1. FUNGAL INFECTIONS
The fungal infections are the most common type of infection worldwide [1]
Classifications [2]:
Cutaneous fungal diseases can be broadly divided into two groups:
– Superficial : limited to the stratum corneum, hair, and/or nails.
– Deep : dermal and/or subcutaneous.
• Superficial fungal infections can be further subdivided into:
 Non-inflammatory : most commonly tinea versicolor.
 Inflammatory : primarily infections due to dermatophytes (Trichophyton, Microsporum,
Epidermophyton; e.g. tinea corporis, tinea cruris) or Candida species (e.g. cutaneous
candidiasis of the groin).
• Deep fungal infections are often secondary to:
 Direct inoculation into the skin by a thorn or other foreign Body [1] and Implantation (e.g.
chromoblastomycosis)
 Hematogenous spread of an underlying systemic infection (e.g. cryptococcosis,
coccidioidomycosis)[2], typically with a primary pulmonary focus[1]
• Opportunistic pathogens (e.g. candida, Aspergillus) can lead to systemic infection in
immunosuppressed hosts.
Candidiasis
Candidiasis is also known as candidosis or moniliasis.
Candida albicans is a common inhabitant of the human gastrointestinal (GI) and genitourinary
tracts, and skin [1]. Candidiasis most commonly occur due to Candida albicans or C. tropicalis.
Predisposing factors for candida infections:
The pathogenesis is not fully understood, but a number of predisposing factors have been shown
to convert C. albicans from the normal commensal flora (saprophytic stage) to a pathogenic
organism (parasitic stage). C. albicans is usually a weak pathogen, and candidiasis is said to
affect the very young, the very old, and the very sick.
 Local predisposing factors as:
o Warmth and moisture

2. o Reductions in competing flora during antibiotic therapy (superinfection)
o Higher skin pH also favors candida growth.
 General predisposing factors : often related to an individual’s immune status and
endocrine status:
 Drugs (immunosuppressant drugs e.g systemic steroids) as well as diseases (e.g.
diabetes and leukemia), which suppress the adaptive or the innate immune system
can affect the susceptibility of the mucosal lining. Both the native and adaptive
immune systems are critical to prevent development of systemic mucocutaneous
candidiasis.
 Pseudomembranous candidiasis is also associated with fungal infections in young
children, who neither have a fully developed immune system nor a fully developed
oral microflora.
Wide spectrum of clinical presentations [1]:
 Mucosal candidiasis:
 Oral candidiasis
 Candidal vulvovaginitis
 Cutaneous: erosive, erythematous patch with satellite pustules
 Candidal intertrigo
 Diaper candidiasis
 Congenital cutaneous candidiasis
 Perianal candidiasis
 Candidal paronychia
 Erosio interdigitalis blastomycetica
 Chronic mucocutaneous candidiasis
 Systemic candidiasis
ORAL CANDIDIASIS
Oral candidiasis is the most prevalent opportunistic infection affecting the oral mucosa. Most
candidal infections only affect mucosal linings, but rare systemic manifestations may have a fatal
course.
Oral candidiasis is divided into :
 The primary infections: restricted to the oral and perioral sites
 Secondary infections: accompanied by systemic mucocutaneous manifestations.

3. Etiology and Pathogenesis:
C. albicans, C. tropicalis, and C. glabrata comprise together over 80% of the species isolated from
human candidal infections.
Virulence factors:
1. To invade the mucosal lining, the microorganisms must adhere to the epithelial surface;
therefore, candida strains with better adhesion potential are more virulent than strains with
poorer adhesion ability.
2. The yeasts’ penetration of the epithelial cells is facilitated by their production of lipases
3. For the yeasts to remain within the epithelium, they must overcome constant desquamation
of surface epithelial cells.
predisposing factors:
 local predisposing
factors:able to promote
growth of the yeast or to
affect the immune response
of the oral mucosa.
 General predisposing factors :
(mentioned previously)
Candida-associated infections (as
bacteria may also cause these
infections):
 Denture stomatitis
 angular cheilitis
 median rhomboid
glossitis
Epidemiology
o The prevalence of candidal
strains, as part of the commensal oral flora, shows large geographic variations.
o Candidal strains are more frequently isolated from women.
o A seasonal variation has been observed, with an increase during summer months.
o Hospitalized patients have a higher prevalence of the yeasts.
o In complete denture-wearers, the prevalence of denture stomatitis has been reported
variously from 11%–67%.

4. Clinical Findings:
1. Pseudomembranous Candidiasis (thrush):
 It is recognized as the classic candidal infection
 Symptoms: Patients infrequently report symptoms from their lesions, although some
discomfort may be experienced from the presence of the pseudomembranes.
 typically presents with loosely attached membranes (comprising fungal organisms and
cellular debris) which leaves an inflamed, sometimes bleeding area if the pseudomembrane
is removed.
 DD: Less pronounced infections sometimes have clinical features that are difficult to
discriminate from food debris like egg and yoghurt.
 The chronic form:
o may emerge as the result of human immunodeficiency virus (HIV) infections
o Patients treated with steroid inhalers
2. Erythematous Candidiasis:
 was previously referred to as atrophic oral candidiasis. However, an erythematous surface
may not just reflect atrophy but can also be explained by increased vascularization.
 may be considered a successor to pseudomembranous candidiasis but may also emerge de
novo.
 DD: The lesion has a diffuse border, which helps distinguish it from erythroplakia, which
usually has a sharper demarcation and often appears as a slightly submerged lesion.
 No quantitative differences exist between isolates of C. albicans from individuals with
healthy oral mucosa and from patients with erythematous candidasis.
 Sites: predominantly seen in the palate and the dorsum of the tongue.
3. Chronic Plaque-Type and Nodular Candidiasis:
o The chronic plaque type of oral candidiasis replaces the older term, candidal leukoplakia.
o typical clinical presentation: A white irremovable plaque
o DD: may be indistinguishable from oral leukoplakia.
o A positive correlation between oral candidiasis and moderate to severe epithelial dysplasia
has been observed, and both the chronic plaque-type and the nodular type of oral
candidiasis have been associated with malignant transformation, but the possible role of
yeasts in oral carcinogenesis is unclear.
4. Denture Stomatitis:
 The most prevalent site: is the denture- bearing palatal mucosa. It is unusual for the
mandibular mucosa to be involved.
 The denture serves as a vehicle that accumulates sloughed epithelial cells and protects the
microorganisms from physical influences such as salivary flow. The microflora is complex

5. and may, in addition to C. albicans contain bacteria from several genera, such as
Streptococcus strain. It is not known to what extent these bacteria participate in the
pathogenesis of denture stomatitis.
5. Angular Cheilitis (Perlèche):
 presents as infected fissures of the commissures of the mouth, often surrounded by
erythema
 lesions are frequently coinfected with both Candida albicans and Staphylococcus aureus.
 DD: VitaminB12 deficiency, iron deficiencies, and loss of vertical dimension have been
associated with this disorder.
 Predisposing factors:
o Atopy has also been associated with the formation of angular cheilitis. Dry skin may
promote the development of fissures in the commissures, allowing invasion by the
microorganisms.
o Thirty percent of patients with denture stomatitis also have angular cheilitis, but this
infection is only seen in 10% of denture-wearing patients without denture stomatitis.
6. Median Rhomboid Glossitis:
 is asymptomatic
 clinically characterized by an erythematous lesion in the center of the posterior part of the
dorsum of the tongue
 the lesion has an oval configuration.
 This area of erythema results from atrophy of the filiform papillae and the surface may be
lobulated.
 Sometimes a concurrent erythematous lesion may be observed in the palatal mucosa
(kissing lesions)
 The etiology is not fully clarified, but the lesion frequently shows a mixed bacterial/fungal
microflora.
 Biopsies yield candidal hyphae in more than 85% of the lesions.
 management is restricted to a reduction of predisposing factors.
 The lesion does not entail any increased risk for malignant transformation.
7. Oral Candidiasis Associated with HIV:
 More than 90% of acquired immune deficiency syndrome (AIDS) patients have had oral
candidiasis during the course of their HIV infection, and the infection is considered a
portent of AIDS development
 The most common types of oral candidiasis in conjunction with HIV are:
o pseudomembranous candidiasis
o Erythematous candidiasis
o angular cheilitis

6. o chronic plaque-like candidiasis.
 the prevalence of oral candidiasis has decreased substantially as a result of the highly
active antiretroviral therapy (HAART).
8. Secondary oral candidiasis : is accompanied by systemic mucocutaneous candidiasis and
other immune deficiencies.
 Chronic mucocutaneous candidiasis (CMC):
o a heterogeneous group of disorders
o charecterised by:
 oral candidiasis: in 90% of the patients, oral manifestations may involve the tongue, and
white plaque-like lesions are seen in conjunction with fissures
 affection of the skin (typically the nail bed) and other mucosal linings, such as the genital
mucosa
 The face and scalp may be involved, granulomatous masses can be seen at these sites.
o Can occur as part of endocrine disorders, including hyperparathyroidism and Addison’s
disease.
o Impaired phagocytic function by neutrophilic granulocytes and macrophages
Diagnosis and Laboratory Findings:
The presence of candidal microorganisms as a member of the commensal flora complicates the
discrimination of the normal state from infection.
It is imperative that both clinical findings and laboratory data are balanced in order to arrive at a
correct diagnosis. Sometimes antifungal treatment has to be initiated to assist in the diagnostic
process.
1. Smear: from the infected area comprising epithelial cells, creates opportunities for
detection of the yeasts. The material stained with periodic acid–Schiff (PAS). The
detection of yeast organisms in the form of pseudohyphae structures is usually considered a
sign of infection although these structures have also been identified in normal oral mucosa.
2. Culture: To increase the sensitivity, a second scrape can be transferred to a transport
medium followed by cultivation on Sabouraud agar.
3. Imprint culture technique can also be used. This method is a valuable adjunct in the
diagnostic process of erythematous candidiasis and denture stomatitis as these infections
consist of fairly homogeneous erythematous lesions.
4. Salivary culture techniques: are primarily used in parallel with other diagnostic methods to
obtain an adequate quantification of candidal organisms. Patients who display clinical
signs of oral candidiasis usually have more than 400 CFU/mL (colony-forming unit (CFU)
is a unit used to estimate the number of viable bacteria or fungal cells in a sample)

7. 5. In chronic plaque-type and nodular candidiasis, cultivation techniques have to be
supplemented by a histopathologic examination. This examination is primarily performed
to identify the presence of epithelial dysplasia.
Management:
Treatment for fungal infections, which usually include antifungal regimens, will not always be
successful unless the clinician addresses predisposing factors that may cause recurrence.
Prognosis of oral candidiasis is good when predisposing factors associated with the infection are
reduced or eliminated. For example:
 treatment of denture stomatitis involves:
o improved denture hygiene, to remove nutrients, including desquamated epithelial cells,
which may serve as a source of nitrogen, which is essential for the growth of the yeasts and
to disturbs the maturity of a microbial environment established under the denture
o recommendation not to use the denture while sleeping.
o As porosities in the denture can harbor microorganisms, which may not be removed by
physical cleaning, the denture should be stored in antimicrobial solutions during the night.
 In smokers, cessation of the habit may result in disappearance of the infection even without
antifungal treatment.
The most commonly used antifungal drugs belong to the groups of polyenes or azoles.
 Polyenes:
 such as nystatin and amphotericin B
 usually the first choices in treatment of primary oral candidiasis and are both well
tolerated.
 Not absorbed from the gastrointestinal tract
 not associated with development of resistance.
 Action:
o negative effect on the production of ergosterol, which is critical for the yeast’s cell
membrane integrity.
o can also affect the adherence of the fungi.
 Azoles:
Topical treatment with azoles such as miconazole is the treatment of choice for angular cheilitis
as this drug has a biostatic effect on S. aureus in addition to the fungistatic effect. If angular
cheilitis comprises an erythema surrounding the fissure, a mild steroid ointment may be required
to suppress the inflammation. To prevent recurrences, patients have to apply a moisturizing
cream, which may prevent new fissure formation.

8. Systemic azoles may be used for:
 deeply seated primary candidiasis, such as chronic hyperplastic candidiasis, denture
stomatitis, and median rhomboid glossitis with a granular appearance
 therapy-resistant infections, mostly related to compliance failure.
 The azoles are also used in the treatment of secondary oral candidiasis associated with
systemic predisposing factors and for systemic candidiasis.
Patients with primary candidiasis are also at risk if systemic predisposing factors arise. For
example, patients with severe immunosuppression as seen in conjunction with leukemia
and AIDS may encounter disseminating candidiasis with a fatal course.
disadvantages :
 interact with warfarin, leading to an increased bleeding propensity. This adverse effect may
also be present with topical application.
 Development of resistance is particularly compelling for fluconazole in individuals with
HIV disease. In such cases, ketoconazole and itraconazole have been recommended as
alternatives.
Sources:
Burket’s Oral Medicine, 12th edition, Michael Glick.(2015). People’s Medical Publishing
House—USA.p: 93-99
With additions from:
1. Andrews’ diseases of the skin: clinical dermatology, twelfth edition, 2016.pages: 11-17
2. Dermatology essentials, Bolognia, Schaffer, Duncan and Ko. (2014) Elsevier inc . Section
12: infections, infestations, and bites. chapter 64, pages: 613