Candidiasis

See separate article on Dermatophytosis (fungal skin infections) and Antifungal Medications.

Candida is a unicellular yeast which is part of the normal flora which can be an invasive pathogen. Infection with Candida varies from a benign local mucosal membrane infection to disseminated disease. Severe disease is associated with an immunodeficiency, e.g. malignancy, HIV infection or immunosuppressive therapy.

Risk factors

• Broad-spectrum antibiotic treatment
• Inhaled corticosteroids and dentures (predispose to oral infection)
• Indwelling intravascular devices
• Recent surgery/trauma
• Chemotherapy or radiotherapy
• Immunodeficiency, e.g. HIV infection, neutropenia, immunoglobulin or complement deficiency

Oral candidiasis

• Symptoms of oral infection include dry mouth, loss of taste, and occasionally, pain with eating.
• Acute pseudomembranous candidiasis (thrush):
  • Causes creamy white, curd-like patches on the tongue and oral mucosa.
  • Usually an acute infection but it may persist for months in patients receiving inhaled corticosteroids, cytotoxics or broad-spectrum antibiotics, and in patients with serious systemic disease associated with reduced immunity, e.g. leukaemia, other malignancies and HIV infection.
  • Treatment with amphotericin or miconazole may be needed.
  • Fluconazole is effective for unresponsive infections, if a topical antifungal drug cannot be used or if the patient has dry mouth.
  • Topical therapy may not be adequate in immunocompromised patients and an oral triazole antifungal (e.g. itraconazole) is preferred.
• Acute erythematous (atrophic) candidiasis:
  • Relatively uncommon and is associated with corticosteroid and broad-spectrum antibacterial use and with HIV disease.
  • Is usually treated with fluconazole.
• Chronic atrophic candidiasis (denture stomatitis):
  • Chronic inflammatory reaction with epithelial thinning under dental plates.
  • Denture stomatitis is not always associated with candidiasis and other factors such as mechanical or chemical irritation, bacterial infection, or allergy to the dental base material may be the cause.
  • Patients should cleanse their dentures thoroughly and leave them out as often as possible during the treatment period. To prevent recurrence, patients should avoid wearing dentures at night.
  • New dentures may be required if these measures fail despite good compliance.
  • Miconazole oral gel can be applied to the fitting surface of the denture before insertion for short periods.
  • Alternatively amphotericin lozenges allowed to dissolve slowly in the mouth can be used but they are less effective at resolving the stomatitis.
• Candidal leucoplakia (chronic hyperplastic candidiasis):
  • Presents as firm, white plaques affecting the cheeks, lips, and tongue which frequently have a protracted course.
  • Candidal leucoplakia may be associated with varying degrees of dysplasia and with oral cancer and so biopsy is essential.
  • Chronic hyperplastic candidiasis is treated with a systemic antifungal such as fluconazole to eliminate candidal overlay. Patients should avoid tobacco.
• Angular cheilitis (angular stomatitis):
  • Causes erythema and fissuring at the corners of the mouth.
  • Angular cheilitis is often associated with denture stomatitis but may also be associated with nutritional deficiency, orofacial granulomatosis or HIV infection.
  • Candida and bacteria (Staphylococcus aureus and Beta-haemolytic streptococci) are often involved as co-existing infective factors.
  • Miconazole and hydrocortisone cream or ointment, miconazole cream or sodium fusidate ointment are all effective.

Candida oesophagitis

• Most often associated with treatment of haematopoietic or lymphatic malignancies. It is also an AIDS-defining illness.
• Presents with dysphagia, retrosternal chest pain, nausea and vomiting.
• Diagnosis is made by endoscopic biopsy.
• Other locations of infection in the gastrointestinal tract, e.g. stomach and intestine, most often occur in patients with malignancy.

Candidal vulvovaginitis

See separate articles on Vaginal and vulval candidiasis and Vaginal discharge.

• The most common form of mucosal candidiasis and is usually secondary to overgrowth of Candida species in the vagina.
• Bacteria such as Lactobacillus acidophilus balance candida and prevent yeast overgrowth and pathogenic infection.
• Causes of disruption of the balance of normal vaginal flora include antibiotic use, oral contraceptives, intrauterine contraceptive devices, high oestrogen levels and immunocompromised states such as diabetes mellitus and HIV.
• Most candida infections are caused by Candida albicans, while the remainder are caused by C. glabrata and C. tropicalis.
• Presentation includes pruritus, vaginal irritation and dysuria. Thick, curd-like discharge is often present but scant discharge may also occur. Vaginal oedema and erythema are present on examination.
• Vaginal candida infections may increase viral shedding in HIV-infected women.
• Candidal vulvitis can be treated locally with cream but is almost invariably associated with vaginal infection which should also be treated.
• Vaginal candidiasis may be treated with antifungals pessaries or cream inserted high into the vagina or with oral fluconazole; for resistant organisms, itraconazole can be given by mouth.
• Vulvovaginal candidiasis is common during pregnancy and can be treated with vaginal application of an imidazole and a topical imidazole cream for vulvitis. Pregnant women need a longer duration of treatment, usually about 7 days, to clear the infection.¹ Oral antifungal treatment should be avoided during pregnancy.²
• For recurrent vulvovaginal candidiasis:
  • Treatment against candida may need to be extended for 6 months, e.g. oral fluconazole 100 mg every week, clotrimazole vaginally 500-mg pessary every week or oral itraconazole 400 mg (as 2 divided doses on one day) every month.
  • Reservoirs of infection may lead to recontamination and should be treated, e.g. infection sites in nail beds, umbilicus, gastro-intestinal tract and the bladder. The partner may also be the source of re-infection and, if symptomatic, should be treated with cream at the same time.

Dermatophytosis (Tinea) is covered in a separate article.

• Candidal skin infections can be treated with a topical imidazole antifungal, such as clotrimazole, econazole, ketoconazole, miconazole, or sulconazole; topical terbinafine is an alternative.
• Refractory candidiasis requires systemic treatment with a triazole such as fluconazole; systemic treatment with terbinafine is not appropriate for refractory candidiasis.
• Generalised cutaneous candidiasis; widespread eruptions with increased severity in the groin folds, anal region, axillae, and hands and feet; occurs in both children and adults.
• Candida folliculitis; this is most frequently seen in immunocompromised hosts and among intravenous drug users.

Candida balanitis

• This infection is usually acquired with sexual intercourse with an infected partner.
• Rash typically begins as vesicles on the penis that develop into patches similar in appearance to thrush.
• Extension may occur to the scrotum and buttocks.
• Symptoms include burning and pruritus.

Intertrigo

• Intertrigo develops in sites where skin surfaces are close in proximity.
• Lesions begin as vesicopustules that enlarge, rupture and develop maceration and fissuring.
• Satellite lesions may be present.
• A variant form of cutaneous candidiasis in the intertriginous region has a miliary appearance.

Candidal paronychia

• Candidal paronychia is associated with frequent hand immersion in water and diabetes mellitus.
• See separate articles on Fungal Nail Infections and Nail Disorders and Abnormalities.

Nappy rash

• Skin irritation in nappy rash is exacerbated by wet nappies.

Perianal candidiasis

• Skin maceration and pruritus are frequent with frequent extension to the perineum.

Chronic mucocutaneous candidiasis

• A heterogeneous group of candida infections of the skin, mucous membranes, hair, and nails, which has a protracted course despite typical therapy.
• It is associated with T-cell lymphocyte dysfunction.

See separates articles on Systemic Mycoses and Fungal Lung Infections.

• Severe and invasive disorders, including candidaemia, disseminated candidiasis, deep organ involvement, endocarditis, endophthalmitis, and meningitis.
• Invasive infection is also described as the isolation of candida from a normally sterile body site, including blood, peritoneal fluid, pleural fluid, intra-articular fluid, or cerebrospinal fluid.
• Risk factors for invasive candidiasis include prolonged intensive care unit stay, presence of a central venous catheter, acute renal failure, treatment with broad-spectrum antibiotics, parenteral nutrition, diabetes, immunosuppressive therapy, surgery (especially upper gastrointestinal tract), haemodialysis, pancreatitis, malignancy, transplantation and organ dysfunction.
• Skin manifestations of disseminated candidiasis include clusters of painless pustules on an erythematous base on any area of the body. These lesions may be macular or pustular or may have central necrosis.
• First line treatment for deep and disseminated candidiasis is amphotericin which can be given by intravenous infusion.
• Fluconazole is an alternative for C. albicans infection in clinically stable patients who have not received an azole antifungal recently.
• Caspofungin or voriconazole can be used for infections caused by fluconazole-resistant candida spp. that have not responded to amphotericin, or in patients intolerant of amphotericin.
• In refractory cases, flucytosine can be used with intravenous amphotericin.
• Prophylaxis with fluconazole or ketoconazole in critically ill patients reduces invasive fungal infections and total mortality.⁴
• Invasive candidiasis has a mortality rate of up to 50%; neonates and children have better outcomes with approximately 20% mortality rate for candidaemia.³
• Risk factors for death or poor prognosis are age, failure to remove central lines, malnutrition, and non-albicans fungaemia.

Acute disseminated candidiasis

• Most often seen in patients with haematological malignancy who have had a recent episode of neutropenia.
• Symptoms include fever, right upper quadrant pain and tender hepatosplenomegaly.
• Multiple organs are frequently involved, and discrete persistent microabscesses occur in the liver, spleen and kidneys.
• A palpable erythematous rash may be present indicating evidence of small vessel vasculitis.

Central nervous system candidiasis

• Usually occurs as a complication of candidaemia.
• Intraventricular drains increase risk of CNS candida infection.
• Candida typically forms multiple microabscesses and small macroabscesses scattered throughout the brain.
• Patients with candida meningitis usually have meningeal irritation and CSF pleocytosis.
• Untreated, the mortality rate is high.

Candidal pneumonia

• Occurs rarely as bronchopneumonia originating from endobronchial inoculation or more commonly a blood-seeded, nodular diffuse infiltrate.
• May be difficult to distinguish from congestive heart failure or Pneumocystis pneumonia.
• Diagnosis is also complicated by the inability to confirm that positive cultures are not oropharyngeal contaminant or colonisation.

Candidal pericarditis and myocarditis

• Candida can infect both the pericardium and myocardium, and these infections are usually associated with disseminated disease.
• Candidal pericarditis is rare but fatal without treatment and has been known to cause tamponade.
• Infective endocarditis with candida is usually seen in patients with a chronic indwelling intravenous catheter or large-calibre haemodialysis catheter.
• Other risk factors include congenital cardiac abnormalities, prosthetic valves, and intravenous illicit drug use.
• Fungal vegetations are often large and more frequently associated with embolic events.
• The mortality rate is approximately 45% with combined medical and surgical therapy.

Urethral candidiasis

• Can occur in both men and women.
• In women, it is commonly secondary to an extension of candida vaginitis.
• In men, it is usually secondary to sexual contact with women with vaginitis.
• Invasive infections of the bladder and kidneys can occur, though it is typically in immunocompromised patients and secondary to candidaemia.

Ocular candidiasis

• Can occur as endophthalmitis.
• Typically, involvement is unilateral, but bilateral cases have been reported.
• C. albicans is the most common cause.
• Endophthalmitis may occur secondary to exogenous spread, such as trauma or surgery, or endogenous spread as a result of haematologic seeding.
• Untreated candidaemia has been associated with retinal lesions in up to one third of patients.
• Candida ophthalmitis begins as a choroidal lesion that progresses to an area of retinal necrosis followed by vitritis and endophthalmitis.
• Endophthalmitis is characterised by retinal infiltrates and vitreous abnormalities.
• Chorioretinal involvement appears as focal, white, infiltrative lesions on the retina.
• Vitreal haze is present with vitreous extension of the infection.
• Symptoms include pain and decreased visual acuity.
• Ophthalmitis will lead to blindness if not treated.

Osseous and intra-articular infections

• May occur secondary to either haematogenous spread or exogenous inoculation during trauma or joint injection.
• Osteomyelitis occurs most commonly in vertebrae in adults and in long bones in children.
• Spinal infection can progress to a discitis.
• Arthritis can be acute and suppurative, and the knee is most commonly affected.
• Diagnosis of osteoarticular infections may be delayed as symptoms are frequently more subtle than bacterial infections in the same location and patients often present several weeks to months after an episode of candidaemia.

Other sites of infection

• Candidal peritonitis occurs most often secondary to peritoneal dialysis catheter seeding or gastrointestinal surgery.
• Candidal mediastinitis may occur after thoracic surgery.

• Occurs with an incidence inversely proportional to birth weight.
• Invasive candida infection is a common cause of late-onset infection among very low birth weight infants in most neonatal intensive care units.⁵
• Sites of infection include blood, urine cerebrospinal fluid and peritoneal fluid.
• C. albicans and C. parapsilosis are the most common species found in neonates.
• Standard therapy has been amphotericin B but fluconazole has also been shown to be effective.⁵
• There is insufficient evidence to support the use of prophylactic oral antifungal agents in very low birth weight infants in the neonatal intensive care unit.⁶

Candida amnionitis

• May occur after prolonged rupture of the membranes in mothers given parenteral antibiotics.
• The neonate may present with pustules, vesicles or diffuse erythema.