we should give the right amount of information at the right time so they can actually get engaged in the choice,” Dr. Ubel said.

Discussion informs choices

The investigators looked at how prediagnosis education materials and discussions with urologists shaped patient decisions about treatment choice. Patients were called before their appointments to ensure that they had read the booklet, and then just before the appointment were asked which way they were leaning if the diagnosis turned out to be positive.

The investigators found that of 44 patients who expressed a preference for active surveillance before the appointment, 55% actually went on to receive active treatment. Among 119 patients with no expressed preference for surveillance or active therapy, 46% went on to treatment, and of 118 expressing previsit preference only for active surveillance, 54% went on to receive it.

“The leaning that they had before seeing the doctor had no influence on what treatment they got,” Dr. Ubel said. Instead, physicians’ recommendations had a strong influence on treatment choice. Recommendations are an essential part of the discussion, “but I don’t think we often do them well,” he said.

Ask patients to think out loud about what they have read or have been told, and ask them to repeat in their own words what they heard the doctor say, Dr. Ubel suggested. It’s incumbent on the physician to try to understand the patient’s preferences, and say something like, “I’m the expert on medical facts, but you’re the expert on you,” or “What sounds good and bad to you about that treatment alternative?”

Finally, physicians need to make recommendations based on patient preferences, he said.

For example, in one recorded encounter, the physician asked the patient, “Are you the kind of person where the idea of just watching your PSA is that unsettling to you?” When the patient replied “Yeah, I think I would be,” the physician was able to make an informed recommendation, saying “then I don’t think you’d be a good candidate for surveillance.”

“This doctor did not just make a recommendation; he tried to find out something about the patient first, and that’s critical to giving good advice,” Dr. Ubel said.

The Diagnosis: Superficial Acral Fibromyxoma

Superficial acral fibromyxoma (SAF) was first described in 2001 by Fetsch et al.¹ Subsequently, the term digital fibromyxoma was proposed in 2012 by Hollmann et al² to describe a distinctive, slow-growing, soft-tissue tumor with a predilection for the periungual or subungual regions of the fingers and toes. The benign growth typically presents as a painless or tender nodule in middle-aged adults with a slight male predominance (1.3:1 ratio).^1,2 In a case series (N=124) described by Hollmann et al,² 9 of 25 patients (36%) who had imaging studies showed bone involvement by an erosive or lytic lesion. Reports of SAF with bone involvement also have been described in the radiologic and orthopedic surgery literature.^3,4 Radiographically, the soft-tissue invasion of the bone is demonstrated by scalloping on plain radiographs (Figure 1).³

Histologically, SAFs are moderately cellular with spindled or stellate fibroblastlike cells within a myxoid or collagenous matrix (Figure 2).¹ The vasculature is mildly accentuated and an increase in mast cells usually is observed. The nuclei have a low degree of atypia with few mitotic figures, and the stellate cells exhibit positive immunohistochemical staining for CD34 (Figure 3), epithelial membrane antigen, and CD99.¹ Hollmann et al² found that 66 of 95 tumors (69.5%) infiltrated the dermal collagen, 26 (27.4%) infiltrated fat, and 3 (3.2%) invaded bone. Of the 47 cases that were evaluated on follow-up, 10 tumors (21.3%) recurred locally (all near the nail unit of the fingers or toes) after a mean interval of 27 months. Although invasion of underlying tissues and recurrence of the tumor has been demonstrated, this growth is considered benign. The histologic differential diagnosis includes neurofibroma, myxoma, fibroma, low-grade fibromyxoid sarcoma, dermatofibroma, superficial angiomyxoma, and dermatofibrosarcoma protuberans.²

The primary treatment of SAF is local excision. The incidence of local recurrence found in the case series by Hollmann et al² was directly linked to positive margins after the first excision (10/47 [21.3%] recurrent lesions had positive margins). To date, there are no known reports of metastatic disease in SAF.² Our case manifested with a late recurrence of the tumor and bone involvement requiring surgical excision, which illustrates the role of adjuvant imaging and close follow-up following excision of any soft-tissue tumors of the fingers and toes that have been histologically confirmed as SAF, particularly those of the periungual region.

The Diagnosis: Superficial Acral Fibromyxoma

Superficial acral fibromyxoma (SAF) was first described in 2001 by Fetsch et al.¹ Subsequently, the term digital fibromyxoma was proposed in 2012 by Hollmann et al² to describe a distinctive, slow-growing, soft-tissue tumor with a predilection for the periungual or subungual regions of the fingers and toes. The benign growth typically presents as a painless or tender nodule in middle-aged adults with a slight male predominance (1.3:1 ratio).^1,2 In a case series (N=124) described by Hollmann et al,² 9 of 25 patients (36%) who had imaging studies showed bone involvement by an erosive or lytic lesion. Reports of SAF with bone involvement also have been described in the radiologic and orthopedic surgery literature.^3,4 Radiographically, the soft-tissue invasion of the bone is demonstrated by scalloping on plain radiographs (Figure 1).³

Histologically, SAFs are moderately cellular with spindled or stellate fibroblastlike cells within a myxoid or collagenous matrix (Figure 2).¹ The vasculature is mildly accentuated and an increase in mast cells usually is observed. The nuclei have a low degree of atypia with few mitotic figures, and the stellate cells exhibit positive immunohistochemical staining for CD34 (Figure 3), epithelial membrane antigen, and CD99.¹ Hollmann et al² found that 66 of 95 tumors (69.5%) infiltrated the dermal collagen, 26 (27.4%) infiltrated fat, and 3 (3.2%) invaded bone. Of the 47 cases that were evaluated on follow-up, 10 tumors (21.3%) recurred locally (all near the nail unit of the fingers or toes) after a mean interval of 27 months. Although invasion of underlying tissues and recurrence of the tumor has been demonstrated, this growth is considered benign. The histologic differential diagnosis includes neurofibroma, myxoma, fibroma, low-grade fibromyxoid sarcoma, dermatofibroma, superficial angiomyxoma, and dermatofibrosarcoma protuberans.²

The primary treatment of SAF is local excision. The incidence of local recurrence found in the case series by Hollmann et al² was directly linked to positive margins after the first excision (10/47 [21.3%] recurrent lesions had positive margins). To date, there are no known reports of metastatic disease in SAF.² Our case manifested with a late recurrence of the tumor and bone involvement requiring surgical excision, which illustrates the role of adjuvant imaging and close follow-up following excision of any soft-tissue tumors of the fingers and toes that have been histologically confirmed as SAF, particularly those of the periungual region.

The Diagnosis: Superficial Acral Fibromyxoma

Superficial acral fibromyxoma (SAF) was first described in 2001 by Fetsch et al.¹ Subsequently, the term digital fibromyxoma was proposed in 2012 by Hollmann et al² to describe a distinctive, slow-growing, soft-tissue tumor with a predilection for the periungual or subungual regions of the fingers and toes. The benign growth typically presents as a painless or tender nodule in middle-aged adults with a slight male predominance (1.3:1 ratio).^1,2 In a case series (N=124) described by Hollmann et al,² 9 of 25 patients (36%) who had imaging studies showed bone involvement by an erosive or lytic lesion. Reports of SAF with bone involvement also have been described in the radiologic and orthopedic surgery literature.^3,4 Radiographically, the soft-tissue invasion of the bone is demonstrated by scalloping on plain radiographs (Figure 1).³

Histologically, SAFs are moderately cellular with spindled or stellate fibroblastlike cells within a myxoid or collagenous matrix (Figure 2).¹ The vasculature is mildly accentuated and an increase in mast cells usually is observed. The nuclei have a low degree of atypia with few mitotic figures, and the stellate cells exhibit positive immunohistochemical staining for CD34 (Figure 3), epithelial membrane antigen, and CD99.¹ Hollmann et al² found that 66 of 95 tumors (69.5%) infiltrated the dermal collagen, 26 (27.4%) infiltrated fat, and 3 (3.2%) invaded bone. Of the 47 cases that were evaluated on follow-up, 10 tumors (21.3%) recurred locally (all near the nail unit of the fingers or toes) after a mean interval of 27 months. Although invasion of underlying tissues and recurrence of the tumor has been demonstrated, this growth is considered benign. The histologic differential diagnosis includes neurofibroma, myxoma, fibroma, low-grade fibromyxoid sarcoma, dermatofibroma, superficial angiomyxoma, and dermatofibrosarcoma protuberans.²

The primary treatment of SAF is local excision. The incidence of local recurrence found in the case series by Hollmann et al² was directly linked to positive margins after the first excision (10/47 [21.3%] recurrent lesions had positive margins). To date, there are no known reports of metastatic disease in SAF.² Our case manifested with a late recurrence of the tumor and bone involvement requiring surgical excision, which illustrates the role of adjuvant imaging and close follow-up following excision of any soft-tissue tumors of the fingers and toes that have been histologically confirmed as SAF, particularly those of the periungual region.

What do your patients need to know at the first visit?

Patients with chronic dermatitis are frequently referred for patch testing. An in-depth conversation reviewing the patch test procedure and the many potential causes of dermatitis (eg, endogenous, allergic, irritant, seborrheic) is needed. Patients should understand the patch test process. The testing extends over a week, requiring 3 days of visits. The patches are applied at day 1 and must be kept dry and in place for 48 hours, then they are removed and evaluated. A second follow-up visit at 96 hours to 1 week after the patches are applied is done to perform a final read, interpret, and explain the final results. The patient needs to know that we are looking for an allergen that might be causing the eruption through contact exposure with the skin. The difference between patch testing and prick testing often needs to be discussed, as patients are not always aware of the difference. Explaining the need to avoid topical steroids at the patch test site, sunburn, or systemic steroids during the patch test period is also important to obtain optimal testing conditions.

Querying all exposures including work, home, personal care products, and hobbies is important to help determine which allergen series should be tested to obtain the best results. Patients need to understand that even small intermittent exposures can cause an ongoing dermatitis. If a causative allergen(s) is identified, strict avoidance can lead to clearance and resolution.

Setting expectations is important, and therefore you should discuss the possibility that no allergen will be identified while letting the patient know that this information is also useful. Also, let patients know there are other things that can be done if patch testing is negative to try and gain control of the dermatitis including laboratory tests and biopsies, which may be needed to help direct future management.

What are your go-to treatments? What are the side effects?

The beauty of patch testing is that finding a relevant allergen and subsequent avoidance of that allergen often is sufficient to improve or clear the dermatitis. Detailed education regarding the allergen, where it is found, and how to avoid it are imperative in patient management. I provide the patient with information sheets or narratives found on the American Contact Dermatitis Society website (http://www.contactderm.org) as well as a list of safe products found on the Contact Allergen Management Program (CAMP) area of the site. These tools help in patient compliance.

Go-to treatments for relevant patch test dermatitis involve topical steroids to calm the acute dermatitis while educating and instituting a personal environment free of the identified allergens. Occasionally, systemic steroids are used to provide relief and calm down an extensive dermatitis while educating, identifying, and eliminating known allergens from the patient’s environment. Identifying and eliminating an allergen can mitigate the need for chronic steroids, and the resultant side effects of hypertension, osteoporosis, avascular necrosis, hyperglycemia, and gastrointestinal tract problems can be avoided. Likewise, avoidance of allergens can lead to the elimination of the need for chronic topical steroids and the resultant atrophy and striae.

Side effects of the patch test procedure itself include an allergic reaction to one of the chemicals tested (eg, gold), which is what you are looking for; persistent reactions; flaring of existing dermatitis; irritation; hyperpigmentation; and rarely anaphylaxis or infection at a patch test site. If no allergy is found, treatment of generalized dermatitis can include topical steroids. Topical calcineurin inhibitors can be useful as well as narrowband UV light. Several oral medications can be used for recalcitrant patch test–negative dermatitis and the selection of the right medication is based on the patient’s comorbidities and extent of dermatitis, including systemic steroids, though long-term use is not recommended. Mycophenolate mofetil, methotrexate, cyclosporine, and azathioprine all have side effects including liver and renal toxicity, immunosuppression, and risk for malignancy and therefore need to be considered on a case-by-case basis.

How do you keep the patient compliant with treatment?

Treating allergic contact dermatitis once an allergen(s) has been identified can be challenging. Education is key so that the patient understands where the allergen is found in his/her environment and how to avoid it. Teaching the patient to read labels also is important. Providing a list of safe products simplifies compliance. Reinforcing the need for ongoing vigilance in allergen avoidance is critical to resolution of the dermatitis. Reinforcing the need for continuous avoidance is imperative, as patients sometimes become less vigilant once the dermatitis resolves and the allergen can sneak back into their environment.

What do I do if a patient refuses treatment?

Sometimes patients are so attached to a product that they do not want to stop using it even though they know it is the cause of their dermatitis. If I can help them identify a comparable product, I introduce them to it, but ultimately they get to decide if they prefer to use a product that they know is the cause of their rash or if they want to avoid it and be clear of the dermatitis. For those who do not have an allergen identified through patch testing, alternative treatments can be used. If they do not want systemic medication, I try and optimize their skin care regimen with mild soaps, bland moisturizing creams, and short lukewarm showers, which often is not enough and eventually due to ongoing itch patients decide to discuss and pursue treatment options.

What do your patients need to know at the first visit?

Patients with chronic dermatitis are frequently referred for patch testing. An in-depth conversation reviewing the patch test procedure and the many potential causes of dermatitis (eg, endogenous, allergic, irritant, seborrheic) is needed. Patients should understand the patch test process. The testing extends over a week, requiring 3 days of visits. The patches are applied at day 1 and must be kept dry and in place for 48 hours, then they are removed and evaluated. A second follow-up visit at 96 hours to 1 week after the patches are applied is done to perform a final read, interpret, and explain the final results. The patient needs to know that we are looking for an allergen that might be causing the eruption through contact exposure with the skin. The difference between patch testing and prick testing often needs to be discussed, as patients are not always aware of the difference. Explaining the need to avoid topical steroids at the patch test site, sunburn, or systemic steroids during the patch test period is also important to obtain optimal testing conditions.

Querying all exposures including work, home, personal care products, and hobbies is important to help determine which allergen series should be tested to obtain the best results. Patients need to understand that even small intermittent exposures can cause an ongoing dermatitis. If a causative allergen(s) is identified, strict avoidance can lead to clearance and resolution.

Setting expectations is important, and therefore you should discuss the possibility that no allergen will be identified while letting the patient know that this information is also useful. Also, let patients know there are other things that can be done if patch testing is negative to try and gain control of the dermatitis including laboratory tests and biopsies, which may be needed to help direct future management.

What are your go-to treatments? What are the side effects?

The beauty of patch testing is that finding a relevant allergen and subsequent avoidance of that allergen often is sufficient to improve or clear the dermatitis. Detailed education regarding the allergen, where it is found, and how to avoid it are imperative in patient management. I provide the patient with information sheets or narratives found on the American Contact Dermatitis Society website (http://www.contactderm.org) as well as a list of safe products found on the Contact Allergen Management Program (CAMP) area of the site. These tools help in patient compliance.

Go-to treatments for relevant patch test dermatitis involve topical steroids to calm the acute dermatitis while educating and instituting a personal environment free of the identified allergens. Occasionally, systemic steroids are used to provide relief and calm down an extensive dermatitis while educating, identifying, and eliminating known allergens from the patient’s environment. Identifying and eliminating an allergen can mitigate the need for chronic steroids, and the resultant side effects of hypertension, osteoporosis, avascular necrosis, hyperglycemia, and gastrointestinal tract problems can be avoided. Likewise, avoidance of allergens can lead to the elimination of the need for chronic topical steroids and the resultant atrophy and striae.

Side effects of the patch test procedure itself include an allergic reaction to one of the chemicals tested (eg, gold), which is what you are looking for; persistent reactions; flaring of existing dermatitis; irritation; hyperpigmentation; and rarely anaphylaxis or infection at a patch test site. If no allergy is found, treatment of generalized dermatitis can include topical steroids. Topical calcineurin inhibitors can be useful as well as narrowband UV light. Several oral medications can be used for recalcitrant patch test–negative dermatitis and the selection of the right medication is based on the patient’s comorbidities and extent of dermatitis, including systemic steroids, though long-term use is not recommended. Mycophenolate mofetil, methotrexate, cyclosporine, and azathioprine all have side effects including liver and renal toxicity, immunosuppression, and risk for malignancy and therefore need to be considered on a case-by-case basis.

How do you keep the patient compliant with treatment?

Treating allergic contact dermatitis once an allergen(s) has been identified can be challenging. Education is key so that the patient understands where the allergen is found in his/her environment and how to avoid it. Teaching the patient to read labels also is important. Providing a list of safe products simplifies compliance. Reinforcing the need for ongoing vigilance in allergen avoidance is critical to resolution of the dermatitis. Reinforcing the need for continuous avoidance is imperative, as patients sometimes become less vigilant once the dermatitis resolves and the allergen can sneak back into their environment.

What do I do if a patient refuses treatment?

Sometimes patients are so attached to a product that they do not want to stop using it even though they know it is the cause of their dermatitis. If I can help them identify a comparable product, I introduce them to it, but ultimately they get to decide if they prefer to use a product that they know is the cause of their rash or if they want to avoid it and be clear of the dermatitis. For those who do not have an allergen identified through patch testing, alternative treatments can be used. If they do not want systemic medication, I try and optimize their skin care regimen with mild soaps, bland moisturizing creams, and short lukewarm showers, which often is not enough and eventually due to ongoing itch patients decide to discuss and pursue treatment options.

What do your patients need to know at the first visit?

Patients with chronic dermatitis are frequently referred for patch testing. An in-depth conversation reviewing the patch test procedure and the many potential causes of dermatitis (eg, endogenous, allergic, irritant, seborrheic) is needed. Patients should understand the patch test process. The testing extends over a week, requiring 3 days of visits. The patches are applied at day 1 and must be kept dry and in place for 48 hours, then they are removed and evaluated. A second follow-up visit at 96 hours to 1 week after the patches are applied is done to perform a final read, interpret, and explain the final results. The patient needs to know that we are looking for an allergen that might be causing the eruption through contact exposure with the skin. The difference between patch testing and prick testing often needs to be discussed, as patients are not always aware of the difference. Explaining the need to avoid topical steroids at the patch test site, sunburn, or systemic steroids during the patch test period is also important to obtain optimal testing conditions.

Querying all exposures including work, home, personal care products, and hobbies is important to help determine which allergen series should be tested to obtain the best results. Patients need to understand that even small intermittent exposures can cause an ongoing dermatitis. If a causative allergen(s) is identified, strict avoidance can lead to clearance and resolution.

Setting expectations is important, and therefore you should discuss the possibility that no allergen will be identified while letting the patient know that this information is also useful. Also, let patients know there are other things that can be done if patch testing is negative to try and gain control of the dermatitis including laboratory tests and biopsies, which may be needed to help direct future management.

What are your go-to treatments? What are the side effects?

The beauty of patch testing is that finding a relevant allergen and subsequent avoidance of that allergen often is sufficient to improve or clear the dermatitis. Detailed education regarding the allergen, where it is found, and how to avoid it are imperative in patient management. I provide the patient with information sheets or narratives found on the American Contact Dermatitis Society website (http://www.contactderm.org) as well as a list of safe products found on the Contact Allergen Management Program (CAMP) area of the site. These tools help in patient compliance.

Go-to treatments for relevant patch test dermatitis involve topical steroids to calm the acute dermatitis while educating and instituting a personal environment free of the identified allergens. Occasionally, systemic steroids are used to provide relief and calm down an extensive dermatitis while educating, identifying, and eliminating known allergens from the patient’s environment. Identifying and eliminating an allergen can mitigate the need for chronic steroids, and the resultant side effects of hypertension, osteoporosis, avascular necrosis, hyperglycemia, and gastrointestinal tract problems can be avoided. Likewise, avoidance of allergens can lead to the elimination of the need for chronic topical steroids and the resultant atrophy and striae.

Side effects of the patch test procedure itself include an allergic reaction to one of the chemicals tested (eg, gold), which is what you are looking for; persistent reactions; flaring of existing dermatitis; irritation; hyperpigmentation; and rarely anaphylaxis or infection at a patch test site. If no allergy is found, treatment of generalized dermatitis can include topical steroids. Topical calcineurin inhibitors can be useful as well as narrowband UV light. Several oral medications can be used for recalcitrant patch test–negative dermatitis and the selection of the right medication is based on the patient’s comorbidities and extent of dermatitis, including systemic steroids, though long-term use is not recommended. Mycophenolate mofetil, methotrexate, cyclosporine, and azathioprine all have side effects including liver and renal toxicity, immunosuppression, and risk for malignancy and therefore need to be considered on a case-by-case basis.

How do you keep the patient compliant with treatment?

Treating allergic contact dermatitis once an allergen(s) has been identified can be challenging. Education is key so that the patient understands where the allergen is found in his/her environment and how to avoid it. Teaching the patient to read labels also is important. Providing a list of safe products simplifies compliance. Reinforcing the need for ongoing vigilance in allergen avoidance is critical to resolution of the dermatitis. Reinforcing the need for continuous avoidance is imperative, as patients sometimes become less vigilant once the dermatitis resolves and the allergen can sneak back into their environment.

What do I do if a patient refuses treatment?

Sometimes patients are so attached to a product that they do not want to stop using it even though they know it is the cause of their dermatitis. If I can help them identify a comparable product, I introduce them to it, but ultimately they get to decide if they prefer to use a product that they know is the cause of their rash or if they want to avoid it and be clear of the dermatitis. For those who do not have an allergen identified through patch testing, alternative treatments can be used. If they do not want systemic medication, I try and optimize their skin care regimen with mild soaps, bland moisturizing creams, and short lukewarm showers, which often is not enough and eventually due to ongoing itch patients decide to discuss and pursue treatment options.

Patients with inflammatory bowel disease (IBD) may have a higher risk of oral cancer, according to a study at Mount Sinai Medical Center. Researchers collected data on 7,294 patients from 2000 through 2011. The results were published in the March issue of Clinical Gastroenterology and Hepatology.

Related: Exercise and Inflammatory Bowel Disease

In the study, the expected incidence of oral cancer was calculated for the patients who were stratified by gender and age using the Surveillance, Epidemiology and End Results (SEER) 18 registry data. Seven men and 4 women had biopsy-proven oral cancer. Six had cancer of the tongue, 2 had cancer of the hard palate, and 3 had tonsillar, buccal, or mandibular sarcoma. Seven patients had been treated for IBD before the cancer diagnosis.

Women had a higher risk of oral cancer. Adjusted for age and sex, the incidence ratio for oral cancer in patients with IBD was 9.77:12.07 for women12.07 and 9.77:8.49 for men. The age-adjusted incidence ratio for tongue cancer was 18.91: 17.06 for men, 22.10 for women.

Related: More Illnesses Linked to Camp Lejeune Water

The authors concluded that, “we found patients with IBD to be at increased risk for oral cancers, especially tongue cancer. Women are at higher risk than men.”

Source:
Katsanos KH, Roda G, McBride RB, Cohen B, Colombel JF. Clin Gastroenterol Hepatol. 2016;14(3):413-420
doi: 10.1016/j.cgh.2015.09.041. 

Patients with inflammatory bowel disease (IBD) may have a higher risk of oral cancer, according to a study at Mount Sinai Medical Center. Researchers collected data on 7,294 patients from 2000 through 2011. The results were published in the March issue of Clinical Gastroenterology and Hepatology.

Related: Exercise and Inflammatory Bowel Disease

In the study, the expected incidence of oral cancer was calculated for the patients who were stratified by gender and age using the Surveillance, Epidemiology and End Results (SEER) 18 registry data. Seven men and 4 women had biopsy-proven oral cancer. Six had cancer of the tongue, 2 had cancer of the hard palate, and 3 had tonsillar, buccal, or mandibular sarcoma. Seven patients had been treated for IBD before the cancer diagnosis.

Women had a higher risk of oral cancer. Adjusted for age and sex, the incidence ratio for oral cancer in patients with IBD was 9.77:12.07 for women12.07 and 9.77:8.49 for men. The age-adjusted incidence ratio for tongue cancer was 18.91: 17.06 for men, 22.10 for women.

Related: More Illnesses Linked to Camp Lejeune Water

The authors concluded that, “we found patients with IBD to be at increased risk for oral cancers, especially tongue cancer. Women are at higher risk than men.”

Source:
Katsanos KH, Roda G, McBride RB, Cohen B, Colombel JF. Clin Gastroenterol Hepatol. 2016;14(3):413-420
doi: 10.1016/j.cgh.2015.09.041. 

Patients with inflammatory bowel disease (IBD) may have a higher risk of oral cancer, according to a study at Mount Sinai Medical Center. Researchers collected data on 7,294 patients from 2000 through 2011. The results were published in the March issue of Clinical Gastroenterology and Hepatology.

Related: Exercise and Inflammatory Bowel Disease

In the study, the expected incidence of oral cancer was calculated for the patients who were stratified by gender and age using the Surveillance, Epidemiology and End Results (SEER) 18 registry data. Seven men and 4 women had biopsy-proven oral cancer. Six had cancer of the tongue, 2 had cancer of the hard palate, and 3 had tonsillar, buccal, or mandibular sarcoma. Seven patients had been treated for IBD before the cancer diagnosis.

Women had a higher risk of oral cancer. Adjusted for age and sex, the incidence ratio for oral cancer in patients with IBD was 9.77:12.07 for women12.07 and 9.77:8.49 for men. The age-adjusted incidence ratio for tongue cancer was 18.91: 17.06 for men, 22.10 for women.

Related: More Illnesses Linked to Camp Lejeune Water

The authors concluded that, “we found patients with IBD to be at increased risk for oral cancers, especially tongue cancer. Women are at higher risk than men.”

Source:
Katsanos KH, Roda G, McBride RB, Cohen B, Colombel JF. Clin Gastroenterol Hepatol. 2016;14(3):413-420
doi: 10.1016/j.cgh.2015.09.041. 

An increased risk of acute lymphoblastic leukemia (ALL) was seen in young children born by prelabor cesarean delivery, in a pooled analysis of 13 case-control studies from nine countries.

The odds ratio was significant at 1.23 for an association between prelabor cesarean delivery and ALL (P = .018); there was not a significant association between ALL and all indications of cesarean delivery nor was there an association with emergency cesarean delivery. Further, the risk for childhood AML was not associated with cesarean delivery, prelabor cesarean delivery, or emergency cesarean delivery, reported Erin L. Marcotte, Ph.D., of the University of Minnesota, Minneapolis, and her associates.

VashiDonsk/Creative Commons/CC ASA 3.0

The association between ALL and prelabor cesarean delivery is based on 13 case-control studies from the Childhood Leukemia International Consortium. Birth delivery method was known for 97%-99% of 8,780 ALL cases, 1,332 AML cases, and 23,459 controls in those studies. In four of the studies, the indications for cesarean delivery were known for 1,061 of 4,313 ALL cases, 138 of 664 AML cases, and 1,401 of 5,884 controls. The multivariable logistic regression models used for the analysis were adjusted for birth weight, sex, age, ethnic origin, parental education, maternal age, and study.

If the association proves to be causal, “maladaptive immune activation due to an absence of stress response before birth in children born by prelabor caesarean delivery could be considered as a potential mechanism,” the researchers wrote (Lancet Haematol. 2016;3[4]:e176–e185).

ALL involves genetic and developmental aberrations that are probably modified by exposure and response to infectious agents. Early exposure to a variety of infections seems to decrease risk, and a vigorous response to infections (quantified by physician visits for infections) increases risk. During vaginal birth, the newborn is exposed to commensal bacteria that modulate immune development, Joseph Weimels, Ph.D., of the University of California at San Francisco, and Xiaomei Ma, Ph.D., of the Yale School of Public Health, New Haven, Conn., wrote in an editorial published in the same issue of The Lancet Haematology. Children delivered vaginally have different gut microbiomes and T-cell reactivity persisting up to age 2 years compared with children born by cesarean, they wrote.

The National Cancer Institute funded the study. The researchers had no relevant disclosures.

mdales@frontlinemedcom.com

On Twitter @maryjodales

An increased risk of acute lymphoblastic leukemia (ALL) was seen in young children born by prelabor cesarean delivery, in a pooled analysis of 13 case-control studies from nine countries.

The odds ratio was significant at 1.23 for an association between prelabor cesarean delivery and ALL (P = .018); there was not a significant association between ALL and all indications of cesarean delivery nor was there an association with emergency cesarean delivery. Further, the risk for childhood AML was not associated with cesarean delivery, prelabor cesarean delivery, or emergency cesarean delivery, reported Erin L. Marcotte, Ph.D., of the University of Minnesota, Minneapolis, and her associates.

VashiDonsk/Creative Commons/CC ASA 3.0

The association between ALL and prelabor cesarean delivery is based on 13 case-control studies from the Childhood Leukemia International Consortium. Birth delivery method was known for 97%-99% of 8,780 ALL cases, 1,332 AML cases, and 23,459 controls in those studies. In four of the studies, the indications for cesarean delivery were known for 1,061 of 4,313 ALL cases, 138 of 664 AML cases, and 1,401 of 5,884 controls. The multivariable logistic regression models used for the analysis were adjusted for birth weight, sex, age, ethnic origin, parental education, maternal age, and study.

If the association proves to be causal, “maladaptive immune activation due to an absence of stress response before birth in children born by prelabor caesarean delivery could be considered as a potential mechanism,” the researchers wrote (Lancet Haematol. 2016;3[4]:e176–e185).

ALL involves genetic and developmental aberrations that are probably modified by exposure and response to infectious agents. Early exposure to a variety of infections seems to decrease risk, and a vigorous response to infections (quantified by physician visits for infections) increases risk. During vaginal birth, the newborn is exposed to commensal bacteria that modulate immune development, Joseph Weimels, Ph.D., of the University of California at San Francisco, and Xiaomei Ma, Ph.D., of the Yale School of Public Health, New Haven, Conn., wrote in an editorial published in the same issue of The Lancet Haematology. Children delivered vaginally have different gut microbiomes and T-cell reactivity persisting up to age 2 years compared with children born by cesarean, they wrote.

The National Cancer Institute funded the study. The researchers had no relevant disclosures.

mdales@frontlinemedcom.com

On Twitter @maryjodales

An increased risk of acute lymphoblastic leukemia (ALL) was seen in young children born by prelabor cesarean delivery, in a pooled analysis of 13 case-control studies from nine countries.

The odds ratio was significant at 1.23 for an association between prelabor cesarean delivery and ALL (P = .018); there was not a significant association between ALL and all indications of cesarean delivery nor was there an association with emergency cesarean delivery. Further, the risk for childhood AML was not associated with cesarean delivery, prelabor cesarean delivery, or emergency cesarean delivery, reported Erin L. Marcotte, Ph.D., of the University of Minnesota, Minneapolis, and her associates.

VashiDonsk/Creative Commons/CC ASA 3.0

The association between ALL and prelabor cesarean delivery is based on 13 case-control studies from the Childhood Leukemia International Consortium. Birth delivery method was known for 97%-99% of 8,780 ALL cases, 1,332 AML cases, and 23,459 controls in those studies. In four of the studies, the indications for cesarean delivery were known for 1,061 of 4,313 ALL cases, 138 of 664 AML cases, and 1,401 of 5,884 controls. The multivariable logistic regression models used for the analysis were adjusted for birth weight, sex, age, ethnic origin, parental education, maternal age, and study.

If the association proves to be causal, “maladaptive immune activation due to an absence of stress response before birth in children born by prelabor caesarean delivery could be considered as a potential mechanism,” the researchers wrote (Lancet Haematol. 2016;3[4]:e176–e185).

ALL involves genetic and developmental aberrations that are probably modified by exposure and response to infectious agents. Early exposure to a variety of infections seems to decrease risk, and a vigorous response to infections (quantified by physician visits for infections) increases risk. During vaginal birth, the newborn is exposed to commensal bacteria that modulate immune development, Joseph Weimels, Ph.D., of the University of California at San Francisco, and Xiaomei Ma, Ph.D., of the Yale School of Public Health, New Haven, Conn., wrote in an editorial published in the same issue of The Lancet Haematology. Children delivered vaginally have different gut microbiomes and T-cell reactivity persisting up to age 2 years compared with children born by cesarean, they wrote.

The National Cancer Institute funded the study. The researchers had no relevant disclosures.

mdales@frontlinemedcom.com

On Twitter @maryjodales

AMSTERDAM – Physical therapy is underused as a first conservative treatment option for knee osteoarthritis, according to a review of data of more than 130,000 men and women serving in the U.S. military.

Data from the Military Health System Data Repository (MDR) show that clinical practice is often out of step with guidelines, as many patients are treated with intra-articular corticosteroid injections rather than physical therapy.

©Nandyphotos/Thinkstock.com

Within a week of an initial episode of knee OA, patients were four times more likely to be given steroid injections than receive physical therapy (14,290 vs. 3,177 patients), although a similar number of patients received injections or physical therapy within 30 days (8,228 vs. 8,407) and 90 days (9,125 vs. 10,059). Of the patients given injections early, 12,311 received them on the day of the index episode.

“What was interesting, anecdotally, was how few patients had been to physical therapy prior to surgery and how many of them had had injections before physical therapy,” Dr. Dan Rhon, director of physical therapy at Brooke Army Medical Center, Houston, said in an interview at the World Congress on Osteoarthritis.

“We wanted to look at the practice patterns because guidelines generally say that you should try physical therapy before surgery and that invasive procedures such as injections should be utilized further down the road,” he said at the meeting, which was sponsored by Osteoarthritis Research Society International.

Dr. Rhon noted that in a study of clinical practice patterns over a 5-year period from the United Healthcare Database, researchers found that physical rehabilitation was used in about one-quarter of patients, with 10% of those who went on to have surgery receiving physical therapy specific for OA, and 16% had been given intra-articular injections (Arthroscopy. 2014;30:65-71).

Results from the MDR data, which considered records from 2008 to 2013 and 1 year of follow-up, now show similar findings with 29% of patients receiving physical rehabilitation, 17.5% prior to knee arthroplasty, and 36% of patients receiving corticosteroid injections first.

What this shows, Dr. Rhon said, is that clinical practice patterns in the Military Health System do not appear to be following established guidelines. “It’s a little bit worrisome because most of these patients should at least have a trial of conservative management.” Perhaps there is some confusion over what constitutes conservative management, but when there is a choice between physical therapy and corticosteroid injections, it seems that the latter is more commonly being selected. Patients themselves could also be opting for injections over physical rehabilitation, so there may be a need for education on what options are available before surgical intervention.

Further research is needed to examine the clinical outcomes of this and perhaps look at how cost savings could be made if clinical practice more closely adhered to the OA guidelines. Looking at a longer follow-up period, say 2-5 years post diagnosis, might also give a better reflection of the use of physical therapy before surgery.

Dr. Rhon had no financial disclosures.

AMSTERDAM – Physical therapy is underused as a first conservative treatment option for knee osteoarthritis, according to a review of data of more than 130,000 men and women serving in the U.S. military.

Data from the Military Health System Data Repository (MDR) show that clinical practice is often out of step with guidelines, as many patients are treated with intra-articular corticosteroid injections rather than physical therapy.

©Nandyphotos/Thinkstock.com

Within a week of an initial episode of knee OA, patients were four times more likely to be given steroid injections than receive physical therapy (14,290 vs. 3,177 patients), although a similar number of patients received injections or physical therapy within 30 days (8,228 vs. 8,407) and 90 days (9,125 vs. 10,059). Of the patients given injections early, 12,311 received them on the day of the index episode.

“What was interesting, anecdotally, was how few patients had been to physical therapy prior to surgery and how many of them had had injections before physical therapy,” Dr. Dan Rhon, director of physical therapy at Brooke Army Medical Center, Houston, said in an interview at the World Congress on Osteoarthritis.

“We wanted to look at the practice patterns because guidelines generally say that you should try physical therapy before surgery and that invasive procedures such as injections should be utilized further down the road,” he said at the meeting, which was sponsored by Osteoarthritis Research Society International.

Dr. Rhon noted that in a study of clinical practice patterns over a 5-year period from the United Healthcare Database, researchers found that physical rehabilitation was used in about one-quarter of patients, with 10% of those who went on to have surgery receiving physical therapy specific for OA, and 16% had been given intra-articular injections (Arthroscopy. 2014;30:65-71).

Results from the MDR data, which considered records from 2008 to 2013 and 1 year of follow-up, now show similar findings with 29% of patients receiving physical rehabilitation, 17.5% prior to knee arthroplasty, and 36% of patients receiving corticosteroid injections first.

What this shows, Dr. Rhon said, is that clinical practice patterns in the Military Health System do not appear to be following established guidelines. “It’s a little bit worrisome because most of these patients should at least have a trial of conservative management.” Perhaps there is some confusion over what constitutes conservative management, but when there is a choice between physical therapy and corticosteroid injections, it seems that the latter is more commonly being selected. Patients themselves could also be opting for injections over physical rehabilitation, so there may be a need for education on what options are available before surgical intervention.

Further research is needed to examine the clinical outcomes of this and perhaps look at how cost savings could be made if clinical practice more closely adhered to the OA guidelines. Looking at a longer follow-up period, say 2-5 years post diagnosis, might also give a better reflection of the use of physical therapy before surgery.

Dr. Rhon had no financial disclosures.

AMSTERDAM – Physical therapy is underused as a first conservative treatment option for knee osteoarthritis, according to a review of data of more than 130,000 men and women serving in the U.S. military.

Data from the Military Health System Data Repository (MDR) show that clinical practice is often out of step with guidelines, as many patients are treated with intra-articular corticosteroid injections rather than physical therapy.

©Nandyphotos/Thinkstock.com

Within a week of an initial episode of knee OA, patients were four times more likely to be given steroid injections than receive physical therapy (14,290 vs. 3,177 patients), although a similar number of patients received injections or physical therapy within 30 days (8,228 vs. 8,407) and 90 days (9,125 vs. 10,059). Of the patients given injections early, 12,311 received them on the day of the index episode.

“What was interesting, anecdotally, was how few patients had been to physical therapy prior to surgery and how many of them had had injections before physical therapy,” Dr. Dan Rhon, director of physical therapy at Brooke Army Medical Center, Houston, said in an interview at the World Congress on Osteoarthritis.

“We wanted to look at the practice patterns because guidelines generally say that you should try physical therapy before surgery and that invasive procedures such as injections should be utilized further down the road,” he said at the meeting, which was sponsored by Osteoarthritis Research Society International.

Dr. Rhon noted that in a study of clinical practice patterns over a 5-year period from the United Healthcare Database, researchers found that physical rehabilitation was used in about one-quarter of patients, with 10% of those who went on to have surgery receiving physical therapy specific for OA, and 16% had been given intra-articular injections (Arthroscopy. 2014;30:65-71).

Results from the MDR data, which considered records from 2008 to 2013 and 1 year of follow-up, now show similar findings with 29% of patients receiving physical rehabilitation, 17.5% prior to knee arthroplasty, and 36% of patients receiving corticosteroid injections first.

What this shows, Dr. Rhon said, is that clinical practice patterns in the Military Health System do not appear to be following established guidelines. “It’s a little bit worrisome because most of these patients should at least have a trial of conservative management.” Perhaps there is some confusion over what constitutes conservative management, but when there is a choice between physical therapy and corticosteroid injections, it seems that the latter is more commonly being selected. Patients themselves could also be opting for injections over physical rehabilitation, so there may be a need for education on what options are available before surgical intervention.

Further research is needed to examine the clinical outcomes of this and perhaps look at how cost savings could be made if clinical practice more closely adhered to the OA guidelines. Looking at a longer follow-up period, say 2-5 years post diagnosis, might also give a better reflection of the use of physical therapy before surgery.

Dr. Rhon had no financial disclosures.

Micrograph showing CML

Image by Difu Wu

The phase 3 EPIC trial, a comparison of tyrosine kinase inhibitors (TKIs), has left some questions unanswered.

The trial did not determine whether the third-generation TKI ponatinib is more effective than the first-generation TKI imatinib for patients with previously untreated chronic myeloid leukemia (CML).

The study was terminated early due to safety concerns associated with ponatinib, so the primary endpoint could only be analyzed in a small number of patients.

Results in these patients showed no significant difference in that endpoint—major molecular response (MMR) at 12 months—between the imatinib and ponatinib arms.

Results in the entire study cohort suggested that, overall, ponatinib was more toxic than imatinib. In particular, ponatinib produced more arterial occlusive events.

However, the trial’s investigators have questioned whether reducing the dose of ponatinib might change that.

Jeffrey H. Lipton, MD, of Princess Margaret Cancer Centre in Toronto, Ontario, Canada, and his colleagues reported results from the EPIC trial in The Lancet Oncology. The trial was supported by Ariad Pharmaceuticals.

Problems with ponatinib

Ponatinib was approved by the US Food and Drug Administration (FDA) in December 2012 to treat adults with CML or Philadelphia chromosome-positive acute lymphoblastic leukemia that is resistant to or intolerant of other TKIs.

In October 2013, follow-up results from the phase 2 PACE trial suggested ponatinib can increase a patient’s risk of arterial and venous thrombotic events. So all trials of the drug were placed on partial clinical hold, with the exception of the EPIC trial, which was terminated.

That November, the FDA suspended sales and marketing of ponatinib, pending results of a safety evaluation. In December, the agency decided ponatinib could return to the market if new safety measures were implemented. In January 2014, ponatinib was put back on the market in the US.

EPIC trial

The trial enrolled 307 patients with newly diagnosed, chronic-phase CML. Patients were randomized to receive ponatinib at 45 mg (n=155) or imatinib at 400 mg (n=152) once daily until progression, unacceptable toxicity, or other criteria for withdrawal were met.

The median age was 55 (range, 18-89) in the ponatinib arm and 52 (range, 18-86) in the imatinib arm. Most patients were male—63% and 61%, respectively—and most had an ECOG performance status of 0—75% and 78%, respectively.

Patients were randomized between August 14, 2012, and October 9, 2013, and the trial was terminated on October 17, 2013.

Because of the early termination, only 10 patients in the ponatinib arm and 13 in the imatinib arm were evaluable for the primary endpoint—MMR at 12 months. Eighty percent (8/10) of the evaluable patients in the ponatinib arm and 38% (5/13) of those in the imatinib arm achieved an MMR at 12 months (P=0.074).

The investigators also evaluated the incidence of MMR at any time in patients with any post-baseline molecular response assessment. This time, the incidence of MMR was significantly higher in the ponatinib arm than the imatinib arm—41% (61/149) and 18% (25/142), respectively (P<0.0001).

All of the patients were evaluable for safety—154 in the ponatinib arm and 152 in the imatinib arm.

Arterial occlusive events occurred in 7% (n=11) of patients in the ponatinib arm and 2% (n=3) in the imatinib arm (P=0.052). These events were considered serious in 6% (n=10) and 1% (n=1), respectively (P=0.010).

Common grade 3/4 adverse events—in the ponatinib and imatinib arms, respectively—were increased lipase (14% vs 2%), thrombocytopenia (12% vs 7%), rash (6% vs 1%), and neutropenia (3% vs 8%).

Serious adverse events that occurred in 3 or more patients in the ponatinib arm were pancreatitis (n=5), atrial fibrillation (n=3), and thrombocytopenia (n=3). There were no serious adverse events that occurred in 3 or more patients in the imatinib arm.

Dr Lipton and his colleagues said the premature termination of the EPIC trial restricts the interpretation of its results, but the available data provide some insight into the activity and safety of ponatinib in previously untreated CML.

The investigators also noted that data from this trial and the clinical development program for ponatinib suggest that lowering doses of the drug could improve its vascular safety profile and, therefore, the benefit-risk balance.

Two ongoing trials (NCT02467270 and NCT02627677) may provide more insight. Both are investigating starting doses of ponatinib at 15 mg or 30 mg.

Micrograph showing CML

Image by Difu Wu

The phase 3 EPIC trial, a comparison of tyrosine kinase inhibitors (TKIs), has left some questions unanswered.

The trial did not determine whether the third-generation TKI ponatinib is more effective than the first-generation TKI imatinib for patients with previously untreated chronic myeloid leukemia (CML).

The study was terminated early due to safety concerns associated with ponatinib, so the primary endpoint could only be analyzed in a small number of patients.

Results in these patients showed no significant difference in that endpoint—major molecular response (MMR) at 12 months—between the imatinib and ponatinib arms.

Results in the entire study cohort suggested that, overall, ponatinib was more toxic than imatinib. In particular, ponatinib produced more arterial occlusive events.

However, the trial’s investigators have questioned whether reducing the dose of ponatinib might change that.

Jeffrey H. Lipton, MD, of Princess Margaret Cancer Centre in Toronto, Ontario, Canada, and his colleagues reported results from the EPIC trial in The Lancet Oncology. The trial was supported by Ariad Pharmaceuticals.

Problems with ponatinib

Ponatinib was approved by the US Food and Drug Administration (FDA) in December 2012 to treat adults with CML or Philadelphia chromosome-positive acute lymphoblastic leukemia that is resistant to or intolerant of other TKIs.

In October 2013, follow-up results from the phase 2 PACE trial suggested ponatinib can increase a patient’s risk of arterial and venous thrombotic events. So all trials of the drug were placed on partial clinical hold, with the exception of the EPIC trial, which was terminated.

That November, the FDA suspended sales and marketing of ponatinib, pending results of a safety evaluation. In December, the agency decided ponatinib could return to the market if new safety measures were implemented. In January 2014, ponatinib was put back on the market in the US.

EPIC trial

The trial enrolled 307 patients with newly diagnosed, chronic-phase CML. Patients were randomized to receive ponatinib at 45 mg (n=155) or imatinib at 400 mg (n=152) once daily until progression, unacceptable toxicity, or other criteria for withdrawal were met.

The median age was 55 (range, 18-89) in the ponatinib arm and 52 (range, 18-86) in the imatinib arm. Most patients were male—63% and 61%, respectively—and most had an ECOG performance status of 0—75% and 78%, respectively.

Patients were randomized between August 14, 2012, and October 9, 2013, and the trial was terminated on October 17, 2013.

Because of the early termination, only 10 patients in the ponatinib arm and 13 in the imatinib arm were evaluable for the primary endpoint—MMR at 12 months. Eighty percent (8/10) of the evaluable patients in the ponatinib arm and 38% (5/13) of those in the imatinib arm achieved an MMR at 12 months (P=0.074).

The investigators also evaluated the incidence of MMR at any time in patients with any post-baseline molecular response assessment. This time, the incidence of MMR was significantly higher in the ponatinib arm than the imatinib arm—41% (61/149) and 18% (25/142), respectively (P<0.0001).

All of the patients were evaluable for safety—154 in the ponatinib arm and 152 in the imatinib arm.

Arterial occlusive events occurred in 7% (n=11) of patients in the ponatinib arm and 2% (n=3) in the imatinib arm (P=0.052). These events were considered serious in 6% (n=10) and 1% (n=1), respectively (P=0.010).

Common grade 3/4 adverse events—in the ponatinib and imatinib arms, respectively—were increased lipase (14% vs 2%), thrombocytopenia (12% vs 7%), rash (6% vs 1%), and neutropenia (3% vs 8%).

Serious adverse events that occurred in 3 or more patients in the ponatinib arm were pancreatitis (n=5), atrial fibrillation (n=3), and thrombocytopenia (n=3). There were no serious adverse events that occurred in 3 or more patients in the imatinib arm.

Dr Lipton and his colleagues said the premature termination of the EPIC trial restricts the interpretation of its results, but the available data provide some insight into the activity and safety of ponatinib in previously untreated CML.

The investigators also noted that data from this trial and the clinical development program for ponatinib suggest that lowering doses of the drug could improve its vascular safety profile and, therefore, the benefit-risk balance.

Two ongoing trials (NCT02467270 and NCT02627677) may provide more insight. Both are investigating starting doses of ponatinib at 15 mg or 30 mg.

Micrograph showing CML

Image by Difu Wu

The phase 3 EPIC trial, a comparison of tyrosine kinase inhibitors (TKIs), has left some questions unanswered.

The trial did not determine whether the third-generation TKI ponatinib is more effective than the first-generation TKI imatinib for patients with previously untreated chronic myeloid leukemia (CML).

The study was terminated early due to safety concerns associated with ponatinib, so the primary endpoint could only be analyzed in a small number of patients.

Results in these patients showed no significant difference in that endpoint—major molecular response (MMR) at 12 months—between the imatinib and ponatinib arms.

Results in the entire study cohort suggested that, overall, ponatinib was more toxic than imatinib. In particular, ponatinib produced more arterial occlusive events.

However, the trial’s investigators have questioned whether reducing the dose of ponatinib might change that.

Jeffrey H. Lipton, MD, of Princess Margaret Cancer Centre in Toronto, Ontario, Canada, and his colleagues reported results from the EPIC trial in The Lancet Oncology. The trial was supported by Ariad Pharmaceuticals.

Problems with ponatinib

Ponatinib was approved by the US Food and Drug Administration (FDA) in December 2012 to treat adults with CML or Philadelphia chromosome-positive acute lymphoblastic leukemia that is resistant to or intolerant of other TKIs.

In October 2013, follow-up results from the phase 2 PACE trial suggested ponatinib can increase a patient’s risk of arterial and venous thrombotic events. So all trials of the drug were placed on partial clinical hold, with the exception of the EPIC trial, which was terminated.

That November, the FDA suspended sales and marketing of ponatinib, pending results of a safety evaluation. In December, the agency decided ponatinib could return to the market if new safety measures were implemented. In January 2014, ponatinib was put back on the market in the US.

EPIC trial

The trial enrolled 307 patients with newly diagnosed, chronic-phase CML. Patients were randomized to receive ponatinib at 45 mg (n=155) or imatinib at 400 mg (n=152) once daily until progression, unacceptable toxicity, or other criteria for withdrawal were met.

The median age was 55 (range, 18-89) in the ponatinib arm and 52 (range, 18-86) in the imatinib arm. Most patients were male—63% and 61%, respectively—and most had an ECOG performance status of 0—75% and 78%, respectively.

Patients were randomized between August 14, 2012, and October 9, 2013, and the trial was terminated on October 17, 2013.

Because of the early termination, only 10 patients in the ponatinib arm and 13 in the imatinib arm were evaluable for the primary endpoint—MMR at 12 months. Eighty percent (8/10) of the evaluable patients in the ponatinib arm and 38% (5/13) of those in the imatinib arm achieved an MMR at 12 months (P=0.074).

The investigators also evaluated the incidence of MMR at any time in patients with any post-baseline molecular response assessment. This time, the incidence of MMR was significantly higher in the ponatinib arm than the imatinib arm—41% (61/149) and 18% (25/142), respectively (P<0.0001).

All of the patients were evaluable for safety—154 in the ponatinib arm and 152 in the imatinib arm.

Arterial occlusive events occurred in 7% (n=11) of patients in the ponatinib arm and 2% (n=3) in the imatinib arm (P=0.052). These events were considered serious in 6% (n=10) and 1% (n=1), respectively (P=0.010).

Common grade 3/4 adverse events—in the ponatinib and imatinib arms, respectively—were increased lipase (14% vs 2%), thrombocytopenia (12% vs 7%), rash (6% vs 1%), and neutropenia (3% vs 8%).

Serious adverse events that occurred in 3 or more patients in the ponatinib arm were pancreatitis (n=5), atrial fibrillation (n=3), and thrombocytopenia (n=3). There were no serious adverse events that occurred in 3 or more patients in the imatinib arm.

Dr Lipton and his colleagues said the premature termination of the EPIC trial restricts the interpretation of its results, but the available data provide some insight into the activity and safety of ponatinib in previously untreated CML.

The investigators also noted that data from this trial and the clinical development program for ponatinib suggest that lowering doses of the drug could improve its vascular safety profile and, therefore, the benefit-risk balance.

Two ongoing trials (NCT02467270 and NCT02627677) may provide more insight. Both are investigating starting doses of ponatinib at 15 mg or 30 mg.