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Atopic March: How can we halt it with modern medicine?

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Atopy refers to a genetic predisposition to developing allergic diseases, while atopic march is the natural progression and evolution of these allergic diseases. Atopy is commonly due to an exaggerated immune response towards allergens in the air or food. Allergic diseases such as atopic dermatitis, allergic asthma and allergic rhinitis affect 1 in 4 people globally, and the incidence of allergy continues to rise over the years.

Allergy diseases are fascinating in the sense that one tends to develop the diseases chronologically from childhood atopic dermatitis and food allergy to eventual progression of asthma and allergic rhinitis. This intriguing allergy progression phenomenon is time-based, involves the evolution and involvement of the skin-gut-respiratory system and is termed the Atopic March.

In this article, we highlight the manifestations in atopic march, the current clinical hypothesis behind these allergic diseases and discuss certain medical strategies to prevent or halt the progression of atopic march.

The Chronological Progress of Atopic March

The initial manifestation of atopic march involves atopic dermatitis, also known as eczema. The atopic march classically continues with food allergy, and eventually ends with progression to allergic asthma and allergic rhinitis. Children with atopic dermatitis have a 6 times higher chance of developing food allergies. 60% of children with atopic dermatitis may eventually develop asthma/ rhinitis later in their childhood. 

Eczema, or atopic dermatitis, is a chronic skin condition causing itchy, inflamed, and dry patches that flare up due to irritants, allergens, or genetics.

Atopic dermatitis

Atopic dermatitis is a recurring and relapsing inflammatory skin disorder whereby one presents with dry skin, inflamed, and itchy skin. Atopic dermatitis tends to occur in early life. It affects about 30% of children and can manifest its symptoms as early as less than 6 months of age. Atopic dermatitis is due to a complex combination of genetic and environmental factors. It is postulated that due to the impaired skin barrier in atopic dermatitis, external allergens are able to interact with the internal skin and immune cells leading to sensitisation of the immune system and manifestation of allergic response.

Food allergy

Food allergy frequently occurs simultaneously with atopic dermatitis during early childhood and is an indicator and risk of a person to be likely to progress with subsequent atopic march. Children and infants with food allergy develop allergic asthma earlier than those without food allergy. Those patients with food allergy can have an exaggerated and hypersensitivity and inflammation of the airway. 

Allergic rhinitis and Allergic asthma

Allergic rhinitis and allergic asthma are two allergic respiratory conditions that are closely linked. Environmental factors such as dust mite particles, air pollution, pollen, pet dander, food proteins/allergens can play a role in the development of allergic rhinitis and allergic asthma.

In allergic rhinitis, there is chronic recurring inflammation of the mucosal layer of the upper respiratory tract with predominant involvement of the nose passage leading to recurring bouts of sneezing, watery and blocked nose, itchy eyes, etc. Recurring allergic rhinitis can also stimulate and trigger contraction of the lower respiratory system such as the lungs muscles and tissues eventually lead to chronic inflammation, spasm and hypersensitivity of the lungs — allergic asthma.

Possible Causes of Atopic March

There remain gaps in the understanding of the progression of atopic march. A few theories have been hypothesised to explain the phenomenon.

Atopic march is the progression of allergic diseases from infancy to childhood, typically starting with eczema, followed by food allergies, asthma, and allergic rhinitis.

Impaired skin barrier

The skin functions as a physical layer to shield the body against external noxious agents. When the skin barrier is inflamed and impaired, it is ineffective in defending the body against environmental triggers such as pollutants, allergens, infections and other pathogens. The term transcutaneous sensitisation describes the allergenic proteins entering the body via leaky skin, leading to sensitisation of the immune system and development of atopic dermatitis — the first step of the atopic march and subsequent other allergic diseases.

Genetic disruption with filaggrin gene mutation

Filaggrin is a protein vital as part of the structure and component of the skin layer (stratum corneum). There is association of genetic mutation of filaggrin protein with those with atopic dermatitis. The integrity of the skin layer is compromised in those with filaggrin gene mutation, causing a weaker skin barrier and, hence, easier access of allergenic protein to the immune system, which can result in atopic diseases.

Interactions with environmental factors 

Airborne and food particles such as dust mites, fungi, pollen, insects, pet dander, peanuts, milk, seafood etc., can behave as allergen proteins. Upon exposure to the skin, gut, respiratory tract, they are able to trigger an exaggerated immune response leading to atopic symptoms. 

Interestingly, certain environmental proteins can also function as an adjuvant (facilitator) to other allergenic proteins to cause allergy.

Microbiome changes

The microbiome in the skin, intestine and the lungs interacts — this is known as ‘inter-organ cross-talk’, and is observed in atopic march. The skin microbiome in a person with atopic dermatitis differs from a person without atopy, with increase in Staphylococcus spp bacteria. It is also noted that the gut microbiome is less diversified in infants with atopic dermatitis and food allergy. The shift of the gut bacteria has been associated with allergic respiratory inflammation. Although the findings in the pattern of microbiome in the human body remain a novel concept, there is strong correlation between alteration of the body’s microbiome and atopic march. 

Can we stop atopic march with modern medicine?

Understanding of the natural progression of atopic march is imperative in managing the progression of atopic march. Although the current understanding of atopic march remains incomplete and there is no easy way to halt the progression of allergy, we can still utilise current clinical knowledge of the disease and manage the allergic progress.

Atopic dermatitis

Moisturiser and appropriate topical medication (commonly involving steroids) remain the key backbone in the management of atopic dermatitis. Aside from this ubiquitously known fact, we would like to share tips that are relevant, yet commonly neglected here:

  • Regular moisturising of the skin to maintain a healthy good skin barrier and prevent exposure of the skin against environmental allergens.
  • Harsh soap should be avoided as they can remove natural skin oil, a protective layer leading to penetration of allergens and pathogens. Over-washing should be avoided.
  • It is important to wash the hands, ensure good hand hygiene before using the same hands to apply moisturiser to eczema skin. This is particularly important in parents/ carers who are applying moisturiser/ topical medication to the child/ others. Contaminated hands can transfer germs or allergens (such as dust/ food proteins) to the broken eczema skin leading to allergy over time.
  • Products (soap/wash/detergent) with fragrant, dye, preservatives should be avoided as they can act as triggers for atopic dermatitis.
  • A person’s living space should be kept clean from aeroallergens such as pollen, mold, dust mites, tobacco smoke, pet furs to reduce development and flares of atopic dermatitis.
  • Avoid recurring skin infections — bacterial/viral infections that can disrupt the skin barrier.

Identifying those who are predisposed to a lifelong chronic atopic disease (atopic march) is paramount as the window period during early life should be targeted for treatment intervention. Maintaining a good skin barrier is essential. Appropriate skin care and management of atopic dermatitis can prevent further sensitisation of food or aero-allergens, subsequently reducing the risk of progression of atopic march.

Food allergy

  • Identifying the culprit food allergen triggers can avoid manifestations of atopic diseases.
  • Keeping a good food diary helps to pinpoint possible food particles that are associated with atopic symptoms.
  • If food elimination is impossible, one can consider food allergy testing in the form of skin prick test or blood RAST test to identify the possible food protein that causes atopic symptoms.
  • Keeping the living space clean is vital as exposure to food allergy can be beyond our food plate. Small quantities of food proteins or allergens can be found in living spaces such as our couch, bed, floor, carpets. Over time, contact with these particles to our body can lead to sensitisation and allergic symptoms. 
  • Understanding food allergy symptoms can be subtle and vague involving unusual gastrointestinal symptoms. Subtle unexplained symptoms such as gastro reflux symptoms, indigestion, failure to gain weight, diarrhea, vomiting, abdominal cramps may be telltale signs of food allergy, though classical symptoms may involve overt allergic symptoms such as skin rash, oral mucosal itch/swelling, breathing difficulties and etc.

Managing food allergy, avoiding repeated triggers is beneficial as those with atopic dermatitis and food allergy has shown to be more likely to continue the atopic march progression to the final respiratory allergic symptoms.

Asthma inhalers help with allergic asthma by relaxing airway muscles and reducing inflammation, making breathing easier and preventing flare-ups.

Allergic rhinitis and allergic asthma

  • Optimising symptomatic medications such as antihistamines, nose sprays, inhalers can manage the allergic symptoms and improve quality of life.
  • Ensuring living space is clean, well-ventilated can minimise exposure to airborne allergens and triggering of allergic symptoms.
  • Picking up airborne allergens or food allergens that trigger the allergic respiratory symptoms helps to prevent further trigger of the allergic symptoms and halt the progression to the end point of atopic march.
  • Skin prick test and blood RAST test can be useful in identifying common airborne and food-based allergens.
  • Allergen-specific-immunotherapy can be offered to identify airborne allergens to re-educate and desensitise the immune system against the allergens, thereafter downregulate and control the allergy. Clinical studies have shown the effective role of using allergen-specific immunotherapy in allergic rhinitis to halt further development of allergic asthma. In allergic asthma, allergen-specific-immunotherapy has a positive role to reduce chronic inflammation of the lower airway tract, reduces recurring asthma flare up and medication burdens. 

While both allergic rhinitis and allergic asthma are considered the end point of atopic march, managing both conditions can improve a person’s quality of life tremendously. The ability to pinpoint the triggering allergens and receive targeted immunotherapy suggest there is a glimpse of hope in managing atopy symptoms.

Take home messages

  • The occurrence of allergic disease is increasing over the years and significantly affects a person’s health and quality of life.
  • Atopic march begins with manifestation of atopic dermatitis with possible concurrent occurrence of food allergy and eventually progresses to respiratory atopic diseases such as allergic rhinitis and allergic asthma.
  • While the background medical mechanism of atopic march remains incomplete, clinical understanding of the condition allows us to incorporate lifestyle and treatment strategies to manage atopy.

References:

  1. Yang L, Fu J, Zhou Y. Research Progress in Atopic March. Front Immunol. 2020 Aug 27;11:1907.
  2. Nibbering B, Ubags NDJ. Microbial interactions in the atopic march. Clin Exp Immunol. 2020 Jan;199(1):12-23.
  3. Hill DA, Spergel JM. The atopic march: Critical evidence and clinical relevance. Ann Allergy Asthma Immunol. 2018 Feb;120(2):131-137.
  4. Bantz SK, Zhu Z, Zheng T. The Atopic March: Progression from Atopic Dermatitis to Allergic Rhinitis and Asthma. J Clin Cell Immunol. 2014 Apr;5(2):202.

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