Fungal Infections of the Orofacial Tissues

Question 1

What is the difference between candidiasis and candidosis?

Answer 1

Candidiasis (systemic candidal infections)

Candidosis (oral candidal infections)

Question 2

What is the causative pathogen for candidosis?

Answer 2

Candida Albicans

50% of the population carries this pathogen in the mouth

Oral commensal (opportunistic pathogen)

Question 3

How does oral candidosis arise?

Answer 3

Candida albicans is usually an oral commensal that lives in harmony with other microflora but it acts as an opportunistic pathogen when the balance tips in its favour through the presence of one or more risk factors (steroid usage, smoking, dry mouth, immunocompromise).

When the balance tips, it is able to cause a clinical fungal infection

Question 4

List the risk factors for the development of candidal infections

Answer 4

Dry mouth (can be caused by smoking/certain medications)

Immunocompromise (treatment for cancer, HIV, diabetes)

Smoking (causes dry mouth)

Topical steroid use (typically for the treatment of asthma or COPD, will change the microflora and give the candida in the mouth the opportunity to overgrow and become pathological)

Systemic antibiotic use (post-antibiotic oral thrush)

Pre-existing mucosal lesions (e.g., lichen planus, these patients will have a predisposition towards candida because the mucosa is not fully intact (there may be some erosions or ulcerations i.e. abnormal tissue) and the inflammation allows the candida to take hold and cause clinical disease)

Dentures/orthodontic appliance wear (as these patients wear an intra-oral appliance, they are at an increased risk of oral candidosis, especially if their OH is sub-optimal)

Low pH intra-oral environment (such as that caused by the presence of GORD acid reflux will favour the development of both oral and oesophageal candidal infections)

Carbohydrate rich diets (source of nutrients for the pathogen allowing survival)

Question 5

List the types of candidosis that can occur

Answer 5

Acute pseudomembranous candidosis (oral thrush)

Erythematous candidosis (red and inflamed candidal infection, typically seen under dentures, also known as denture stomatitis)

Angular cheilitis (fungal OR bacterial infection at the commissures of the mouth. May be sore, usually due to maceration from saliva at the site)

Chronic hyperplastic candidosis (uncommon but important as it’s a potentially malignant condition)

Chronic mucocutaneous candidosis (rare group of overlapping syndromes that have in common persistent, severe and diffuse mucocutaneous candidal infections of the skin, nails and the mucous membranes).

Question 6

Describe the features of acute pseudomembraneous candidosis (oral thrush)

Answer 6

Creamy white plaques all over the intraoral mucosal surfaces including edentulous ridges, the tongue, the buccal mucosae, the palate.

These plaques will wipe off, if a piece of gauze was used to remove them and their removal would typically reveal an erythematous base

Usually asymptomatic

Most commonly affected patients include babies (developing immune systems) and elderly patients (as they’re more likely to be wearing dentures or suffer from immunocompromise)

Common after a broad spectrum antibiotic

Significant improvement in OH/denture hygiene and modification of other co-existing risk factors should be sufficient to control this condition

Question 7

How do we treat acute pseudomembranous candidosis?

Answer 7

Significant improvement in OH/denture hygiene and modification of other co-existing risk factors should be sufficient to control this condition

Question 8

Describe the features of erythematous candidosis

Answer 8

Erythema and inflammation restricted to the denture bearing area.

Candida colonises a denture surface due to poor denture / oral hygiene

Or it could simply be an irritant reaction to the bacteria which tend to grow on the surface of the denture, especially for patients with a reluctance to remove the appliance for any prolonged period of time, some tending to even refuse to go to bed without their denture in situ

Where patients have had denture stomatitis of bacteria/fungal origin, for a very long time, there’s a degree of papillary hyperplasia (nodular appearance to the vault of the palate).

Occasionally, there can be additional risk factors other than an intra-oral appliance e.g., nutritional deficiencies (low ferritin) or diabetes. A blood test will be required where we suspect this (usually only with severe, recurrent or persistent disease)

Can be painful sometimes with patients complaining of soreness but pain symptoms are somewhat variable.

Also known as denture stomatitis

Question 9

If a patient has denture stomatitis and are a known immunocompromised patient. What should a dentist do?

Answer 9

Consider referral to oral medicine or maxillofacial department

Question 10

A 75 year old patient presents to your clinic complaining of soreness. You ask the patient to remove their denture, having a look at the denture bearing surfaces and you notice a patchy erythema affecting this area. The tissues appear to be inflamed where the denture sits. What is the diagnosis and management protocol for this patient?

Answer 10

Erythematous candidosis / denture stomatitis

Inform the patient that they have an infection

Make strong recommendations that they remove the denture overnight

Or if not, that they at least brush it thoroughly with soap and water, rinse it well and try to soak it in a diluted solution of Sodium Hypochlorite solution for at least 30 minutes (if not overnight), rather than using commercially available denture cleaning tablets which have weak or limited cleansing properties.

An alternative to suggest is soaking the denture in a dilute solution of Corsodyl or Chlorhexidine mouthwash (however this may cause discolouration of the plastic components of the denture creating an aesthetic issue, requiring professional cleaning to remove)

Reinforce denture hygiene and identify risk factors that may be contributing to the candidal infection and modify them where possible

If the candida completely colonises the denture, it will be very difficult to eradicate the infection. Will need to remake the denture and ensure vastly improved OH/denture hygiene in severe or persistent cases

Manage patient expectations (may need to accept this will be a continuous problem despite professional input or improved hygiene measures)

Question 11

A patient presents with denture stomatitis. What would we observe clinically that would indicate that they have had this condition for a very long time?

Answer 11

Papillary hyperplasia (nodular appearance to the vault of the palate)

Question 12

Describe the features of angular cheilitis

Answer 12

Often a candidal infection at the commissures of the mouth, resulting in a macerated, cracked, red appearance that may be crusting.

However, can also be a bacterial infection, in which case, it is often the skin commensal staphylococcus aureus which is at fault (when there is a typically golden crusty appearance, this is the likely pathogen).

This soreness/cracking can be painful for patients but it may also be asymptomatic.

Huge variation between presention. Can vary from a fairly minor irritation where there’s little erythema and no crusting to some evidence of redness/inflammation and some crusting developing to bilateral lesions with a lot of redness and some hyperkeratosis developing.

Question 13

How does angular cheilitis arise?

Answer 13

When patients have a reduced face height in the lower third (complete denture wearers) or pronounced nasolabial folding, their saliva can accumulate in the corners of the mouth and lead to maceration (and in turn, colonisation by either fungal or bacterial organisms)

Maceration is where the skin just outside the vermillion border is wet, and as skin is not meant to be constantly wetted by saliva, a macerated, red and angry appearance develops at the commissures of the mouth

Also often seen in patients who have OFG (orofacial granulomatosis, effectively a variant of Crohn’s disease that only affects orofacial tissues)

And in those children with developmental abnormalities or syndromes or congenital problems that lead to persistent drooling

Question 14

What is an important consideration to make when treating fungal angular cheilitis?

Answer 14

When the angular cheilitis is a fungal infection, the reservoir for the candida is the intraoral environment. This influences management

If we were to give a topical anti-fungal to use at the commissures only and not prescribe something to use inside the mouth, we would not eradicate the source of the candida and it would likely lead to the development of a recurrent infection

Question 15

List the patients that are most likely to present with angular cheilitis

Answer 15

Patients who have a reduced face height in the lower third (complete denture wearers)

Patients who have pronounced nasolabial folding

Patients who have OFG (orofacial granulomatosis, effectively a variant of Crohn’s disease that only affects orofacial tissues)

Children with developmental abnormalities or syndromes or congenital problems that lead to persistent drooling

Question 16

A patient re-attends your clinic following a prescription of topical anti fungal to use at the commissures of his mouth. He presents with a recurrent angular cheilitis infection, complaining that his symptoms have not resolved. Why has this occurred?

Answer 16

When the angular cheilitis is a fungal infection, the reservoir for the candida is the intraoral environment

Only giving a topical anti-fungal to use at the commissures and not prescribing something to use inside the mouth means we have not eradicated the source of the candida and a recurrent infection is therefore likely

Question 17

Describe the features of Chronic Hyperplastic Candidosis (CHC)

Answer 17

Mixed red and white patches at the commissures which may extend posteriorly along the buccal mucosa, usually along the length of the occlusal plane

Potential for malignant transformation (lesion progresses from a simple candidal infection to become dysplastic or even a carcinoma in situ)

Not a superficial infection. The fungal hyphae actually burrow into the mucosa and are somewhat resistant to simple topical anti-fungal such as nystatin

Affected patients are commonly smokers

Question 18

A patient presents with mixed red and white patches at the commissures, which extend posteriorly along the buccal mucosa, along the length of the occlusal plane. There is evident redness in the centre and some stippling/white dots within the background redness. What is the likely diagnosis and management protocol for this patient?

Answer 18

Chronic hyperplastic candidosis

Patient should be flagged as a priority and referral for an incisional biopsy should be undertaken to look for evidence of dysplasia or malignancy.

As the condition isn’t just a superficial infection and the fungal hyphae actually burrow into the mucosa, being somewhat resistant to simple topical anti-fungal such as nystatin, a systemic course of anti fungal treatment will need to be prescribed (usually fluconazole 50-100mg 1x daily for 10-14 days).

This may be sufficient to cause the lesion to regress clinically and a follow-up is advised with clinical photographs to monitor progression for any hint of malignant change. In the chance that this is observed, a re-biopsy would be indicated.

All modifiable risk factors should be addressed-
Strong recommendation to the patient to give up smoking
Treatment for dry mouth
Denture hygiene advice advocated and reinforced for denture wearers

Question 19

Describe the features of median rhomboid glossitis

Answer 19

Presents as an area of de-papillation on the dorsal surface of the tongue, mostly due to a chronic fungal infection.

At rest the tongue is usually in apposition to the palate, sometimes leading to corresponding lesions (red/pink patches) on the palatal mucosa

Most commonly asymptomatic, noticed on routine examination.

Question 20

How do we treat median rhomboid glossitis?

Answer 20

Explain the aetiology to the patient (chronic fungal infection)

Address any modifiable risk factors

Reassure patient that this appearance is not a cause for concern

Question 21

Describe the features of chronic mucocutaneous candidosis (CMC)

Answer 21

Fungal infections of the skin, mucous membranes, nails etc. from early infancy

White patches/lesions that can affect all intra-oral mucosal surfaces such as the vault of the hard palate, lateral borders of the tongue, dorsal surface of the tongue etc.

Can cause significant morbidity to affected patients

Some patients will be symptomatic, whilst others will be asymptomatic

Rare to die from a disseminated candidal infection but still a possibility

Question 22

How does chronic mucocutaneous candidosis arise?

Answer 22

Caused by a rare group of overlapping syndromes that all have a disorder in cell mediated immunity (T cells) against candida i.e., the patients can’t fight off fungal infections in the same way that an immunocompetent patient might.

Question 23

A patient presents with patchy erythema to the vault of the hard palate. He reports no pain and there are no other symptoms except the redness and inflammation in the vault of the hard palate. Whilst taking the medical history, the patient reports she is an asthmatic who is using a steroid inhaler. What is the likely diagnosis?

Answer 23

Erythematous candidosis

Steroid inhalers can the change the composition of microflora allowing Candida to over grow and become pathological, causing clinical disease

Question 24

What special investigations may be needed where we suspect a candidal infection

Answer 24

None. Sometimes history-taking and examination (clinical diagnosis) are enough to determine the definitive diagnosis

Swabs/oral rinses (important for diagnosis/management of a recurrent or persistent candidiasis that appears to be resistant to multiple courses of treatment. In these cases, samples of the clinical lesion/fungi taken through swabs or an oral rinse may be sent to the lab to grow any unusual fungal organisms, to give us potential sensitivity to less commonly used anti-fungals to prescribe for the patient).

Blood tests (useful in cases of recurrent, persistent infections, would give some useful information about any underlying sources of the candidal infection)

HIV test (important to consider for particularly troublesome candidal infections as immunocompromise is a risk factor for these infections)

Question 25

When would you consider taking a sample of the fungal organisms in a candidal infection (via swab / oral rinse) and sending it MC+S

Answer 25

Patients with clinical lesions can be swabbed or be made to take an oral rinse for diagnostic/management purposes, however this should not be considered initially as resistance to commonly used anti-fungal agents is extremely rare in most fungal infections.

Most patients will respond to a simple prescription of an agent such as nystatin without the need for MC+S.

These investigations become relevant for those that have a recurrent or persistent candidiasis and appear to be resistant to multiple courses of treatment.

In these cases, samples may be sent to the lab to grow any unusual fungal organisms to give us potential sensitivity to less commonly used anti-fungals to prescribe for the patient

Question 26

Describe the rationale behind taking a blood test where a patient presents with oral candidosis

Answer 26

For a one-time occurrence of candidiasis, a blood test wouldn’t be indicated but in cases of recurrent, persistent infections, a blood test would give some useful information.

Allows the identification of underlying factors that could make them more susceptible to recurrent and persistent candidosis. Until these are addressed, the infection will never truly be cured

For example, the patient could be anaemic which would predispose them to a candidiasis.

HbA1C is a measure of glucose control over the previous 90 days and could indicate an undiagnosed diabetic or a poorly controlled diabetic.

Folate, ferritin and B12 are haematinics and these can reflect nutritional deficiencies which again may predispose the patient to a candidal infection. These 3 may also be indicators of an underlying systemic disorder not otherwise known or not fully controlled (immunocompromise)

Question 27

A patient presents to your clinic with recurrent candidal infections. You have provided them with treatment that has failed to eradicate the infection. A blood test has come back with no causes for concern. A sample taken of the clinical lesions reveals Candida Albicans with good sensitivity to standard anti-fungal treatment. What other test may be necessary in this context?

Answer 27

A HIV test as this presents as a particularly troublesome candidal infection

Patient should be referred to the oral medicine department for appropriate counselling and management going forwards.

Question 28

What is the general management protocol for oral candidosis

Answer 28

Identify any underlying risk/predisposing factors and modify any that you can:
Treating a dry mouth which has a myriad of causes.

Identifying untreated/poorly controlled diabetes and HIV. Patient would need to be referred to the appropriate clinician to manage these conditions

If a patient is on a steroid inhaler on a regular basis, an inquiry into whether they rinse their mouth out with water or mouthwash after using it should be made. If they do not, we would need to consider whether the prescription of a spacer device is appropriate to give a better aerodynamic flow and increase the chances of the steroid getting into the lungs rather than depositing onto the oral mucosa where they are not required.

OHI and denture/appliance hygiene advice

Smoking cessation

Consider a broad spectrum antimicrobial mouthwash 2-3x a day (0.2% Chlorhexidine digluconate)

Consider topical anti fungal such as nystatin (1:100,000 1ml 4/day 2 weeks), miconazole gel (4/day 2 weeks), amphotericin lozenges

Consider appropriate antifungal prescription for patients with extra-oral and intra-oral fungal colonisation such as angular cheilitis

Systemic antifungals as the first line of treatment for CHC. Where this is suspected, patient should be referred to oral medicine for an incisional biopsy to look for evidence of dysplasia/malignancy. Oral medicine clinician would usually prescribe 50-100mg fluconazole 1/day 10-14 days to attempt to eradicate the burrowing infection and the fungal hyphae that have invaded the oral mucosa in CHC

Question 29

What medications can be prescribed for oral candidosis?

Answer 29

A broad spectrum antimicrobial mouthwash 2-3x a day (0.2% Chlorhexidine digluconate). Activity against fungi can be helpful in suppressing recurrent candidal infections. Dentures and appliances can be soaked in dilute Corsodyl to prevent fungal colonisation.

Topical anti fungal as such as nystatin (1:100,000 1ml 4/day 2 weeks), miconazole gel (4/day 2 weeks), amphotericin lozenges

Appropriate antifungal prescription for patients with extra-oral and intra-oral fungal colonisation such as angular cheilitis

Systemic antifungals as the first line of treatment for CHC. Where this is suspected, patient should be referred to oral medicine for an incisional biopsy to look for evidence of dysplasia/malignancy. Oral medicine clinician would usually prescribe 50-100mg fluconazole 1/day 10-14 days to attempt to eradicate the burrowing infection and the fungal hyphae that have invaded the oral mucosa in CHC

Question 30

Which medications can interact with anti-fungal medications such as Fluconazole and Miconazole?

Answer 30

Carbamazepine

Cyclosporin (immunosuppressive following organ transplant)

Anti-retro viral drugs (HIV)

Warfarin

Apixaban (interacts with Fluconazole)

Statins (anti-cholesterol drugs)

Question 31

What important considerations need to be made before prescribing anti-fungal medicines such as Fluconazole/Miconazole?

Answer 31

When prescribing a drug to a patient, we need to check their medical history for any potential CIs, allergies and their social history for alcohol usage.

If there’s a cause for concern or any doubts, we need to liaise with their GP/pharmacist/specialist looking after them e.g., cardiologist, infectious disease specialist etc. to identify a suitable prescription for the patient in question.

Question 32

What effect does Miconazole/Fluconazole have when taken in combination with Carbamazepine?

Answer 32

Both miconazole and fluconazole can interact with carbamazepine, by potentiating (increasing) its effects.

As they can make the drug more potent, dose adjustments will be required and advice will need to be sought before prescribing.

Carbamazepine is an anti-convulsant medication that is used for epilepsy and other seizure related conditions alongside chronic neuropathic pain conditions (including trigeminal neuralgia).

Question 33

What effect does Miconazole/Fluconazole have when taken in combination with Warfarin?

Answer 33

Both azole antifungals can cause increased bleeding if given to a patient taking warfarin.

Should consider whether nystatin may be appropriate alone for any fungal infections.

Question 34

What effect does Fluconazole have when taken in combination with Apixaban?

Answer 34

Can cause increased bleeding if taken in combination

Question 35

What effect does Miconazole/Fluconazole have when taken in combination with statin drugs?

Answer 35

Both azole antifungals can interact with statins (anti cholesterol drugs) of various different forms to cause significant toxicity.

Typically patients are advised to stop their statins for the duration of their treatment (for instance after diagnosis of chronic hyperplastic candidiasis). And they can restart their statin on completion of their course

Question 36

What is the protocol for prescription where patients are on Cyclosporin (to enable immunosuppression following organ transplant)

Answer 36

As this drug can interact with azole antifungals such as Miconazole/Fluconazole, we should not risk giving these azole drug to patients who have had an organ transplant.

Instead, these patients should be referred to someone with more detailed medical knowledge

Question 37

What is the protocol for prescription where patients are on anti-retro viral drugs (for the treatment of HIV)

Answer 37

As these drugs can interact with azole antifungals such as Miconazole/Fluconazole, we should not risk giving these azole drugs to patients who have previously well controlled HIV suppression

Instead, these patients should be referred to someone with more detailed medical knowledge

Question 38

What effect does Miconazole/Fluconazole have when taken in combination with alcohol?

Answer 38

Can increase the risk of liver damage if drunk in large quantities

Can increase the severity of side effects (nausea, vomiting, diarrhoea) when taking azole drugs

Patients should be advised not to drink alcohol during their anti-fungal course