Clinical Topic A-Z Clinical Speciality

Fungal skin infection - body and groin

Fungal skin infection - body and groin
D003881Dermatomycoses
Infections and infestationsSkin and nail
2013-08-01Last revised in August 2013

Fungal skin infection - body and groin - Summary

Fungal infection of the skin (also known as ringworm or tinea) is caused by dermatophytes.

Tinea corporis (fungal infection of the body) is usually caused by Trichophyton rubrum.

Tinea cruris (fungal infection of the groin) is most commonly caused by autoinoculation from dermatophyte infection of the hands, feet, or nails and is caused by Trichophyton rubrum, Trichophyton mentagrophytes, or Epidermophyton floccosum.

Fungal skin infections are more common in men than in women. They can be caught by:

Direct contact with an infected person or animal.

Indirect contact with items contaminated with the fungus.

Contact with soil (rare).

Tinea corporis typically presents as one or more red or pink, flat or slightly raised patches of skin which enlarge to become ring-shaped lesions with red, scaly borders and a clear central area.

Tinea cruris commonly presents as red to red-brown, flat or slightly raised plaques with active borders (pustules or vesicles), which are often itchy.

Diagnostic tests are not usually required, but microscopy and culture of skin samples should be taken if:

The diagnosis is unclear.

The infection has not responded to standard topical antifungals.

Oral antifungal treatment is being considered.

Topical clotrimazole, miconazole, or econazole is recommended. Topical ketoconazole and topical terbinafine are alternatives, but they are not licensed for use in children.

For skin that is particularly inflamed, a topical antifungal may be combined with a mildly potent corticosteroid. The topical corticosteroid should be used once or twice a day for a maximum of seven days. For fungal infection of the groin the topical corticosteroid should be used once a day because of the increased risk of adverse effects with topical corticosteroids in occluded areas.

Any associated fungal nail infection should be treated at the same time to prevent re-infection.

For adults with severe or extensive disease, or when topical treatment has failed, options include:

Oral antifungal treatment (terbinafine, griseofulvin, or itraconazole) — a positive microscopy or a positive culture of skin scrapings is recommended before starting treatment.

Referral to a dermatologist.

People with fungal infection of the body or groin should be advised to wash the affected skin daily and dry thoroughly afterwards (particularly in the skin folds), wash clothes and bed linen frequently to eradicate the fungus, not share towels (and to wash them frequently), and to wear loose-fitting clothes made of cotton or a material designed to keep moisture away from the skin.

It is not necessary to keep children away from school.

Referral to a dermatologist may be required for:

Uncertain diagnosis.

Unsuccessful treatment.

Severe or extensive infection.

Recurrent infection.

A person who is immunocompromised.

Have I got the right topic?

1months3060monthsBoth

This CKS topic covers the management of dermatophyte fungal skin infection (ringworm or tinea) of the body or groin.

This CKS topic does not cover fungal infection at other sites, candidal infection of the skin, or pityriasis versicolor.

There are separate CKS topics on Candida - skin, Fungal nail infection, Fungal skin infection - foot, and Fungal skin infection - scalp.

The target audience for this CKS topic is healthcare professionals working within the NHS in the UK, and providing first contact or primary health care.

CKS gratefully acknowledges the contribution of the British Association of Dermatologists in the development of this topic.

How up-to-date is this topic?

How up-to-date is this topic?

Changes

Last revised in August 2013

January 2014 — minor update. Minor update to the text to include information from the manufacturer regarding how much clotrimazole to apply to the skin [ABPI Medicines Compendium, 2014].

December 2013 — minor update. Text updated to reflect that the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has suspended the marketing authorisation for oral ketoconazole, and it should not be prescribed for the treatment of fungal infections [MHRA, 2013].

August 2013 — reviewed. A literature search was conducted in July 2013 to identify evidence-based guidelines, UK policy, systematic reviews, and key RCTs published since the last revision of the topic. No major changes to clinical recommendations have been made. Prescribing information has been added to support the prescribing of topical and oral antifungal treatments.

Previous changes

August 2013 — minor update. Nizoral® cream (ketoconazole 2%) is no longer licensed for use in children.

August 2013 — minor update to the text to reflect recent guidance from the European Medicines Agency regarding the use of oral ketoconazole [MHRA, 2013].

November 2012 — minor update. The links to the electronic medicines website (www.medicines.org.uk) have been updated.

January 2012 — minor typographical error corrected. Issued in February 2012.

August 2010 — minor update. Sulconazole 1% cream (Exelderm®) has been discontinued. The prescription has been removed. Issued in August 2010.

May 2009 — minor update. Econacort® cream (econazole 1% plus hydrocortisone 1% cream) has been discontinued. This prescription has been removed. Issued in June 2009.

January to May 2009 — converted from CKS guidance to CKS topic structure. The evidence-base has been reviewed in detail, and recommendations are more clearly justified and transparently linked to the supporting evidence.

Together with the CKS topics on Fungal skin infection - foot and Fungal skin infection - scalp, this CKS topic replaces the former topic on Fungal skin infections.

September 2008 — minor correction to the Changes section. Issued in September 2008.

August 2008 — minor update. Nystatin cream and ointment discontinued; text amended. Issued August 2008.

April 2008 — minor update to the text for oral ketoconazole, this now reflects the most recent Medicines and Healthcare products Regulatory Agency (MHRA) guidance.

March 2008 — minor update. New text inserted regarding rare cases of changes in INR when warfarin and oral terbinafine have been given concomitantly. Issued March 2008.

October to December 2005 — written. Validated in March 2006 and issued in May 2006.

Update

New evidence

Evidence-based guidelines

No new evidence-based guidelines since 1 July 2013.

HTAs (Health Technology Assessments)

No new HTAs since 1 July 2013.

Economic appraisals

No new economic appraisals relevant to England since 1 July 2013.

Systematic reviews and meta-analyses

No new systematic reviews since 1 July 2013.

Primary evidence

No new randomized controlled trials published in the major journals since 1 July 2013.

New policies

No new national policies or guidelines since 1 July 2013.

New safety alerts

No new safety alerts since 1 July 2013.

Changes in product availability

No changes in product availability since 1 July 2013.

Goals and outcome measures

Goals

Early recognition of features suggestive of fungal infection of the body and groin

Making an accurate diagnosis and excluding similar conditions

Making an accurate assessment (for example of severity)

Appropriate treatment in primary care settings

Appropriate referral to secondary care or other specialist service

Providing appropriate advice to a person with fungal infection of the body or groin

Background information

Causes

What causes it?

Fungal infection of the skin (also known as ringworm or tinea) is caused by dermatophytes [Hainer, 2003].

Fungal skin infections are more common in men than in women. They can be caught by [Hainer, 2003]:

Direct contact with an infected person (anthropophilic infection) or animal, for example dogs, cats, guinea pigs, and cattle (zoophilic infection).

Indirect contact with items contaminated with the fungus, for example clothing, towels, bedclothes, and chairs handled by people with the infection.

Contact with soil (geophilic infections), although this is rare.

Tinea corporis (dermatophyte fungal infection of the body) is usually caused by Trichophyton rubrum [Weinstein and Berman, 2002; Gupta et al, 2003; Havlickova and Friedrich, 2008].

Tinea cruris (dermatophyte fungal infection of the groin) is most commonly caused by autoinoculation from dermatophyte infection of the hands, feet, or nails and is caused by Trichophyton rubrum, Trichophyton mentagrophytes, or Epidermophyton floccosum [Hainer, 2003; Loo, 2004; Andrews and Burns, 2008].

It occurs when temperature and humidity are high (such as occlusion from wet or tight-fitting clothing) [Hainer, 2003].

It usually affects adolescent and young adult men, although it may be seen in post-pubertal females who are overweight or wear tight clothing [Andrews and Burns, 2008].

Diagnosis

Diagnosis of fungal skin infection - body and groin

Diagnosis

How should I diagnose a fungal skin infection?

Diagnosis is usually made on the basis of clinical appearance.

On the body:

The rash typically presents as one or more red or pink, flat or slightly raised patches of skin which enlarge to become ring-shaped lesions with red, scaly borders with a clear central area.

However, more rarely, the lesions can appear as:

Numerous overlapping concentric circles (tinea imbricate).

Herpetiform subcorneal vesicles or pustules (bullous tinea corporis).

In the groin:

The most commonly affected areas are the inguinal folds and proximal medial thighs. The perianal skin and buttocks may be affected, but in men the penis and scrotum are often spared.

The clinical presentation is variable, but the lesions are commonly red to red-brown, flat or slightly raised plaques with active borders (pustules or vesicles). They often itch, and in some cases there is uniform scale without central clearing.

Fluorescence is not seen when the rash is examined with a Wood's light.

Exclude other skin disease that looks like a dermatophyte infection of the body or groin.

Basis for recommendation

Basis for recommendation

Information on how to diagnose a fungal skin infection is based on expert opinion in review articles [Weinstein and Berman, 2002; Hainer, 2003; Loo, 2004; Andrews and Burns, 2008; Havlickova and Friedrich, 2008] and in Rook's Textbook of Dermatology [Hay and Ashbee, 2010].

Differential diagnosis

What else might it be?

Skin conditions which can look similar to fungal infection of the body include:

Discoid eczema — plaques of papulo-vesicles tend to occur symmetrically on the limbs.

Pityriasis rosea — symmetrical, and typically affects the trunk and the proximal limbs. The herald patch is almost impossible to differentiate from ringworm without microscopy of scales.

Pityriasis versicolor — patchy, sharply demarcated macules with fine scale. Usually there is less inflammation than with tinea corporis. Under Wood's light, the scaly lesions may show pale yellow fluorescence.

Psoriasis — usually present on the knees, elbows, and scalp. Pitting of the nails may be present.

Granuloma annulare — single or multiple rings of small, smooth, red or flesh-coloured papules. Itch may be present.

Skin conditions which can look similar to fungal infection of the groin include:

Candidal intertrigo — usually more uniformly red, with no central clearing, and may have satellite lesions (see the CKS topic on Candida - skin).

Erythrasma — more uniformly brown with slight scaling and no active border. Fluoresces a brilliant coral-red.

Mechanical intertrigo — sharp edge, no central clearing or scale.

Psoriasis — sharp margination, pitted nails, and knee, elbow, and scalp lesions.

Seborrhoeic dermatitis — greasy scales, associated with scalp dandruff (see the CKS topic on Seborrhoeic dermatitis).

Basis for recommendation

Basis for recommendation

Information on differential diagnosis of fungal skin infection is based on expert opinion in Rook's Textbook of Dermatology [Hay and Ashbee, 2010].

Investigations

Are diagnostic tests required?

Diagnostic tests are not usually required, but take samples for microscopy and culture if:

The diagnosis is unclear.

The infection has not responded to standard topical antifungals.

Oral antifungal treatment is being considered.

To take samples for fungal investigation:

Wipe off any treatment creams from the skin before sampling.

Scrape skin from the advancing edge of the lesion using a blunt scalpel blade or similar implement.

Collect 5 mm2 of skin flakes for microscopy and culture.

Collect the sample into folded dark paper squares (secure with a paper clip) or use a commercially available fungal packet.

Keep samples at room temperature. Do not refrigerate.

Ensure clinical details are stated, including any treatment, animal contact, and overseas travel.

Swabs are usually of no value for dermatophyte infections but may provide a culture result if scrapings are inadequate.

Basis for recommendation

Basis for recommendation

When to take samples for microscopy and culture

This is based on recommendations developed from expert opinion in a guideline issued by the Health Protection Agency (HPA): Fungal Skin & Nail Infections: Diagnosis & Laboratory Investigation (Quick Reference Guide) [HPA, 2011] and on expert opinion in review articles [Weinstein and Berman, 2002; Hainer, 2003; Andrews and Burns, 2008].

How to take samples

The information on how to take a sample is based on recommendations developed from expert opinion in a guideline issued by the HPA [HPA, 2011].

Management

Management

Scenario: Management : covers the management of people with dermatophyte fungal skin infection (ringworm or tinea) of the body or groin.

Scenario: Management

Scenario: Management of fungal skin infection - body and groin

1months3060monthsBoth

Advice

What advice should I give about fungal infections of the skin and groin?

Advise the person:

To wash the affected skin daily and dry thoroughly afterwards, particularly in the skin folds.

To wash clothes and bed linen frequently to eradicate the fungus.

Not to share towels and to wash them frequently.

To wear loose-fitting clothes made of cotton or a material designed to keep moisture away from the skin.

The Health Protection Agency advises that exclusion from school is not normally necessary, but treatment should be started as soon as possible.

Basis for recommendation

Basis for recommendation

These recommendations are based on expert opinion in review articles [Weinstein and Berman, 2002; Hainer, 2003] and on a guideline issued by the Health Protection Agency: Guidance on infection control in schools and other childcare settings [HPA, 2010].

Treatment

How should I treat fungal infections of the body and groin?

For mild, non-extensive disease, treat with topical clotrimazole, econazole, or miconazole. Topical ketoconazole and topical terbinafine are alternatives, but they are not licensed for use in children.

The timing of application and duration of treatment depends on the topical antifungal used. For more information, see Topical antifungals.

For skin that is particularly inflamed, consider prescribing a mildly potent topical corticosteroid (for example hydrocortisone 1%), to be used in addition to the topical antifungal, for a maximum of seven days.

Do not give a corticosteroid preparation alone.

For fungal infection of the skin, advise that the topical corticosteroid should be used once or twice a day.

For fungal infection of the groin, advise that the topical corticosteroid should only be used once a day because of the increased risk of adverse effects with topical corticosteroids in occluded areas.

For more information on prescribing topical corticosteroids, see Scenario: Topical treatment in the CKS topic on Corticosteroids - topical (skin), nose, and eyes.

In an adult with severe or extensive disease, or when topical treatment has failed, options include:

Oral antifungal treatment.

A positive microscopy or a positive culture of skin scrapings is recommended before starting treatment.

If test results are negative but the clinical appearance is very suggestive of fungal infection, repeat the sample and start treatment.

Referral to a dermatologist.

In a child with severe or extensive disease, or when topical treatment has failed, seek specialist advice.

If there is infection of the nails, consider treating in order to prevent re-infection. See the CKS topics on Fungal nail infection and Fungal skin infection - foot for more information.

Basis for recommendation

Basis for recommendation

Topical antifungal treatments

CKS found evidence from randomized trials that topical imidazoles and topical terbinafine are effective for the treatment of fungal infections of the body and groin. They are also widely recommended by experts in reviews of the literature [Gupta et al, 2004; Loo, 2004; Andrews and Burns, 2008].

The information on the licensing of topical ketoconazole and topical terbinafine in children is based on the manufacturers' Summaries of Product Characteristics [ABPI Medicines Compendium, 2013b; ABPI Medicines Compendium, 2013e].

There was insufficient trial evidence to recommend one preparation over another, but imidazoles are currently the most commonly used topical treatments for fungal infections of the skin [Havlickova and Friedrich, 2008].

A mixed treatment comparison meta-analysis of 65 trials did not show any statistically significant differences among topical antifungals for the outcome of mycologic cure at the end of treatment. However, for the outcome of sustained cure outcome, topical terbinafine was significantly more efficacious than topical clotrimazole [Rotta et al, 2013].

Topical antifungals have advantages over oral antifungals including [Havlickova and Friedrich, 2008]:

Less risk of adverse effects.

Fewer drug interactions.

No requirement for laboratory tests to monitor treatment.

Topical corticosteroids

Expert opinion varies on the use of topical corticosteroids. Some prefer not to use them alone because of the potential for fungal proliferation, worsening of symptoms, and the development of tinea incognito (an atypical skin appearance due to local corticosteroid application, which may mask true dermatophyte infection) [Erbagci, 2004; Gupta et al, 2004].

Topical antifungal combined with corticosteroid

The recommendation to consider prescribing a mildly potent topical corticosteroid in addition to a topical antifungal for severely inflamed infections is based on expert opinion that this will provide more rapid symptom relief than a topical antifungal alone [Erbagci, 2004; Havlickova and Friedrich, 2008]. However, the evidence to support this approach is limited to moderately potent and potent corticosteroids [Weinstein and Berman, 2002].

Clotrimazole and miconazole are available as combination products (combined with hydrocortisone 1%) licensed for the treatment of fungal skin infections with co-existing inflammation [BNF 65, 2013].

Some experts recommend avoiding treating areas of thin skin and naturally occluded body areas (such as the groin) with combination treatment [Weinstein and Berman, 2002] because of possible adverse effects from topical corticosteroids (for example skin thinning, telangiectasia and striae). Others recommend using short-term courses of combination products for this purpose.

CKS does not recommend these products, because they are licensed to be used once or twice a day for a maximum of 7 days [ABPI Medicines Compendium, 2010; ABPI Medicines Compendium, 2013f]; however, topical antifungal treatment is usually required for a longer period. For example:

Clotrimazole should be applied 2–3 times a day and continued for at least 4 weeks after the affected area has healed [ABPI Medicines Compendium, 2012b].

Miconazole should be applied twice a day and continued for 10 days after all skin lesions are healed [ABPI Medicines Compendium, 2013c].

Prescribing a topical corticosteroid separately to the topical antifungal allows the corticosteroid to be used once or twice a day for the recommended maximum duration of 7 days, and the antifungal treatment to be continued for the recommended frequency and duration.

Oral antifungal treatment

Topical antifungal treatment is generally successful. However, if the infection covers an extensive area or is resistant to initial treatment, experts recommend oral antifungals [Weinstein and Berman, 2002; Gupta et al, 2004; Havlickova and Friedrich, 2008].

It is recommended that specialist advice is sought before prescribing an oral antifungal for a child younger than 16 years of age because:

Terbinafine and itraconazole are not licensed for use in this age group [ABPI Medicines Compendium, 2013a; ABPI Medicines Compendium, 2013d].

Although oral griseofulvin is licensed for use in children, the age range is not specified by the manufacturer in the product literature [MHRA, 2010], and there is no UK-approved liquid paediatric formulation.

Choice of oral antifungal

Which oral antifungal should I prescribe?

If an oral antifungal is indicated, prescribe terbinafine, griseofulvin, or itraconazole, based on consideration of their contraindications, cautions, and drug interactions.

Oral fluconazole and oral ketoconazole are not recommended.

Terbinafine is generally better tolerated and has fewer interactions than griseofulvin and itraconazole, but it is not suitable for all people (such as children and people with chronic or active liver disease).

For more information on contraindications, cautions, key interactions, adverse effects, and recommended dosage of terbinafine, see the prescribing information section on terbinafine.

If terbinafine is not a suitable choice, or it has not been well tolerated, consider prescribing itraconazole or griseofulvin. However:

Oral itraconazole:

Should be used with caution in people at high risk of heart failure.

Should be avoided by women, one month before, and during, pregnancy.

Is not recommended for use in children or elderly people.

Oral griseofulvin:

Is more frequently associated with serious adverse effects than itraconazole and terbinafine.

Should be avoided by women one month before, and during, pregnancy; men should avoid fathering a child during treatment and for 6 months after completing treatment.

Should be used cautiously in people with mild to moderate hepatic impairment.

For more information on cautions, key interactions, adverse effects, and dosages, see the prescribing information sections on itraconazole and griseofulvin.

Basis for recommendation

Basis for recommendation

Recommended treatments

There is evidence that oral griseofulvin, terbinafine, and itraconazole are effective treatments for fungal infections of the body and groin, but there is a lack of evidence about their comparative efficacy. CKS therefore recommends basing the choice of treatment on consideration of their contraindications, cautions, and drug interactions.

Information about contraindications and cautions are from the manufacturers' Summaries of Product Characteristics [ABPI Medicines Compendium, 2013a; ABPI Medicines Compendium, 2013e; ABPI Medicines Compendium, 2013d] and the British National Formulary (BNF) [BNF 65, 2013].

Treatments not recommended

Oral fluconazole: although there is evidence that fluconazole is effective for treating fungal infections of the body and groin, there is more evidence to support the use of griseofulvin, terbinafine, and itraconazole.

Oral ketoconazole: the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has recommended that oral medicines containing ketoconazole should no longer be used for the treatment of fungal infections because of their relatively high risk of causing liver damage compared to other treatments [MHRA, 2013].

Referral

When should I refer to dermatology?

Consider referral to dermatology if:

The diagnosis is uncertain.

There is no response to primary care management.

Infection is severe or extensive.

Infection is recurrent.

The person is immunocompromised.

Basis for recommendation

Basis for recommendation

CKS found no evidence or expert reviews on referral, and has therefore based this recommendation on common clinical practice.

Important aspects of prescribing information relevant to primary healthcare are covered in this section specifically for the drugs recommended in this CKS topic. For further information on contraindications, cautions, drug interactions, and adverse effects, see the electronic Medicines Compendium (eMC) (http://medicines.org.uk/emc), or the British National Formulary (BNF) (www.bnf.org).

Topical antifungals

Topical antifungals

Clotrimazole [BNF 65, 2013; ABPI Medicines Compendium, 2014]:

Clotrimazole 1% is licensed for the treatment of skin infections due to dermatophytes, including ringworm (tinea) infections.

Clotrimazole should be applied to the affected area 2–3 times a day and continued for at least 4 weeks. A strip of cream about half a centimetre long is enough to treat an area about the size of the hand.

Adverse effects include local skin irritations such as rash, pruritus, oedema, and skin peeling.

The person should be advised that clotrimazole may cause damage to latex contraceptives and can inactivate spermicidal contraceptives. Alternative contraceptive precautions should be used for at least 5 days after using clotrimazole.

Miconazole [ABPI Medicines Compendium, 2009; BNF 65, 2013]:

Miconazole 2% is licensed for the treatment of mycotic infections of the skin and nails.

Miconazole should be applied to the affected area twice a day and continued for 10 days after all skin lesions are healed.

Systemic miconazole is known to interact with oral anticoagulants. Due to the limited systemic availability of topical preparations, clinically relevant interactions are rare; however, the manufacturer of miconazole advises that caution should be exercised and anticoagulant effect should be monitored during concurrent use of miconazole and an oral anticoagulant.

Econazole [ABPI Medicines Compendium, 2012]

Econazole is licensed for the treatment of fungal infections of the skin.

Econazole should be applied to the affected area twice a day and continued until all skin lesions are healed.

Systemic econazole is known to interact with oral anticoagulants. Due to the limited systemic availability of topical preparations, clinically relevant interactions are rare; however, the manufacturer of econazole advises that caution should be exercised and anticoagulant effect should be monitored during concurrent use of econazole and an oral anticoagulant.

Ketoconazole (for adults only) [ABPI Medicines Compendium, 2013; BNF 65, 2013]:

Ketoconazole is licensed for the treatment of dermatophyte infections of the skin, including tinea corporis and tinea cruris.

Ketoconazole should be applied to the affected area once or twice a day and continued for a few days after all skin lesions are healed. The usual duration of treatment for a tinea corporis infection is 3–4 weeks.

Adverse effects include local skin irritations such as rash and pruritus.

Terbinafine (for adults only) [ABPI Medicines Compendium, 2013]

Terbinafine is licensed for the treatment of fungal infections of the skin.

For the treatment of tinea corporis and tinea cruris infections, terbinafine should be applied thinly to the affected area once or twice a day for 7–14 days.

Adverse effects include local skin irritations such as rash, burning sensation, and pruritus. These symptoms must be distinguished from hypersensitivity reactions such as widespread pruritus, rash, bullous eruptions and hives, which are reported in sporadic cases and require discontinuation of treatment with terbinafine.

Oral antifungals

Oral antifungals

Terbinafine

Terbinafine

Dosage [ABPI Medicines Compendium, 2013d; BNF 65, 2013]

For adults, the recommended dosage is 250 mg once per day.

Oral terbinafine is not licensed for use in children.

Duration [ABPI Medicines Compendium, 2013d]

For ringworm, treatment should be given for 4 weeks.

For fungal infection of the groin, treatment should be given for 2–4 weeks.

Contraindications and cautions [ABPI Medicines Compendium, 2013d; BNF 65, 2013]

Terbinafine is contraindicated in people with:

Severe, chronic, or active hepatic disease.

Severe renal impairment.

Terbinafine should be avoided in:

Pregnant women — manufacturer advises use only if potential benefit outweighs risk.

Breastfeeding women — terbinafine is secreted in breast milk.

Terbinafine should be used with caution in people with:

Psoriasis — increased risk of exacerbation of psoriasis.

Autoimmune disease — risk of lupus erythematosus-like effect.

Renal impairment — the British National Formulary states that half the normal dose of terbinafine should be used if estimated Glomerular Filtration Rate (eGFR) is less than 50 mL/minute/1.73 m2 and there is no suitable alternative [BNF 65, 2013]. However, the manufacturer states that the use of terbinafine tablets in this group of people has not been adequately studied, therefore it is not recommended [ABPI Medicines Compendium, 2013d].

Adverse effects [ABPI Medicines Compendium, 2013d; BNF 65, 2013]

Common adverse effects reported include rash; urticaria; arthralgia; myalgia; decreased appetite; headache; and gastrointestinal adverse effects such as abdominal distension, dyspepsia, nausea, abdominal pain, and diarrhoea. Less commonly, taste disturbance has been reported.

Rare adverse effects include:

Liver toxicity (including jaundice, cholestasis, and hepatitis).

Hepatotoxicity may occur in people with and without pre-existing liver disease; therefore, periodic monitoring (after 4–6 weeks of treatment) of liver function tests is recommended [ABPI Medicines Compendium, 2013d].

Terbinafine should be immediately discontinued if liver function tests are elevated.

People taking terbinafine tablets should be warned to report immediately any signs and symptoms of unexplained persistent nausea, decreased appetite, fatigue, vomiting, right upper abdominal pain, or jaundice, dark urine or pale faeces. People with these symptoms should discontinue taking terbinafine and their liver function should be immediately evaluated.

Dizziness, malaise, paraesthesia, hypoaesthesia, and photosensitivity.

Very rare adverse effects include:

Psychiatric disturbances.

Blood disorders (including leucopenia and thrombocytopenia) — people on terbinafine who develop a high fever or sore throat should be examined for possible haematological reactions.

Serious skin reactions (including Stevens-Johnson syndrome and toxic epidermal necrolysis) — treatment should be discontinued if a progressive skin rash occurs.

Lupus erythematosus-like effect, exacerbation of psoriasis, pancreatitis, vasculitis, influenza-like symptoms, rhabdomyolysis, and disturbances in smell.

Drug interactions [ABPI Medicines Compendium, 2013d; Baxter and Preston, 2013]

Effect of other drugs on terbinafine

The plasma clearance of terbinafine may be accelerated by drugs which induce metabolism and inhibited by drugs which inhibit liver enzymes. Where co-administration of such drugs is required, it may be necessary to adjust the dose of terbinafine accordingly.

Rifampicin increases the clearance of terbinafine by 100%.

Cimetidine decreases the clearance of terbinafine by 33%, due to the inhibition of cytochrome P450 enzyme. Fluconazole, ketoconazole, and amiodarone may also decrease the clearance of terbinafine.

Effects of terbinafine on other drugs

Terbinafine is a CYP2D6 inhibitor and may increase the plasma concentration of drugs predominantly metabolised by CYP2D6, thereby increasing or prolonging their effects, including adverse effects. Examples include:

Amitriptyline, imipramine, nortriptyline, and desipramine (in one study terbinafine decreased the clearance of desipramine by 82%).

Beta-blockers (carvedilol, metoprolol, nebivolol, propranolol, and timolol).

Selective serotonin reuptake inhibitors such as paroxetine.

Antiarrhythmics such as flecainide, mexiletine, and propafenone.

Monoamine oxidase inhibitors Type B, especially if they also have a narrow therapeutic window.

Terbinafine increases the clearance of ciclosporin by 15%. Although this interaction is not usually clinically significant, monitoring should be considered in people whose ciclosporin levels are at the lower end of the therapeutic range.

Terbinafine does not interfere with the clearance of antipyrine or digoxin.

Cases of irregular menstruation have been reported in some women taking terbinafine tablets concomitantly with oral contraceptives, although the incidence of this effect remains within the background incidence for women taking oral contraceptives alone.

Griseofulvin

Griseofulvin

Dosage

For adults, the recommended dose is 500 mg once a day or 250 mg twice a day [BNF 65, 2013].

Griseofulvin is recommended to be taken after a high fat meal for increased absorption and to minimise the risk of gastrointestinal (GI) distress [MHRA, 2010].

Duration [MHRA, 2010]

Treatment should be given for 2–4 weeks and continued for at least 2 weeks after all signs of infection have disappeared.

Contraindications and cautions [MHRA, 2010]

Griseofulvin is contraindicated in:

Severe liver disease.

Acute porphyria.

Systemic lupus erythematosus — risk of exacerbation of lupus.

Pregnant women — griseofulvin is potentially teratogenic.

Women of childbearing age should be advised to avoid pregnancy during, and for 1 month after, treatment with griseofulvin.

Men should avoid fathering a child during treatment and for 6 months after completing treatment due to potential adverse effects on the male reproductive system.

Breastfeeding women.

Griseofulvin should be used with caution in people with mild to moderate hepatic impairment — griseofulvin may cause further deterioration of hepatic function in this group of people; regular periodic liver function test is recommended.

Adverse effects [MHRA, 2010; BNF 65, 2013]

The most common adverse effects are headache and GI effects (such as nausea, vomiting, diarrhoea, abdominal pain, and dyspepsia); however, these usually disappear as treatment is continued.

Griseofulvin may enhance the effects of alcohol and impair performance of skilled tasks (for example driving).

Other adverse effects include:

Uncommonly, anorexia, taste disturbance, rash (erythema multiforme, toxic epidermal necrolysis), and photosensitivity (people should be cautioned to avoid excessive and unnecessary exposure to sunlight or sunbeds during treatment with griseofulvin).

Rarely, leucopenia, neutropenia, and anaemia which usually resolve on treatment cessation; impaired co-ordination and hearing, peripheral neuropathy, sleep disturbances, dizziness, fatigue, confusion, agitation, and irritability; precipitation of systemic lupus erythematosus, bullous reactions (including Lyell's syndrome), urticarial reactions, and skin rashes.

Very rarely, alteration in liver function tests (with elevations to more than three times the upper normal limit), intrahepatic cholestasis, and hepatitis.

Drug interactions [MHRA, 2010; Baxter and Preston, 2013]

Alcohol — very limited evidence suggests that concurrent use of alcohol and griseofulvin may cause flushing, tachycardia, and increased alcohol effect. People should be warned of this possible reaction.

Oral contraceptives — the risk of contraceptive failure is uncertain but probably very small; however, since griseofulvin is potentially teratogenic, additional contraceptive protection (such as a condom) should be used with oral contraceptives (combined and progestogen-only) during, and for one month after, treatment with griseofulvin.

Oral combined contraceptives — the effects of oral combined hormonal contraceptives may be disturbed if griseofulvin is taken concurrently (either inter-menstrual bleeding or amenorrhoea). There are few cases of women who became pregnant during concurrent use of a combined hormonal contraceptive and griseofulvin.

Progestogen-only contraceptives — the effect of griseofulvin on progestogen-only contraceptives is unclear, but it has been suggested that progestogen-only contraceptives are unsuitable for woman taking griseofulvin, due to increased menstrual irregularities. The manufacturer of the levonorgestrel intra-uterine system predicts that griseofulvin may reduce its contraceptive reliability; however, there is no evidence to support this.

Oral anticoagulants (such as warfarin) — the efficacy of the anticoagulant may be reduced in people also taking griseofulvin, necessitating anticoagulant dosage adjustment. It is recommended that both prothrombin time and international normalised ratio (INR) are monitored regularly during treatment with griseofulvin and for eight days after treatment is stopped.

Methadone — reduction of methadone plasma levels may occur during concurrent treatment with griseofulvin. The person should be monitored closely for any loss of efficacy, and dose adjustment of methadone should be made if required.

Concurrent use of griseofulvin and other drugs that induce liver enzymes may result in a decreased plasma level of griseofulvin, leading to a reduction in efficacy. The following drugs are known to have this effect:

Barbiturates, such as phenobarbital. If appropriate, a non-interacting antiepileptic drug, such as sodium valproate, may be a suitable alternative.

Doxercalciferol.

Primidone.

Itraconazole

Itraconazole

Dosage and duration

For adults, the recommended dosage is either:

100 mg once a day for 15 days, or

200 mg once a day for 7 days.

Itraconazole is recommended to be taken immediately after a meal for maximal absorption.

Contraindications and cautions

Itraconazole is contraindicated in:

Acute porphyria.

Pregnancy. However, the manufacturer states it may be given if the fungal infection is life-threatening and the potential benefit is considered to outweigh the potential risk to the foetus.

Adequate contraceptive precautions should be taken by women of childbearing age using itraconazole until the next menstrual period following the end of treatment.

Itraconazole should be avoided in:

People with ventricular dysfunction or a history of heart failure, unless the infection is serious.

People with a history of hepatotoxicity with other drugs, and in active liver disease. Itraconazole should be used only if the potential benefit outweighs the risk of hepatotoxicity; dose reduction may be necessary.

Breastfeeding women — small amounts are present in milk and may accumulate.

Itraconazole should be used with caution in:

People at high risk of heart failure.

People with HIV infection and neutropenia — absorption of itraconazole is reduced in this group of people. Plasma itraconazole concentration should be monitored and dose increased if necessary.

The manufacturer recommends that itraconazole should be used in the elderly and in children younger than 12 years of age if the potential benefits of treatment outweigh the risks. There is a lack of data on the safety and efficacy of itraconazole in these groups of people [ABPI Medicines Compendium, 2012a].

Adverse effects

About 9% of people can be expected to experience adverse effects while taking itraconazole. In people receiving prolonged (approximately 1 month), continuous treatment, the incidence of adverse events is higher (about 15%).

The most common adverse effects are nausea, abdominal pain, and rash.

Less common adverse effects include vomiting, dyspepsia, taste disturbances, flatulence, diarrhoea, constipation, oedema, headache, dizziness, paraesthesia (treatment should be discontinued if neuropathy occurs), menstrual disorder, and alopecia.

Rare adverse effects include heart failure, pancreatitis, dyspnoea, hypoaesthesia, urinary frequency, leucopenia, visual disturbances, tinnitus, hypertriglyceridaemia, erectile dysfunction, thrombocytopenia, hypokalaemia, myalgia, arthralgia, photosensitivity, toxic epidermal necrolysis, and Stevens–Johnson syndrome.

Following treatment with itraconazole, potentially life-threatening hepatotoxicity has been reported very rarely.

Treatment should be discontinued if signs of hepatitis develop.

Liver function should be monitored if treatment continues for longer than one month, if the person is receiving other hepatotoxic drugs, if the person has a history of hepatotoxicity with other drugs, or if the person has hepatic impairment.

The person should be counselled on how to recognise signs of liver disorder, and advised to seek prompt medical attention if symptoms such as anorexia, nausea, vomiting, fatigue, abdominal pain, or dark urine develop.

Drug interactions [ABPI Medicines Compendium, 2012a; Baxter and Preston, 2013]

Effect of other drugs on the metabolism of itraconazole:

Antiepileptic drugs — studies have shown decreased bioavailability of itraconazole following concurrent use with rifampicin, rifabutin, and phenytoin. Concurrent use of itraconazole with these potent enzyme inducers is therefore not recommended. No formal study data are available for other enzyme inducers, such as carbamazepine, phenobarbital, and isoniazid, but similar effects should be anticipated.

Potent inhibitors of CYP3A4 — itraconazole is mainly metabolised through CYP3A4, therefore, potent inhibitors of this enzyme (such as ritonavir, indinavir, clarithromycin, and erythromycin) may increase the bioavailability of itraconazole.

Effects of itraconazole on the metabolism of other drugs:

Itraconazole can inhibit the metabolism of drugs that are substrates for cytochrome 3A isoenzymes. This can result in an increase or prolongation of their effects, including adverse effects. After stopping treatment itraconazole plasma levels decline gradually, depending on the dose and duration of treatment. This should be taken into account when the inhibitory effect of itraconazole on co-administered drugs is considered:

Cytochrome 3A substrates which must not be used during treatment with itraconazole include terfenadine, astemizole, mizolastine, cisapride, triazolam, oral midazolam, dofetilide, quinidine, pimozide, and CYP3A4 metabolised HMG-CoA reductase inhibitors such as simvastatin.

Cytochrome 3A substrates which should be used with caution during treatment with itraconazole include calcium channel blockers. In addition to possible pharmacokinetic interactions involving the drug metabolising enzyme CYP3A4, calcium channel blockers can have negative inotropic effects which may be additive to those of itraconazole.

If the following drugs are co-administered with itraconazole, their plasma levels, clinical effects, and possible side effects should be monitored, as their doses may need to be reduced:

Oral anticoagulants such as warfarin.

HIV protease inhibitors such as ritonavir, indinavir, and saquinavir.

Certain antineoplastic agents such as vinca alkaloids, busulphan, docetaxel, and trimetrexate.

CYP3A4 metabolised calcium channel blockers such as dihydropyridines and verapamil.

Certain immunosuppressive drugs such as cyclosporin, tacrolimus, and sirolimus.

Other drugs including digoxin, carbamazepine, buspirone, alfentanil, alprazolam, rifabutin, methylprednisolone, ebastine, and reboxetine.

[ABPI Medicines Compendium, 2012a; BNF 65, 2013]

Evidence

Evidence

Supporting evidence

Topical antifungals

Evidence on topical antifungal treatments for fungal skin infection

There is good evidence that topical terbinafine, and weak evidence that topical imidazoles, are effective for the treatment of fungal infections of the groin and body compared with placebo.

Topical antifungal treatment compared with placebo

Topical clotrimazole compared with placebo:

In one randomized controlled trial (RCT) people with mycologically-confirmed athlete's foot, ringworm of the body, fungal groin infection, pityriasis versicolor, or cutaneous candidiasis were randomized to receive one of four treatments: clotrimazole cream, its placebo vehicle alone, clotrimazole solution, or its placebo vehicle alone, for 4–6 weeks.

Significantly more people with fungal infection of the body or groin treated with clotrimazole cream or with clotrimazole solution had negative microscopy at 6 weeks, compared with people treated with the placebo vehicles (p < 0.001 for clotrimazole cream compared with placebo, p < 0.001 for clotrimazole solution compared with placebo) [Spiekermann and Young, 1976].

Topical terbinafine compared with placebo:

A systematic review identified six RCTs (n = 298) comparing terbinafine 1% with placebo for the treatment of tinea cruris (fungal infection of the groin) and tinea corporis (fungal infection of the body) [Rotta et al, 2012]. Treatment periods ranged from 7 to 14 days and follow-up periods ranged from two to seven weeks after the end of the treatment. A meta-analysis of the data showed that terbinafine was superior to placebo for the two outcomes analyzed:

Mycological cure at the end of treatment (5 RCTs) — odds ratio (OR) 6.40 (95% CI 2.64 to 15.49); absolute risk (AR) 48%; absolute risk reduction (ARR) 33%; and number needed to treat (NNT) of 3.

Sustained cure (5 RCTs) — OR 14.43 (95% CI 7.62 to 27.33); AR 85%; ARR 58%; and NNT of 2.

Comparative trials of topical antifungal treatments

Topical imidazoles compared with topical allylamines:

A systematic review identified two RCTs comparing topical imidazoles with topical allylamines for the treatment of tinea cruris and tinea corporis [Rotta et al, 2012]. One RCT compared terbinafine 1% cream (used once a day for 7 days) with bifonazole 1% cream (used once a day for 21 days) in people with tinea cruris (follow up for five weeks). The second RCT compared econazole 1% cream with naftifine 1% cream, both used twice a day for 28 days, in people with tinea cruris and/or tinea corporis (follow up for 2 weeks). A meta-analysis of the data showed no statistically significant difference in efficacy between the two classes of drugs for the two outcomes analyzed; however, the results favoured allylamines:

Mycological cure at the end of treatment — OR 0.66 (95% CI 0.28 to 1.54); AR 91%; ARR 2%; and NNT 40.

Sustained cure — OR 0.73 (95% CI 0.37 to 1.44); AR 86%; ARR 4%; and NNT 26.

Topical terbinafine compared with topical ketoconazole:

One RCT (n = 65) found that terbinafine was more effective than ketoconazole [Bonifaz and Saul, 2000]. Topical terbinafine 1% gel, applied once a day for 1 week was compared with ketoconazole 2% cream applied once a day for 2 weeks.

At week 2, 94% of the terbinafine group were cured, compared with 69% of the ketoconazole group (p < 0.027).

Topical miconazole compared with topical sulconazole:

One RCT (n = 94) found similar cure rates for miconazole and sulconazole [Tanenbaum et al, 1982]. People with athlete's foot, skin ringworm, or fungal groin infection were randomized to receive sulconazole nitrate 1% cream or miconazole 2% cream, twice a day for 3 weeks.

At week 3, the cure rate for sulconazole nitrate (29/32) was similar to the cure rate for miconazole (31/31) for people with skin ringworm or fungal groin infection. No p-values were quoted.

Oral antifungals

Evidence on oral antifungal treatments for fungal skin infection

There is a lack of direct evidence from placebo-controlled trials to support the use of oral antifungals to treat fungal infection of the body and groin. However, there is moderate indirect evidence, from a number of small randomized controlled trials (RCTs) comparing different oral antifungals, to support their use. In general, there was a large variation between the trials with respect to follow-up period and duration of treatments. Based on the current published data, there is insufficient information to recommend one oral antifungal over another on the basis of efficacy.

Oral antifungals compared with placebo

CKS found one placebo-controlled trial of itraconazole. No placebo-controlled trials for other oral antifungal drugs for fungal infection of the body or groin were found.

One RCT (n = 67) compared the efficacy of oral itraconazole, 100 mg each day for 2 weeks with placebo, in people with fungal groin infection or skin ringworm.

The mycological cure rate in the itraconazole group was significantly higher (57%) than the cure rate in the placebo group (17%) after 2 weeks of treatment (p = 0.02) [Pariser et al, 1994].

Oral terbinafine compared with oral griseofulvin

One small randomized controlled trial (RCT) found that oral terbinafine and oral griseofulvin, for up to 6 weeks, were similarly effective for the treatment of fungal groin and skin ringworm infections. A second RCT found evidence that terbinafine treatment led to significantly higher cure rates than griseofulvin, although the treatment with griseofulvin only lasted for 2 weeks.

One RCT (n = 92) randomized people with mycologically-confirmed fungal groin infection or skin ringworm to receive terbinafine (125 mg twice a day) or griseofulvin (500 mg twice a day) for up to 6 weeks.

At week 10 (8 weeks after the end of treatment), mycological cure rates for both drugs were similar, being 95% for griseofulvin and 93% for terbinafine [del Palacio et al, 1990].

One RCT (n = 64) randomized people with mycologically-confirmed fungal groin infection or skin ringworm to receive terbinafine (250 mg once a day) or griseofulvin (500 mg once a day), for 2 weeks [Voravutinon, 1993].

At week 6, 87% of the terbinafine group were cured, compared with 54% of the griseofulvin group (p < 0.05).

Oral griseofulvin compared with oral fluconazole

One RCT (n = 230) compared oral treatment with griseofulvin (250 mg once a day) with fluconazole (150 mg once a week) for 4–6 weeks, in people with fungal groin infection or skin ringworm [Faergemann et al, 1997].

The clinical cure rate at 6 weeks was similar for both groups, 74% for the fluconazole group and 62% for the griseofulvin group (p = 0.06).

Mycological cure rates were not available for 37% of participants, but the cure rates for those that could be evaluated were 78% for the fluconazole group and 80% for the griseofulvin group (no p-values were quoted).

Oral griseofulvin compared with oral itraconazole

One RCT (n = 40) randomized people with mycologically-confirmed fungal groin infection or skin ringworm to receive itraconazole (100 mg once a day) or griseofulvin (500 mg once a day), for 15 days [Panagiotidou et al, 1992].

At 15 days post-treatment there was no statistically significant difference in mycological cure rates between the two groups: 16/18 (88%) for people receiving itraconazole and 16/21 (76%) for people receiving griseofulvin (no p-values were quoted).

One RCT (n = 78) randomized people with skin ringworm or fungal groin infection to receive either itraconazole (100 mg each day) or griseofulvin (500 mg each day) for 15 days (this is shorter then the usual recommended course of griseofulvin).

At week 4, mycological cure was achieved in 87% of people in the itraconazole group and in 57% of people in the griseofulvin group [Bourlond et al, 1989].

Oral terbinafine compared with oral fluconazole

One RCT (n = 42) found that terbinafine and fluconazole achieved similar cure rates. Fluconazole 100 mg a day was compared with terbinafine 250 mg a day, for 2–6 weeks. Participants had mycologically confirmed fungal groin infection or skin ringworm as well as athlete's foot.

At the end of follow up (8 weeks) mycological cure was achieved in 14/16 (87%) of people treated with fluconazole, compared with 11/15 (73%) of people treated with terbinafine. No p-values were quoted [Baldari et al, 2000].

Itraconazole 100 mg daily compared with 200 mg daily

One RCT (n = 114) randomized people with tinea corporis or tinea cruris to receive itraconazole 100 mg each day for 2 weeks or itraconazole 200 mg each day for 1 week.

After 6 weeks follow up, mycological cure was achieved in 70% of people taking 100 mg itraconazole, compared with a cure rate of 60% in those taking 200 mg itraconazole [Boonk et al, 1998].

Search strategy

Scope of search

A literature search was conducted for guidelines, systematic reviews and randomized controlled trials the on primary care management of fungal skin infections of the body and groin.

Search dates

April 2009 - July 2013

Key search terms

Various combinations of searches were carried out. The terms listed below are the core search terms that were used for Medline and these were adapted for other databases. Further details are available on request.

exp Dermatomycoses/, dermatomycos?s.tw., tinea corporis.tw., tinea cruris.tw., ringworm.tw.

Table 1 . Key to search terms.
Search commands Explanation
/ indicates a MeSH subject heading with all subheadings selected
.tw indicates a search for a term in the title or abstract
exp indicates that the MeSH subject heading was exploded to include the narrower, more specific terms beneath it in the MeSH tree
$ indicates that the search term was truncated (e.g. wart$ searches for wart and warts)
Topic specific literature search sources

Health Protection Agency

Sources of guidelines

National Institute for Health and Care Excellence (NICE)

Scottish Intercollegiate Guidelines Network (SIGN)

Royal College of Physicians

Royal College of General Practitioners

Royal College of Nursing

NICE Evidence

Health Protection Agency

National Guidelines Clearinghouse

Guidelines International Network

TRIP database

GAIN

Institute for Clinical Systems Improvement

National Health and Medical Research Council (Australia)

Royal Australian College of General Practitioners

British Columbia Medical Association

Canadian Medical Association

Towards Optimal Practice

University of Michigan Medical School

Michigan Quality Improvement Consortium

Patient UK Guideline links

Driver and Vehicle Licensing Agency

Medline (with guideline filter)

Sources of systematic reviews and meta-analyses

The Cochrane Library :

Systematic reviews

Protocols

Database of Abstracts of Reviews of Effects

Medline (with systematic review filter)

EMBASE (with systematic review filter)

Sources of health technology assessments and economic appraisals

The Cochrane Library :

NHS Economic Evaluations

Health Technology Assessments

Canadian Agency for Drugs and Technologies in Health

International Network of Agencies for Health Technology Assessment

NIHR Health Technology Assessment programme

Sources of randomized controlled trials

The Cochrane Library :

Central Register of Controlled Trials

Medline (with randomized controlled trial filter)

EMBASE (with randomized controlled trial filter)

Sources of evidence based reviews and evidence summaries

Drug & Therapeutics Bulletin

Central Services Agency COMPASS Therapeutic Notes

Sources of national policy

Department of Health

Health Management Information Consortium (HMIC)

Patient experiences

Healthtalkonline

BMJ - Patient Journeys

Patient.co.uk - Patient Support Groups

Sources of medicines information

The following sources are used by CKS pharmacists and are not necessarily searched by CKS information specialists for all topics. Some of these resources are not freely available and require subscriptions to access content.

British National Formulary (BNF)

electronic Medicines Compendium (eMC)

European Medicines Agency (EMEA)

LactMed

Medicines and Healthcare products Regulatory Agency (MHRA)

REPROTOX

Scottish Medicines Consortium

Stockley's Drug Interactions

TERIS

TOXBASE

Micromedex

UK Medicines Information

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