Fungal skin and soft tissue infections

 

Fungal skin and soft tissue infections

 

Pityriasis versicolor

 

This chronic, superficial yeast infection of the skin can present with areas of hyperpigmentation or hypopigmentation.

It is caused by the budding yeast Malassezia furfur, which is the mycelial phase of the yeast Pityrosporum orbiculare, which is part of the normal skin flora.

The hypopigmentation is due to tyrosinase inhibition by dicarboxylic acids produced by the pityrosporum, with consequent suppression of melanin production. Abnormal melanosomes may also be produced by a disruption in this pathway, accounting for the hyperpigmentation seen in other patients with this disorder.

 

Pityriasis versicolor is seen in young patients, with a peak incidence between 20 and 30 years of age. It is common in tropical climates. The sex incidence is equal and there may be a genetic predisposition to develop this reaction to normal skin flora.

Patients present with well demarcated pale or tan-coloured macules, some of which may coalesce, with fine scale, usually on the upper trunk alone. However, the condition may involve the whole trunk, the upper arms and the neck. There may be a slight itch.

Skin scrapings reveal spherical budding yeasts and coarse mycelia on microscopy.

Topical therapy is with

ketoconazole 2% shampoo applied daily for 10 minutes and washed off, for 10 days

OR

selenium sulfide 2.5% shampoo applied daily for 10 minutes for 7 days

OR

sodium thiosulfate 20% solution applied twice daily for 2 weeks.

 

If the disease is localised to a small area it is reasonable to use

imidazole cream or lotion (see Table 1) topically, twice daily for 10 days.

 

In unresponsive cases, use systemic therapy with

ketoconazole 200mg orally, daily for 10 days OR itraconazole 200mg orally, daily for 5 days.

 

Note:

Griseofulvin is ineffective against this yeast.

 

The hypopigmentation may persist for some months until adequate sun exposure repigments the areas of pallor. It can be recurrent in some individuals and repeated courses of treatment may be necessary. Alternatively, intermittent doses of systemic medication (pulse therapy) can be used to suppress the growth of the yeast. Use

ketoconazole 400mg OR itraconazole 200mg orally, once every 30 to 90 days.

 Tinea

 

Tinea: introduction


The causative agents in this condition are dermatophyte species, which may be acquired from animals, other humans or soil. Any part of the skin, hair and nails may be affected. Typically, tinea on the body presents with itchy, scaly erythematous lesions, with an annular or geographic shape and a tendency to clear centrally. Lesions may sometimes be pustular. The lesions expand slowly in most cases but an acute onset of multiple annular lesions can occur.

If the diagnosis has been missed and the infection treated with a topical corticosteroid, the typical morphology is lost, but it can usually be appreciated that the lesions have a definite edge.

Tinea of the hands and feet presents with interdigital maceration, and a nonspecific scaly erythema with fissuring and pustules that is often asymmetrical, distinguishing it from dermatoses such as psoriasis and dermatitis, which are usually bilaterally symmetrical. The infection commonly spreads to involve the nails with white or yellow discolouration, nail plate dystrophy and subungual debris. Foot tinea is often associated with tinea of the groin.

Tinea of hair-bearing areas presents with patchy alopecia, scaling and broken hairs. Hair may break at the scalp surface, producing a ‘black dot’ appearance. Inflammation is variable and ranges from nonexistent to the pustular, boggy mass seen with a kerion.

Diagnosis of tinea in hair-bearing areas is supported by fluorescence under Wood’s light examination, but many species do not fluoresce and a negative test does not rule it out. Diagnosis is confirmed by microscopy and culture of skin scrapings, subungual debris, clipped nail or plucked hair. Culture results are available in 3 to 4 weeks.

As fungal culture is a simple and inexpensive test, confirmation of diagnosis is always recommended prior to treatment with antifungals, particularly systemic agents, as tinea is often confused with eczema and other annular or patchy conditions such as pityriasis rosea and granuloma annulare. If microscopy is positive or there is a high index of suspicion of fungal infection, it is reasonable to begin treatment prior to the results of microscopy and culture. If antifungals have recently been used, these should be ceased for 1 week prior to attempting culture. When taking a fungal culture, scaly material should be scraped with a scalpel blade from the edge of the lesion. This may be deposited in a sterile container or inoculated straight onto a fungal culture plate. Material should be sent for direct microscopy. False negative results may be encountered with fungal culture, particularly with nail clippings, where the rate may be up to 40%. Negative culture may occur after positive microscopy. Reasons for negative culture include sampling error and overgrowth of nonpathogenic species in the laboratory. If there is still a strong diagnostic suspicion, a trial of therapy may be the ultimate diagnostic tool.

 

Tinea corporis, pedis and cruris


1

bifonazole 1% topically, once daily, continued for 14 days after symptoms resolve.

 

OR

1

terbinafine 1% topically, once or twice daily, continued for 14 days after symptoms resolve.

 

OR

2

clotrimazole 1% topically, 2 or 3 times daily, continued for 14 days after symptoms resolve.

 

OR

2

econazole 1% topically, 2 or 3 times daily, continued for 14 days after symptoms resolve.

 

OR

2

ketoconazole 2% topically, twice daily, continued for 14 days after symptoms resolve.

 

OR

2

miconazole 2% topically, twice daily, continued for 14 days after symptoms resolve.

 

If unresponsive, use

1

terbinafine (child <20 kg: 62.5 mg; 20 to 40 kg: 125 mg) 250 mg orally, daily for at least 2 weeks, depending on the response

 

OR

2

griseofulvin fine particle (child: 10 mg/kg up to) 500 mg or ultrafine particle (child >2 years: 5.5 mg/kg up to) 330 mg orally, daily for at least 4 weeks.

Tinea of the nails (onychomycosis, tinea unguium)

 

Onychomycosis is the term used for fungal infection of the nail. The condition is unsightly and may cause discomfort. Toenails are affected more commonly than fingernails. It is most commonly produced by dermatophyte moulds such as Trichophyton rubrum and Trichophyton mentagrophytes var interdigitale. T. rubrum infections usually also involve the sole of the foot, particularly the areas of thick skin, and frequently produce moccasin tinea pedis. T. rubrum is an anthropophilic fungus—humans are the natural reservoir of infection. Infections are frequently chronic and resistant to therapy. T. mentagrophytes var interdigitale is also an anthropophilic fungus and frequently infects the toe web spaces or the soft parts of the sole of the foot.

The first stage of onychomycosis is hyperkeratosis of the undersurface of the distal nail plate and the distal nail bed (hyponychium). This is known as distal subungual onychomycosis (DSO). The fungus seems to travel underneath the nail plate in the longitudinal folds of the nail bed to produce spears of subungual hyperkeratosis. These spears are one of the most useful clues to the diagnosis of onychomycosis. Progressive nail involvement produces total dystrophic onychomycosis (TDO).

T. mentagrophytes var interdigitale may also produce an unusual form known as white superficial onychomycosis (WSO). The diagnosis is confirmed by taking scrapings from the nail surface. WSO is responsive to topical imidazoles, whereas DSO and TDO are unresponsive.

Because many other disorders can mimic tinea of the nail, it is important to establish a diagnosis of tinea microbiologically before commencing treatment. This is done by first taking clippings of the affected distal nail plate and then scraping any subungual hyperkeratosis.

Microscopy and then culture will be positive in approximately 80% of cases of onychomycosis. Nail plate histology can be used if the culture is negative. For histology, a clipping of the distal nail plate is sent to the pathologist in formalin and stained with PAS (periodic acid Schiff reaction) to demonstrate the fungal hyphae. This increases the diagnostic yield in difficult cases.

Treatment options must be carefully considered, particularly if treatment is for cosmetic reasons only, as effective drugs are expensive and can have serious adverse drug reactions. However, the toenails can be a reservoir of infection which can precipitate recurrent cellulitis in association with tinea pedis.

First-line treatment for all types of nail tinea consists of

1

terbinafine (child <20 kg: 62.5 mg; 20 to 40 kg: 125 mg) 250 mg orally, daily for 6 weeks for fingernails and 12 weeks for toenails

 

OR (if terbinafine is not tolerated)

2

itraconazole 400 mg orally daily for 7 days every month for 3 to 4 months

 

OR

3

fluconazole 150 mg to 450 mg orally, once weekly for 12 to 52 weeks.

 

Terbinafine has a cure rate of 70% to 80%. Itraconazole and fluconazole have been used extensively overseas and a 3-month course has a cure rate of 60% to 70%. There is limited published data for use of itraconazole or fluconazole for tinea of the nails in children; terbinafine is currently the drug of choice.

Prior to the release of terbinafine, ketoconazole and griseofulvin were the main treatments, both of which needed to be taken continuously for 12 to 18 months. Ketoconazole use was limited by the potential complication of severe hepatic toxicity. Griseofulvin is safe but relatively ineffective; it has a cure rate of around 30% after 12 or more months of continuous therapy.

Topical nail lacquers are also available over-the-counter in pharmacies for the treatment of onychomycosis. These agents have no effect on TDO, but may have limited efficacy on DSO in patients intolerant of oral antifungals or not wanting to take oral medication for this problem.

For superficial or distal nail involvement, use

 

amorolfine 5% nail lacquer topically, weekly (may require up to 12 months therapy).

 

One difficulty in treating onychomycosis is determining when treatment has failed and a second course is required. At the end of the 3-month treatment period most nails still look abnormal, as a totally dystrophic nail takes up to 9 months to grow out. If normal nail is emerging proximal to the dystrophic nail, a scratch with a scalpel blade should be made at the base of the dystrophy. This scratch can then be followed by the patient until it grows out. If the dystrophic nail is growing out it remains distal to the scratch and no further treatment is required. If the dystrophy moves proximal to the scratch, this indicates ongoing fungal invasion of the nail which requires further treatment.

Tinea in children

 

 

Introduction

In children, tinea (dermatophyte infection) most commonly involves the scalp, face and body. Tinea pedis is less common in children than in adults, but is seen often in children with Down syndrome. The incidence rises with increasing age, reaching adult levels by late adolescence. In children, tinea is commonly acquired from dogs, cats and guinea pigs but human pathogens may also be responsible, especially in the case of tinea pedis. The animal dermatophytes tend to produce a more inflammatory and acute form of tinea. A kerion is a very acute form of tinea capitis, usually caused by an animal dermatophyte, in which a large boggy, pustular mass appears on the scalp.

 

Tinea capitis, including kerion

These dermatophyte infections like tinea capitis are caused by fungi of the genera Trichophyton, Microsporum and Epidermophyton. Confirm the diagnosis by fungal culture of scrapings and plucked hairs prior to commencing therapy. This is important to confirm the diagnosis and for future monitoring. Topical therapy is ineffective in treating tinea capitis.

1

terbinafine (child <20 kg: 62.5 mg; 20 to 40 kg: 125 mg) 250 mg orally, daily for 4 weeks

 

OR

2

griseofulvin fine particle (child: 10 mg/kg up to) 500 mg or ultrafine particle (child >2 years: 5.5 mg/kg up to) 330 mg orally, daily for 4 to 8 weeks.

 

Hair may not have completely regrown at the end of therapy, but this improves with time. Scarring alopecia is unusual as a sequel of tinea capitis.

Ketoconazole and selenium sulfide shampoos are a useful adjunct to therapy, in that they reduce shedding of spores; however, used alone they are ineffective as treatment.

The use of antibiotics, oral corticosteroids and surgical debridement does not add to the management of kerion and is contraindicated.

 

Tinea corporis, faciei or pedis

Prior to commencing treatment, perform a fungal scraping for culture. Many rashes that are common in children, such as dermatitis and psoriasis, may mimic tinea.

For mild or localised cases, use

imidazole cream applied 3 times daily for a minimum of 3 weeks

OR

terbinafine 1% cream applied twice daily for minimum of 2 weeks.

 

For extensive cases or tinea that has received prolonged treatment with topical corticosteroid, use

griseofulvin fine particle (child: 10 mg/kg up to) 500 mg or ultrafine particle (child >2 years: 5.5 mg/kg up to) 330 mg orally, daily for minimum of 3 weeks.

 

Clinical improvement usually occurs promptly, but premature cessation of treatment will result in relapse. .

Antifungal agents used in dermatology (Table 1)

 

Drug

Dose form and strength

Indication

 

Note: Dose requirements for antifungal agents are given in individual sections

imidazoles, topical

 

 

 

- bifonazole

cream (1%)

tinea corporis, candidiasis, pityriasis versicolor

 

- clotrimazole

cream, solution (1%)

tinea corporis, candidiasis, pityriasis versicolor

 

- econazole

cream, lotion, dusting powder, foaming solution (1%)

tinea corporis, candidiasis, pityriasis versicolor

 

- ketoconazole

cream (2%)

shampoo (1%, 2%)

tinea corporis, candidiasis, pityriasis versicolor, adjunct to treatment of tinea capitis

 

- miconazole

cream, lotion, ointment, oral gel, powder, shampoo, solution, spray, tincture (2%)

tinea corporis, candidiasis, pityriasis versicolor

 

nystatin

cream (100 000U/g)

candidiasis

 

selenium sulfide

shampoo (2.5%)

pityriasis versicolor

 

terbinafine

cream, gel (1%)

tinea corporis, candidiasis

 

amorolfine

nail lacquer (5%)

tinea of nails

 

fluconazole

oral (50mg, 100mg, 150mg, 200mg, 50mg/5mL)

candidiasis, pityriasis versicolor, tinea

 

griseofulvin

oral (125mg, 330mg, 500mg)

tinea capitis, tinea resistant to topical therapy

 

itraconazole

oral (100mg, 10mg/mL)

candidiasis, pityriasis versicolor, tinea

 

ketoconazole

oral (200mg)

candidiasis, pityriasis versicolor, tinea

 

terbinafine

oral (250mg)

tinea onychomycosis, tinea resistant to griseofulvin or patients unable to take griseofulvin

 

Candidiasis

 

Candida infection occurs on skin and mucosal surfaces, and is usually seen in subjects with predisposing factors, including therapy with broad-spectrum antibiotic, diabetes, iron deficiency, obesity and immobility, particularly where the skin is macerated and overheated. Candida infection may supervene on other dermatoses, particularly in the genital area and the flexures. General debility and immune incompetence also predispose to this infection. Otherwise healthy infants may suffer from oral candidiasis.

The clinical presentation is patches of moist, confluent erythema with a soggy, scaly edge, sometimes with vesicles and satellite pustules. The location is usually the flexures, submammary area and other skin folds. On mucosal surfaces, curd-like white material is seen on a red base. Diagnosis is readily confirmed by culture of a swab; however, a scraping for microscopy and fungal culture may also be done.

As the underlying factors predisposing to Candida albicans infection may not be readily modified, suppressive treatment is often required. Investigate for diabetes mellitus and iron deficiency. Treat underlying dermatoses if present. Cease oral antibiotics unless essential. In immunocompetent patients, use

imidazole cream (see Table 2) OR nystatin 100 000U/g cream applied 2 to 3 times daily. Continue treatment for 2 weeks after symptoms resolve.

 

Note:

Griseofulvin is not active against Candida albicans.

 

If necessary for inflammation, use

hydrocortisone 1% cream topically, 2 to 3 times daily.

 

If there is a poor response to therapy, or it is impracticable to apply topical treatment, use a course of an oral antifungal agent

ketoconazole 200mg orally, daily for 10 days OR itraconazole 100mg orally, twice daily for 7 days OR fluconazole 150mg orally, as a single dose.

 

In immunodeficient patients, use

ketoconazole 200mg OR itraconazole 100mg OR fluconazole 50mg orally, daily.

 

Treatment is continued until all clinical signs of candidiasis have subsided; however culture may remain positive. Long-term intermittent dosing is usually required to maintain remission of symptoms. Ketoconazole should be monitored by monthly liver function tests (LFTs) and fluconazole and itraconazole should be monitored by LFTs at 6-monthly intervals once the patient is on maintenance therapy.