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AD sleep disturbance, antihistamines and osteoporosis

Presented by
Prof. Jonathan Silverberg, Northwestern University’s Feinberg School of Medicine, USA
AAD 2018
AD is not only skin deep but can have a profound influence on the life of AD patients. As Prof. Jonathan Silverberg of Northwestern University’s Feinberg School of Medicine pointed out, a substantial proportion of patients will also have sleep disturbance due to the intense itching associated with AD [1].

This is demonstrated by a US survey of 91,642 children up to the age of 17. About 10% of children with only mild to moderate AD had more than four nights of disturbed sleep per week, a percentage that climbed to more than 20% for children with severe AD [2]. Severe eczema was also associated with a higher prevalence of other comorbid chronic health disorders including asthma, hay fever, and food allergies (P<0.0001). In addition, the severity of eczema was directly related to the severity of the comorbidities [2]. Are adult AD patients better off? Obviously not, as a 2012 US Health Interview Survey of 34,500 adult patients demonstrated: “Even adult patients with mild AD can suffer from fatigue, daytime sleepiness and insomnia,” said Prof. Silverberg [3]. This relationship was still evident after controlling for sleep duration, history of allergic disease, sociodemographics, and body mass index. Fatigue, sleepiness, and insomnia were also predictors of poorer overall health status, number of sick days, and doctor visits. Eczema plus any of the sleep symptoms were associated with higher odds of poorer outcomes than either eczema or sleep symptoms alone [3]. “Patients have difficulty in a variety of activities, hobbies and even with their finances when they are tired,” said Prof. Silverberg. Besides sleep disturbances, other mental health comorbidities are increased in patients with more severe AD. A telephone survey conducted in >91,000 households across the US showed that children with AD have a significantly higher rate of depression and anxiety compared to healthy controls: even conduct disorder and autism seem more frequent in children with AD [4]. One in five adult US patients has symptoms of depression or is treated for depression. Whether or not there is a genetic correlation with AD is unclear. “Many comorbid conditions will vanish if we treat patients properly,” said Prof. Silverberg.

Are we too comfortable using antihistamines?

A study published this year suggests a relation between antihistamine use and the development of attention-deficit/hyperactivity symptoms (ADHD) [5].

In this prospective clinical trial, four groups of children aged 6–12 years were compared using a factorial design: AD-only (without ADHD), ADHD-only (without AD), AD+ADHD, and healthy controls. Compared to the controls, children with AD-only, ADHD-only and comorbid AD+ADHD had significantly increased behavioural problems and decreased QoL.

Interestingly, in AD-only children, previous use of antihistamines was significantly associated with increased ADHD symptoms (OR 1.88; 95% CI 1.04-3.39), although current clinical signs and AD symptoms were unrelated to the level of ADHD symptoms.

“I think we are too comfortable using antihistamines at the moment and this study calls for further investigations to determine whether early antihistamine exposure is a risk factor for ADHD,” said Prof. Silverberg

Sleep disturbances warrant step-up therapy

”At the very least, improving sleep and mental health should improve the QoL of our patients,” said Prof. Silverberg. Therefore, patients with AD should be asked about their sleep and mental health.

“Patients with a major component of sleep and/or mental health disturbances may require more aggressive treatment. These are the patients where you should consider systemic agents,” recommended Prof. Silverberg. Adjunctive treatments for sleep and mental health—such as gabapentin, mirtazapine and selective serotonin reuptake inhibitors—have demonstrated efficacy for itchiness as well [6,7].

According to Prof. Silverberg, high dose melatonin is an alternative sedative without the safety issues observed with antihistamines. In many cases, it might be sufficient to improve sleep hygiene or to start relaxation therapy or meditation.

Osteoporosis: another neglected AD comorbidity

Another US survey comprising 4,972 adult patients ages 20–85 showed that eczema is also associated with osteoporosis and fractures in adults with AD [8]. This relationship was confirmed in a database from Taiwan [9].

In this Taiwanese cohort, risk factors included older age, being female, increased comorbidity, depression, and systemic corticosteroid use. “What we can do to reduce this risk is really to minimise systemic steroids and rather use other systemic agents or phototherapy. In addition, we should try to motivate patients to an active lifestyle,” said Prof. Silverberg.

In addition, sweat and heat can lead to a flare-up of the disease. “We have to decrease ambient temperature and treat underlying itch effectively to enable patients to be active,” recommended Prof. Silverberg.

1. Silverberg, J. oral presentation session F012, AAD Annual Meeting, February 16–20 2018.
2. Silverberg, JI. & Simposon, EL. Pediatri Allergy Immunol 2013;24:476-86.
3. Silverberg, JI. et al. J Invest Dermatol 2015;135:56–66.
4. Yaghmaie, P. et al. All Clin Immunol 2013;131:428–33.
5. Schmitt, J. et al. Allergy 2018;73:615–26.
6. Ständer, S. et al. Acta Derm Venereol 2009;89:45–51.
7. Biyik, Z. et al. Int Urol Nephrol 2013;45:831–7.
8. Gark, NK & Silverberg, JI. J Allergy Clin Immunol 2015;135:1085–7.
9. Wu, CY. et al. PLoS One 2017;12:e0171667.

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