Cellular and molecular immunologic mechanisms in patients with atopic dermatitis

Atopic dermatitis is one of the most common chronic skin diseases among both adults and children.  Although it is often thought of as a skin disease, it also affects many organ systems. There remain a lot of gaps in our knowledge of atopic dermatitis, but researchers are developing a greater appreciation for its complexity of atopic dermatitis and introducing new treatments for this frustrating disease.

From an immunologic point of view, atopic dermatitis appears to be a collection of many different variants.  These endotypes are just recently beginning to be described, but involve the various arms of the immune system.  Defects in the innate immune system skew the skin towards inflammation; polarization of T-cells (Th2, Th17, and Th22) lead to further inflammation.  Other cell types, like dendritic cells, eosinophils, and mast cells, play important roles in the development of atopic dermatitis.  The interplay between immune cells and skin barrier proteins, like filaggrin, is also being explored.  Filaggrin influences cell differentiation, prevents water loss, and maintains the integrity of the skin barrier.  With defects in filaggrin, allergens penetrate deeper into the skin and bacteria like staphylococcus aureus are more likely to colonize the skin.

To make things even more complicated, as time progresses, so too does the disease, and patients can have an “atopic march” towards asthma, allergic rhinitis, and other allergic diseases.  Additionally, patients with atopic dermatitis have changes in the bacteria that colonize their skin and gut.  They have less microbial diversity, particularly when there is greater inflammation.  The role of these bacteria are being increasingly fleshed out with basic science and clinical research.

These insights are helping to guide new therapies.  In particular, dupilumab, an antagonist of the IL-4 receptor alpha chain, is showing promise in the treatment of atopic dermatitis.  And in those that don’t respond to dupilumab, there’s interest in other therapies like the IL-6 receptor antagonist tocilizumab.  As Werfel and colleagues note, it is difficult to find the best treatment for atopic dermatitis without knowing the pathophysiology behind the disease and its various endotypes (J Allergy Clin Immunol 2016; 138(2): 336-349).  In the future, with better knowledge, it may be possible to personalize appropriate treatment by identifying the correct endotype for each patient.

Comments

Post a Comment

Popular posts from this blog

Features of the bronchial bacterial microbiome associated with atopy, asthma and responsiveness to inhaled corticosteroid treatment

It’s been known that asthmatic lungs are different from healthy lungs in many aspects, including housing different strains of bacteria.  So far, studies haven’t been able to tell whether these differences are due to asthma, associated allergies (atopy), or treatment with different drugs.  They also haven’t been able to determine how these differences affect the way asthma manifests itself and how asthma can be treated.  In this month’s issue of JACI, Durack and colleagues aim to answer these pressing questions ( J Allergy Clin Immunol 2017; 140(1): 63-75 ). Durack and other investigators looked at the bacterial communities in 84 individuals, split into three groups: (1) 42 atopic asthmatic subjects, (2) 21 atopic non-asthmatic subjects, and (3) 21 non-atopic non-asthmatic, otherwise healthy, subjects.  They also looked at inflammatory markers and changes in bronchial hyperresponsiveness after 6 weeks of treatment with fluticasone, an inhaled steroid commonly used for...
Read more

Introducing an environmental assessment and intervention program in inner-city schools

Few studies have comprehensively examined the role the school environment plays in asthma and how effectively changing the environment may reduce morbidity, when adjusting for exposures in the home. In their review, Huffaker and Phipatanakul summarize the importance and common challenges of school-based environmental assessment and intervention studies linked to health effects ( J Allergy Clin Immunol 2014; 134: 1232-1237 ). They discuss the challenges and potential benefits of comprehensive environmental assessment and health outcomes in inner-city schools. The school environment has been shown to be a significant reservoir for allergens and pollutants. Indoor allergens known to be important in urban home environments may also be important in schools, including cockroach, cat, dog, mouse, dust-mite, and molds. Studies have identified children with asthma in inner-cities have markedly higher levels of mouse allergen in their schools compared to levels in their individual bedrooms. Give...
Read more

Role of viral infections in the development and exacerbation of asthma in children

Wheezing is a common complaint among parents of infants.  About 1 in 5 children have acute wheezing illnesses in their first two years of life.  This is important because an overwhelming majority of these wheezing illnesses are related to viruses, and are linked to asthma development.  In this month’s issue of JACI, Jartti and Gern review the role of viral infections in the development of asthma in children ( J Allergy Clin Immunol 2017; 140(4): 895-906 ).  They survey the viruses -rhinoviruses, respiratory syncytial viruses, and others – and how they impact the developing set of lungs.  Genetic variation and low interferon responses are two factors that increase the risk of these types of infections.  In addition, increased eosinophil counts in blood and nasal mucus and atopic eczema all increase the risk of later asthma.  Additionally, viral infections can lead to exacerbations in children who already have asthma.  This may explain why the rates...
Read more