Inflammatory Diseases in Little Kids: Part 1

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Inflammatory Disease in Little Kids

Lawrence F. Eichenfield, MD

 

In this presentation, Dr. Eichenfield discussed inflammatory diseases in children in a clinically relevant manner.  Dr. Eichenfield provided a review of the pathogenesis of atopic dermatitis (AD), the role of filaggrin, and allergies in AD.  He also updated us on new findings in pediatric psoriasis.

Atopic Dermatitis

When reviewing AD, it is important to consider the issues noted below:

  • Barrier dysfunction
  • Infection
  • Inflammation
  • Allergy
  • Itching

PEARL:  The phenotype, associated with ichtyhosis vulgaris, is associated with peanut allergy.  Be careful when you take your atopic child or nephew to a baseball game or circus.

Filaggrin Insufficiency

Filaggrin haploinsufficiency is defined as a 50% reduction in the expression of the filaggrin protein, an important functional protein that influences epidermal function.   Filaggrin mutations are associated with decreased filaggrin production, as well as higher rates of development of associated conditions.  The odds ratios for the risk of peanut allergy, asthma, or atopic dermatitis with Filaggrin mutations are greater as compared to individuals without Filaggrin mutations. The odds ratios for atopic dermatitis and asthma, from meta-analyses involving several thousand patients display that FLG mutations confer an overall risk of asthma of 1.5, but this risk is restricted to patients with atopic dermatitis. The odds ratio for the complex phenotype of asthma plus atopic dermatitis is 3.3. The odds ratio for peanut allergy is 5.3 and is based on data from a single study.  Of interest is that there is no filaggrin in the mucosal surfaces of the mouth or esophagus so it likely that the peanut allergy is the result of epicutaneous sensitization. (Irvine AD, McLean I, Leung DYM. N Engl J Med 2011;365:1315-27)

The question is how does filaggrin deficiency affect the skin barrier?  The answer is a decrease in filaggrin expression increases skin permeability, increases skin pH, decreases natural moisturizing factor and decreases cell-to-cell cohesion impacting barrier function.

Of importance, even in individuals who do not have the filaggrin mutation, there are decreased filaggrin byproducts in actively, inflamed eczema.

Atopic dermatitis can be triggered by the chronic exposure of barrier-disrupted skin to percutaneous antigens due to abnormalities in fillaggrin; however, only 30-50% have FLG mutations and most outgrow AD.  40% of patients with FLG-null alleles do not get AD. Therefore, there are other factors that influence AD development and course other than just filaggrin.

What are some of the traditional approaches and targeted therapies?

  • Moisturizing after bathing
  • Use of emollients
  • Targeted barrier repair products

These measures are part of maintenance care for all patients, and primary intervention for mild AD in infants.

What are some of the things that can be done for the prevention of Atopic Dermatitis? In the past, physicians have considered:

  • Formula
  • Maternal diet
  • Infant diet
  • Allergen avoidance (both environmental and food)
  • Probiotics
  • Prebiotics

So far, none of strategies mentioned above have solid data for their efficacy. Several international studies are currently looking at the role of early intervention in skin care in order to stop AD.

Anti-inflammatory therapy

There are typically two ways that a dermatologist handles a child with AD.

1. “As low as you can go (or just above where they were)”, i.e., the least strong topical steroid that can be used and 2: “Stronger steroids” to start, with tapering to less potent corticosteroids as the AD improves. Both of these approaches are reasonable. Many clinicians tend to “mix and match” the topical corticosteroids with the non-steroid topicals and utilize wet wraps with topical corticosteroids in patients with more difficult remissions.

Over the next few years, dermatologists will be seeing some new agents for the treatment of AD. These therapies include selective glucocoid agonist receptor stimulants, histamine 4 blockers as well as other molecules.

Wet Wrap Dressing with TCS Use: Effective, Rapid Control of Severe AD

Dawn Davis and colleagues conducted a study on wet wrap dressing in 218 patients who were hospitalized. The mean age of application was 6 years (2 months-17 years), the mean duration of hospital stay was 3.61 days (range 1-16) and all patients showed improvement.  45% of the patients showed 75-100% improvement; 38% of patients showed 50-75% improvement and 6% of patients showed a 25-50% improvement.

There are many methods to the use of wet wrap with topical corticosteroids and the benefits are clearly demonstrated.

Another important therapeutic intervention for AD, now recognized internationally, is education.   A struggle that clinicians face is how to educate patients within the limited time of busy office settings, so that patients understand how to utilize their medicines while also managing their fears with respect to the utilization of steroids and medications.

Pediatric Pearls and Conclusions

  • Prescribe specific amounts
  • Assess quantities of time
  • Discuss strengths and safety
  • Use educational and instructional materials
  • Handouts, web-sites, video training modules:  www.eczemacenter.org
  • Follow-up soon!  Studies show that there is more chance that patients will follow their regimen and will have better clinical outcomes

Maintenance Therapy

  • Emollients alone? In 30-40% of infants, this may be sufficient
  • Intermittent corticosteroids
  • TCIs (delicate areas, persistent, frequently recurrent)
  • Targeted-Barrier-repair products
  • BRING THEM BACK while they are still under control

What about the patients who are better, but not great or have persistent, frequent flaring?

  • Ask about feeding practices, atopic history
  • Establish aggressive maintenance plan
    • Intermittent CS and/or TCIs
    • Assess sleep and itching as endpoints
    • Trials of TBRP (targeted barrier repair products) and/or emollients
    • Consider anti-infectives, bleach baths/products
    • Check growth, infection history, differential diagnosis
    • Consider allergy referral

TCI Safety Information

New information has been collected with regards to TCI safety, but the data have not yet been published. The FDA Pediatric Advisory Committee evaluated emerging data as part of a routine evaluation of TCI safety and use.   They looked at the epidemiology studies, the clinical studies, Data Safety Monitoring Boards and Post-marketing surveillance/Adverse Events Reporting System (AERS). The FDA found that there is no evidence of an association between TCIs and B-cell lymphomas but because of the limited data available, one cannot necessarily form conclusions from the published literature. The FDA also said that a literature review suggests a possible association between topical tacrolimus use and an increased risk of T-cell lymphoma.  The T-cell lymphoma association, however, may be due to use of the TCI in individuals reported as having eczema prior to the diagnosis of cutaneous T-cell lymphoma (known as protopathic effect).

It is important to remember that these are retrospective studies; so drawing conclusions can be difficult for the clinician.

An epidemiologic survey published by Tennis and Gelfand came to the same conclusions, i.e., there is little to no evidence of an increased risk of lymphomas overall or specific sub-types of lymphoma with topical TCI use and there is no evidence indicating that melanoma or non-melanoma skin cancer is associated with topical TCI use.

Microbes

Dr Eichenfield posed the following question to the audience…

Staph aureus in patients with atopic dermatitis:

A.  Is more likely to be MRSA than staph in infections in non-atopics

B.  Is less common than streptococcal infection

C.  Is less likely to be MRSA than staph in infections in non-atopics

D.  None of the above

MRSA and Atopic Dermatitis

Dermatologists should be aware that atopics have lower rates of MRSA infection than community-acquired staph infections. From an ecological perspective, the question is “does MSSA protect against MRSA?”

Translation into Clinical Practice

Bleach Baths and Alternatives*

  • ¼ to ½ cup for ½ to full tub of standard bleach (6%).
    • 5 cup for 40 gallon full tub is 0.005% concentration
    • Dilute Na hypochlorite and hypochlorous acid (Aurstat: marketed with HylatopicPlus)*
    • Na Hypochlorite body wash (CLn BodyWash)*

The AD market has responded to this and there are now at least two alternatives currently available to bleach baths. One of which is a tube of sodium hypochlorite and hypochlorous acid and it is paired with a ceramide-containing moisturizer. The other product is available over the internet that is a sodium hypochlorite body wash in a can.ir

Comorbidities and Atopic Dermatitis

Over the last few years atopic dermatitis has been associated with higher rates of attention deficit disorder and other mental health disorders.  Recent evaluation of a large healthcare database displayed higher rates of ADD in individuals with atopic dermatitis as compared to those without atopic dermatitis, with evidence of higher rates proportionate to severity of ADD.   Depression was also higher in teens and adults with AD.  While there is may not be enough evidence to mandate screening of atopic dermatitis patients, clinicians should be aware of the association.

Food Allergy and Eczema

About 17% of children with mild AD and 30-40% of moderate to severe children have at least one clinically relevant food allergy.  Food allergy testing (skin testing and IgE testing), however, yields many false positive tests; in fact, it is estimated that 4 out of 5 positive tests may not be associated with true food allergy, but only with IgE sensitization (e.g. Milk: 238 of 1000 tested will have false + ;  vs. 50 having clinically relevant allergy). 

Highlights from the NIH Food Allergy Guidelines

The current guidelines suggest that children less than 5 years of age with moderate to severe AD be considered for FA evaluation for milk, egg, peanut, wheat, and soy, if at least one of the following conditions is met:

  • The child has persistent AD in spite of optimized management and topical therapy.
  • The child has a reliable history of an immediate reaction after ingestion of a specific food

Dr Eichenfield feels that it is appropriate to ask about food allergies; if a child has had a food allergy, then an EPIPEN or EPIPEN Jr. should be prescribed.

Clinical Pearls for Atopic Dermatitis

  • Great skin care
  • Anti-inflammatory medication as needed, with most care as topical regimens
  • Maintenance care “as needed”
  • Keep regimens simple
  • Educate…in the office, on the net, wherever!
  • If really hard, seek help!