Healthcare e-Compendium
A joint initiative of DPSRU & DRSC
Healthcare e-Compendium
A joint initiative of DPSRU & DRSC
Author: Dr. Ram Gulati
MD (Dermatology & Sexually Transmitted Diseases), MRCPCH (UK); Former Consultant, NHS Greater Glasgow Group of Hospitals, Glasgow UK; Santokba Drulabhji Memorial Hospital & Medical Research Institute, Jaipur
download ArticleABSTRACT
Onychomycosis is a fungal infection of nails. It is most common disease accounting up to 50% of nail disorders and effecting 10% of world population. Mild forms of onychomycosis are typically considered a cosmetic issue, but it can develop into a serious health risk if not addressed early, especially for diabetics and the elderly. The disease is highly contagious and is caused by a group of fungi – dermatophytes, moulds and yeasts. Current treatments are potentially toxic or have low efficacy. A novel topical agent, nailKALM®, based on a naturally-derived extract (AMYCOT®) from the microalgae Spirulina, is a promising addition to the arsenal in the fight against onychomycosis.
Keywords: Onychomycosis, Fungal Infection, Tinea unguium, Arthrospira maxima, nailKALM, AMYCOT
Introduction
Onychomycosis is the fungal nail infection which causes nail's discoloration, thickening and separation from nail bed to occur. It takes place in both fingernails or toenails but the most commonly takes place in toenails. It is caused by variety of organisms but in most of the cases it is caused by dermatophytes. Widely, onychomycosis is considered to be a cosmetic problem but it can be more harmful and can cause cellulitis in older adults [1] and foot ulcers in patients with diabetes. [2] Onychomycosis can cause discomfort, disturbance and pain and serious physical limitations may occur.
Onychomycosis significantly affect negatively patient's social, emotional and occupational status. Patients affected by onychomycosis may experience embarrassment socially and occupationally due to their unclean and unhygienic nails. Employment also suffers in the cases, if field of work is related to interacting with persons, food handling or modelling. In this case, possibility of transferring pathogen from infected person to unaffected always exists. In persons with low immunity such as HIV patients or Dialysis patients, onychomycosis may cause severe health problems [3].
Epidemiology
Onychomycosis was found to be the most common fungal disease in foot diseases in a 2003 survey of 16 European countries and its universality in that survey estimates at 27% [4, 5]. Almost one in three of diabetics is affected by onychomycosis [6] and is 56% more frequent in people suffering from psoriasis [7].
Around 5-10% of the global population is estimated to be suffering from onychomycosis [8-14]. It is prevalent in hot and humid areas but is also known to persist in temperate regions, especially during the winter months. During this time, the feet are heavily covered from the cold, generating a moist environment from sweat and poor aeration, which promotes fungal growth.
The incidence of onychomycosis is observed to be increased with age, 20% among 60-year old adults and 50% of any adult older than 70 years [12]. Incidence among children is very low at <0.5% but with increasing incidence of tinea infections among infants in India this may change. Surveys indicate that onychomycosis is more prevalent among adults than children below 18 years old.
Risk Factor
The major risk factors for onychomycosis are age, obesity and diabetes. The correlation of increasing age and incidence of the disease can be attributed to changes in the nail structure related to poor blood circulation, auto-immune disease, reduced immunity and even altered biomechanics that may cause nail trauma. These factors may increase an individual's susceptibility to fungal infection [8-14].
The disease is also common among pregnant or nursing women which may be related to their increased risk for diabetes. Neuropathy or decrease in the sense of touch including poor circulation among diabetics, increase their risk to nail trauma which makes them susceptible to onychomycosis.
Weakened immune system is also a major risk factor for this condition. Cancer [15], immunodeficiency [16] and peripheral arterial disease [17] have been associated with increased susceptibility to onychomycosis. A genetic predisposition to susceptibility to onychomycosis has also been identified [18].
Onychomycosis is highly contagious. Community spread is a major source of transmission of the disease. Going bare foot in damp places like shower rooms, gyms, swimming pools, having minor skin or nail injury, sweating heavily, as well as shared clothing and gear; are also risk factors for the infection. Therefore, basic hygienic practice can go a long way in preventing transmission and contracting the disease [11-14].
Clinical Impact
Onychomycosis may initially appear as a blemish orcosmetic defect on the nail. However, if it is leftuntreated, it can worsen into nail dystrophy, which can lead to pain, discomfort and disfigurement. These complications can lead to physical and occupational limitations as well as reduction of quality of life. If onychomycosis is not managed well, especially among diabetics, it can develop into serious complications such as cellulitis, paronychia and gangrene which can eventually lead to limb loss or amputation [11-14].
Since onychomycosis is readily transmitted, early treatment and management of the disease can prevent the disease from spreading within the household and to the community [11-14].
Onychomycosis
Onychomycosis often arises from a damaged nail that is infected by a fungus or develops from pre-existing fungal skin infections of the hand and feet spreading towards the nail bed or cuticle and eventually penetrating the nail plate (Figure 1b) [13-14].
Almost 90% cases of onychomycosis of toenails and 50% of the fingernail infections are caused by Dermatophytes. Dermatophytes include the members of genera Microsporum, Trichophyton, and Epidermophyton. Onychomycosis is due to a dermatophyte infection on nails, it is termed tinea unguium. But Onychomycosis can also be caused by non-dermatophyte molds (such as Scytalidium and Scopulariopsis) on skin, nail or hair [19] and is termed as Dermatomycoses; estimated to cause 2% of fungal nail infection. The other agent being yeasts (mainly Candida) accounting for 8% of total onychomycosis cases.
Anatomy of Nail
Nail is a keratinous structure at the tip of the fingers and toes. Anatomy of nail (Figure 1a) consists of the structures as cuticle, matrix, nail plate (commonly called the nail), proximal and lateral folds, nail bed, and hyponychium.
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Figure 1: Anatomy of a human nail and onychomycosis
Classification of Onychomycosis
Onychomycosis can be classified into 5 different types (Figure 2) depending on its location, morphology, aetiological fungal agent and progression of the disease [14]. Patients can have one or a combination of the different subtypes in different digits of the patient’s hands or feet. Total dystrophic onychomycosis is the most advanced form among the different subtypes and typically presents itself as a thickened, opaque and yellowish-brown nail.
Distal Lateral Subungual Onychomycosis (DLSO): The most common form of tinea unguium. Commonly caused by Trichophyton rubrum, which invades the underside of the nail plate and nail bed [19]. The infected nail is usually yellowish-white in colour. Streaks of yellow or yellowish onycholytic areas are observed in the central portion of the nail plate.
White Superficial Onychomycosis (WSO): This is usually confined to toenails. Commonly infected by moulds; but Trichophyton mentagrophytes, a dermatophyte is the common aetiological agent. It is caused by invasion of the superficial layers of the nail plate to form ‘white islands’ on the plate and can progress into the nail bed. Typically, small, white, speckled or powdery patches are observed on the surface of the nail plate which roughens the nail and makes it to crumble easily.
Proximal Subungual Onychomycosis (PSO): It is a very rare infection and the least form of tinea unguium but can be found more commonly when the patient is immunodeficient [19]. Characterised by white lines or dots near proximal nail fold in newly formed nail plate that moves distally with nail growth. Fungi (mainly dermatophytes, especially Tricophyton rubrum) invade the cuticle and then penetrate the nail plate.
Endonyx Onychomycosis (EO): It is characterized by Leukonychia, a condition where white lines or dots appears on finger or toe nails, along with a lack of subungual hyperkeratosis or onycholysis [20]. Fungi invade the nail plate via direct spreading from the skin instead of the nail bed.
Candidal Onychomycosis: It is the invasion of the fingernails by Candida species. It is typically found on fingernails and usually occurs in the persons whose hands frequently comes in contact with or immersed in water. Prior damage of the nail by infection or trauma is normally required in this.
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Distal Lateral Subungual Onychomycosis (DLSO) |
White Superficial Onychomycosis (WSO) |
Proximal Subungual Onychomycosis (PSO) |
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Endonyx Onychomycosis (EO) |
Candidal Onychomycosis |
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Figure 2: Different types of onychomycosis, a fungal infection
Antifungal Therapy for Onychomycosis
Treatment can range from direct killing of the fungi (fungicidal) or limiting fungal cell division and propagation (fungistatic) or to removal of the infected nail (debridement). The approaches range from pharmaceutical, physico-mechanical and natural agents.
Oral Anti-Fungal Drugs: The most effective class of anti-fungal drugs against onychomycosis are oral anti-fungals which act systemically. This class of drugs inhibit certain metabolic enzymes of fungi required for its growth and survival. However, these drugs have serious liver toxicity limiting its application especially for the elderly, diabetics, children and women. Terbinafine, Itraconazole and Griseofulvin are examples of these drugs.
Topical Anti-Fungal Drugs: Although local and topical application of anti-fungal drugs would be more convenient and safe than the oral route, re-formulation of known effective drugs such as terbinafine as topical agents have been not as successful to date. The major challenge has been the difficulty of the drug penetrating the tough nail plate and its keratinous structure. Given the limited efficacy of topical anti-fungal drugs, they are often prescribed for treating mild to moderate onychomycosis and is not used with patients with total dystrophic onychomycosis. Ciclopirox, Amorolfine, Efinaconazole and Tavaborole are few drugs under this category.
Debridement: Debridement is the physical removal of an infected nail bed or viable nail plate. It is a common practice among podiatrists and represents an option for 30% of onychomycosis patients [21]. The practice can be applied mainly to improve appearance of the nail and comfort, but does not necessarily cure the infection. Thus, any residual fungal spores or fungi may not be totally eliminated, therefore the possibility of recurrence is high.
Laser Therapy: Laser therapy is an emerging modality for treating onychomycosis [10, 14]. There are limited clinical studies to validate its efficacy, but it is considered a promising option. Lasers improve cosmetic appearance by increasing the clarity of nail in the patients with onychomycosis. Thus are approved for the temporary clearance [10], as noted that there is insufficient data to confirm the fungicidal property of lasers.
Natural Treatment: There have been reports of natural treatments for onychomycosis such as vinegar (acetic acid) and tea tree oil. In addition, there are numerous generic formulations of over-the-counter onychomycosis treatments that contain an organic acid such as lactic acid, undecylenic acid and acetic acid. It is known that organic acids have anti-fungal activities. However, there are limited controlled clinical studies demonstrating the efficacy of these treatments [13].
Combination Therapy: Since most of therapies have low efficacies, combination therapy may have an additive effect especially if the modalities have different mechanisms of action and can complement each other. For mild to moderate infections, a combination of an oral and topical drugs is the current strategy employed in India. However, this may not be an option for pregnant or nursing women due to toxicity concerns with the oral drugs. However, a combination of laser therapy or debridement with topical agents may offer a better alternative.
Managing Onychomycosis and Educating Patients to Avoid Relapse
Relapse of onychomycosis is relatively high due the presence of fungal spores which may not be eliminated from the different treatments. Furthermore, fungi are ubiquitous and one can readily contract either the organism or its spores. Once the right conditions of humidity and temperature are reached, fungal growth can readily initiate. Therefore, it is important to avoid contraction as well as keeping a clean and well-ventilated environment for the hands and feet [11-13].
Educating patients about their role in treatment plays a very crucial role in eradicating the infection. Patient should take appropriate measures for the nail care like new healthier habits should develop instead of old bad habits to support the treatment and to prevent from reinfection. Physician support staff plays a very important role in educating the patients about the treatment which is going on and the preventions they should take to prevent from reinfection.
nailKALM® Dermaceutical Lotion: A Novel Treatment for Onychomycosis
nailKALM is a very effective topical antifungal agent indicated for relief of onychomycosis. It consists of AMYCOT, a patented key ingredient derived from naturally occurring species of spirulina.
AMYCOT®: Naturally Occurring Key Ingredient, Patented
AMYCOT is a proprietary extract derived from Spirulina, a microalgae or cyanobacterium, specifically from the Arthrospira maxima species. It is the most widely produced microalgae in large-scale production. It is a single celled, water borne plant that has a long history of being used as a food source in different parts of the world. It is high nutritious source of food containing very high levels of essential vitamins and anti-oxidants.
AMYCOT®: Mode of Action
The antifungal activity of AMYCOT is due to a putative enzymatic action that destroys the chitin/chitosan polymers, the structural component of the fungal cell wall. Damage to the polymers causes the fungal walls to collapse, eventually killing the fungus (fungicidal). However, AMYCOT is composed of a complex variety of proteins, lipids and carbohydrates that have been known to collectively exhibit anti-fungal properties. Thus, it is possible that all of these molecules act synergistically to manifest efficacy [22].
AMYCOT®: Efficacy
In vitro studies of AMYCOT has shown its efficacy against fungi associated with onychomycosis such as Trichophyton mentagrophytes, Trichophyton rubrum, Candida albicans, Epidermophyton floccosum, and Microsporum canis. Additional clinical studies confirmed AMYCOT efficacy against other related mycological skin infections such as Tinea cruris, Tinea corporis, Tinea pedis and Tinea capitis.
In vitro studies indicate that AMYCOT has no skin irritating side effects; stimulates the growth and protein synthesis of skin cells such as keratinocytes; and has anti-inflammatory properties. Moreover, AMYCOT does not stimulate the cellular immune response indicating that it is most likely non-allergenic. These multi-functional properties of AMYCOT address the inflammation associated with onychomycosis, and is one of nailKALM unique attributes which may help explain its high efficacy against onychomycosis.
AMYCOT®: Safety
Spirulina (Arthrospira maxima), the source of AMYCOT, has been ingested orally as human food for centuries. There has been no reported toxicity even with up to 8 grams consumed per day [23, 24]. AMYCOT has no skin irritating side-effects and show anti-inflammatory properties. Thus, the application of a Spirulina extract such as AMYCOT as a topical agent may be considered relatively harmless and may be an option for immuno-compromised patients such as the elderly, infants, diabetics and pregnant women.
AMYCOT®: Clinical Trials
One of the study conducted in Germany (2005) shows the antifungal effect of AMYCOT preparations (8% Lotion and 12% Cream) tested in ten patients with heavy to moderate infections for 14 days. In the beginning of the trial all the subjects showed an extreme fungal activity (< 96%, assessed by spore count). One week after beginning the treatment, the degree of infection reduced to less than 72% and all the patients shows positive change in the original symptoms. The fungal activity had reduced to less than 18% at the end of the study (14 days later) in nearly all test subjects. This study shows that the AMYCOT preparations are more effective than previously known medications [25].
Another study conducted in 2011 (Queensland) showed 100% clearance of onychomycosis when treated with nailKALM. This is the independent trial conducted with 10 subjects diagnosed with Onychomycosis (verified by microscopy and/or culture) and treated with nailKALM Lotion over 3 months with a follow up at 6 months. 100% clearance on 70% of the subjects after 3 months, 100% clearance of 80% of the subjects after 6 months and 20% of the subjects did not complete the treatment. nailKALM Lotion has a definite clinical benefit in the treatment of Dermatophyte Onychomycosis infections [25].
The clinical efficacy of AMYCOT was confirmed in a randomized double-blind, placebo-controlled trial of subjects with severe to very severe tinea and onychomycosis infections, who were treated with different AMYCOT formulations. The subjects treated with AMYCOT showed significantly greater than 90% mycological cure and 100% clinical cure rates compared with the subjects treated with placebo. There was no reported adverse effect associated with the treatment [26].
Applications and Benefits of nailKALM®
nailKALM has been used as a stand-alone product for managing onychomycosis with high rates of success. The product has also been found to work anecdotally as well on other nail problems such as nail damage and nail psoriasis, presumably due to its skin repair and anti-inflammatory properties. Moreover, these aforementioned properties of AMYCOT may contribute in helping the new nail to grow after the fungi are eliminated. Concomitantly, nailKALM can hasten nail re-growth as well as reduce any inflammation arising from treatment such as laser therapy. Due to the natural source of AMYCOT and apparent safety profile, nailKALM can be used as a combination treatment with other modalities.
Conclusion
Onychomycosis is a highly contagious disease with no effective treatment to date. Although the disease initially appears as a cosmetic problem, it poses a serious health risk if not addressed early. With an aging population and rising incidence of diabetes, onychomycosis represents a disease with an unmet need in search for more safe and effective treatments. nailKALM is made up of AMYCOT and has a definite clinical benefit in the treatment of onychomycosis infections. AMYCOT has skin repair abilities, anti-inflammatory properties and no skin irritating side effects. This means nailKALM is harmless for skin. Beside these, various studies showed that AMYCOT preparations are more effective than previously known medications. nailKALM represents a new option and/or an adjunct to current modalities available in the management of onychomycosis.
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