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Home , Candidiasis, Nail disease, Onychomycosis

www.ijapbc.com IJAPBC – Vol. 2(1), Jan- Mar, 2013 ISSN: 2277 - 4688 ______INTERNATIONAL JOURNAL OF ADVANCES IN PHARMACY, BIOLOGY AND CHEMISTRY Review Article

Onychomycosis and Its Treatment Amartya De, NN. Bala and Abu Taher B.C.D.A College of Pharmacy & Technology, 78, Jessore Road(S), Hridaypur, Barasat, Kolkata, West Bengal, India.

ABSTRACT is a very common problem affected many people more much in rural area. This condition may affect toenails or fingernails, but toenail are particularly common. In this article we discuss about etiology,pathophysiology,prevention and treatment of the disease.

Keywords: Onychomycosis, subungual onychomycosis, , Laser Treatment.

INTRODUCTION the Finnish study, only 2 of the 91 patients with Onychomycosis (also known as "dermatophytic -related onychomycosis of the onychomycosis," "ringworm of the ," and "tinea toenails also had fingernail involvement. Toenail unguium")1 means fungal of the nail2. It infections were approximately 20 times more is the most common disease of the nails and common than fingernail infections in the Ohio constitutes about a half of all nail abnormalities3. cohort The increased frequency of toenail in This condition may affect toenails or fingernails, comparison to fingernail infections probably but toenail infections are particularly common. The reflects the greater incidence of tinea pedis than of prevalence of onychomycosis is about 6-8% in the tinea manuum5. adult population4.

CLASSIFICATION OF ONYCHOMYCOSIS Four types of onychomycosis, characterized according to clinical presentation and the route of invasion, are recognized. i. Distal Subungual Onychomycosis Distal subungual onychomycosis (DSO) is the most common form of onychomycosis. It is characterized by invasion of the nail bed and underside of the nail plate beginning at the Fig: Distal subungual onychomycosis. hyponychium.The infecting organism migrates proximally through the underlying nail matrix. ii. Proximal Subungual Onychomycosis Mild develops, resulting in focal Proximal subungual onychomycosis (PSO) is parakeratosis and subungual , with also known as proximal white subungual two consequences: (detachment of the onychomycosis (PWSO), a relatively nail plate from the nail bed) and thickening of the uncommon subtype, and occurs when subungual region. This subungual space then can organisms invade the nail unit via the proximal serve as a reservoir for superinfecting and nail fold through the cuticle area, penetrate the , giving the nail plate a yellowish brown newly formed nail plate, and migrate distally. appearance. The clinical presentation includes subungual DSO is usually caused by the dermatophyte T. hyperkeratosis, proximal onycholysis, rubrum (although T. mentagrophytes, T. tonsurans, , and destruction of the proximal and E. floccosum also are known to be causative. nail plate. In the United States T. rubrum is the DSO may develop on the fingernails, toenails, or principal causative agent of PSO. both, with infection of the toenails being much more common than infection of the fingernails; in

123 www.ijapbc.com IJAPBC – Vol. 2(1), Jan- Mar, 2013 ISSN: 2277 - 4688 ______iv. Infections of the Nail Candida nail infections occur in patients with chronic mucocutaneous candidiasis, and are caused by C. albicans .The organism invades the entire nail plate. Candida spp. may cause other syndromes, including onycholysis and . These forms occur more commonly in women than in men and often affect the middle finger, which may come Fig: Proximal subungual onychomycosis. into contact with Candida organisms that reside in the intestine or .Candida onychomycosis The pattern of growth in PSO is from the proximal can therefore be divided into three general nail fold on the lunula area distally to involve all categories. layers of the nail Although PSO is the most (i) Infection beginning as a paronychia (infection of infrequently occurring form of onychomycosis in the structures surrounding the nail; also called a the general population, it is common in AIDS “”), the most common type of Candida patients and is considered an early clinical marker onychomycosis, first appears as an edematous, of HIV infection (.In one study of 62 patients with reddened pad surrounding the nail plate. Invasion AIDS or AIDS-related complex and by Candida spp., unlike dermatophytic invasion, onychomycosis, 54 patients (88.7%) had PSO, with penetrates the nail plate only secondarily after it T. rubrum being the etiologic agent in more than has attacked the soft tissue around the nail .After half of these patients. In 54 patients, the feet were infection of the nail matrix occurs, transverse affected, and in 5 patients, the hands were infected; depressions (Beau’s lines) may appear in the nail infections of both toenails and fingernails were plate, which becomes convex, irregular, and rough present in 3 patients6. Infection may also and, ultimately, dystrophic . occasionally arise secondary to trauma. (ii) Patients with chronic mucocutaneous candidiasis are at risk for the second type of , called iii. White Superficial Onychomycosis Candida , which accounts for fewer than White superficial onychomycosis (WSO) is less 1% of onychomycosis cases .This condition is seen common than DSO (estimated proportion of in immunocompromised patients and involves onychomycosis cases, 10%) and occurs when direct invasion of the nail plate .The organism certain fungi invade the superficial layers of the invades the nail plate directly and may affect the nail plate directly (Later, the infection may move entire thickness of the nail, resulting, in advanced through the nail plate to infect the cornified layer of cases, in swelling of the proximal and lateral nail the nail bed and hyponychium.) It can be folds until the digit develops a pseudo-clubbing or 8 recognized by the presence of well-delineated “ drumstick” appearance . opaque “white islands” on the external nail plate, (iii) Finally, Candida onycholysis can occur when which coalesce and spread as the disease the nail plate has separated from the nail bed. This progresses. At this point, the nail becomes rough, form is more common on the hands than the feet soft, and crumbly. Inflammation is usually minimal .Distal subungual hyperkeratosis can be seen as a in patients with WSO, because viable tissue is not yellowish gray mass lifts off the nail plate. The involved (WSO) occurs primarily in the toenails. lesion resembles that seen in patients with DSO.

v. Total Dystrophic Onychomycosis Total dystrophic onychomycosis is used to describe end-stage , although some clinicians consider it a distinct subtype. It may be the end result of any of the four main patterns of onychomycosis. The entire nail unit becomes thick and dystrophic .9

ANATOMY OF THE NAIL Fig: White superficial onychomycosis To have a better understanding of how onychomycosis affects the nail, a general The most common etiologic agent in WSO is T. knowledge of the anatomy of the nail is helpful. mentagrophytes .In addition, several The nail, or nail unit, consists of the following nondermatophyte molds, including parts: terreus, Acremonium roseogrisum (later confirmed  The nail matrix (where the nail starts) is to be Acremonium potronii), and where nail cells multiply and keratinize oxysporum, have been implicated by Zaias et al.7 (harden and form into nail material) before being incorporated into the fingernail or

124 www.ijapbc.com IJAPBC – Vol. 2(1), Jan- Mar, 2013 ISSN: 2277 - 4688 ______toenail. Most of the matrix is not visible.  The cuticle is a fold of modified The matrix starts under the skin 5 mm where the finger or meets the nail. The below the nail fold (the area of the cuticle cuticle protects the matrix from infection. where the finger or toe skin meets the nail)  The nail plate is the nail itself. and covers the area called the lunula, or  The nail bed is the soft tissue underneath half moon (the white half moon-shaped the nail, anchoring the nail plate. The nail area at the bottom of the nail). plate protects the nail bed.9

CAUSES OF ONYCHOMYCOSIS more rarely, WSO can be caused by Onychomycosis is caused by three main classes of of nondermatophyte molds. organisms: (fungi that infect ,  The is the most skin, and nails and feed on nail tissue), , and common cause of chronic mucocutaneous nondermatophyte molds. All three classes cause the candidiasis (disease of mucous membrane very similar early and chronic symptoms or and regular skin) of the nail appearances, so the visual appearance of the  candidiasis (disease of mucous membrane infection may not reveal which class is responsible and regular skin) of the nail. for the infection. Dermatophytes (including , Microsporum, and EPIDEMIOLOGY species) are, by far, the most common causes of Frequency onychomycosis worldwide. Yeasts cause 8% of United States:-The recent proliferation of fungal cases, and nondermatophyte molds cause 2% of infections in the United States can be traced to the onychomycosis cases. large immigration of dermatophytes, especially  The dermatophyte is Trichophyton rubrum, from West Africa and the most common causing distal Southeast Asia to North America and Europe. lateral subungual onychomycosis (DLSO) International:-The incidence of onychomycosis and proximal subungual onychomycosis has been reported to be 2-13% in North America. A (PSO). multicenter survey in Canada showed the  The dermatophyte Trichophyton prevalence of onychomycosis at 6.5%. mentagrophytes commonly causes white Onychomycosis accounts for half of all nail superficial onychomycosis (WSO), and disorders, and onychomycosis is the most common

125 www.ijapbc.com IJAPBC – Vol. 2(1), Jan- Mar, 2013 ISSN: 2277 - 4688 ______nail disease in adults. Toenails are much more PATHOPHYSIOLOGY likely to be infected than fingernails. Thirty percent The pathogenesis of onychomycosis depends on the of patients with a cutaneous fungal infection also clinical subtype. In distal lateral subungual have onychomycosis. The incidence of onychomycosis, the most common form of onychomycosis has been increasing, owing to such onychomycosis, the fungus spreads from plantar factors as , , and skin and invades the nail bed via the hyponychium. increasing age. Inflammation occurring in these areas of the nail Studies in the United Kingdom, Spain, and Finland apparatus causes the typical physical signs of distal found prevalence rates of onychomycosis to be 3- lateral subungual onychomycosis. In contrast, 8%. white superficial onychomycosis is a rarer presentation caused by direct invasion of the Race surface of the nail plate. In proximal subungual Onychomycosis affects persons of all races. onychomycosis, the least common subtype, fungi penetrate the nail matrix via the proximal nail fold Sex and colonize the deep portion of proximal nail Onychomycosis affects males more commonly than plate. Endonyx onychomycosis is a variant of distal females. However, candidal infections are more lateral subungual onychomycosis in which the common in women than in men. fungi infect the nail via the skin and directly invade the nail plate. Total dystrophic onychomycosis Age involves the entire nail unit. Studies indicate that adults are 30 times more likely Nail invasion by Candida is not common because to have onychomycosis than children. the yeast needs an altered immune response as a Onychomycosis has been reported to occur in 2.6% predisposing factor to be able to penetrate the nails. of children younger than 18 years but as many as Despite the frequent isolation of Candida from the 90% of elderly people. proximal nail fold or the subungual space of patients with chronic paronychia or onycholysis, in these patients Candida is only a secondary colonizer. In chronic mucocutaneous candidiasis, the yeast infects the nail plate and eventually the proximal and lateral nail folds. 13

DIAGNOSIS OF ONYCHOMYCOSIS Onychomycosis (OM) can be identified by its appearance. However, other conditions and infections can cause problems in the nails that look like onychomycosis. OM must be confirmed by laboratory tests before beginning treatment, because treatment is long, expensive, and does have some risks.14 The most common symptom of a fungal nail  A sample of the nail can be examined infection is the nail becoming thickened and under a microscope to detect fungi. See discoloured: white, black, yellow or green. As the Anatomy of the Nail for information on infection progresses the nail can become brittle, the parts of the nail. with pieces breaking off or coming away from the  The nails must be clipped and cleaned toe or finger completely. If left untreated, the skin with an alcohol swab to remove bacteria can become inflamed and painful underneath and and dirt so the fungal structures can be around the nail. There may also be white or yellow more easily visualized with a microscope. patches on the nail bed or scaly skin next to10 the 11  If the doctor suspects distal lateral nail. . There is usually no pain or other bodily subungual onychomycosis (DLSO), a symptoms, unless the disease is severe People with sample (specimen) should be taken from onychomycosis may experience significant the nail bed to be examined. The sample psychosocial problems due to the appearance of the should be taken from a site closest to the nail, particularly when fingers – which are always 12 cuticle, where the concentration of fungi is visible – rather than toenails are affected. the greatest. are fungus-free skin lesions that  If proximal subungual onychomycosis sometimes form as a result of a fungus infection in (PSO) is suspected, the sample is taken another part of the body. This could take the form from the underlying nail bed close to the of a or in an area of the body that is not lunula. infected with the fungus. Dermatophytids can be thought of as an allergic reaction to the fungus.

126 www.ijapbc.com IJAPBC – Vol. 2(1), Jan- Mar, 2013 ISSN: 2277 - 4688 ______ A piece of the nail surface is taken for infection, and having diabetes, circulation problems examination if white superficial or a weakened . onychomycosis (WSO) is suspected.  To detect candidal onychomycosis, the ONYCHOMYCOSIS PREVENTION doctor should take a sample from the Although it may be impossible to prevent affected nail bed edges closest to the onychomycosis infections in everyone, there are cuticle and sides of the nail. ways to reduce a person's chance to get infected.  In the laboratory, the sample may be The following are some of the methods to avoid treated with a solution made from 20% nail infections: potassium hydroxide (KOH) in dimethyl  Remember that nail infections can be sulfoxide (DMSO) to help rule out or passed from person to person so washing more easily verify the presence of fungi by hands (and feet) after contacting another reducing debris and human tissue in the person with nail infections is a good sample. The specimen may also be treated pratice. with dyes (a process called staining) to  Do not go barefoot in public showers or make it easier to see the fungal structure locker rooms. through the microscope that help identify  Use spray or powder in shoes, the precise species of the . especially gym shoes.  If fungi are present in the infected nail,  Be sure that if a manicure or pedicure is they can be seen through a microscope, done, instruments are sterilized before but the exact type (species) cannot be each person is exposed to them. determined by simply looking through a  Keep feet dry and clean as possible. microscope. To identify what exactly is Keep finger and toe nails trimmed; do not pick at or causing onychomycosis, a fungal culturing chew on fingernails or the skin around them. is used. Using a fungal culture to identify the particular fungus is important because TREATMENT OF ONYCHOMYCOSIS regular therapy may not work on nondermatophyte molds. In the past, used to treat onychomycosis  The infected nail is scraped or (OM) were not very effective. OM is difficult to clipped. treat because nails grow slowly and receive very  The scrapings or clippings are little supply. However, recent advances in crushed and put into containers. treatment options, including oral (taken by mouth) Any fungus in the samples can and topical (applied on the skin or nail surface) grow in the laboratory in these medications, have been made. Newer oral special containers. This is true for medicines have revolutionized treatment of most molds and yeast also. onychomycosis. However, the rate of recurrence is  The species of pathogen (usually high, even with newer medicines. Treatment is a fungus) can be identified from expensive, has certain risks, and recurrence is the cultures grown in the lab by possible.15 technicians trained to recognize  Topical are medicines applied the microscopic structures that to the skin and nail area that kill fungi and are identifiers of the fungal some other . species.  These topical agents should only be used if less than half the nail is RISK FACTORS involved or if the person with Aging is the most common risk factor for onychomycosis cannot take the onychomycosis due to diminished blood oral medicines. Medicines circulation, longer exposure to fungi, and nails include (approved for which grow more slowly and thicken, increasing use outside the United States), susceptibility to infection. Nail fungus tends to olamine (Penlac, affect men more often than women, and is which is applied like nail polish), associated with a family history of this infection. 14 sodium pyrithione, Other risk factors include perspiring heavily, being / (available outside in a humid or moist environment, , the United States), propylene wearing socks and shoes that hinder ventilation and glycol-urea-lactic acid, do not absorb , going barefoot in damp , such as public places such as swimming pools, gyms and (Nizoral Cream), and shower rooms, having athlete's foot (tinea pedis), allylamines, such as minor skin or nail , damaged nail, or other (Lamisil Cream).

127 www.ijapbc.com IJAPBC – Vol. 2(1), Jan- Mar, 2013 ISSN: 2277 - 4688 ______ Topical treatments are limited usually should be deferred to a surgeon or because they cannot penetrate the dermatologist. nail deeply enough, so they are  Surgically removing the nail plate is not generally unable to cure effective treatment of onychomycosis onychomycosis. Topical without additional therapy. This procedure medicines may be useful as should be considered an adjunctive additional therapy in combination (additional) treatment combined with oral with oral medicines. This results medical therapy. in treatment  A combination of oral, topical, and concentrations that come from surgical therapy may increase the two directions, topically and from effectiveness of treatment and reduce the within the body via oral cost of ongoing treatments. medicine.  Newer oral medicines are available. These Laser Treatment antifungal medicines are more effective One of the newest treatments to kill pathogens because they go through the body to infecting the nails is laser therapy. The laser beam penetrate the nail plate within days of can penetrate the nail tissue and disrupt fungal and starting therapy. other pathogens enough to kill them. Some patients  Newer oral antifungal may experience some mild discomfort during the terbinafine (Lamisil Tablets) and procedure. Reports suggest that laser therapy is (Sporanox Capsules) about as effective as medical therapy19. Some have replaced older therapies, patients may require more than one treatment. This such as , in the treatment can be very expensive. treatment of onychomycosis. They offer shorter treatment Alternative Treatments periods (oral antifungal There are many claims made that home remedies medications usually are can be used to treat a fungal nail infection. Products administered over a three-month such as Listerine, VapoRub, beer soaks, peroxide, period), higher cure rates, and and others are purported to be effective. fewer side effects. These Unfortunately, there is little or no data to support medications are fairly safe, with these claims; some of the commercially available few contraindications (conditions products do not promote their use for nail that make taking the medicine infections although some individuals may use them inadvisable), but they should not for alternative treatments19. be taken by patients with or heart failure. Before CONCLUSION prescribing one of these Although regional and temporal variability exists medications, doctors often order among the that are pathogenic in a blood test to make sure the liver onychomycosis, this disease is caused primarily by is functioning properly. Common dermatophytes. After decades of frustration and side effects include nausea and disappointment with this stubborn infection, stomach pain. dermatologists and other clinicians now have  (Diflucan) is not access to drugs with high cure rates and excellent approved by the Food and safety profiles. Moreover, short treatment times Administration (FDA) for increase patient compliance, reduce treatment treatment of onychomycosis, but costs, and allow patients to feel hopeful that their it may be used by some clinicians unsightly infections will be ended. as an alternative to itraconazole Perhaps the most important task of the clinician is and terbinafine. accurate diagnosis of the causal agent. Direct  To decrease the side effects and duration microscopy and culture are both necessary to of oral therapy, topical and surgical ensure this. Selection of an optimal antifungal drug treatments (see below) may be combined whose spectrum of activity encompasses the with oral antifungal management.17 infecting can proceed only with accurate diagnosis. In the last decade, there have been significant Surgical approaches to onychomycosis treatment advances in the development of effective and safe include surgically or chemically removing the drugs for onychomycosis. What remains to be nail.18 achieved? Unfortunately, onychomycosis is likely  Thick nails may be chemically removed to remain a disease of modern civilization20. The by using a urea compound. This technique environmental conditions that foster it, longer life

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