Infections of skin, hair and nails by various species of dermatophytes.

Dermatophytoses: synonym tinea.

Dermatophytes belong to a group of moulds with common physiological and morphological properties. As saprophytes, they break down keratin and use it as a growth substrate. This is referred to as keratinophilia. Only those that are also able to do this in vivo are potentially pathogenic. The morphology they exhibit in their parasitic growth phase differs from their normal saprophytic morphology.

The difference between geophilic, zoophilic and anthropophilic dermatophytes is of importance epidemiologically. Geophils live as saprophytes in the soil. Exceptionally, geophilic dermatophytes are pathogenic (e.g. Microsporum gypseum).

Zoophilic dermatophytes are more or less specific pathogens for their host. E.g.:

• Trichophyton verrucosum - cattle
• Trichophyton equinum - horse
• Microsporum canis - cat (dog)
• Trichophyton mentagrophytes var. mentagrophytes - rodent

Anthropophilic dermatophytes are only pathogenic to humans. E.g.:

• Epidermophyton floccosum
• Trichophyton mentagrophytes var. interdigitale
• Microsporum langeroni
• Trichophyton rubrum
• Trichophyton schonleini

In contrast to all other mycoses, some dermatophytoses are infectious. The fungal elements – hyphae or spores - present in skin scales or in parasitised hair are infectious to others. Infection usually occurs indirectly. This is apparent from the enormous number of dermatophyte colonies, which can be obtained from clothing, bed linen, chairs, carpets, etc, in a Microsporum canis infection in a cat, even after a cure. The same applies to dermatophytes which cause tinea pedis. Not infrequently 100 to 200 colonies/m² are found on the floor of showers and changing rooms in swimming baths or sports complexes. Lesions of geophilic dermatophytes are not infectious. In this case the spores are infectious and they come from saprophytic growth in the ground.

• Microsporosis: in which large, round, bare, desquamating plaques arise where the hairs are broken off a few millimetres from the follicle. Affected hairs display green fluorescence under Wood’s light (UV 360 nm or black light). On microscopic examination of these hairs, a sheath of small spherical spores is seen surrounding the hair (ectothrix). In Western Europe, microsporosis is usually caused by the zoophilic Microsporum canis. In Central Africa, anthropophilic dermatophytes such as Microsporum langeroni are involved. Sometimes imported cases are seen in Belgium.

• Trichophytosis: is characterised by several small, desquamating plaques in which the affected hairs are broken off at scalp level at the follicular openings. The hairs do not fluoresce under Wood’s light. On microscopic examination the spores can be seen in dilated hair shafts (endothrix). Trichophytosis is caused exclusively by anthropophilic dermatophytes. In Central Africa up to 25% of cases are associated with pus formation.
• Kerion: is a tinea in which raised, red, purulent lesions develop as a result of the violent inflammatory reaction. The hairs normally do not fluoresce under Wood’s light. Affected hairs fall out. Microscopic examination shows chains of small (T. mentagrophytes var. mentagrophytes) or large spores (T. verrucosum) on the outside of the hairs (ectothrix). The pathogens are zoophilic dermatophytes. Microsporum canis sometimes also causes kerion (Wood positive).
• Favus: is characterised by the formation of yellow, cup-shaped crusts centred on the hair follicles. Wood positive. The hair does not break off but is not produced because of the destruction of the follicles. This results in permanent alopecia. A single anthropophilic dermatophyte, T. schonleini, causes this form of tinea. Favus occurs particularly in North Africa and the Middle East. In Europe it is still found sporadically in families who live, cut off in remote areas.

b) Tinea barbae:

Tinea barbae exhibits the same clinical presentation as kerion – raised purulent lesions - and is caused by the same zoophilic dermatophytes.

In tinea corporis, one or more red, desquamating, circularly growing lesions form on non-hairy skin. Vesicles and desquamation are seen on the edges of this 'herpes circinatus', which clears from the centre. The microscopic examination of scales taken from the active edges of the lesions shows the presence of mycelial filaments.

Tinea cruris is a 'herpes circinatus' that occurs in the fold of the groin. The microscopic picture is the same as in tinea corporis. The pathogens are almost exclusively three anthropophilic species, Trichophyton rubrum, Epidermophyton floccosum and Trichophyton mentagrophytes var. interdigitale, and are always found on the feet in these patients (tinea pedis). Erythrasma and intertrigo caused by yeasts must be included in the differential diagnosis.

Athlete's foot is an infection of the feet caused by bacteria, yeasts or dermatophytes. The term tinea pedis should only be used if the pathogen is a dermatophyte. Tinea pedis is caused by the same three pathogens as tinea cruris.

Clinically a distinction can be made between

• a chronic form, in which the infection remains limited to one (usually the 4^th) or more interdigital spaces and which is associated with redness, desquamation, maceration and possibly painful cracking. This form is frequently associated with hyperhidrosis.
• a chronic, dry, plantar form with an erythematous, desquamating, hyperkeratotic sole of the foot. This form is usually associated with dyshidrosis.
• an acute form with vesicles, pustules and sometimes even bullae on the plantar side of the arch of the foot and possibly the back of the foot (sometimes hyperacute with erosions and bacterial superinfections).

Epidemiologically, the distinction between geophilic, zoophilic and anthropophilic dermatophytes is important. Close contact with soil in which spores of saprophytic origin are present can lead to infections caused by geophilic dermatophytes such as Microsporum gypseum. These occur predominantly in children and are localised on the face. In Western Europe, two dermatophytoses caused by zoophils occur regularly. Cattle breeders and veterinarians are infected with Trichophyton verrucosum, the causative agent of tinea in cattle. Microsporum canis causes familial infections in which the cat serves as the source of infection.

In terms of the anthropophilic species, a distinction must be drawn between the causative agents of tinea capitis and those of tinea cruris, pedis and unguium (nails).

• Tinea capitis occurs particularly in young children. People become resistant to microsporosis and trichophytosis after puberty for as yet unknown reasons. This spontaneous recovery is not seen in favus which can be lifelong without treatment. The vertical transmission of favus from parents to children explains why this disease is sometimes considered congenital. The high prevalence of tinea capitis in some developing countries is the result of poor hygiene.
• Tinea cruris, pedis and unguium are a consequence of our modern civilisation. Communal sport, particularly frequent visits to swimming pools, plays an important role in the epidemiology of tinea pedis. These infections are sometimes considered an occupational disease if they occur as a result of the use of communal showers at work. Two factors play a role here: firstly the source of infection, and secondly host factors, such as the wearing of safety shoes and other occlusive footgear that promote warmth and moisture.

Prevention is directed at eliminating sources of infection (thorough cleaning of floors, detection and treatment of infected individuals) and avoiding predisposing factors (keeping feet dry, use of antifungal powder). Some patients suffer from chronic and sometimes extensive forms of tinea that are very difficult to treat. A series of general underlying factors play a role (atopy, diabetes, Cushing’s syndrome).

Skin scrapings and nail fragments are examined microscopically in a drop of KOH (20-30%) for the detection of mycelium and arthrospores. For hairs, chloral lactophenol is best used. It is important here whether the spores are inside (endothrix) or outside (ectothrix) the hairs. With ectothrix, a further distinction is made between the type of microsporosis with small spores forming either a sheath or chains as are found in kerion. Isolation of the causative dermatophyte is made on Sabouraud containing actidione and chloramphenicol.

The result of the direct examination is important to distinguish patents from healthy carriers. Culture is important to identify the causative agent and to obtain evidence of the source of infection.

Griseofulvin is a secondary metabolite of Penicillium griseofulvium. This product was first used as an antifungal agent in agriculture. It causes distortion of the hyphae (curling factor). After taking orally (with a fat-rich meal) it accumulates in the stratum corneum. It is still indicated in infections with M. canis.

In developing countries it has been used in mass treatments of tinea capitis as a single dose of 1500 mg with an 80-93% cure rate in the case of small lesions. Spontaneous recovery is possible. Re-infections can occur (no protective immunity), but no resistant fungi have been described. If there is no response to therapy, consideration may be given to patient related factors such as poor circulation, absorption disorder or excessive sweating. Griseofulvin interacts with other drugs: oral contraceptives, coumarin derivatives and barbiturates. It is an antimitotic and should therefore not be administered to pregnant women.

• Children: 10-20 mg/kg/day for 6-8 weeks
• Adults 0.5-1 g/day for 4-6 weeks

• Children < 20 kg: 62.5 mg/day for 4 weeks
• Children 20-40 kg: 125 mg/day for 4 weeks
• Adults and child > 40 kg: 250 mg/day for 4 weeks (6-8 weeks if M. canis)

• 3-5 mg/kg/day for 4 weeks

Fluconazole:

• 8 mg/kg/day for 8-12 weeks

Azoles in shampoo or selenium sulphide shampoo as prevention?

In kerion possibly corticosteroids systemically, never locally.

Local treatment may be given in the case of a geophilic mould or a limited lesion.

Magistral preparation of 0.5-5% acetylsalicylic acid (keratinolytic) and 1-10% benzoic acid (antifungal) (Whitfield’s ointment).

Creams, ointment, spray with 1-2% azoles, 2x/day for 2-3 weeks

Terbinafine cream 2x/day for 1 week (children 1x/d)

Terbinafine:

• 250 mg/day for 2 weeks

• Tinea pedis and tinea manum: 400 mg/day for 7 days
• Tinea corporis and tinea cruris: 200 mg/day for 7 days
• 3-5 mg/kg/day (children)

• Adults 500 mg/day for 4-6 weeks
• Children-20 mg/kg/day for 2-4 weeks for tinea corporis
• 4-8 weeks for tinea pedis

Malassezia furfur is a small, oval or round, lipophilic yeast which proliferates by unipolar budding. This yeast is present on the skin of everyone (scalp, chest, auditory canal). Pityriasis versicolor and other infections caused by M. furfur are therefore considered not to be infectious diseases. As yet unelucidated factors -seborrhoea, sweat secretion– mean that this yeast may be pathogenic in certain individuals.

In pityriasis versicolor, short, thick hyphae and groups of more or less round yeast cells are seen in a KOH preparation of the scrapings. In the other infections in which M. furfur plays a possible aetiological role, only numerous round or oval yeast cells are found with the typical unipolar budding. M. furfur can only be cultured on nutrient media containing lipids.

The discontinuation of parenteral administration of lipids is usually sufficient to cause the fungaemia in deep pityrosporoses to disappear.

Cutaneous, oral and genital infections caused by yeasts of the Candida genus.

Candida albicans is the principal causative agent of candidosis. In addition, there are other potential pathogenic species: C. glabrata, C. guilliermondii, C. krusei, C. parapsilosis, C. tropicalis, etc. C. albicans is an obligate endosaprophyte. Promoting factors provide the conditions in which this common saprophyte becomes a pathogenic agent. The same applies to the other species. Infections with Candida sp. thus usually indicate an underlying disease.

Classic thrush is characterised by a white, curd-like coating on the tongue or elsewhere in the oral cavity. Stomatitis due to Candida is often associated with painful infection of the lips -cheilitis- and corners of the mouth -perleche-.

Oral candidosis is a frequent complication of oral administration of broad-spectrum antibiotics (disturbance of the normal microflora). It also occurs in wearers of dentures (local factor that encourages colonisation with Candida). In patients with cell-mediated immunity disorders, large number of Candida are found in the oral cavity with or without lesions. Oropharyngeal and oesophageal candidosis is the most frequent opportunistic mycosis in HIV-positive patients.

The diagnosis of (vulvo)vaginitis due to Candida is based both on clinical criteria (pruritis, leukorrhoea, erythema, oedema, white lining on the vaginal wall) and on laboratory criteria (direct examination and culture).

Contamination of the vagina with Candida stems from the endogenous endosaprophytic flora of the gastro-intestinal tract. The causal strain almost always comes from the woman herself. Vaginitis due to yeasts must therefore not be seen as a sexually transmitted disease. It is only the strain and not the infection which is passed on to the partner. Colonisation and possible infection occur when predisposing factors alter the vaginal biotope (hormonal changes, changes in pH, etc.). When balanitis or balanoposthitis (erythema and a whitish coating on the coronary sulcus) by yeasts is diagnosed in the male, consideration must be given to an underlying factor (disorders of glucose metabolism).

Here again the first step is the detection of yeasts by direct examination of a fresh preparation. Oval yeast cells are seen with budding and possibly pseudomycelium. In C. glabrata infection only yeast cells are found. Culture is carried out on a standard Sabouraud nutrient medium with chloramphenicol. Identification of yeasts is based principally on physiological characteristics (fermentation and oxidative assimilation of sugars). Candida albicans can be recognised by two morphological characteristics: the formation of germ tubes and chlamydospores.

In all these infections, the underlying factors should always be identified (diabetes, use of steroids, HIV, …). It is usually advisable to limit the number of yeast cells in the oral cavity and G.I. tract, possibly preventively even by administration of polyenes or azoles. There is the risk here, however, of selecting resistant strains.

Topical azoles (clotrimazole, ketoconazole, econazole, miconazole) and polyenes (nystatin)

• Topical miconazole (gel), nystatin
• Fluconazole 100 mg/day PO
• Itraconazole oral solution 200 mg/day for 7-14 days
• BEWARE OF inherent resistance of C. krusei and C. glabrata and acquired resistance of C. albicans to fluconazole.

• Topical azoles (clotrimazole, miconazole, econazole) in the form of 2% creams, 100-500 mg tablets, 100-1200 mg vaginal ovules. Treat for 1-14 days.

10-15% of patients never become negative. In recurrent vaginitis (4/year) 1x150 mg fluconazole or 2x200 mg itraconazole PO.

• In the event of resistance to azoles: capsules with boric acid locally (600 mg/day for 14 days).

Nail infections are usually caused by fungi. A laboratory test is necessary to establish whether a yeast is involved (predominantly C. albicans and C. parapsilosis) or a dermatophyte (predominantly T. rubrum and T. mentagrophytes var. interdigitale) or sometimes other filamentous fungi such as Scopulariopsis brevicaulis. Onychomycosis of toenails is usually, but not exclusively, caused by dermatophytes while on fingernails it is due to yeasts. S. brevicaulis and other filamentous fungi almost exclusively affect the toenails.

The mycological diagnosis of onychomycosis is based on a direct microscopic examination (KOH), possibly a histological examination and isolation of the causative agent in culture.

Local (to be combined with systemic therapy): terbinafine, azoles, amorolfine, elimination of the affected keratin (40% urea paste ± butenafine).

• Formerly griseofulvin, but very long treatment necessary with disappointing results
• Terbinafine: 250 mg/day for 12 weeks (6 weeks for hands)
• Itraconazole: 200 mg/day for 3 months or pulse therapy: 2x200 mg/day for 1 week per month and for 3-4 months sometimes even up to one year (2 months for the hands).
• Fluconazole: 150-300 mg/week for 6-12 months (3-6 months for the hands).

Itraconazole, fluconazole

In vitro terbinafine is not active except against C. parapsilosis

Local or systemic terbinafine, itraconazole, local amorolfine, surgery?