Eczema is a dermatological condition that can arise from environmental factors, genetic mutations, or hereditary causes. While it can appear on any part of the body, it most commonly manifests on the hands, face, and neck. Eczema can develop at any stage of life, although it is particularly prevalent among infants, adults, and individuals aged between 13 to 18 years. Environmental changes can trigger the onset of eczema, and one of the primary causes is a mutation in the FLG gene .
The FLG gene is situated on chromosome 1 in Homo sapiens (humans), specifically within the range of 152,302,165 to 152,325,239. This gene goes by various names, including BFGFR, CD331, CEK, ECCL, FGFBR, FGFR-1, FLG, FLT-2, and FLT2. It belongs to the Fibroblast Growth Factor Receptor (FGFR) family and is responsible for producing a protein essential for forming keratin intermediate filaments in the mammalian epidermis. The protein's amino acid sequence is highly conserved .
More information about the FLG gene:
When transcribed, the FLG gene performs various roles, including those related to cancer and disease, as well as plasma proteins. The FLG protein is primarily located in the cytoplasmic layers of squamous epithelia, where it carries out its functions. It resides in intracellular structures known as cytoplasmic-bodied structures and plays a crucial role in producing keratin, the moisturizing factor, in the skin. A mutation in the FLG gene can lead to dry skin, indicating a deficiency of keratin .
Example of layers in Squamous Epithelia and illustration of FLG in Cytoplasmic cells. (Source):
Mutation in the FLG gene significantly contributes to the development of eczema. Filaggrin (FLG) genetic variants play a vital role in this condition and are less common in African populations compared to Europeans and Asians. The FLG gene, located on Chromosome 1 in Homo sapiens, is also present in various other species, with the house mouse being the most prominent. Its primary role is to act as a skin barrier by transcribing into filaggrin protein .
Fig3. FLG gene after being transcribed into a filaggrin protein. (Source)
The process of gene transcription is crucial yet complex in terms of protein development. Even a minor mutation or error during DNA replication of the FLG gene can alter the gene's nucleotide sequence, resulting in a mutated protein. These mistakes can occur through deletion, substitution, or insertion . One of the most frequent mutations observed in the FLG gene is a missense substitution, accounting for 78.57% of reported occurrences. This substitution leads to the incorporation of a different amino acid at a specific site, potentially affecting protein formation .
Mutations in the FLG gene can be passed down to future generations. If the gene is recessive (meaning an allele is not expressed with a dominant allele), its effects may only be noticeable in the second generation. However, if a mother carries the mutated FLG gene, it can have a more dominant effect in the next generation. A Family Association Study conducted by Han Chinese researchers collected data on how mutated and unmutated FLG genes are expressed in 100 family groups .
Fig6. Data collected by the Han Chinese researchers on how different expressions of the FLG can affect dermatitis and epidermis layer of the patients (Source)
Various factors can lead to gene mutations. Radiation exposure is one such factor. Ionizing radiation, which includes x-rays, gamma radiation, and alpha particles, can cause genetic sequences in reproductive cells to be disrupted, resulting in mutations that can be passed on to subsequent generations. Exposure to certain chemicals, commonly found in our diet and products, is another mutational factor .
Fig7. Environmental Factors that cause genetic mutation. Source: Model by Mary Hakeem
Research has indicated that eczema is more prevalent in European and Asian populations compared to African populations. In the United States, an estimated 31 million individuals are affected by eczema, with infants being the most vulnerable group. While the condition can occur at any age, approximately 10 to 20% of infants develop eczema.
Fig8. Analytical data on the percentage of different races developing Eczema from 2000 to 2010. (Source)
Around 60% of adults and 80% of infants exhibit severe symptoms of eczema within a short period. Symptoms include skin dryness, itchiness, skin rash, bumps, thick and leathery patches, flaky or crusty skin, and swelling. The appearance of the eczema rash can vary based on an individual's skin tone, with darker skin tones showing different shades of rash compared to lighter skin tones. Eczema can affect various body parts, including the hands, neck, face, elbows, ankles, knees, feet, ears, and lips. It can also develop in areas such as the nipples, breasts, and genital region .
Fig9. Examples of Eczema symptoms in different affect body areas. Source
Eczema typically presents as a rash and is not inherently painful. However, the severity of symptoms can vary based on factors such as humidity, clothing material, exposure to irritants, and inadequate moisturization. Certain food triggers, like peanuts, eggs, and dairy, can also exacerbate symptoms. The urge to scratch the affected skin can lead to a breakout, causing swelling and a burning sensation .
In the diagnosis of Eczema, a series of tests are carried out to determine the most appropriate treatment and the specific conditions of the skin condition. Initially, allergy tests are conducted, followed by blood tests to confirm Eczema's presence and rule out the possibility of an autoimmune disease or a rash unrelated to Eczema. Finally, a skin biopsy is performed to distinguish Eczema from other types of dermatitis. As Eczema is a lifelong condition, no medication fully cures Eczema but can only help soothe the symptoms. Available treatments for Eczema are Tacrolimus ointment and corticosteroid cream (hydrocortisone).
Protopic ointment with calcineurin inhibitor is usually prescribed to those age over 2 years old. _ Pros: _ It has direct interaction with Keratinocytes and prevents allograft rejection. Also, it is rare to develop severe allergic reactions from this drug. _ Cons: _ It lowers the body's ability to fight off infections and can cause muscle, joint pain and chest pain, headaches, acne, flu-like symptoms, and skin sensitivity.
Corticosteroid Cream "Hydrocortisone":
Elidel ointment has multiple types but mainly hydrocortisone skin cream is the most commonly prescribed topical for Eczema. It has a certain amount of FTU "fingertip units" for every affected area; for example, 1 FTU for hands, elbows, or knees and 2.5 FTU for the face and neck. _ Pros: _ It can lower redness and burning, itching, dry skin sensation, and control flare. _ Cons: _ can worsen the spread of a skin infection, inflamed hair follicles, skin thinning, stretch marks, contact dermatitis, rosacea, change in skin color, acne, and excessive hair growth on the treated area.
Mechanism of Action of Hydrocortisone :
Hydrocortisone is a medication that reduces the immune response and has anti-inflammatory properties. It uses cortisol, a hormone produced by the adrenal gland's Zona Fasciculata, known as the "stress hormone ," due to its connection to the body's response to stress. Cortisol is regulated by Corticotropin-releasing hormone (CRH) and works through the Corticosteroid Hormone Receptor as a transcription factor. By negatively affecting the transcription rates of glucocorticoid-responsive genes, it reduces inflammation. The FDA has approved it for topical treatment.
Fig10. How Corticosteroid Hormone Receptor affects Glucocorticoid genes activity. (Source)
Research focuses on finding a permanent cure for Eczema using JAK inhibitors. However, using inhibitor drugs that can block the activation of inflammatory genes responsible for Eczema is a noteworthy step forward. Overusing steroids may make the body reliant on them, and preventing their use suddenly can worsen symptoms. Although there is still a lot to learn, non-steroid inhibitors are the best treatment for Eczema. In addition, maintaining a healthy diet and thoroughly moisturizing your skin can be helpful. A new suggestion for treatment is light therapy.
In conclusion, eczema is a complex dermatological condition influenced by genetic mutations and environmental factors.It can also arises from a genetic mutation in the FLG gene, which impacts the production of filaggrin protein responsible for skin keratinization. A variety of environmental factors can trigger this mutation. Eczema affects the epidermal and dermal layers of the skin and can display anywhere on the body. Its symptoms correspond to those of inflammation. Tacrolimus ointment and hydrocortisone are the two most common treatments for Eczema, but they are not a permanent solution and have limitations due to the use of steroids. Eczema can impact individuals of all ethnicities and is known to affect 31 million Americans. Non-steroidal treatments for Eczema are currently being researched, focusing on JAK inhibitor injections.
By Mary Hakeem: La Serna High School
Hello! My name is Mary Hakeem, and I am currently a Senior. Joining the Elio Academy of Biomedical Sciences was a significant movement in pursuing my passion for Biology, especially the biomedical research field. I was determined to seek more information about Immunology, and I found that Elio Academy is the reach and resourceful destination to support my exploration of Immunology. My project topic is Chronic Eczema, a fascinating subject for study. The reason that drove me to research more about this disease was that it is a life-long disease with no permanent cure. I have experienced many people suffering from endless pain. In my research paper, I have conducted a complete analysis and a breakdown of the genetic information on the gene responsible for the disease, why the condition occurs, and how much Scientists have found about this disease. Because of the Elio Academy instructors' efforts, I was able to search and discover more about Chronic Eczema, one of the types of Atopic Dermatitis disease. My two-week course experience with Elio Academy shaped how I see genomics and how precise genetic coding is. I conducted research that would benefit many of those with the disease to learn more about it.
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