Mouth Sores: Symptoms, Treatment, Causes

Mouth sores are a prevalent condition that impacts multiple individuals at some point in their lifetimes. Mouth sores manifest on any of the delicate tissues of the mouth, such as the lips, inside the cheeks, gums, tongue, and floor and roof of the mouth. They are a relatively minor irritation that persists for only one or two weeks. They suggest a more severe condition, such as oral malignancy or an infection in certain instances. Each mouth sore is unique. Most canker sores are small, white, or yellow ulcers with red edges caused by minor trauma or stress. Candida albicans create creamy white tongue or inner cheek sores during oral thrush for individuals with compromised immune systems. Smoking causes cancer-causing leukoplakia, thick, white gums, and mouth lining. Red erythroplakia lesions are high-risk for cancer and require biopsy. Oral lichen planus, which forms white, lacy patches or red, swollen tissues in the mouth, is more common in elderly women and raises oral cancer risk. Hand, foot, and mouth disease in children causes painful red blisters in the mouth and a rash on the hands and feet. Mouth cancer spreads anywhere in the mouth and produces ulcers, white or red patches, and swallowing problems, requiring medical intervention.

Mouth sore symptoms harm oral health. Red, inflamed rims and white, yellow, or grey cores are common in canker sores of various sizes. These sores, which hurt when eating or talking, are classified as basic or complex based on frequency and duration. Early warning signs include burning or tingling before sores. Mouth sores make chewing and swallowing difficult, affecting eating habits and nutrition. Ulcers' acidity and bacterial overgrowth cause bad breath. Fever, lethargy, and enlarged lymph nodes accompany severe cases, especially with numerous lesions.

Mouth sores emanate from a variety of sources, such as viral infections like herpes simplex and varicella-zoster, bacterial infections like syphilis and gonorrhoea, and systemic disorders like celiac disease, inflammatory bowel disease, and Behçet disease. Other contributing factors include the overgrowth of Candida albicans as a result of weakened immune systems, nutritional deficiencies, tobacco use, and physical trauma to the mouth as a result of biting, braces, or inappropriately fitting dentures. Specific foods and medications, such as radiation therapy and cancer treatments, precipitate mouth sores. These sores cause substantial discomfort but resolve independently due to accidental bites or irritation from braces and dentures. Mouth ulcers are prevented and managed by identifying triggers, maintaining good oral hygiene, and seeking medical advice for persistent or severe symptoms.

Mouth sores are managed through a variety of methods. Chlorhexidine and other antiseptic gels effectively treat periodontal disease, ulcers, and infections by reducing the presence of bacteria in the mouth. Mouthwashes are frequently employed with anaesthetics, such as benzocaine, to cleanse and numb the ulcers. Maintaining proper oral hygiene by regularly flossing, using a soft-bristled toothbrush, and using non-abrasive toothpaste is imperative. It helps prevent infection and irritation. Inflammation is diminished, and the healing process is expedited by steroid ointments, including triamcinolone acetonide paste and fluocinonide gel. Immunosuppressants, such as corticosteroids and azathioprine, are employed to manage sores caused by autoimmune conditions in severe cases. However, careful medical supervision is necessary due to the potential adverse effects.

Canker and other ulcerative mouth sores hurt the cheeks, lips, tongue, and throat. White or yellow lesions with a crimson halo make eating, drinking, and speaking painful. Stress, injuries, hormonal changes, certain foods, Crohn's disease, and vitamin deficiencies cause it. Oral, topical, and anti-inflammatory medications reduce pain and speed recovery. Gingivitis (red, swollen gums) leads to periodontitis (bone loss and tooth loss). Smoking, diabetes, poor tooth hygiene, genetics, and medications increase risk. Bad breath, bleeding gums, gum recession, and loose teeth are signs. Dental hygiene, expert cleanings, scaling, root planing, pocket reduction surgery, and regenerative therapies are improved. These illnesses require regular dental checkups and oral hygiene to prevent and treat symptoms. Early detection and treatment avoid major issues and improve dental health and life satisfaction.

A genome-wide association study (GWAS) involving over 461,000 individuals identified 97 genetic variations linked to mouth ulcers, confirmed in 355,744 participants, with the primary variable rs76830965 near IL12A showing a protective effect. The study underscores the genetic basis of mouth ulcers and suggests immune regulatory regions as therapeutic targets. Research from the Sahlgrenska Academy found that recurrent aphthous stomatitis (RAS) is due to genetic, bacterial, immunological, and environmental factors, not a virus like herpes, affecting daily activities. The study highlights changes in bacterial flora between RAS patients and healthy individuals, suggesting a complex genetic-immune interaction. A British Dental Journal study surveyed 1,000 Israelis on where they seek advice for mouth ulcers, revealing that most consult general practitioners first, followed by dental practitioners and community pharmacies. It emphasie the need for better coordination among healthcare providers to improve patient care and information access.

What are the Types of Mouth Sores?

The types of mouth sores are listed below.

Canker sores: Canker sores are the most prevalent form of oral ulcers. Healthcare providers are uncertain as to the precise cause of these conditions or the reasons why certain individuals are more susceptible to them than others. Minor trauma, such as biting one's cheek, acidic foods, and tension, are all potential causes. Canker sores are typically white or yellow, with crimson edging.
Oral thrush: Oral thrush, or oral candidiasis, is a condition where the fungus Candida albicans accumulates on the lining of the mouth. Candida is normally present in the mouth but sometimes overgrows and causes symptoms. Oral thrush results in creamy white lesions on the tongue or inner cheeks, spreading to the roof of the mouth, gums, tonsils, or throat. Oral thrush is more common in babies, older adults, people with weakened immune systems, certain health conditions, or people taking specific medications, although it affects anyone. It is usually a minor issue for healthy individuals but is more severe and difficult to control for people with compromised immunity.
Leukoplakia: Leukoplakia causes thick, white patches that form on the gums, insides of the cheeks, bottom of the mouth, and sometimes on the tongue. These patches cannot be scraped off. The exact cause of leukoplakia is unknown, but ongoing irritation from tobacco use, whether smoked, dipped, or chewed, is the most common cause. Long-term alcohol use is another potential cause. Most leukoplakia patches are benign, but some show early signs of cancer, particularly speckled leukoplakia, which consists of white areas mixed with red areas. Cancers develop next to areas of leukoplakia, see a dentist or doctor for any persistent changes in the mouth. A type of leukoplakia known as hairy leukoplakia primarily affects people with weakened immune systems, especially individuals with HIV/AIDS.
Erythroplakia: Erythroplakia is characterised by the presence of aberrant red lesions on the mucous membranes of the mouth, which are frequently observed on the tongue or the floor of the mouth. These lesions, which are unable to be scratched off, frequently co-occur with leukoplakia lesions, which are similar but white in appearance. Erythroplakia and leukoplakia are classified as precancerous or potentially cancerous lesions, according to the American Academy of Oral Medicine. Dysplasia, a symptom of cells that are more susceptible to cancer, necessitates a biopsy for diagnosis. The risk of malignant transformation in erythroplakia lesions is substantial, with a range of 14 to 50 percent, particularly if they exhibit dysplasia at the time of diagnosis. Erythroplakia has a higher probability of progressing to cancer if not detected and monitored early, in contrast to leukoplakia. Dentists identify erythroplakia during routine examinations, frequently observing lesions that appear to haemorrhage readily, which suggests a higher risk of cancer. Regular follow-up and early diagnosis are essential for the effective management of erythroplakia.
Oral lichen planus: An itchy rash and lacelike, white lesions within the mouth result from such a condition. An immune system response, oral lichen planus, is most frequently observed in women and individuals assigned female at birth (AFAB) who are 50 or older. Oral lichen planus is a chronic inflammatory condition affecting the mucous membranes inside the mouth. It presents as white, lacy patches, red, swollen tissues, or open sores that cause burning, pain, or discomfort. The disorder arises when the immune system mistakenly attacks the cells of the oral mucous membranes for unknown reasons and is not contagious. A person with oral lichen planus require regular monitoring due to an increased risk of developing mouth cancer in the affected areas, although symptoms are typically manageable.
Hand, foot, and mouth disease: Hand, foot, and mouth disease is caused by viruses in the enterovirus family and is common in children under 5. It leads to painful red blisters in the mouth and on the tongue and gums, as well as flat or raised red spots on the palms of the hands, soles of the feet, buttocks, or genital area. These bumps appear skin-coloured or greyish-brown on darker skin tones. Other symptoms include fever, sore throat, unwellness, and skin rash. The disease is contagious during the first week but is not serious and typically resolves within 7 to 10 days.
Mouth Cancer: Mouth cancer, referred to as oral cancer or oral cavity cancer, develops in any area of the mouth, such as the lips, gums, tongue, inner lining of the cheekbones, roof of the mouth, and floor of the mouth (under the tongue). Mouth cancer is categorised under head and neck malignancies, frequently employing comparable treatment strategies. Symptoms of mouth cancer include persistent sores on the lips or mouth, white or reddish regions within the mouth, loose teeth, lumps or growths in the mouth, mouth pain, ear pain, and difficulty or pain while swallowing. Consult with a physician or dentist if these symptoms persist for more than two weeks, as they initially determine that there are other common causes, such as infections.

What are the Symptoms of Mouth Sores?

The symptoms of mouth sores are listed below.

Red edges: It is common for mouth sores to induce inflammation in the surrounding tissues, resulting in redness and swelling. It makes the discomfort and sensitivity in the mouth even worse.
The centre is white, yellow, or grey: Canker sores, or aphthous ulcers, begin as small white or yellowish lesions with a red border. They are less than 1 millimetre but grow to 1/2 inch or even 1 inch in diameter. These sores appear on the tongue, gums, roof of the mouth, inside the lips, or under the tongue, causing pain and discomfort while eating or talking. There are two types of canker sores: simple canker sores, which occur three or four times a year and last up to a week, and complex canker sores, which are less common but recur more frequently in individuals who have previously had them.
Burning or tingling sensations: A burning or tingling sensation in the afflicted area occur before the appearance of the sores. It function as an indicator of an imminent ulcer.
Difficulty chewing or swallowing: Sores in the mouth result in discomfort and difficulty in chewing and swallowing, leading to changes in eating patterns and potentially impacting nutrition.
Bad Breath: Mouth ulcers are acidic and cause unpleasant odours. The acid dissolves the enamel on the teeth, resulting in an unpleasant odour. The bacteria that cause poor breath are managed by rinsing the mouth with water.
Fever: Individuals experience a general sense of unwellness (malaise), fever, and enlarged lymph nodes involving multiple sores in severe cases.

What are the Causes of Mouth Sores?

The causes of mouth sores are listed below.

Viral infections: Mouth sores are most frequently caused by viruses. The most well-known are cold sores of the lip and, less frequently, ulcers on the pharynx, which are caused by the herpes simplex virus. A variety of other viruses cause mouth sores. Varicella-zoster, the virus that causes chickenpox and the excruciating skin disorder shingles, form numerous sores on one side of the mouth. These lesions are the consequence of a virus flare-up, which, similar to herpes simplex virus, is unable to exit the body. The mouth remains painful occasionally for months, years, or even permanently after the sores have recovered.
Other types of infections: A bacterial infection causes sores and swelling in the pharynx. Infections result from a proliferation of organisms found in the mouth or the introduction of new organisms, such as the bacteria that cause syphilis or gonorrhoea. Bacterial infections from the teeth or gums cause less localised inflammation (cellulitis) or disseminate to form a pus-filled infection (abscess). Syphilis results in the development of a scarlet during the initial stages of the infection, a painless sore (chancre) on the lips or in the mouth. The irritation resolves within a few weeks. A white area (mucous patch) develops on the lip or inside the mouth approximately 4 to 10 weeks later if the syphilis has not been treated. The disease is transmitted through kissing and mucous patch, as both are extremely contagious. A hole (gumma) develops in the mandible or tongue during late-stage syphilis. The illness is not transmissible at that time. The yeast Candida albicans is a typical inhabitant of the oral cavity. It experiences an overgrowth in individuals who have been administered antibiotics or corticosteroids or who have a weakened immune system, such as people with AIDS. Candida produces whitish, cheese-like regions that, when removed, degrade the uppermost layer of the oral mucosa (thrush). Only crimson, flat areas are visible sometimes.
Systemic disorders: The mouth is impacted by numerous maladies, affecting other body parts. Behçet disease, an inflammatory condition encompassing numerous organs, such as the eyes, genitals, epidermis, joints, blood vessels, brain, and gastrointestinal tract, results in recurring, painful mouth sores. Skin lesions and oral ulcers are symptoms of Stevens-Johnson syndrome, an allergic reaction. Some individuals who have inflammatory bowel disease develop mouth ulcers. Mouth sores are frequently experienced by patients with severe celiac disease, caused by an intolerance to gluten (a component of wheat and certain other cereals). Lichen planus, a skin disease, occasionally results in mouth sores, which are less unpleasant than the ones on the skin. Blisters develop in the pharynx due to pemphigus vulgaris and bullous pemphigoid, both skin diseases. Mouth sores are caused by nutritional deficiencies of iron, niacin (vitamin B3), vitamin B6, vitamin B12, and vitamin C.
Tobacco: Mouth sores result from tobacco use. Tobacco products contain irritants, toxins, and carcinogens that are likely to cause sores. However, they result from the drying effects on the mouth lining, high temperatures in the mouth, changes in the mouth's acidity, or a decreased resistance to viral, bacterial, and fungal infections.
Injury or irritation: Injuries or damage to the mouth, like biting or scraping the inside of the face with broken or jagged teeth or dentures that don't fit right, lead to blisters (vesicles or bullae) or ulcers in the mouth. A blister's skin breaks down quickly, becoming an ulcer. Chemicals and foods irritate the mouth or cause an allergic reaction that leads to sores. Acidic foods, foods with cinnamon flavouring, and astringents are irritating. Other common items like toothpaste, mouthwash, candy, and gum sometimes contain irritating ingredients.
Medications and radiation therapy: Cancer treatment drugs are the most common medicines that cause mouth sores. Radiation treatment causes mouth sores. Gold-based medicines, which were once used to treat rheumatoid arthritis and some other autoimmune diseases, cause mouth sores. These medicines aren't used anymore, though, because better and more effective medicines are available. People who take medicines sometimes get mouth sores.
Braces: Canker sores are sometimes caused by braces, but each sore has a different reason. The metal frames and wires of braces irritate the mouth and cause small cuts and ulcers that turn into canker sores. Braces make sores because they rub against the face and lips, which leads to small cuts or irritation. Sores from braces happen if an individual doesn't brush and floss their teeth properly while they have them on. Food bits get stuck in the hardware and cause inflammation.
Ill-fitting dentures: Denture stomatitis is a prevalent condition among denture wearers, affecting up to 70% of the population according to research studies. It is more common in individuals who wear full dentures compared to people with partial dentures. Symptoms of denture stomatitis vary and often include pain or discomfort when swallowing. Soreness in the mouth or throat, white or red patches on the tongue, gums, lips, inner cheeks, or roof of the mouth, and sores or cracks in the corners of the mouth are common symptomps.
Accidentally biting the tongue, lip,or cheek: Biting the tongue, lip, or cheek inadvertently results in oral sores. These injuries result in an open laceration that becomes infected and progresses to a sore. The delicate tissues in the mouth are damaged by the trauma caused by biting, resulting in inflammation and discomfort. Mouth sores that result from accidental biting recover on their own typically; however, they are uncomfortable until they do. These accidental injuries are prevented by carefully chewing and refraining from talking or being distracted while consuming.
Food sensitivity: Mouth sores are common and mostly harmless inside the mouth, caused by stress, anxiety, biting the cheek, and smoking. Certain foods contribute to their formation. Acidic fruits like pineapples, oranges, lemons, and nuts high in L-Arginine, such as walnuts and almonds, trigger canker sores. Chocolate and spicy foods irritate the mouth lining, due to the alkaloid bromide. Hard foods like raw vegetables, toast, and chips are abrasive and cause sores. Allergies to specific foods, dairy products, and acidic drinks like coffee and alcohol exacerbate mouth ulcers. Identifying and avoiding these triggers and consulting a dentist or doctor for persistent sores help manage and prevent mouth ulcers effectively.

What are the Treatments for Mouth Sores?

The treatments for mouth sores are listed below.

Antiseptic gels: Chlorhexidine is an antiseptic and disinfectant that helps reduce bacteria in the mouth and skin. It is used to treat mouth infections, ulcers, gum disease, sore throats, and for denture care. Chlorhexidine is commonly combined with other ingredients and comes in various forms, including mouthwashes, lozenges, gels, sprays for oral use, creams, ointments, and lotions for skin treatments. Naseptin nasal cream, which combines chlorhexidine with the antibiotic neomycin, is a prescription-only formulation available over the counter. Chlorhexidine is used in hospitals to clean skin and surgical equipment before and in some bladder procedures.
Mouthwashes: Anaesthetics are commonly used with other drugs to relieve symptoms of mouth sores. An agent called benzocaine 5–20% is most often used. Benzocaine is known to cause allergies, so people who are already allergic must not use it. Over-the-counter (OTC) anaesthetics are on the market. Cleansing agents and antiseptics eliminate germs on the ulcer surface and clean the area. Cleaning products are made from things that give off air. The foaming of the air does a mechanical job that removes dirt and cleans the wound. Getting hydrogen peroxide as a 3% solution, it needs to be mixed with water in equal parts before using it on the sore or as a mouthwash. Clean wounds with sodium bicarbonate as a paste or solution (½ to 1 teaspoon in 4 ounces of water).
Proper oral hygiene: Proper oral hygiene is crucial for preventing and managing mouth ulcers. It involves cleansing teeth with a soft-bristled toothbrush at least twice a day to prevent irritation of the sensitive tissues in the mouth. Employ a delicate and non-abrasive toothpaste. Flossing daily assists in the removal of food particles and plaque that exacerbate oral sores. Bacteria is diminished, and healing is facilitated by rinsing the mouth with an antiseptic mouthwash or saline solution. Maintaining hydration and avoiding consuming foods that cause oral irritation, such as spicy, acidic, or sharp-edged foods, is crucial. Undergo routine dental examinations to promptly identify and address any oral health concerns contributing to the development of mouth ulcers. It is advisable to consult with a professional medical professional if sores continue to cause significant distress or persist.
Steroid ointments: Steroids are an additional treatment option for individuals with more severe canker lesions. Steroids alleviate inflammation and discomfort by reducing the immune system's response. Steroids are available in liquid and gel forms and are directly applied to canker lesions or used as a rinse. Choices include fluocinonide gel, clobetasol 0.05% gel or ointment, and triamcinolone acetonide 0.1% paste. Studies have demonstrated that steroids expedite the healing process and alleviate discomfort.
Immunosuppressants: Patients with autoimmune diseases like lupus, Behçet's disease, or severe cases of oral lichen planus find immunosuppressants helpful for controlling mouth sores. These medicines lower the body's immune reaction, which helps reduce the swelling and pain of mouth sores caused by an overactive immune system attacking the mouth's mucous membranes. Corticosteroids, azathioprine, and cyclosporine are common immunosuppressants used for such a reason. However, people who take immunosuppressants need to be closely watched by a doctor because they have side effects and make people more likely to get infections. Immunosuppressants help people with severe or recurring mouth sores that don't get better with other treatments. They make life better. Talk to a medical worker to determine the best treatment method based on each patient's cause and needs.

Can Mouth Sores Be Treated At Home?

Yes, mouth sores can be treated at home. Treating mouth sores at home is easy. Use readily available items at home to treat mouth sores. Most canker spots heal in about a week, but bigger ones take up to four weeks. Canker sores on the tongue are treated by rinsing the mouth with warm salt water or gentle over-the-counter rinses. Using a soft-bristled toothbrush for good oral hygiene, drinking plenty of water, avoiding hot, spicy, and acidic foods, and taking recommended medicines are ways to manage mouth sores..

Using mouth rinses with salt or baking soda, putting magnesia milk on the sore, and using topical products all help ease the symptoms and speed up healing. Canker spots on the gums are treated similarly by rinsing with salt water, alcohol-free mouthwashes, numbing rinses, or mixed milk of magnesia and Benadryl liquid. It has been shown that honey and aloe vera gel help canker spots feel less painful, heal faster, and be smaller. Honey, known for its antibacterial properties, is a natural coating agent that protects the sore from irritation.

Hydrogen peroxide mixed equally with water must be dabbed on the sore, followed by a coating of magnesia milk to aid in healing and pain relief up to four times a day. B12 supplements, available in pharmacies and health food stores, have been shown in some studies to speed up healing. Avoid irritating foods and drinks, such as spicy, citrus, and coffee, which aggravate the sore. Home remedies provide comfort and potentially speed up the healing process, even though canker sores heal on their own in one to two weeks the need for medication. Eat a healthy diet, avoid foods that irritate the mouth, don't chew gum, use a soft-bristled toothbrush, and avoid foods that cause canker sores.

What are the Researches about Mouth Sores?

The research about mouth sores includes a genome-wide association study (GWAS) involving over 461,000 individuals who identified 97 genetic variants associated with mouth ulcers, confirming these findings in an independent cohort of 355,744 participants. The lead variant, rs76830965 near IL12A, demonstrated a significant protective effect against developing mouth ulcers. Functional analyses indicated that immune regulation, particularly T cell regulation, plays a crucial role in the pathogenesis of mouth ulcers. The study underscores the genetic basis of mouth ulcers and suggests that immune regulatory loci are pivotal in their development, offering insights into potential therapeutic targets.

Recurrent aphthous stomatitis (RAS), a common and painful condition characterised by burning sensations and non-healing ulcers in the mouth, has long been misunderstood. Research from the Sahlgrenska Academy sheds new light on its causes, challenging the misconception that it is virus-related, like herpes. RAS is suggested to be a general symptom of bodily imbalance influenced by genetic, bacterial, immune, and environmental factors. Patients with RAS experience significant discomfort, including difficulties in eating, speaking, and daily activities, with no definitive cure available. Treatment focuses on symptom relief rather than addressing the underlying causes. The study highlights the differences in bacterial flora between RAS sufferers and healthy individuals, suggesting a complex interplay of genetics and immune responses. The new understanding could lead to improved management strategies and a better quality of life for individuals affected by RAS.

A study published in the British Dental Journal investigated where the public in Israel seeks advice for mouth ulcers. Researchers surveyed 1,000 individuals in Haifa and Tel Aviv and found that nearly one-third had experienced mouth ulcers. The majority (66–69%) initially consult their general medical practitioner, only 13–17% seek advice from a general dental practitioner, and a mere 4–10% turn to a community pharmacy. Laypeople are usually unable to distinguish potentially malignant ulcers from benign ones. The study concluded that there is a need for better collaboration between dental, medical, and pharmaceutical professionals to improve patient access to information and care.

What are the Differences between Mouth Sores and Gum Problems?

The differences between mouth sores and dental problems lie in their causes, symptoms, and treatments, though they share similarities in their impact on oral health and well-being.

Mouth sores, including canker sores (recurrent aphthous stomatitis) and other ulcerative conditions, are characterised by painful lesions inside the cheeks, lips, tongue, and throat. These sores manifest as white or yellow lesions with a red halo and cause significant discomfort, making eating, drinking, or speaking difficult. The causes of mouth sores are multifaceted, including stress, injury (such as accidentally biting the cheek or tongue), hormonal changes, certain foods, and underlying health conditions like Crohn's disease or vitamin deficiencies. Treatments for mouth sores focus on relieving pain and promoting healing through topical treatments, mouth rinses, and, in some cases, medications to reduce inflammation.

Periodontal disease, or gum disease, involves inflammation and infection of the tissues surrounding the teeth. The condition progresses through stages, from gingivitis, characterised by red, swollen gums that bleed easily, to more severe forms like periodontitis, where the infection destroys the supporting bone structure, leading to tooth loss. Poor oral hygiene is a cause of gum disease, but genetic factors, smoking, diabetes, and certain medications increase the risk. Symptoms include bleeding gums, bad breath, gum recession, and loose teeth. Treatment ranges from improved oral hygiene and professional cleanings to more advanced procedures like scaling and root planing, pocket reduction surgery, and regenerative therapies.

Mouth sores and gum problems are linked to systemic health issues and share common risk factors such as stress and compromised immune function. Gum problems are more directly related to bacterial plaque buildup and inadequate oral hygiene, while mouth sores result from localised irritation or systemic conditions. These two conditions emphasise the importance of regular dental check-ups and good oral hygiene practices to prevent and manage symptoms effectively. Early detection and treatment are crucial to avoid more serious complications and ensure better oral health and quality of life.

Dentist Dr. Dt. Erdem CETIN

He started his professional career in a private practice in Antalya in 2005 and served there until 2012. Between 2012 and 2016, he continued his work as a partner at the institution named KlinikAntalya. In 2016, he founded Myra Dental Centre Turkey and continues his professional activities there. Additionally, he has strengthened his expertise in the field with his membership in the International Congress of Oral Implantology (ICOI).