Eczema: A Comprehensive Overview of Atopic Dermatitis and Treatments

An example of mild-to-moderate eczema

What is Eczema?

Atopic Dermatitis (AD), more colloquially known as Eczema, is a skin condition characterized as “an itch that leaves a rash behind”, commonly leaving the skin red, blotchy, flaking, dry, and itchy. 15-30% of children and 2-10% of adults experience some degree of AD, with 60% of cases developing within the first year of life. AD most commonly localizes to the flexural surfaces of the skin (elbow-crease, knee-pits, hands, and other places that bend on itself or have frequent movement). While not life threatening, moderate-to-severe or chronic cases of AD can significantly impede sleep, increase irritability, and remarkably impact the social life, work life, and general quality of life. [1][2]

Examples of Flexural Rashes

What Causes Eczema?

Itch itself is a sensation that is currently the subject of scientific study. There are many different types of itch, with many different pathophysiologies and mechanisms and can be produced by mechanical, heat, chemical, or electrical stimuli. The most common type of pruritoceptive itch, which is roughly described as “itch borne from skin damage and inflammation”. Evolutionarily, this type of itch was developed to protect against parasites that latch onto the skin, with itching as a mechanism to dislodge and remove the parasites. In modern times, most people experience itch in response to mosquito bites, poison ivy, or other skin irritations. As such, the itching sensation usually subsides when the wound heals and the source of inflammation clears out. However, those with AD tend to experience skin damage and inflammation without the acute injury. Continued itching and scratching creates more areas of inflammation and skin damage, creating an endless feedback loop of itching and inflammation. The seemingly spontaneous itchiness and inflammation is what makes eczema so persistent. [1][2][3][4][5]

Because there are many different things that can cause inflammation, there is no one single etiologic source of AD. A litany of genetic and environmental factors all influence each other, and affect skin damage, skin inflammation, and subsequent itch, leading to the wide variation of eczematous presentation. Ordinarily, your body uses the immune system to fight against potentially dangerous foreign entities like bacteria or viruses, and react differently with each organ system. For example, the immune system localizes to the lungs during an influenza infection. During a skin barrier disruption, such as a cut or wound, the immune system produces heat, swelling, and inflammation to the exposed area to fight against potential infection. While good against harmful foreign entities, the immune system can over react to neutral foreign entities, creating unnecessary itchiness and inflammation, resulting in conditions such as AD (fun fact: the immune system mistakenly targeting good and beneficial entities is the basis of autoimmune diseases). [1][2][3][6][7]

Different genetic and environmental factors can affect the severity of the inflammatory immune response to the otherwise neutral stimuli. A genetic predisposition for impaired skin barrier can make the skin more likely to break and prompt endogenous inflammation, and general immune dysregulation can make the immune system more likely to induce inflammation with no real threat present. Additionally, different exogenous environmental triggers such as allergies, infections, exogenous physical stimuli, and emotional stress can irritate the skin and create inflammatory responses. These combined factors cause the immune system to overreact to neutral stimuli, leading to inflammation and eczematous outbreaks. [1][2][3][8][9]

Genetic Causes of Eczema

Genetic factors play a significant role in skin barrier production, inflammation, and subsequent eczematous onset and severity. Most cases of eczema begin with a genetic component that becomes exacerbated by other environmental factors. Additionally, affected individuals with eczema usually see their children also develop eczema at some point in their life. While acute environmental instances of inflammation like a mosquito bite can create temporary itchiness, environmental factors alone cannot develop into the persisting itchiness characteristic of AD without genetic predisposition.  [1][2][3][8][9]

When the immune system senses potential threat, it begins pumping different signaling chemicals into the body. The specific family of immune cells that release these chemicals are called Interleukins. Interleukins help produce pro-inflammatory immune system molecules such as cytokines and histamines that increase inflammation. Pruriceptors (neurons specifically calibrated for itchiness) detect that inflammation and eventually initiate the pruritic, itch sensation in that area. As such, genetic modulators that increase the production of those chemicals are more likely to induce inflammation, create an itchy sensation, and lead to the subsequent development of eczema. [1][2][3][4][5][8][9][10]

Genetic mutations in genes that affect skin barrier function are commonly found in affected individuals with AD. One of the most well-known skin barrier genes involved is the filaggrin gene (FLG), which produces the filaggrin protein that helps maintain skin barrier function. Filaggrin mutations are present in up to 30% of affected individuals. Other genes, such as the ceramide synthase gene and the ABCA12 gene, are responsible for lipid synthesis and transport respectively, and may also increase eczema onset or severity when mutated, further impairing barrier maintenance. With multiple different mutations, affected individuals experience increased severity to eczema and susceptibility to environmental irritants, allergens, and infections. [1][2][3][8][9]

With the skin barrier dysfunctional or generally disrupted, the skin becomes more susceptible to inflammation. Infection, dryness, bacterial infection, or even the mechanical stimulation of itching deteriorates the already weak skin barrier, creating cuts and open wounds that elicit an inflammatory response. Interleukins then secrete those pro-inflammatory molecules, which make the area itchier, leading to a feedback loop of itching inflammation leading to chronic eczema. [1][2][3][4][5]

Environmental Trigger Factors for Eczema

Many exogenous sources of inflammation can aggravate preexisting inflammation and exacerbate the eczematous skin lesions, worsening how itchy things feel. Different environmental trigger factors affect AD differently, with different treatment methods. [8][9]

Allergens 

Allergens, which include aeroallergens like pollen or pet dander and food allergens like milk, fish, or eggs, tend to exacerbate current or recent eczematous outbreaks. While not fully understood, aeroallergens have been tested and are believed to interact with the skin directly and induce the itch sensation at the point of contact. Food allergies are better understood, with itchiness to problem areas manifesting within two hours of food allergen digestion. In rare cases, itchiness manifests 2-6 hours after food allergen digestion, and will additionally cause the development of eczematous skin lesions even without scratching it. [8][9][11]

Removing these allergens from the environment are often insufficient to stop AD. Allergens generally do not create eczema (i.e., rubbing pet hair on an unaffected individual won’t give them eczema), and oftentimes children outgrow their allergies, yet AD persists. While useful for reducing acute eczematous instances, religious allergen aversion is ill-advised for treating chronic eczema. Instead, use of antihistamines and allergy medicine can be used to control acute instances of allergic eczematous outbreaks. [8][9][11]

Infections

One specific bacteria, Staphylococcus aureus, is the predominant bacteria found in 70-90% eczematous skin lesions. Rarely found on healthy skin, higher concentrations of S. aureus generally correlate with increased eczematous severity. S. aureus are known as opportunistic pathogens, meaning they are generally present in small numbers and remain neutral, neither positively or negatively affecting the body. They become contentious when they multiply and increase in numbers and infiltrate somewhere they shouldn’t be. The immune system responds to the abnormally high amounts of S. aureus, creating more inflammation and redness that, when itched, allows S. aureus to spread more, creating a feedback loop that increases the severity of AD. As such, antibiotics are commonly used to treat out-of-control AD. [8][9][12]

Physical Stimuli 

Another environmental trigger factor is broadly subcategorized as exogenous physical stimuli. These involve any touch or sensation that can cause irritation, such as uncomfortably wooly clothing, heat and humid weather, cold and dry weather, irritable soaps, solvents, or sweat, or external chemicals like cigarette smoke, perfumes, or contaminated lotions. Dehydrating skin through harsh soaps (soaps that strip away natural moisturizing oil), hot weather (heat evaporates moisture from the skin), or cold weather (dryness in the air reduces the moisture content from your skin) further disrupts the skin barrier and irritates the already under-moisturized skin. Additionally, wool, chemicals, and other irritable materials also increase inflammation. Retaining skin moisture using simple moisturizers, regulating your local temperature and humidity, and avoiding mechanically irritable clothing and cosmetic materials can prevent eczematous skin lesions from worsening. [8][9]

Psychological Stress

Instead of the tangible, physiological triggers of AD previously mentioned, psychological triggers such as stress can additionally exacerbate eczematous symptoms in AD. While the exact mechanisms are not understood, studies have found strong correlation between chronic stress and eczema flare-ups. Affected individuals in focus groups and subjective studies have reported increased eczematous exacerbation during intense episodes of chronic stress such as financial issues, familial issues, work or school stress, and other high-stress environments. Additionally, some studies record observations of how the brain, behavior, and immune system biochemically interact through psychoneuroimmunological studies. The brain releases specific stress-molecules when under psychological stress. If these molecules find their way to the skin, they upregulate the interleukin immune cells that release pro-inflammatory molecules, causing inflammation and subsequent itchy sensations. In short, feeling psychologically stressed can manifest as inflammatory responses in your skin and exacerbate eczema. [8][9][13][14]

Acute Treatments for Mild AD and Symptom Management  

While treating and adapting to exogenous environmental stimuli can reduce flare-ups, the underlying biological eczematous mechanisms still persist, and the corresponding endogenous stimuli require medical intervention to properly address. ~53% of reported AD diagnoses are mild-AD, with small and localized patches. While some cases only require frequent moisturization, others require more prescription strength solutions. Topical drugs are commonly used to treat mild AD, and come in lotions, creams, and ointments, and vary in strength from over-the-counter doses to prescription-level doses. They also double as moisturization to help rehydrate eczematous skin. [6][8][9][15]

Topical Corticosteroids

Topical corticosteroids are often used as a first option for curbing AD and its symptoms, and has been the norm for 40+ years. It can also be used to treat psoriasis, phimosis, and other rarer but similar skin conditions. Natural corticosteroids are a subclass of steroid molecules produced in the adrenal cortex (“cortico-”) of the brain, and can be involved in managing stress, immune system regulation, and inflammatory regulation. Synthetic corticosteroid drugs are designed to mimic these regulatory activities, enabling the administration of on-command anti-inflammatory signals to eczematous skin. When applied to eczematous skin, topical corticosteroids reduce the inflammation by slowing immune cell production and subsequent pro-inflammatory signals, restricting the body’s ability to deliver chemical signals to the area and providing itch relief. Oral corticosteroids are also an option to calm down the rampant inflammation in moderate-to-severe flare-ups of AD; applying topical drugs is no longer feasible when the entire body has eczema. [15][16][17][18]

Concerns for topical corticosteroids involve the prevalence of short-term and long-term adverse effects. Topical corticosteroids must be carefully administered to children under dermatologic specialist supervision. Corticosteroids may increase vulnerability to hormone imbalances and issues with growth and development. In adults, adverse effects such as skin thinning, epidermal striation, topical steroid addiction and topical steroid withdrawal may occur, resulting in furthering complications beyond AD. While typically onset through inappropriate or prolonged corticosteroid use, conflicting research produces contentious attitudes towards developing procedural adverse reaction countermeasures, and whether excessive corticosteroid use merits the risk of topical corticosteroid addiction and withdrawal. [15][16][17][18][19][20]

Alternatives to topical corticosteroids have emerged in recent years in response to the growing concerns, which include topical calcineurin inhibitors and topical phosphodiesterase-4 inhibitors. Both alternatives specialize in stopping new inflammation from occurring, whereas topical corticosteroids focus on reducing current inflammation. Therefore, current treatments typically involve both corticosteroids and topical inhibitors, with sparse topical corticosteroid use to handle flare-ups, and regular topical inhibitor use to keep inflammation away. [15][16][17][18][19][21][22]

Topical Calcineurin Inhibitors

Calcineurins are proteins involved in calcium-dependent biological pathways, with the most relevant example being T Cell activation (a specific type of immune cell). Calcineurin inhibitors are traditionally used to suppress inflammatory autoimmune disorders like lupus nephritis and idiopathic inflammatory myositis. They are also used in short term high doses as a general immunosuppressant for surgeries like organ transplants. Preventing calcineurin from working subsequently prevents the T Cell immune cells from working. In the context of AD, it stops the interleukins’ production of cytokines and pro-inflammatory molecules, thereby preventing inflammation and itch sensation from forming in the first place. Additionally, children as young as 2 years old are allowed to use certain topical calcineurin inhibitors with professional supervision. [15][21]

Topical calcination inhibitors are not good at reducing currently present inflammation. Therefore, temporary corticosteroids are frequently prescribed alongside calcineurin inhibitors to reduce flare-up symptoms and maintain asymptomatic presentation respectively. Additionally, like most drugs, overuse or long-term leads to complications and adverse effects. Excessive calcineurin inhibitor use can cause nephrotoxicity, with the kidneys shutting down from trying to filter the excess amount of drug. Proper dosing is essential for safe drug use. [15][16][18][21]

Topical Phosphodiesterase-4 Inhibitors 

Topical phosphodiesterase-4 inhibitors function similarly to calcineurin inhibitors in the sense that they prevent symptom onset, but are less efficient in treating current symptoms. In general, the phosphodiesterase class of enzymes exist to break phosphodiester bonds in cAMP and cGMP, a type of chemical signal used in many different molecular pathways and cells, making them inactive. By inhibiting phosphodiesterase, cAMP and cGMP can exist for longer and transmit stronger chemical signals. Phosphodiesterase inhibitors are used in diseases involving insufficient cAMP and cGMP signaling, such as chronic obstructive pulmonary disease, erectile dysfunction, and pulmonary arterial hypertension. Phosphodiesterase-4 originally exists in lung cells, but when put inside skin cells, they reduce inflammation and subsequent itch sensation. [15][16][18][21][22][23]

The exact mechanism of how decreasing phosphodiesterase and increasing cAMP in skin reduces inflammation is not well known. Clinical trials have shown efficacy with using topical phosphodiesterase-4 inhibitors in reducing inflammation and AD symptoms, proving that it works despite our lack of thorough understanding. Because of this lapse in knowledge, there is also no knowledge of predicting or combating adverse side effects. With the only current complaint is a burning sensation upon initial topical application, further research is required to elucidate the exact mechanism and determine short-term and long-term effects. [15][22][23]

Biologic Treatments for Moderate-to-Severe AD

Topical drugs (via lotions, creams, and ointments) require constant administration and maintenance, and are sufficient for mild AD and acute flare ups, allowing for sporadic use when necessary. However, those with moderate-to-severe AD and or chronic AD would need to consistently apply the topical drugs to their entire body. Roughly ~38% of patients report moderate-AD, and 8% report severe-AD. With concerns surrounding continuous and excessive topical drug administration, more intensive and permanent treatments are preferred. Many current biologic treatments focus on continuous inhibition of interleukin and cytokine production, constantly slowing down inflammatory processes throughout the entire body. These drugs inhibit the same interleukins that the topical treatments inhibit. However, because they are designed to circulate through your bloodstream to find areas of inflammation from the inside, no topical administration is required. The body finds each and every inflamed cell and stops the source of the inflammation automatically, providing prolonged and widespread relief from itch sensations. [15][16][23][24]

The most significant downsides to biologic treatments are mostly logistical. As they are more expensive to make, insurance companies will only allow prescriptions if previous topical therapies are proven ineffective. Furthermore, because of their novelty, they are much more expensive and require specialty pharmacies to deliver. Additionally, certain biologics are not advised for children under 12 years old. Finally, these biologics often have very high dosages and require subcutaneous injection with a needle, which can be intimidating for needle-adverse people. However, once administered, many AD patients report significant improvements to their symptoms and quality of life. [15][24]

The Atopic Triad: Eczema, Asthma, and Allergies

Those with eczema are also at a higher risk to also have asthma or allergies, with the interrelated three conditions commonly referred to as the “atopic triad”. Eczema, asthma, and allergies all involve improper inflammation, whether it’s in your skin, lungs, or nose. These conditions are genetically linked, one gene or environmental factor can contribute to any three of those processes. As such, those with one condition will more often than not have another condition, if not both. [1][2][3][25][26]

In Conclusion

Atopic Dermatitis, more commonly known as Eczema, can cause intense discomfort and significantly reduce quality of life. While there are a wide range of treatment options, research is still being conducted to deepen our understanding of the disease, and consequently make it easier to combat in the future. As someone with moderate-to-severe eczema, I hope to one day not have to worry about whether wearing certain clothes, staying in the sun too long, or being around dogs and cats will exacerbate my eczema. Alleviating my symptoms would significantly improve my stress and quality of life, and I hope that future generations won’t experience the same chronic discomfort that I and many others have. 

---

References 

1. Nemeth, V., Syed, H.A., Evans, J. Eczema. [Updated 2024 Mar 1]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK538209/ 

2. Kolb, L., Ferrer-Bruker, S.J. Atopic Dermatitis. [Updated 2023 Aug 8]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK448071/ 

3. Garibyan, L., Rheingold, C. G., Lerner, E. A. Understanding the pathophysiology of itch. Dermatologic Therapy. 2013 Mar-Apr;26(2):10.1111/dth.12025. doi: https://doi.org/10.1111/dth.12025.

4. Garcovich, S., Maurelli, M., Gisondi, P., Peris, K., Yosipovitch, G., Girolomoni, G. Pruritus as a Distinctive Feature of Type 2 Inflammation. Vaccines (Basel). 2021 Mar 23;9(3):303. doi: https://doi.org/10.3390/vaccines9030303. 

5. Ringkamp, M., Meyer, R. Itch: Mechanisms and Treatment. Carstens, E., Akiyama, T., editors. Boca Raton (FL): CRC Press; 2014. Chapter 9: Pruriceptors. doi: https://doi.org/10.1201/b16573. 

6. Martin, G., Aldredge, L., DiRuggiero, D., Young, M., Simpson, E. An Overview of Atopic Dermatitis Disease Burden, Pathogenesis, and the Current Treatment Landscape: Recommendations for Appropriate Utilization of Systemic Therapies. Journal of Clinical and Aesthetic Dermatology. 2025 Mar;18(3):51–66. 

7. Klomp, M., Ghosh, S., Sohail, M., Nadeem Khan, M. From virus to inflammation, how influenza promotes lung damage. Journal of Leukocyte Biology. 2020 Sep 8;110(1):115–122. doi: https://doi.org/10.1002/JLB.4RU0820-232R. 

8. Hong, J., Buddenkotte, J., Berger, T. G., Steinhoff, M. Management of Itch in Atopic Dermatitis. Seminars in Cutaneous Medicine and Surgery. 2011 Jun;30(2):71–86. doi: https://doi.org/10.1016/j.sder.2011.05.002.

9. Lazor, J.E., Bozsoki, B.A., Bharadwaj, P. Cure for the itch: current clinical standards and therapies in allergic eczema. Frontiers in Allergy. 2025 Apr 3;6:1569292. doi: https://doi.org/10.3389/falgy.2025.1569292.

10. Justiz Vaillant, A. A., Qurie, A. Interleukin. [Updated 2022 Aug 22]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK499840/. 

11. Chong, A. C., Chwa, W.J., Ong, P. Y. Aeroallergens in Atopic Dermatitis and Chronic Urticaria. Current Allergy and Asthma Reports. 2022 Jul;22(7):67-75. doi: https://doi.org/10.1007/s11882-022-01033-2. 

12. George, S. M., Karanovic, S., Harrison, D. A., Rani, A., Birnie, A. J., Bath-Hextall, F. J., Ravenscroft, J. C., Williams, H. C. Interventions to reduce Staphylococcus aureus in the management of eczema. Cochrane Database of Systematic Reviews. 2019 Oct 29;2019(10):CD003871. doi: https://doi.org/10.1002/14651858.CD003871.pub3. 

13. Lönndahl, L., Abdelhadi, S., Holst, M., Lonne-Rahm, SB., Nordlind, K., Johansson, B. Psychological Stress and Atopic Dermatitis: A Focus Group Study. Annals of Dermatology. 2023 Oct;35(5):342–7. doi: https://doi.org/10.5021/ad.22.035. 

14. Suárez, A. L., Feramisco, J. D., Koo, J., Steinhoff, M. Psychoneuroimmunology of psychological stress and atopic dermatitis: pathophysiologic and therapeutic updates. Acta Dermato-Venereologica, 2012 Jan;92(1):7–15. doi: https://doi.org/10.2340/00015555-1188. 

15. Caffarelli, C., Giannetti, A., Giannì, G., Ricci, G. Anti-inflammatory and biologic drugs for atopic dermatitis: a therapeutic approach in children and adolescents. Frontiers in Medicine. 2023 Aug 16;10:1214963. doi: https://doi.org/10.3389/fmed.2023.1214963. 

16. Draelos, Z. D., Feldman, S. R., Berman, B., Olivadoti, M., Sierka, D., Tallman, A. M., Zielinski, M. A., Ports, W. C., Baldwin, S. Tolerability of Topical Treatments for Atopic Dermatitis. Dermatology and Therapy. 2019 Jan 24;9(1):71–102. doi: https://doi.org/10.1007/s13555-019-0280-7. 

17. Nussey, S., Whitehead, S. Endocrinology: An Integrated Approach. Oxford: BIOS Scientific Publishers; 2001. Chapter 4, The adrenal gland. Available from: https://www.ncbi.nlm.nih.gov/books/NBK26/ 

18. Gabros, S., Nessel, T. A., Zito, P. M. Topical Corticosteroids. [Updated 2025 Apr 26]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK532940/ 

19. Maskey, A. R., Sasaki, A., Sargen, M., Kennedy, M., Tiwari, R.K., Geliebter, J., Safai, B., Li, X.M. Breaking the cycle: a comprehensive exploration of topical steroid addiction and withdrawal. Frontiers in Allergy. 2025 Mar 31;6:1547923. doi: https://doi.org/10.1007/s13555-019-0280-7. 

20. Harvey, J., Lax, S.J., Lowe, A., Santer, M., Lawton, S., Langan S.M., et al. The Long-Term Safety of Topical Corticosteroids in Atopic Dermatitis: A Systematic Review. Skin Health and Disease. 2023 Oct;3(5):ski2.268. doi: https://doi.org/10.1002/ski2.268.

21. Safarini, O. A., Keshavamurthy, C., Patel, P. Calcineurin Inhibitors. [Updated 2023 Nov 12]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK558995/. 

22. Padda, I. S., Tripp, J. Phosphodiesterase Inhibitors. [Updated 2023 Jun 26]. In: StatPearls Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK559276/. 

23. McDowell, L., Olin, B. Crisaborole: A Novel Nonsteroidal Topical Treatment for Atopic Dermatitis. Journal of Pharmacy Technology. 2019 Aug;35(4):172-178. doi: https://doi.org/10.1177/8755122519844507. 

24. Moyle, M., Cevikbas, F., Harden, J. L., Guttman‐Yassky, E. Understanding the immune landscape in atopic dermatitis: The era of biologics and emerging therapeutic approaches. Experimental Dermatology. 2019 Apr 15;28(7):756–68. doi: https://doi.org/10.1111/exd.13911. 

25. Steinke, J. W., Borish, L. Th2 cytokines and asthma — Interleukin-4: its role in the pathogenesis of asthma, and targeting it for asthma treatment with interleukin-4 receptor antagonists. Respiratory Research. 2001 Feb 19;2(2):66–70. doi: https://doi.org/10.1186/rr40. 

26. Ryan, J. Interleukin-4 and its receptor: Essential mediators of the allergic response. The Journal of Allergy and Clinical Immunology. 1997 Jan;99(1):1–5. doi: https://10.1016/s0091-6749(97)70293-8. 

Assessed and Endorsed by the MedReport Medical Review Board