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 Table of Contents  
REVIEW ARTICLE
Year : 2018  |  Volume : 19  |  Issue : 2  |  Page : 102-107

Comorbidities in pediatric atopic dermatitis


1 Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
2 Department of Medicine, Division of Dermatology, Women's College Research Institute, Women's College Hospital, University of Toronto, Toronto, Ontario, Canada

Date of Web Publication26-Mar-2018

Correspondence Address:
Aaron M Drucker
Room 6401, Women's College Hospital, 76 Grenville Street, Toronto, ON M5S 1B2
Canada
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijpd.IJPD_129_17

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  Abstract 


Atopic dermatitis is a common chronic condition that often begins in early childhood. In addition to associations with other atopic conditions such as asthma, food allergy and hayfever, recent research has uncovered a number of other important potential comorbidities. In this review article, we summarize the reported comorbidities of pediatric atopic dermatitis including mental health disorders, infections, obesity, hypertension, injuries and anemia.

Keywords: Atopic dermatitis, asthma, hayfever, mental health, infection, obesity, hypertension, injury, anemia


How to cite this article:
Pope EI, Drucker AM. Comorbidities in pediatric atopic dermatitis. Indian J Paediatr Dermatol 2018;19:102-7

How to cite this URL:
Pope EI, Drucker AM. Comorbidities in pediatric atopic dermatitis. Indian J Paediatr Dermatol [serial online] 2018 [cited 2018 Oct 16];19:102-7. Available from: http://www.ijpd.in/text.asp?2018/19/2/102/228346



Atopic dermatitis is a chronic inflammatory disorder of the skin that usually presents in childhood and can extend throughout the lifespan.[1] It is the most common chronic disease in childhood,[2] with a prevalence of approximately 10%–20% of the population.[3] Atopic dermatitis is characterized by eczematous lesions accompanied by pruritus. Atopic dermatitis stems from a combination of genetic skin barrier defects, as well as environmental stimuli. The distressing symptoms of atopic dermatitis contribute to decreased quality of life for patients,[4] immense psychosocial and financial burden for them and their families,[5] and an increased utilization of the health-care system.[6] Given its early onset and chronic nature, its total burden across the lifespan can be enormous.[7] Atopic dermatitis has also been linked to diverse comorbidities, including atopic conditions, such as asthma, rhinitis, and food allergy,[8] mental health conditions,[9] infections,[10] injuries,[11] metabolic disorders,[12] and anemia,[13] suggesting that it is more of a systemic disorder than was once believed.[14] This review will provide an overview of the literature on various comorbidities associated with atopic dermatitis in children.


  Atopic March Top


Atopic dermatitis is thought to initiate the “atopic march,” which refers to the increased risk of subsequent atopic diseases: asthma,[15],[16] food allergy,[17] and allergic rhinitis.[16] Given that up to 60% of atopic dermatitis cases begin within the 1st year of life, skin manifestations of atopy are often the first to present, followed by food allergy, asthma, and finally allergic rhinitis.[16] The current evidence suggests that the atopic march is a product of impaired skin barrier function in atopic dermatitis, leading to increased permeability to allergens and heightened activation of the immune system.[8],[17],[18] In particular, defects in the filaggrin gene have been identified as a risk factor for allergic sensitization and atopic dermatitis severity.[17] As such, the atopic march often exists in the setting of early-onset, severe, and persistent atopic dermatitis.

In the United States, 19.8% of children with atopic dermatitis have comorbid asthma, and 34.3% have allergic rhinitis.[19] Comorbid asthma and allergic rhinitis are typically associated with increased severity of atopic dermatitis.[19],[20] Longitudinal studies have also demonstrated a relationship between early atopic dermatitis and food allergy.[21]

These comorbidities are extremely distressing to patients and families and can lead to further decrements in quality of life. It is also possible that recently reported comorbidities of adult atopic dermatitis, including potential for cardiovascular disease [22] and osteoporosis,[23] are in part attributable to atopic comorbidities and use of various formulations of corticosteroids. Therefore, it is critical to be aware of these other atopic conditions and tailor-effective interventions to minimize disease burden.


  Mental Health Top


The link between atopic dermatitis and mental health was suggested in the 20th century, with the inception of the term “neurodermatitis.”[24] Since then, further research has reinforced the association between atopic dermatitis and a number of mental health comorbidities. In general, children with atopic dermatitis see mental health-care providers more often and receive more mental health care than their nonaffected peers.[9] Attention deficit hyperactivity disorder (ADHD), behavioral problems, and mood disorders have emerged as being strongly associated with atopic dermatitis in the pediatric population.

Attention deficit hyperactivity disorder

A prospective birth cohort study found that children diagnosed with atopic dermatitis up to the age of 4 had 5.17 times higher risk of developing ADHD before age 8 (early ADHD) compared to children without atopic dermatitis.[25] This association remained significant when controlling for allergic rhinitis and allergic conjunctivitis. On the other hand, there was a nonsignificant 3-fold increased risk of ADHD diagnosis from 9 to 11 years (late ADHD) if the atopic dermatitis onset occurred after age 4.[25] A recent US population-based study found similar results, delineating a relationship between atopic dermatitis in children aged 2–17 years and attention deficit disorder Correspondence Address:
Aaron M Drucker
Room 6401, Women's College Hospital, 76 Grenville Street, Toronto, ON M5S 1B2
Canada
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijpd.IJPD_129_17

Rights and Permissions/ADHD diagnosis. Higher odds of ADD/ADHD correlated with atopic dermatitis severity, sleep disturbance, as well as a history of anemia, headaches, and obesity.[9],[26] The increased risk of ADD/ADHD with atopic dermatitis was independent of the presence of other atopic diseases.[26],[27] In contrast, one study from Taiwan found that atopic dermatitis was not a risk factor for ADHD.[28] Yet this study estimated the prevalence based on treatment rates, which may underestimate actual prevalence rates of these conditions.[28]

The causal link between atopic dermatitis and ADHD is unknown, but there are a number of interesting hypotheses. Atopic dermatitis has directly been linked to sleep disturbances,[29] which in turn may lead to daytime inattention, irritability, and hyperactivity. A recent study documented increased ADHD symptoms among atopic dermatitis patients who use antihistamines.[30] ADHD has also been associated with systemic inflammation; it is possible that inflammation associated with atopic dermatitis may be contributing to the pathophysiology of ADHD.[31]

Behavioral problems

Aside from ADHD, children with atopic dermatitis have also been shown to be at higher risk for other behavioral issues. One systematic review found that parents of children with atopic dermatitis were significantly more concerned about their children's behavior compared to parents of children without atopic dermatitis.[9] More specifically, scratching to get attention, stubbornness, aggressiveness, and oppositional behavior have been documented in children with atopic dermatitis. Furthermore, atopic dermatitis has been associated with conduct disorder,[9],[32] particularly in the context of concurrent sleep problems. Sleep is well known to mediate the relationship between atopic dermatitis and behavior in children.[33] However, parenting has also emerged as playing a major role in mediating the relationship between atopic dermatitis and children's behavior. For example, parental self-efficacy for managing their child's difficult behavior was positively correlated to their ability to manage their child's atopic dermatitis.[34] Similarly, parents who felt confident managing atopic dermatitis were less likely to use permissive or authoritarian parenting styles,[34] which are known to contribute to behavioral problems in children. Furthermore, greater use of these ineffective parenting strategies was associated with increasing atopic dermatitis severity.[34] These findings suggest that it is important to address children's sleep, as well as supports and strategies for parents of children with atopic dermatitis when evaluating behavioral difficulties in this population.

Mood disorders

Atopic dermatitis in adults is related to a greater prevalence of mood disorders, such as anxiety and depression.[35] However, this relationship has only recently been examined in children. A small number of studies have identified a significant relationship between atopic dermatitis and depressive symptoms in children.[9],[11] Females in this population may be at higher risk for depressive symptoms, compared to their male counterparts.[36] Atopic dermatitis is also associated with a greater likelihood of developing anxiety.[9],[11]

Suicidal ideation, planning, and attempts have been linked with atopic dermatitis in adolescents.[36] Again, a discrepancy emerged between the risk for females versus males; when stratified by sex, an association remained significant for adolescent females, but not for males.[37] This association was independent of school year, academic achievement, socioeconomic status, family structure, distorted weight perception, sleep satisfaction, perceived stress, and depressed mood.[37]


  Infection Top


Atopic dermatitis is associated with a number of bacterial and viral infections. This susceptibility stems from the marriage of epidermal barrier dysfunction and a counterproductive response from the innate and acquired immune system. This ultimately allows for increased entry of pathogens and failure to fight off imminent infections, respectively.[38],[39]

Bacterial

Children with atopic dermatitis are at especially high risk of skin colonization with Staphylococcus aureus.[40] Not only does the increased presence of this bacterium increase the likelihood of infection through skin lesions but also colonization alone is thought to perpetuate inflammation exacerbating the condition.[41] This model has been confirmed by numerous studies, which have demonstrated that S. aureus is present in increased density on both lesions and unaffected skin of atopic dermatitis patients [42] and that the colonization density of S. aureus on the skin in atopic dermatitis is positively correlated with lesion severity.[43],[44],[45] Furthermore, children with atopic dermatitis have been shown to be at an increased risk of impetigo (odds ratio 1.80; 95% confidence interval [CI], 1.16–2.81).[46]

The rates of S. aureus colonization in children with atopic dermatitis also raise a legitimate concern over whether these patients are at an increased risk of being colonized with or infected by methicillin-resistant S. aureus (MRSA). At present, limited evidence exists on the topic, and findings are conflicting. Some work has demonstrated higher MRSA colonization rates in children with atopic dermatitis.[47] However, recent studies do not confirm increased MRSA colonization in patients with atopic dermatitis.[45],[48] A longitudinal study from Australia also found that from 1999 to 2014, the risk of MRSA infection in a population of atopic dermatitis children rose 24-fold.[49] However, when compared to the increasing rates in the general population, it is currently unclear whether children with atopic dermatitis are more susceptible than nonaffected children.

Viral

Children with atopic dermatitis are also at increased risk for a number of viral infections.[50] The most common comorbid viral infections are human papillomavirus (HPV) infection resulting in warts, molluscum contagiosum virus (MCV) infection (i.e., eczema molluscatum), and most dangerously, herpes simplex virus (HSV) infection (i.e., eczema herpeticum).

Warts are a relatively common finding in the general population, but their presence in the context of atopic dermatitis is largely unexplored. The majority of evidence surrounding HPV infection in children with atopic dermatitis comes from a large population study conducted in the United States. Results indicated that atopic dermatitis alone decreased the odds of having warts, compared to children without atopic dermatitis (odds ratio 0.91; 95% CI, 0.90–0.92).[51] However, when atopic dermatitis occurred alongside another atopic condition, the odds of developing warts increased significantly (odds ratio 1.83; 95% CI, 1.82–1.84).[51] Conversely, children with atopic disease and no atopic dermatitis had higher odds of warts, but the odds almost doubled in those who had both atopic disease and atopic dermatitis.[51] Warts were also associated with increased odds of concurrent extracutaneous infections, but only those children with a background of atopic dermatitis had an increased number of infections.[51] In contrast, older studies reported a lower prevalence of warts in teenagers with atopic dermatitis compared to those without atopic dermatitis.[52],[53] This may suggest that atopic dermatitis plus comorbid atopic conditions, perhaps indicative of more severe atopic dermatitis, predisposes patients to warts, compared to atopic dermatitis alone.

MCV is a poxvirus that causes molluscum contagiosum, a condition presenting with umbilicated, skin-colored papules typically on the face, trunk, or limbs in children.[50] In non-AD populations, the infection is usually minor and self-limited. However, in children with atopic dermatitis, widespread eruptions are more common.[50],[54]

HSV infection is a dangerous cutaneous viral infection in children with atopic dermatitis and requires immediate medical attention. In atopic dermatitis, skin barrier dysfunction allows the HSV virus to enter more easily compared to nonaffected skin.[55] When this infection occurs in the context of atopic dermatitis, it may result in eczema herpeticum, a condition characterized by an eruption of vesicles and punched-out grouped lesions over the head, neck, and trunk, alongside systemic features such as fever, malaise, and lymphadenopathy.[56] The natural history of the infection is crusting over of the blisters within 2 weeks and then a full recovery within 2–6 weeks.[56] However, a number of complications may occur, including keratoconjunctivitis and viremia, which may lead to multiple organ involvement and potentially death.[57],[58] In a cohort study of eczema herpeticum, 57% of children were hospitalized.[59] These children were also found to be at an increased risk of recurrence.[59] Predisposing factors to eczema herpeticum include early onset of atopic dermatitis, presence of other atopic conditions, and high total serum IgE levels, which often correlate with more severe atopic dermatitis.[57],[60] Use of systemic corticosteroids was also associated with a longer hospital stay for eczema herpeticum in children, but there was no difference with topical corticosteroid use.[61] The effect of calcineurin inhibitors on the onset and course of eczema herpeticum is conflicting; there is evidence that they may increase the incidence of the infection [62] but were not shown to have an impact on hospitalization length in affected children.[61]


  Metabolic Conditions Top


Obesity

Somewhat contradictory evidence has emerged regarding the relationship between atopic dermatitis in children and obesity status. While the majority of evidence points to an association between childhood obesity and atopic dermatitis,[12],[26],[63],[64] there are several studies that have found no relationship between the two.[65],[66] In studies demonstrating a relationship, early obesity was associated with more severe forms of atopic dermatitis.[63],[64] Specifically, central obesity was associated with moderate-to-severe pediatric atopic dermatitis.[12] These findings may suggest a role for maintaining a healthy weight in preventing or managing atopic dermatitis in children.

Hypertension

Atopic dermatitis was linked to both high systolic and diastolic blood pressure in children.[12] Furthermore, severe atopic dermatitis was associated with high systolic blood pressure independently of obesity status.[12] However, further work is required to fully elucidate the relationship between atopic dermatitis and hypertension, as well as to describe the mechanisms underlying this association.


  Injuries Top


Patients with atopic dermatitis are at increased risk of accidental injury. Atopic dermatitis was associated with injury in a home setting but was inversely associated with injury in other places.[11] Atopic dermatitis was also significantly associated with injury requiring medical attention, even when controlling for risk factors such as psychiatric and behavioral disorders.[11] However, psychiatric and behavioral disorders were found to mediate the relationship between atopic dermatitis and injury.[11]


  Anemia Top


A recent analysis of large population-based US cross-sectional studies found that children with any type of atopic dermatitis had significantly higher odds of anemia.[13] Furthermore, the study found that children with a current presentation of atopic dermatitis were almost twice as likely to have anemia, with an even greater likelihood of having microcytic anemia in particular.[13] It is important to note, however, that the findings require replication, preferably with a longitudinal analysis, before drawing conclusions on the directionality of the relationship. The mechanism of the association between these conditions remains unknown.


  Conclusion Top


As researchers begin to expand their understanding of how the skin and other body systems are related, there is an emerging role for dermatologists to examine the broader implications of conditions such as atopic dermatitis that are classically considered to predominantly involve the skin. This review has attempted to highlight a number of diverse comorbidities related to atopic dermatitis that have the potential to add to the morbidity and decreased quality of life that is associated with the condition. Future work should continue to explore these comorbidities in longitudinal datasets to help inform patients and clinicians as to which conditions require screening and intervention. It also remains to be seen whether improved atopic dermatitis control decreases the incidence and prevalence of comorbidities and vice versa. The more that is learned about these complex conditions, the more we will be able to improve the overall health of our patients.

Financial support and sponsorship

Dr. Drucker served as an investigator and has received research funding from Sanofi and Regeneron and has been a consultant for Sanofi, RTI Health Solutions, and Eczema Society of Canada. He has received honoraria from Astellas Canada, Prime Inc, Spire Learning and Eczema Society of Canada.

Conflicts of interest

There are no conflicts of interest.



 
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  In this article
Abstract
Atopic March
Mental Health
Infection
Metabolic Conditions
Injuries
Anemia
Conclusion
References

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