Fungal infections

Abstract

Fungal infections are common, and are a significant burden to patients. In the UK, a wide range of pathogens commonly affect the skin. The clinical manifestations differ depending on the site of the infection. Rashes are often mistaken for dermatitis as well as psoriasis, and effective treatment can be delayed. The majority of these conditions can be managed in primary care, but will occasionally need referral to a dermatologist. Systemic fungal infection can involve other organs, including the respiratory, cardiovascular and central nervous systems, and occur particularly in patients who are immunosuppressed or who have recently travelled to areas where specific fungal infections are endemic. It is important for GPs to be aware of these conditions and to refer appropriately.

The GP curriculum and fungal infections

Clinical module 3.03: Care of acutely ill people requires GPs to be able to:

Recognise those illnesses where immediate action is needed to reduce death and/or significant morbidity

Know when it is safe and appropriate to manage a patient in the community and when the patient needs to be referred to hospital for assessment or admission

Know how to manage acute respiratory problems, such as asthma

Clinical module 3.19: Respiratory health requires GPs to be able to:

Know the boundaries of primary care management and the role of specialist services in supporting the patient

Clinical module 3.21: Care of people with skin problems requires GPs to be able to:

Ensure that skin problems are not inappropriately dismissed as trivial or unimportant by healthcare professionals

Recognise the importance of skin-specific symptoms, e.g. itching and rash distribution

Recognise the spectrum of patterns and distributions of rashes of different skin disorders

Understand how to carry out more detailed tests where indicated, including skin scrapings and the use of Wood’s light

Understand how to recognise common skin conditions in primary care, e.g. eczemas, psoriasis and infections, and instigate appropriate treatment

Be aware of primary care resources and when to refer to secondary care so that patients receive appropriate treatment (such as light therapy, biological therapies or immunosuppressant therapy)

Fungal skin infections

Fungal skin infections are very common throughout the world. There is a variety of causative organisms, which will be discussed below. Spread may occur through direct contact with infected animals, often pets, as well as through indirect contact with objects, such as furniture, that are contaminated with fungal spores.

Dermatophytosis (tinea) infections

Tinea infections grow in dead keratin. They present as raised red or pink areas of the skin. They grow outwards, producing a ring-like pattern with central clearing and affect many different parts of the body.

Tinea infections are very common throughout the world, with an annual incidence of 16 per 10 000 in the UK. Tinea capitis is most common in children, whereas tinea pedis is most common in adults. They are more common in immunocompromised patients and people who play contact sports. Infection is caused by species including trichophytons, microsporum and epidermophyton. The infection usually presents as a highly pruritic rash, occasionally accompanied by hair loss or superadded bacterial infection. Infections can be classified based on the part of the body affected as shown in Table 1.

Table 1.

Types of tinea infection by area affected.

Area of body	Classification
Scalp	Tinea capitis
Feet	Tinea pedis
Hands	Tinea manuum
Nail	Tinea unguium
Beard Area	Tinea barbae
Groin	Tinea cruris
Trunk and arms	Tinea corporis

Tinea capitis

Tinea capitis causes hair loss with broken hairs at the surface forming distinctive ‘exclamation mark’ hairs within distinct bald patches (not seen in alopecia areata), as shown in Fig. 1. Tinea capitis can be spread through shared combs, hairbrushes, hats, towels, pillowcases and helmets. Once treatment has started, hairbrushes and combs should be discarded or disinfected with bleach. Clothing and towels should be washed in warm, soapy water and dried. Sharing of such items should be discouraged. It is important to observe other household contacts for any signs of infection, but as the infection is likely to have spread before diagnosis, there is little to be gained from keeping children away from school. Diagnosis can be confirmed using microscopy or skin scrapings, and Wood’s light can be useful in confirming the diagnosis. Treatment may start with oral antifungals. Griseofulvin is recommended in rural areas and terbinafine in urban areas as first line treatment. Discussion of treatment with secondary care, particularly in children, is recommended, and may be changed based on microscopy results (Bennassar & Grimalt, 2010). Treatment with a topical antifungal, such as ketoconazole shampoo, can reduce the likelihood of the infection spreading during the first 2 weeks. Secondary infections should be treated with oral antibiotics, and referral to dermatology should be considered if there is any evidence of a pustular boggy mass known as a kerion. Patients should also be referred if there is diagnostic uncertainty or if there is no response to treatment in primary care (Moriarty, Hay, & Morris-Jones, 2012).

Figure 1.

Tinea capitis.

Tinea corporis

Tinea corporis enlarges slowly to form ring-shaped plaques with central clearing and a scaly red border, hence the term ‘ringworm’. The trunk, arms and legs are most commonly affected, as shown in Fig. 2. There may also be atypical presentations including tinea imbricate, involving numerous overlapping concentric circles, as well as bullous tinea corporis involving herpetiform vesicles. It is commonly mistaken for contact or seborrheic dermatitis, and subsequent treatment with steroids leads to further confusion as the border becomes faded. Microscopy and skin scrapings can be useful here if there is diagnostic uncertainty (Andrews & Burns, 2008). Most of these infections respond well to twice daily applications of topical imidazoles, such as clotrimazole, miconazole and ketoconazole. Treatment must be continued for 1–2 weeks after the lesions have healed. Terbinafine can also be used and usually only needs to be used for 1 week. If there is no response, recheck mycology. Topical corticosteroids can be helpful as an adjunct if there is severe inflammation, but should not be used for longer than a week (Erbagzi, 2004). Patients should be advised to change and wash linen, to avoid sharing towels and to wear loose fitting clothing. Oral antifungal treatment is not usually required, and diagnosis should be confirmed on mycology before this is considered. If required, terbinafine is generally well-tolerated. Oral itraconazole or griseofulvin can be considered as second line treatment (Bourlond et al., 1989).

Figure 2.

Tinea corporis.

Tinea cruris

Tinea cruris is common in men and causes itching in the affected area of skin. The medial aspect of the thighs is affected, as are the inguinal folds, while the penis and scrotum are often spared. It is more common in athletes, overweight patients and can be associated with clothing likely to promote infection by raising local temperature and humidity around the groin. It is also known as ‘jock itch’. It is treated in the same way as tinea corporis.

Tinea pedis, also known as athlete’s foot, causes erythema and maceration in the web spaces between toes. It is more common in athletes and those living in climates with a high humidity. Vesicles and pustules can develop over the plantar aspect of the foot. Tinea manuum often occurs concomitantly and presents as an erythematous scaling over the hand, usually unilaterally. The infection is often incorrectly treated with steroids, exacerbating the problem. Patients are advised to change their shoes regularly, to keep feet and hands dry and to wear open footwear or cotton socks. It is important to avoid sharing towels. Minor infection responds well to topical imidazoles and a preparation combined with a corticosteroid can be used if the inflammation is more severe. If the inflammation is very severe, consider taking skin scrapings and dermatology referral (Andrews & Burns, 2008).

Tinea barbae

Tinea barbae is also more likely to affect males, and leads to redness, scaling and pustules. This usually responds well to topical imidazoles.

It is important to consider the side effects of antifungal medication, which can be significant, particularly with oral medication.

Griseofulvin should be avoided in patients with liver disease and in patients with systemic lupus erythematous and is contra-indicated in pregnancy. Griseofulvin may be teratogenic and female patients should use effective contraception while taking griseofulvin and for a month after stopping. Men should use contraception for 6 months after taking it. Patients may experience nausea or vomiting, or even fatigue and sleep disturbance.

Terbinafine may cause exacerbations of psoriasis, as well as other auto-immune conditions. Liver function should be checked prior to starting and every 4–6 weeks during treatment, the drug should be discontinued if the liver function becomes abnormal. There may also be abdominal discomfort, nausea, arthralgia and headache.

Fluconazole also increases the risk of hepatotoxicity, and should be used with caution with other hepatotoxic drugs or those with a prolonged QT interval on an electrocardiogram. Prolonged courses should be avoided in pregnancy. Patients should be warned of side effects, including nausea, abdominal discomfort and headaches.

Pityriasis versicolor

Pityriasis versicolor is a common skin complaint where flaky discoloured patches appear on the chest and back. It is caused by Malassezia species that normally exist as commensal organisms in seborrheic regions such as the scalp. However, they may transform into more pathological forms. Teenagers and young adults are most commonly affected, most often during humid times of year and particularly in tropical countries. It is more likely to affect patients with hyperhidrosis, as well as those who are more physically active and patients wearing more occlusive clothing and with excessive use of ointments and dressings.

It usually presents insidiously, with macular lesions and depigmentation seen over the trunk as well as over the neck, upper arms and abdomen. This is illustrated in Fig. 3. The patches may initially appear brown and then resolve through a pale stage. Pruritus is mild. It is commonly mistaken for vitiligo or guttate psoriasis, and may resemble discoid eczema. Diagnosis is usually made clinically; however, if this is unclear it may helpful to take skin scrapings for microscopy (Nenoff, Kruger, & Mayser, 2015).

Figure 3.

Pityriasis versicolor.

Treatment is usually with topical imidazoles, including clotrimazole and ketoconazole. These come in various forms and shampoos are often first line. Ketoconazole shampoo may be applied to the affected area, left on for 3 to 5 minutes, and then rinsed off. This is repeated daily for 5 days. Selenium shampoo may also be used; however, this needs to be diluted and is contra-indicated in pregnancy.

If the rash is widespread or resistant to treatment, oral intraconazole or fluconazole may be used. It is important to explain to patients that the skin may take months following treatment to return to normal colour, and that there is a risk of recurrence. It is also possible to use ketoconazole prophylactically 3 days before sun exposure in patients at risk of recurrent infections (Renati, Cukras, & Bigby, 2015).

Candidal skin infections

Candida is a commensal organism on the skin as well as mouth and gastrointestinal tract. Infections generally are opportunistic. The skin is most commonly affected in moist opposing folds, as well as in obese patients. Other patients at risk include those who have recently had broad-spectrum antibiotics as well as patients on high doses of steroids or those with Cushing’s disease. Candidal skin infections are also more common in diabetic patients and those with underlying skin disorders. There may also be infection of the axillary, sub mammary and inguinal folds, as well as in between the digits of wet workers. An example of this is shown in Fig. 4. It is also known as intertrigo.

Figure 4.

Intertrigo.

There is often pruritus or erythematous patches raised from the underlying skin, often with satellite lesions. There may also be scaling in pustules, and in infants the nappy area may be affected. These infections usually respond to clotrimazole cream, if there is no response, then underlying causes, such as diabetes or poor hygiene, should be explored. Other differential diagnoses, such as psoriasis, seborrheic dermatitis and bacterial skin infections should also be considered (Pappas et al., 2004).

Fungal nail infections

Tinea unguium affects approximately 3–8% of the UK population at some stage of life. There is often spread from tinea pedis, as well as from candida infections. Patients with diabetes, psoriasis, immunosuppression and reduced circulation are more susceptible, as are patients who work in wet environments. They appear similar to candida nail infections. The extent of the infection is variable, and ranges from mild nail infections with superficial onycholysis and white spots to more extensive infection with proximal spread from the distal nail edge to involve the whole nail. Spread of infection is indicated by thickening and discolouration of the nail with eventual crumbling and disruption of the nail plate. If the infection is mild and the patient is untroubled by the symptoms, it is appropriate to advise self-care. If treatment is required, use a nail lacquer such as Amorolfine 5% for 6 months in fingernails, up to 9–12 months in toenails. It is helpful to take nail clippings for mycology culture to establish the causative organism, and if treatment is not satisfactory to repeat testing. It may also be helpful to monitor nail growth closely. If topical treatment is unsuccessful, with proximal nail involvement or when more than two nails are affected, oral antifungals are recommended. If infection persists in a child, referral to a dermatologist should be considered. Occasionally bacterial paronychia may be associated with fungal infection and patients should be warned to watch for signs of spreading redness and pain. Bacterial paronychia should be treated with antibiotics (Del Rosso, 2014).

Gastrointestinal fungal infections

Candidiasis also causes oral thrush, which most commonly presents with white plaques in the mouth and on the tongue. There may also be pain and erythema in the mouth, while some older patients may complain of difficulty swallowing or angular cheilitis. The main differential diagnosis is oral hairy leucoplakia, which presents as white plaques on the tongue. Oral hairy leucoplakia is common in patients with immunosuppression, and the plaques usually do not dislodge easily.

Patients who have recurrent episodes of oral candidiasis should be tested for an underlying cause. Consider carrying out a full blood count and testing for diabetes, as well as a human immunodeficiency virus (HIV) test. Encourage smokers to stop, and patients wearing dentures or using inhaled corticosteroids to maintain good oral hygiene. In patients who are suffering from HIV infection, it is important to treat these infections with oral fluconazole, and to have a low threshold for involving secondary care.

Infants with oral candidiasis can have difficulty feeding. Treat infants initially with miconazole ointment. If there is some response after 7 days, continue treatment for a further 7 days, if there is no response, prescribe a course of nystatin suspension. Miconazole is best given by smearing 1ml on the inside of the mouth four times daily, and is contra-indicated in patients with liver dysfunction (Goins, Ascher, Waecker, Arnold, & Moorefield, 2002).

Oesophageal candidiasis is a more serious condition, and presents with odynophagia. Weight loss may occur if the infection has been longstanding. There may also be evidence of oral thrush. Patients with oesophageal candidiasis usually have a more serious underlying cause, such as immunosuppression, secondary to HIV infection, prolonged corticosteroid use or organ transplantation. This is best managed by using a trial of therapy, using oral fluconazole and assessing the response to this treatment. If treatment is not successful, an oesophago-gastro-duodenoscopy should be considered (Hamza et al., 2008).

Genitourinary fungal infections

Candidal infections commonly affect the genital tract. They are most common in patients recently treated with antibiotics, but can also occur in patients who are pregnant, as well as diabetic patients and those on chemotherapy. There is a pruritic, painful vulvo-vaginitis, with plaques on the mucous membranes and a white discharge. If examined, there may be vulval oedema, excoriation and fissuring in more severe cases. Satellite lesions are often seen. Treatment is with clotrimazole cream, with or without a clotrimazole pessary. If this is not successful, consider an alternative diagnosis. Consider lichen planus or lichen sclerosis and take swabs to exclude other infections. If the infection persists, consider using oral fluconazole as a single dose. Patients should be advised to wear loose-fitting clothes and to avoid using potentially irritant chemicals within cosmetics (Achkar & Fries, 2010).

In male patients candidiasis can cause balanitis (inflammation of the glans penis), leading to pain and pruritus at the tip of the penis, as well as inflammation and satellite lesions. Patients may also complain of pain on intercourse and in more severe cases of balanitis there may be associated phimosis. Balanitis often occurs in the context of other underlying dermatoses, such as psoriasis, seborrheic dermatitis or lichen planus. It is more common in patients with poor hygiene, as well as those wearing tightly-fitting clothes. There is also an increased risk in obese patients and patients with oedema secondary to cardiac failure. When candida is the causative agent, balanitis will respond well to clotrimazole or miconazole applied twice daily until symptoms resolve. If there is no improvement, consider swabbing the area or testing for diabetes mellitus. In more severe cases, a single dose of 150 mg of fluconazole may be used. Patients should be advised to keep the area clean (Achkar & Fries, 2010).

Pulmonary fungal infections

Allergic bronchopulmonary aspergillosis

Fungal infections can affect the lungs. Aspergillosis is caused by aspergillus fumigatus, aspergillus flavus or aspergillus niger, which is a ubiquitous fungus. Infection and disease takes place sporadically in at-risk populations (Agarwal, 2009).

Aspergillosis presents in several forms, firstly as allergic bronchopulmonary aspergillosis (APBA), a chronic type-1 hypersensitivity response to persistent endobronchial infection in atopic individuals. Patients may suffer with asthma and a chronic cough, producing mucoid plugs, as well as dyspnoea. ABPA affects 1% of patients with asthma, and approximately 5% of patients with cystic fibrosis (Skov, McKay, Koch, & Cooper, 2005).

Patients with APBA may be systemically unwell, with malaise, headaches, fevers and symptoms of sinusitis with purulent discharge. The condition should be suspected in patients with symptoms resistant to conventional asthma treatment. Useful investigations include a chest X-ray, which may show infiltrates peripherally, and a full blood count revealing eosinophilia. There may also be raised immunoglobulin E (IgE) levels, positive skin tests and serology to aspergillus species and evidence of aspergillus species in sputum culture. These patients usually require management in secondary care, and should be referred at the earliest opportunity. The mainstay of treatment is with steroids, although there is some evidence of benefit with itraconazole (Tillie-Leblond & Tonnel, 2005).

If treated early the prognosis is good, however, once pulmonary fibrosis is established impaired lung function may be irreversible. Complications can include destabilisation of asthma, atelectasis, bronchiectasis, steroid dependence, respiratory failure and pulmonary heart disease.

Severe asthma with fungal sensitisation

Symptoms of severe asthma with fungal sensitisation can develop in patients who have a high rate of fungal sensitivity in the context of severe asthma. There is often dramatic improvement after antifungal treatment. There is evidence of fungal sensitisation, however, the total IgE is lower than for patients with ABPA. There is significant overlap with ABPA. The condition should be suspected when there is little response to maximal asthma therapy. Patients usually react to Aspergillus fumigatus and Candida albicans (Knutsen et al., 2012). Initial treatment is as for severe asthma, however, in 60% of patients there is a dramatic improvement in quality of life in response to oral antifungals (Denning et al., 2009).

Aspergilloma

An aspergilloma is a fungal ball that develops in a pre-existing cavity, commonly due to tuberculosis. The initial symptoms may be limited to persistent cough or fever. Haemoptysis often occurs in patients who have large areas of lung affected, and the scale of symptoms is proportional to the size of the aspergilloma. Aspergillomas can cause life-threatening complications and may require urgent admission. Some patients may be asymptomatic and lesions may be found on chest X-ray. These lesions are also seen in patients with HIV and associated pneumocystis jirovecii pneumonia.

Chest X-ray usually reveals a well-defined upper lobe mass with a crescentic outline and a computerised tomography scan is needed to further assess the abnormalities. Patients are usually managed in secondary care and require urgent referral. Surgical resection is an option if there is sufficient pulmonary reserve, although some aspergillomas respond to prolonged itraconazole therapy. The prognosis after surgery is usually very good, however, there is significant mortality associated with massive haemoptysis (Lee et al., 2004).

Invasive aspergillosis

Invasive aspergillosis occurs far more commonly in immunocompromised patients. It should be considered particularly in patients who have received chemotherapy or who have received organ transplants. It also affects patients with advanced acquired immunodeficiency syndrome (AIDS). Almost any organ may be affected, but sinopulmonary disease is most common. Symptoms include fever, cough, haemoptysis and pleuritic chest pain. There may be signs of respiratory distress. These patients require admission to an infectious disease unit for treatment with potentially toxic antifungals, including amphotericin B and voriconazole. There is a high risk of haematogenous spread to the liver, kidneys and central nervous system, leading to multi-organ failure and a high mortality rate. As a result, treatment is started before awaiting investigations, which may include cultures, chest X-ray and further imaging (Karthaus & Buchheidt, 2013).

Pneumocystis jirovecii pneumonia

Pneumocystis jirovecii pneumonia is a major cause of morbidity and mortality among immunocompromised patients and remains an AIDS-defining illness. It should also be considered in patients who are taking prolonged courses of steroids or other immunosuppresants, as well as those with haematological malignancies and patients with pre-existing lung conditions.

Patients present with a non-productive cough, exertional dyspnoea and chest pain. On examination, there are often few signs on auscultation apart from scattered crackles and wheeze, however, patients’ oxygen saturation levels drop on exertion. Patients are often tachypnoeic and tachycardic, and there may be signs of AIDS such as Kaposi’s sarcoma or widespread thrush. The differential diagnosis includes tuberculosis as well as a wide variety of bacterial and viral pulmonary infections. Pulmonary embolism should also be considered, and as such urgent hospital admission is usually required. Treatment is with co-trimoxazole (Llibre et al., 2013).

Endemic fungal infections

Endemic fungal infections are found in certain areas of the world, and should be considered in travellers returning from these regions. Histoplasmosis is a fungal infection caused by inhalation of fungal spores often found in bird and bat droppings that become airborne with disturbance of contaminated soil or buildings. Farmers and landscapers in endemic areas of the United States, including the valleys of the Mississippi and Ohio Rivers, are particularly at risk. Infection may be asymptomatic, but infections can be life-threatening. There is a chronic progressive form seen in patients who have underlying chronic obstructive pulmonary disease. Patients usually require admission and treatment with itraconazole or amphotericin (McKinsey & McKinsey, 2011).

Coccidioidomycosis is a similar infection, presenting with respiratory tract symptoms as well as fever, arthralgia and joint swelling. It is endemic to areas of Central America, particularly northern areas of Mexico, as well as some arid to semi-arid parts of the United States. It is caused by a mould growing in the soil. These patients also require admission for treatment with antifungals as well as drainage of cavities or abscesses (Seitz, Prevots, & Holland, 2012).

Cryptococcal meningitis

Cryptococcal meningitis is a rare condition in immunocompetent individuals. It is caused by yeast that exists as a commensal in most patients. It is far more common in HIV-infected patients, although it should also be considered in any immunocompromised patient. The presentation is insidious, with headache, malaise, low-grade fever and an altered mental state. There may be associated pneumonia. In many patients neck stiffness and photophobia are absent; however, immunocompromised patients with malaise, low-grade fever and altered mental state should be admitted urgently. Any patient with symptoms of meningitis requires urgent admission, and the specific diagnosis is confirmed after lumbar puncture. Many patients with cryptococcal meningitis require lifelong antifungal treatment (Jarvis, Dromer, Harrison, & Lortholary, 2008).

Fungal endocarditis

Fungal endocarditis is substantially rarer than bacterial endocarditis. It is more common in patients who have recently had cardiac surgery or after central venous catheter insertion in immunocompromised patients. Patients may present with an insidious onset of fever, lethargy and worsening shortness of breath, signs may include new cardiac murmurs as well as signs of cardiac failure. Patients again require admission for echocardiography and blood cultures (Pierrotti & Baddour, 2002).

Key points

A variety of different fungal infections commonly affect the skin and nails; misdiagnosis can be avoided with careful history and examination

Fungal skin and nail infections can be treated with topical treatments, however, it is important to consider diagnosis with mycology of skin scrapings/nail clippings when topical treatments are ineffective

Candidal infections predominantly affect the skin, particularly skin folds, but can also cause genitourinary and gastrointestinal infections

If fungal skin infections are persistent or recurrent, consider testing for underlying diseases

Fungal infections are an important cause of respiratory symptoms, particularly in patients who are immunocompromised or have pre-existing respiratory disease

Cryptococcal meningitis and fungal endocarditis are both rare and usually occur in the presence of immunosuppression

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(2005) Allergic bronchopulmonary aspergillosis. Allergy 60(8): 1004–1013.