Vol.2, No.7, 726-731 (2010) Natural Science http://dx.doi.org/10.4236/ns.2010.27090 Review on dermatomycosis: pathogenesis and treatment Deepika T. Lakshmipathy, Krishnan Kannabiran* Division of Biomolecules and Genetics,School of Biosciences and Technology, VIT University, Vellore, India; *Corresponding Author: [email protected] Received 24 February 2010; revised 25 March 2010; accepted 3 April 2010. ABSTRACT developing countries like India where the hot climate and humid weather is favourable to the acquisition and Dermatophytes, a group of keratinophilic fungi maintenance of the disease [5,6] and currently no race is thriving on the keratin substrate are the etio- totally free from dermatophytoses. logical agents responsible for causing cutane- ous infections. Dermatophytosis is currently 2. ECOLOGICAL CLASSIFICATION treated with the commercially available topical and oral antifungal agents in spite of the exist- In the course of evolution these pathogens have devel- ing side effects. Treatment of these cutaneous oped host specificity. This host specificity is ascribed to infections with secondary metabolites produced the difference in the composition of keratin [7]. Based by marine microorganisms is considered as a on their host specificity dermatophytes are classified into novel approach. For many years these organ- three ecological groups namely geophiles (soil), anthro- isms have been explored with the view of de- pophiles (man) and zoophiles (animals) [8]. The geo- veloping antibacterial, antifungal, antiviral, anti- philic dermatophytes are generally saprophytic and de- cancer and antiparasitic drugs. Exploring the rive nutrients from keratinous substrates. Rarely these unexplored aspect of actinobacteria for devel- pathogens cause infection in animals and man. Examples oping antidermatophytic drugs is a novel at- include Trichophyton ajelloi, Trichophyton terrestre, tempt which needs further investigation. Microsporum fulvum, Micropsorum gypseum, Micro- sporum cookie and Epidermophyton stockdaleae [9-11]. Keywords: Trichophyton; Microsporum; Zoophiles are pathogens with only one animal host Epidermophyton; Tinea Infections; Novel and grow as saprophytes on animal materials. Zoophiles Approach; Actinobacteria are also reported to infect human beings. Human beings acquire the infection from infected animals. Examples 1. INTRODUCTION include Trichophyton simii (monkeys), Trichophyton mentagrophytes (rodents), Trichophyton equinum (hor- 1.1. Dermatophytes ses), Microsporum canis (cats) and Micropsorum nan- num (pigs) [12,13]. Infections pertaining to mankind particularly those af- The primary hosts of anthropophilic species are hu- fecting the keratinized tissues are of serious concerns man beings but they may also cause infection in animals. worldwide and are increasing on a global scale. Derma- Transmission of infection is from man to man. Examples tomycoses are infections of the skin, hair and nail caused include Trichophyton rubrum, Trichophyton kanei, as a result of colonization of the keratinized layers of the Trichophyton schoenleini, Trichophyton concentricum, body. This colonization is brought about by the organ- Trichophyton tonsurans, Micropsorum gypseum, audou- isms belonging to the three genera namely Trichophyton, inii, Microsporum ferrugineum and Epidermophyton Microsporum and Epidermophyton [1,2]. Infection may floccosum [14,15]. also be caused rarely by the members of the genus Can- dida and by non-dermatophytic moulds belonging to the 2.1. Trichophyton genera Fusarium, Scopulariopsis and Aspergillus [3,4]. The genus Trichophyton includes 24 species. The colo- Interestingly dermatophytic infections are predominant nies on agar media are powdery, velvety or waxy. The in the tropical and subtropical countries; especially in the predominant spore type is micro conidia with sparse Copyright © 2010 SciRes. OPEN ACCESS D. T. Lakshmipathy et al. / Natural Science 2 (2010) 726-731 727 macro conidia [16]. Reverse side pigmentation is char- phytic infection [26]. acteristic of the species and is used for the identification of the species within the genus [17,18]. The macro co- 4. PATHOGENESIS AND CLINICAL nidia are thin walled with smooth surface and variable PRESENTATION shape [19]. Some of the Trichophyton species are fas- tidious in their requirement for amino acid as nitrogen The possible route of entry for the dermatophytes into source. Trichophyton tonsurans requires ornithine, the host body is injured skin, scars and burns. Infection citrul-line and Arginine whereas Trichophyton men- is caused by arthrospores or conidia. Resting hairs lack tagrophytes requires methionine. This nutritional speci- the essential nutrient required for the growth of the or- ficity has been used by many authors in the identifica- ganism. Hence these hairs are not invaded during the tion of the Trichophyton species [19]. process of infection [27]. The pathogen invades the up- 2.2. Microsporum permost, non-living, keratinized layer of the skin namely the stratum corneum, produces exo-enzyme keratinase The genus Microsporum includes 16 species. The colony and induces inflammatory reaction at the site of infection morphology of Microsporum species on agar surface is [28-31]. The customary signs of inflammatory reactions either velvety or powdery with white to brown pigmen- such as redness (ruber), swelling (induration), heat and tation [16]. Both macro and micro conidia are produced alopecia (loss of hair) are seen at the infection site. In- but the predominant conidial structures are macro co- flammation causes the pathogen to move away from the nidia. Micro conidia are less abundant. The macro co- site of infection and take residence at a new site. This nidia are multi septate with thick wall and rough surface movement of the organism away from the infection site [20]. Rarely some species produce neither micro nor produces the classical ringed lesion [32] (Figure 1). macro conidia [21]. They do not have any special nutri- The infections caused by dermatophytes are com- tional requirements. monly referred to as “tinea” or “ring-worm” infections due to the characteristic ringed lesions [33]. Based on 2.3. Epidermophyton the site of infection the tinea infections are referred to as The genus Epidermophyton includes only 2 species. The tinea capitis (scalp), tinea corporis or tinea circinata colonies are slow-growing, powdery and unique brow- (non-hairy, glaborous region of the body), tinea pedis nish yellow in colour. This genus is devoid of micro co- (“Athletes’ foot”; foot), tinea ungium (“Onychomycosis”; nidia. Macro conidia are abundant and produced in clus- nail), tinea mannum (hands), tinea barbae (“Barbers’ ters [16]. These macro conidia are thin walled with itch”; bearded region of face and neck), tinea incognito smooth surface [20]. (steroid modified), tinea imbricata (modified form of 3. DISTRIBUTION FREQUENCY OF DERMATOPHYTES AND DERMATOPHYTOSIS All the three genera of dermatophytes namely Tricho- phyton, Microsporum and Epidermophyton are world- wide in geographical distribution. The predominant cause of dermatophytic infections is Trichophyton fol- lowed by Epidermophyton and Microsporum. Within the genus Trichophyton, Trichophyton rubrum is the pre- dominant etiological agent accounting for 69.5% fol- lowed by Trichophyton mentagrophytes, Trichophyton verrucosum and Trichophyton tonsurans [22-24]. According to the World Health Organization (WHO) survey on the incidence of dermatophytic infection, about 20% the people world wide present with cutaneous infections [25]. The disease does not spare people of any age [26]. Among the tinea infections the most predomi- nant type of infection is tinea corporis or tinea circinata Figure 1. The schematic route of entry of dermatophytes into followed by tinea cruris, tinea pedis and Onychomycosis. the host system and onset of immune response in the host in Tinea corporis accounts for about 70% of the dermato- response to the pathogen entry. Copyright © 2010 SciRes. OPEN ACCESS 728 D. T. Lakshmipathy et al. / Natural Science 2 (2010) 726-731 tinea corporis), tinea gladiatorium (common among synthesized and added to this list during the same period. wrestlers’) and tinea cruris (“Jocks’ itch”; groin) [34]. These antimycotic drugs belonged to the Azoles class of antifungal drugs. The major target of the azoles unlike 5. IMMUNITY BEHIND DERMATOPHYTIC the other antifungal agents is the cytochrome P450 en- INFECTION zyme [40] (Figure 2). Based on the number of nitrogen atoms the azoles derivatives are classified into 2 groups Host immune response to the invading pathogen is re- as imidazoles and triazoles [16]. sponsible for the clinical manifestations. The fungal Imidazoles include miconazole (1970), clotrimazole, pathogens induce both immediate hypersensitivity as ketaconazole (1978), econazole, bifonazole, tioconazole well as cell mediated or delayed type hypersensitivity. and oxiconazole [41]. The chronological order of the Acquired resistance to the infection may also result from imidazoles to get FDA approval in United States is as dermatophytic infection. The fungal growth is restricted follows miconazole (1974), econazole (1982), keta- by the inflammatory reactions produced as a result of conazole (1985), oxiconazole (1988) and clotrimazole infection with dermatophytes [35]. (1993) [42]. The most recent drug to clear the FDA trials (2003) is Sertaconazole, a novel imidazole with broad 6. TREATMENT spectrum antifungal activity [43]. In general the imida- zoles exhibit side effects