Chapter 4 Fungal Diseases Essentials of Mycology In the course of time more than 69000 species of fungi have been recognized and described. It has been estimated that the total number of fungal species, known and as yet unknown, is of the order of 1.5 million. They range from giant puff-balls through mushrooms(edible and poisonous )to moulds and yeasts visible only with the aid of a economic losses and even famines when they infect food crops (relative massive microscope. Many moulds are known that parasitize plants, sometimes causing ent historical examples are the potato blight in Ireland and the many widespread agricultural depredations caused by mildews and rusts). However, the number of fungi with a known capability to infect man is relatively small Only a few of the fungi pathogenic for humans are sufficiently virulent to infect a healthy host. Most are relatively harmless unless they encounter an immunosuppressed patient, in which case they may invade readily and rapidly, sometimes with fatal consequences. A comprehe ensive opportunistic human pathogens may well exceed 400 species, even if the list is restricted solely to those species for which definitive evidence of infection is available. (Such evidence consists ideally of histopathology. demonstrating tissue invasion rather than mere culture of a fungus from an infected site. ) However, many of the specie would have been encountered clinically on very few occas ions indeed- often only once-so that fewer than 100 fungal species approach the status of regular human pathogens Pathogenesis of fungal diseases . o Three types of human disease are associated with fungal elements or their metabolic ducts. They are based primarily on 1. Allergenicity In this group disease is caused by interaction of a sensitized host with immunologically reactive fungal antigens. These occur on airborne fungal spores, or are associated with fungal elements growing commensally within the host. Spores are common causes of extrinsic asthma and other manifestations of type I allergy. Allergenictiy is also a contributing factor in the pathogenesis of several diseases where hypersensitivity is a major component, such as allergic bronchopulmonary aspergillosis 2. Toxigenictiy Many of the secondary metabolites produced by fungi are highly toxic for mammalian cells. Disease can follow ingestion of foodstuffs on which saprophytic fungi have grown and produced extracellular toxins(mycotoxins ) Many mycotoxins have been identified m, includ ing aflatoxin, ochratoxin, rubratoxin and zearalenone. Some cause diseases (mycotoxicoses )of commercial importance in animals. Human mycotoxicoses such as aflatoxicosis are relatively uncommon and generally occur in the setting of diminished 3. Pathogenicity Diseases in this category(mycoses )have an infective basis the causal agents possess ualities which enable them to act as primary or opportunistic pathogens The margins between these categories are not always clear cut. Thus, hypersensitive ity contributes to the pathology of many fungal infections. Some fungi, includ ing those
Chapter 4 Fungal Diseases Essentials of Mycology In the course of time more than 69000 species of fungi have been recognized and described. It has been estimated that the total number of fungal species, known and as yet unknown, is of the order of 1.5 million. They range from giant puff-balls through mushrooms (edible and poisonous) to moulds and yeasts visible only with the aid of a microscope. Many moulds are known that parasitize plants, sometimes causing massive economic losses and even famines when they infect food crops (relatively recent historical examples are the potato blight in Ireland and the many widespread agricultural depredations caused by mildews and rusts). However, the number of fungi with a known capability to infect man is relatively small. Only a few of the fungi pathogenic for humans are sufficiently virulent to infect a healthy host. Most are relatively harmless unless they encounter an immunosuppressed patient, in which case they may invade readily and rapidly, sometimes with fatal consequences . A comprehensive list of all fungi that have been incriminated as opportunistic human pathogens may well exceed 400 species , even if the list is restricted solely to those species for which definitive evidence of infection is available .(Such evidence consists ideally of histopathology . demonstrating tissue invasion rather than mere culture of a fungus from an infected site.)However, many of the species listed would have been encountered clinically on very few occasions indeed-often only once-so that fewer than 100 fungal species approach the status of regular human pathogens. Pathogenesis of Fungal Diseases Three types of human disease are associated with fungal elements or their metabolic products . They are based primarily on: 1. Allergenicity In this group disease is caused by interaction of a sensitized host with immunologically reactive fungal antigens . These occur on airborne fungal spores , or are associated with fungal elements growing commensally within the host. Spores are common causes of extrinsic asthma and other manifestations of type I allergy .Allergenictiy is also a contributing factor in the pathogenesis of several diseases where hypersensitivity is a major component , such as allergic bronchopulmonary aspergillosis 2. Toxigenictiy Many of the secondary metabolites produced by fungi are highly toxic for mammalian cells . Disease can follow ingestion of foodstuffs on which saprophytic fungi have grown and produced extracellular toxins (mycotoxins ). Many mycotoxins have been identified m, including aflatoxin, ochratoxin , rubratoxin and zearalenone . Some cause diseases (mycotoxicoses)of commercial importance in animals . Human mycotoxicoses such as aflatoxicosis are relatively uncommon and generally occur in the setting of diminished food supplies. 3. Pathogenicity Diseases in this category (mycoses)have an infective basis ;the causal agents possess qualities which enable them to act as primary or opportunistic pathogens The margins between these categories are not always clear cut . Thus , hypersensitivity contributes to the pathology of many fungal infections . Some fungi, including those
causing ringworm, Some fungi, including those causing ringworm, produce pathology without living tissue being invaded. Disorders associated principally with allergy and mycotoxins are outside the normal sphere of interest of clinical microbologists and infectious disease physic ians and only those with an infective basis will be considered further Within the large and heterogeneous complex that represents the fungal kingdom, only a small fraction, perhaps 400species in all, have the ability to acuse human infections With few exceptions, mycotic diseases of man are acquired from the environment. Fungal spores are common and widespread in both urban and rural local ities, and individuals can be exposed to enormous numbers of these airborne propagules in the workp lace as well Exposure to fungal spores is an everyday occurrence. It is fortunate that most fungi lack the necessary attributes which enable them to invade and persist in livin mammalian tissues Pityriasis Versicolor Pityriasis(tinea) versocolor is a chronic superficial fungal d isease usually located on the upper trunk neck , or upper arms lesions are slightly scaling and paprlar or nummular They may coalese to involve greater parts of the body and may vary in color from red to brown to white. the spores and short hyphae of the lipophilic yeast p. ovale can be detected by microscopy Potyriasis versicolor has a world wide aistribution It is more common in tropic areas with high temperature and a high relative humidity. The incidence is. much lower in temperte climates(1. 1%-3.7%) There is a great variation of age. The sex ratio also varies among studies l Pathogenesis Under the influence of pred isposing factors p. ovalr changes in pityriasis versicolor from the round blastospore form to the mycelial form. The most importantexogenous factors are high temperatures and a high relativehumid ity, which probably explain why potyriasis versicolor is more common in the tropics. In a temperate climat endogenous factors such as greasy skin, hyperhidrosis, hered itary factors, corticosteroid treatment and immunodeficiency are of mauor importance. The depigmentation seen in many patients may be explained by the presence of dicarbocycli acids. These acids have both a tyrosinase inhibitor effect and a cytotoxic effect on melanocytes Potyrosporum ovale is lipophilic and repuires the add ition of lipids to the culture med ium for optimal growth. It is a member of the normal human cutaneous flora and can be cultured from almost all body areas. the colonization starts during puberty and is uncommon on the skin of children. In elderly persons the number of p. ovale diminish perhaps owing to a decrease in skin lipids 2. Clinical Manifestation Pityriasis vers icolor is generally a disease of postpubertal and mature ages when the sebaceous glands are most active and is generally seen in otherwise healthy people It is foumd on skin where sebaceous glands are present and it is most often localized to the seborrheic areas of the trunk often those occluded by clothing. Lesions are slightly scaling, popular, nummular , or confluent and from red to brown to white most patients present with cosmetic problems, and pruritus, sometimes troublesome and more
causing ringworm, Some fungi, including those causing ringworm , produce pathology without living tissue being invaded . Disorders associated principally with allergy and mycotoxins are outside the normal sphere of interest of clinical microbologists and infectious disease physicians and only those with an infective basis will be considered further. Within the large and heterogeneous complex that represents the fungal kingdom, only a small fraction , perhaps 400species in all, have the ability to acuse human infections . With few exceptions, mycotic diseases of man are acquired from the environment. Fungal spores are common and widespread in both urban and rural localities, and individuals can be exposed to enormous numbers of these airborne propagules in the workplace as well as the home. Exposure to fungal spores is an everyday occurrence. It is fortunate that most fungi lack the necessary attributes which enable them to invade and persist in living mammalian tissues. Pityriasis Versicolor Pityriasis(tinea) versocolor is a chronic superficial fungal disease usually located on the upper trunk ,neck ,or upper arms .lesions are slightly scaling and paprlar or nummular . They may coalese to involve greater parts of the body and may vary in color from red to brown to white. the spores and short hyphae of the lipophilic yeast p .ovale can be detected by microscopy . Potyriasis versicoior has a worldwide aistribution .It is more common in tropic areas with high temperature and a high relative humidity. The imcidence is . much lower in temperte climates (1.1%-3.7%).There is a great variation of age .The sex ratio also varies among studies . 1.Pathogenesis Under the influence of predisposing factors p. ovalr changes in pityriasis versicolor from the round blastospore form to the mycelial form. The most importantexogenous factors are high temperatures and a high relativehumidity, which probably explain why potyriasis versicolor is more common in the tropics. In a temperate climat endogenous factors such as greasy skin , hyperhidrosis,hereditary factors, corticosteroid treatment, and immunodeficiency are of mauor importance. The depigmentation seen in many patients may be explained by the presence of dicarbocycli acids. These acids have both a tyrosinase inhibitor effect and a cytotoxic effect on melanocytes. Potyrosporum ovale is lipophilic and repuires the addition of lipids to the culture medium for optimal growth. It is a member of the normal human cutaneous flora and can be cultured from almost all body areas . the colonization starts during puberty and is umcommon on the skin of children. In elderly persons the number of p. ovale diminish perhaps owing to a decrease in skin lipids. 2.Clinical Manifestation Pityriasis versicolor is generally a disease of postpubertal and mature ages when the sebaceous glands are most active and is generally seen in otherwise healthy people .It is foumd on skin where sebaceous glands are present ,and it is most often localized to the seborrheic areas of the trunk ,often those occluded by clothing. Lesions are slightly scaling, popular,nummular ,or confluent and vary from red to brown to white .Most patients present with cosmetic problems ,and pruritus ,sometimes troublesome and more
pronounced when the patients are sweating 3. DiagnosIs The diagnosis is primarily based on the typical clinical picture in combination with bright yellow fluorescence under wood's light examination and direct microscopy. Direct microscopy is of major importance, and the round budding cells and hyphae can be easily identified. the two most important diseases to consider in differential diagnosis are vitiligo and the pityriasis alba variant of atopic dermatitis 4. Treatment There are numerous ways of treating poytriasis versicolor topically and systemically Regardless of the active material used in topical preparation, it is preferable to use solutions or lathering agents, because they are easy to apply to extensive body areas. the patients should treat the entire trunk, neck, arms, and legs down to the knees, even when only small areas are affected. The high rate of recurrence is an outstanding problem, reaching 60% in lyearand 80%after 2year. Consequenlly a prophylactic treatment regimen is necessary to avoid recurrence An application of propylene glycol 50% in water twice daily for 2 weeks is my current standard treatment for pityriasis versicolor. This treatment is effective, inexpensive, and presents little risk or skin irritation. Topical application of bifonazole, clotrimazole, econazole, miconazole, or ketoconazole once or twice daily for 2weeks is also effective Another effective treatment is zinc py rithione shampoo. It is applied on affected areas after showering, allowed to remain for approx imately 5 minutes, and then rinsed off. The procedure should, be repeated every evening for 2 weeks. Seleium sulfide is also effective but the patient sometimes complains about the offensive odor and stinging sensation on the skin after application Systemic therapy is primarily ind icated for extensive lesions, for lesions resistant to topical treatment, and for frequent relapse. Ketoconaole is an effective oraldrug, with a broad antimycotic spectrunm. Overall results have showm cure rates of 92% with a mean treatment period of 4 weeks. Hay and associates have treated patients successfrlly with 200-mg tablets taken once daily for 5 days. Rausch and Jacobs have shown that even a single dose of 400 mg may be effective. a triazole derivative( itraconazole by Janssen Pharmaceutical, Belgium has been shown to be effective orally days. Recently in an open study I treated patients with pityriasis vers icola aily for 5 to well-conducted control trials. An effective treatment schedule is 200 mgwith a single dose of 400mg fluconazole( Pfizer, New York, USA). At 3 weeks after treatment, 17of 23or 75%were cleared, showing that this treatment is an effective and elegant alternative to other treatments The risk of side effects is minimized with short-term treatment The conversion of p ovale from saprophyte to pathogen depends on predispos-ing factors which may be difficult to eradicate. a permanent cure is therefore difficult to achieve which explains the chronic ity. Prophylactic treatment should be initiateb to avoid tecurrence. An effective prophylactic treatment is 200 mg ketoconazole on 3 consecutive days every month, rausch and Jacobs have suc- cessfully treaed patients by prescribi 400 mg of the drug once monthly. It is important to inorm patients that depigmented patches may remain remain for several months after treatment, especially during the winter
pronounced when the patients are sweating. 3.Diagnosis The diagnosis is primarily based on the typical clinical picture in combination with bright yellow fluorescence under wood’s light examination and direct microscopy. Direct microscopy is of major importance, and the round budding cells and hyphae can be easily identified . the two most important diseases to consider in differential diagnosis are vitiligo and the pityriasis alba variant of atopic dermatitis. 4.Treatment There are numerous ways of treating poytriasis versicolor topically and systemically Regardless of the active material used in topical preparation, it is preferable to use solutions or lathering agents,because they are easy to apply to extensive body areas. The patients should treat the entire trunk, neck, arms, and legs down to the knees ,even when only small areas are affected . The high rate of recurrence is an outstanding problem, reaching 60% in 1yearand 80%after 2year. Consequenlly ,a prophylactic treatment regimen is necessary to avoid recurrence. An application of propylene glycol 50% in water twice daily for 2 weeks is my current standard treatment for pityriasis versicolor. This treatment is effective, inexpensive,and presents little risk or skin irritation. Topical application of bifonazole, clotrimazole, econazole, miconazole, or ketoconazole once or twice daily for 2weeks is also effective. Another effective treatment is zinc pyrithione shampoo. It is applied on affected areas after showering, allowed to remain for approximately 5 minutes, and then rinsed off. The procedure should, be repeated every evening for 2 weeks. Seleium sulfide is also effective but the patient sometimes complains about the offensive odor and stinging sensation on the skin after application. Systemic therapy is primarily indicated for extensive lesions, for lesions resistant to topical treatment, and for frequent relapse. Ketoconaole is an effective oraldrug, with a broad antimycotic spectrunm. Overall results have showm cure rates of 92% with a mean treatment period of 4 weeks. Hay and associates have treated patients successfrlly with 200-mg tablets taken once daily for 5 days. Rausch and Jacobs have shown that even a single dose of 400 mg may be effective. A triazole derivative(itraconazole by Janssen Pharmaceutical, Belgium )has been shown to be effective orally in several well-conducted control trials. An effective treatment schedule is 200 mg daily for 5 to 7days. Recently in an open study I treated patients with pityriasis versicolor with a single dose of 400mg fluconazole(Pfizer, New York, USA). At 3 weeks after treatment, 17of 23or 75%were cleared, showing that this treatment is an effective and elegant alternative to other treatments. The risk of side effects is minimized with short-term treatment. The conversion of p.ovale from sapropbyte to pathogen depends on predispos- ing factors which may be difficult to eradicate. A permanent cure is therefore difficult to achieve which explains the chronicity. Prophylactic treatment should be initiateb to avoid tecurrence. An effective prophylactic treatment is 200 mg ketoconazole on 3 consecutive days every month, rausch and Jacobs have suc- cessfully treaed patients by prescribing 400 mg of the drug once monthly. It is important to inorm patients that depigmengted patches may remain remain for several months after treatmentm, especially during the winter
Pityrosporum Folliculitis Pityrosporum foll icul itis is characterized by follicular papules and pustules lo-calized to the back, chest and upper arm, sometimes the neck, and more seldom the face. It is often associated with a troublesome itching o. The pityrosporum yeast had prev iously been mentioned in relation to folliculitis and o ne, but the first well-documented study of potyrosporum folliculitis was reported by potter and co-workers in 1973. this was later questioned, but today several studies indicate that p ovale is the etiologic agent of pityrosporum folliculitis Circulating antibodies against P. ovale were found to be present in higher titer s in patients with potyrosprum folliculitis than in healthy controls or in patients with pityriasis versicolor. When high nubers of yeast calls are present deep in the follicle, as in the case of pityrosporum folliculitis, antibody production may be better stimulated than when the rears cells are present primarily in the stratum corneum, as in pityriasis versicolor Cellular immunity is also present; the cellular response in the skin lesions is more pronounced and the cell infiltrates are larger than in poytriasis versicolor. Potyrosporum follicul itis is more prevalent in tropical countries with high temperatures and high elative humid ity. Other predisposing factors are antibiotic treatmet, dibetes mellitus, and Immunosuppression 1. Pathogenesis Under the influence of pred isposing factors, pityrosporum follicul itis may be explained by an extensive growth following dominance of p. ovale in the hair follicle. Local occlusion may play an important role. The inflammation may be due both to products produced by the yeast and to free fatty acids produced as a result of the lipase activity of 2. Clinical Manifestations The typical patient is a young woman reporting itching and with follicular papules and pustules local ized to the back, chest, and upper arms, sometimes the meck, and more seldom the face. The distribution of lesions predominantly on the trunk, the itching, and the lack of comedones differentiate the cond ition from acne. Other important differential diagnoses are other forms of follicul itis, systemic and cutaneous cand idiasis, neurotic excoriations, chronic urticaria, eczema, and other pruritic conditions 3. Diagnosis The diagnosis is based on a typical clinical picture with itching papules and pustules as the dominating symptoms, direct microscopy, and culture in combination with the histopathology and the effect of antimycotic treatment 4. Treatment The effect of antimycotic treatment is often dramatic. Many different treatments both topical and systemic and treatment schedules have been used I prefer propylene glycol, 50%in water, for the treatment of pityrospoum follicul itis. This agent is effective, cosmetically acceptable, and inexpensive. It is applied twice daily with a gauze d for 3 weeks and, after that, twice weekly as maintenance therapy. Other documented effective topical treatments include the imidazoles and selenium sulfide Most cases respond well to topical treatment. In patients with extensive lesions or in those who do not respond to topicat treatment, oral ketoconazole may be an effective altermative. Lesions and itching will recur in most patients if treatment is not maimtained intermittently. Therefore, a prophylactic treatment schedule, such as treatment once or
Pityrosporum Folliculitis Pityrosporum folliculitis is characterized by follicular papules and pustules lo-calized to the back, chest and upper arm, sometimes the neck, and more seldom the face. It is often associated with a troublesome itching. The pityrosporum yeast had previously been mentioned in relation to folliculitis and acne, but the first well-documented study of potyrosporum folliculitis was reported by potter and co-workers in 1973. this was later questioned, but today several studies indicate that p. ovale is the etiologic agent of pityrosporum folliculitis. Circulating antibodies against P. ovale were found to be present in higher titer s in patients with potyrosprum folliculitis than in healthy controls or in patients with pityriasis versicolor. When high nubers of yeast calls are present deep in the follicle, as in the case of pityrosporum folliculitis , antibody production may be better stimulated than when the years cells are present primarily in the stratum corneum, as in pityriasis versicolor. Cellular immunity is also present; the cellular response in the skin lesions is more pronounced and the cell imfiltrates are larger than in poytriasis versicolor. Potyrosporum folliculitis is more prevalenht in tropical countries with high temperatures and high relative humidity. Other predisposing factors are antibiotic treatmet, dibetes mellitus,and immunosuppression. 1. Pathogenesis Under the influence of predisposing factors, pityrosporum folliculitis may be explained by an extensive growth following dominance of p . ovale in the hair follicle. Local occlusion may play an important role. The inflammation may be due both to products produced by the yeast and to free fatty acids produced as a result of the lipase activity of the fungus. 2. Clinical Manifestations The typical patient is a young woman reporting itching and with follicular papules and pustules localized to the back, chest ,and upper arms, sometimes the meck, and more seldom the face. The distribution of lesions predominantly on the trunk, the itching, and the lack of comedones differentiate the condition from acne. Other important differential diagnoses are other forms of folliculitis, systemic and cutaneous candidiasis, neurotic excoriations, chronic urticaria, eczema, and other pruritic conditions. 3. Diagnosis The diagnosis is based on a typical clinical picture with itching papules and pustules as the dominating symptoms, direct microscopy, and culture in combination with the histopathology and the effect of antimycotic treatment. 4. Treatment The effect of antimycotic treatment is often dramatic. Many different treatments both topical and systemic and treatment schedules have been used. I prefer propylene glycol, 50%in water, for the treatment of pityrospoum folliculitis. This agent is effective ,cosmetically acceptable, and inexpensive. It is applied twice daily with a gauze pad for 3 weeks and, after that, twice weekly as maintenance therapy. Other documented effective topical treatments imclude the imidazoles and selenium sulfide. Most cases respond well to topical treatment. In patients with extensive lesions or in those who do not respond to topicat treatment, oral ketocomazole may be an effective altermative. Lesions and itching will recur in most patients if treatment is not maimtained imtermittently. Therefore,a prophylactic treatment schedule, such as treatment once or
twice a week, is mandatory Dermatophytosis e Dermatophytosis primarily represents superficial infections of the keratinized tissues of he epidermis, pilosebaceous follicles and nails caused by dermatophytic fungi. In contrast, the term dermatomycosis' refers to any non-dermatophytic fungal infection of the skin, including the systemic or deep my coses, that may have prominent cutaneous manifestations in add ition to visceral involvement 1. Pathogenesis Dermatophytes, uniquely qualified to invade thhe hair, nails, and skin of lower animals nd humans, are collectively the largerst group of molds infecting keratinous tissue. They are cutaneous pathogens with minimal virulence The host immune system also affects dermatophyte pathogenicity. Effective cell-mediated immune systems and the antimicrobial activity of polymorphonuclear leukocytes restrict dermatphyte pathogenicity to the stratum corneum When defects in the immune system develop, locally invasive dermatophyte disease may ensue. In addition to limiting the invasiveness of dermatophytosis, the immune system affects the clinical picture. Indeed, cutaneous findings resulting from dermatophyte colonization are a product of the host immune system rather than tissue toward fungal antigens and metabolic product sponse prod uced by the host is directed invasion by the organism. The inflammatory r The abil ity of a dermatophyte to produce chronic infections is another important pathogenic feature. Prolonged dermatophytoses are multifactorial but their causes can be divided into two categories, host factors and unique dermatophyte factors. The ensuing infection is, perhaps, a compromise between an inadequate host defense system and the limited virulence of dermatophytes, yielding chronic, minimal inflammatory changes on the host Host factors favoring chronic dermatophytoses include atopy, Cushing's syndrome icthyosis, and collagen vascular disease. In addition, sweat, occlusion(eg, shoes) occupational exposure, geographic location, tropical ambient temperatures, and genetic factors may lead to a cutaneous environment favoring chronic dermatophytosis Dermatophyte factors permitting chronic dermatophytosis include anthropophilic ecology and certain fungal products. Anthropophilic organisms, such as T rubrum and .conentricum, generally yield dermatoses with minimal inflammation, whereas zoophilic organisms, such as T. verrucosum, produce inflammatory responses includ ing bullous reactiongs of pustular reactions in humans. This variability ensures species survival because an exuberant inflammatory response could potentially rid the organism from the substance produced by the dermatophte. A cell wall glycoprotein(mannan) fromp9 natural host. a recently determined organism factor ensuring dermatophyte chronicity is a rubrum was ovserved to suppress cell-mediated immune function in vitro, thereby preventing elimination from the host and favoring chronicity. In other words, the fungus is fighting for its own survival. It is likely that other immunoinhibitory fungal substances are produced that almost promote both infection and chronicity The anatomic site infected also mediates the clinical presentation of dermatophytoses For example, if the organism invades hair-bearing skin, folliculitis(tineafollicul itis/tinea barbae)or alopecia(tinea capitis)or both can result. Infection on palms and soles may be
twice a week, is mandatory. Dermatophytosis Dermatophytosis primarily represents superficial infections of the keratinized tissues of the epidermis, pilosebaceous follicles and nails caused by dermatophytic fungi. In contrast, the term’ dermatomycosis’ refers to any non-dermatophytic fungal infection of the skin, including the systemic or deep mycoses, that may have prominent cutaneous manifestations in addition to visceral involvement. 1. Pathogenesis Dermatophytes, uniquely qualified to invade thhe hair,nails, and skin of lower animals and humans, are collectively the largerst group of molds infecting keratinous tissue. They are cutaneous pathogens with minimal virulence. The host immune system also affects dermatophyte pathogenicity. Effective cell-mediated immune systems and the antimicrobial activity of polymorphonuclear leukocytes restrict dermatphyte pathogenictity to the stratum corneum. When defects in the immune system develop, locally invasive dermatophyte disease may ensue. In addition to limiting the invasiveness of dermatophytosis,the immune system affects the clinical picture. Indeed, cutaneous findings resulting from dermatophyte colonization are a product of the host immune system rather than tissue invasion by the organism. The inflammatory response produced by the host is directed toward fungal antigens and metabolic products. The ability of a dermatophyte to produce chronic infections is another important pathogenic feature. Prolonged dermatophytoses are multifactorial but their causes can be divided into two categories,host factors and unique dermatophyte factors. The ensuing infection is, perhaps, a compromise between an inadequate host defense system and the limited virulence of dermatophytes, yielding chronic, minimal inflammatory changes on the host. Host factors favoring chronic dermatophytoses include atopy, Cushing’s syndrome, icthyosis, and collagen vascular disease. In addition, sweat, occlusion(eg,shoes), occupational exposure, geographic location,tropical ambient temperatures, and genetic factors may lead to a cutaneous environment favoring chronic dermatophytosis. Dermatophyte factors permitting chronic dermatophytosis include anthropophilic ecology and certain fungal products. Anthropophilic organisms, such as T. rubrum and T.conentricum, generally yield dermatoses with minimal inflammation,whereas zoophilic organisms,such as T. verrucosum,produce inflammatory responses including bullous reactiongs of pustular reactiongs in humans. This variability ensures species survival because an exuberant inflammatory response could potentially rid the organism from the natural host. A recently determined organism factor ensuring dermatophyte chronicity is a substance produced by the dermatophte. A cell wall glycoprotein (mannan) from T. rubrum was ovserved to suppress cell-mediated immune function in vitro, thereby preventing elimination from the host and favoring chronicity. In other words, the fungus is fighting for its own survival. It is likely that other immunoinhibitory fungal substances are produced that almost promote both infection and chronicity. The anatomic site infected also mediates the clinical presentation of dermatophytoses. For example, if the organism invades hair-bearing skin, folliculitis(tineafolliculitis/tinea barbae) or alopecia(tinea capitis) or both can result. Infection on palms and soles may be