Candidiasis

Oral Candidiasis also referred to as oral thrush is commonly encountered in a daily life of a dentist. An overview on this topic for undergraduate students.

1. CANDIDIASIS

2. CONTENTS INTRODUCTION CLASSIFICATION PREDISPOSING FACTORS PATHOGENESIS PRIMARY ORAL CANDIDIASIS SECONDARY ORAL CANDIDIASIS LABORATORY DIAGNOSIS TREATMENT REFERENCES

3. INTRODUCTION It was first described by the French paediatrician Francois Valleix in 1838. Candidiasis is one of the most common fungal infections affecting human beings. It occurs mainly as a secondary infection in patients with some underlying immunosuppression and the primary form of disease is rare. It affects the skin, mucous membranes, nails gastrointestinal tract, vaginal tract, urinary tract and internal organs. Oral involvement is the most common manifestation of human candida infection.

4. CAUSATIVE ORGANISMS It is mainly caused by yeast-like fungus Candida albicans . Other candida species which cause candidiasis are :- Candida tropicalis , Candida stellatoidea , Candida parapsillasis , Candida pseudotropicalis , Candida rugosa, Candida krusei , Candida glabrata, Candida guilliermondi , Candida dubliniensis and Candida viswanathii . It is present in three forms : yeast form, hyphal form and chlamydospore form. It reproduces by asexual budding and form pseudo hyphae. These species grow rapidly at 25º - 37º c. It is relatively a common inhabitant of the oral cavity, gastrointestinal tract and vagina of clinically normal persons.

5. CLASSIFICATION

6. FIRST CLASSIFICATION ACUTE CHRONIC Acute pseudomembranous candidiasis (thrush) Acute atrophic candidiasis 2) CHRONIC MUCOCUTANEOUS CANDIDIASIS Familial CMC Localized CMC Diffuse CMC Candidiasis endocrinopathy syndrome CHRONIC Chronic atrophic candidiasis Denture stomatitis Median rhomboid glossitis Angular cheilitis b) Id reaction c) Chronic hyperplastic candidiasis 3) EXTRAORAL CANDIDIASIS Oral candidiasis associated with extraoral lesions, orofacial and intertriginous sites ( candida vulvovaginitis, intertriginous candidiasis. Gastrointestinal candidiasis Candida hypersensitivity syndrome 4) SYSTEMIC CANDIDIASIS

7. SECOND CLASSIFICATION Classification of oral candidiasis [ as proposed by Samaranayake (1991) and modified by Axéll et al (1997)] PRIMARY ORAL CANDIDIASIS ACUTE FORMS CHRONIC FORMS CANDIDA – ASSOCIATED LESIONS KERATINIZED PRIMARY LESIONS SUPERINFECTED WITH CANDIDA PSEUDOMEMBRANOUS HYPERPLASTIC DENTURE STOMATITIS LEUKOPLAKIA ERYTHEMATOUS NODULAR ANGULAR CHELITIS LICHEN PLANUS PLAQUE – LIKE MEDIAN RHOMBOID GLOSSITIS LUPUS ERYTHEMATOUS ERYTHEMATOUS PSEUDOMEMBRANOUS

8. SECONDARY ORAL CANDIDIASIS FAMILIAL CHRONIC MUCOCUTANEOUS CANDIDIASIS DIFFUSE CHRONIC MUCOCUTANEOUS CANDIDIASIS CANDIDIASIS ENDOCRINOPATHY SYNDROME FAMILIAL MUCOCUTANEOUS CANDIDIASIS SEVERE COMBINED IMMUNODEFICIENCY DiGEORGE SYNDROME CHRONIC GRANULOMATOUS DISEASE ACQUIRED IMMUNE DEFICIENCY SYNDROME (AIDS)

9. THIRD CLASSIFICATION ORAL MUCOSA CHRONIC ORAL CANDIDIASIS GASTROINTESTINAL MUCOSA ACUTE ORAL CANDIDIASIS CHRONIC ATROPHIC CANDIDIASIS PHARYNGEAL CANDIDIASIS ACUTE PSEUDOMEMBRANOUS CANDIDIASIS CHRONIC HYPERPLASTIC CANDIDIASIS ESOPHAGEAL CANDIDIASIS ACUTE ATROPHIC CANDIDIASIS INTESTINAL CANDIDIASIS 1) CANDIDIASIS CONFINED TO THE MUCOSAE

10. CONFINED TO MUCOCUTANEOUS SURFACES - IN CONDITIONS WITH MAJOR IMMUNOLOGIC DEFECT IN CONDITIONS WITH MINOR IMMUNOLOGIC DEFECT - CHRONIC MUCOCUTANEOUS CANDIDIASIS (CMC) SYNDROMES CONFINED TO MUCOCUTANEOUS JUNCTIONS SWISS – TYPE AGAMMAGLOBULINEMIA FAMILIAL MUCOCUTANEOUS CANDIDIASIS CANDIDAL ANGULAR CHELITIS HEREDITARY THYMIC DYSPLASIA CANDIDIASIS ENDOCRINOPATHY SYNDROME PERIANAL CANDIDIASIS DI GEORGE SYNDROME LOCALIZED CHRONIC MUCOCUTANEOUS CANDIDIASIS AIDS CHRONIC MUCOCUTANEOUS CANDIDIASIS ASSOCIATED WITH THYMOMA 2) MUCOCUTANEOUS CANDIDIASIS

11. 3) CANDIDIASIS CONFINED TO SKIN 4) CANDIDIASIS OF NAILS AND SKIN 5) RESPIRATORY MUCOSA 6) GENITOURINARY MUCOSA 7) SYSTEMIC CANDIDIASIS INTERDIGITAL CANDIDIASIS CANDIDAL ONYCHIA BRONCHIAL CANDIDIASIS CANDIDAL VULVOVAGINITIS CANDIDAL ENDOCARDITIS INTERTRIGINOUS CANDIDIASIS CANDIDAL PARONYCHIA CANDIDAL SEPTICEMIA CANDIDIDS (MONOLIDS) CANDIDAL MENINGITIS

12. CANDIDA THE SILENT EPIDEMIC

13. PREDISPOSING FACTORS LOCAL GENERAL Denture wearing Immunosuppressive diseases Smoking Impaired health status Inhalation steroids Immunosuppressive drugs Topical steroids Chemotherapy Hyperkeratosis Endocrine disorders Imbalance of oral microbial flora Hematinic deficiencies Quality and quantity of saliva

14. PREDISPOSING FACTORS 1) CHANGES IN ORAL MICROBIAL FLORA Administration of antibiotics (broad-spectrum), excessive use of antibacterial mouth rinses, xerostomia secondary to anticholinergic agent or salivary gland disease. 2) LOCAL IRRITANTS Chronic local irritant ( denture, orthodontic appliance and heavy smoke). 3) DRUG THERAPY Administration of corticosteroids, cytotoxic drugs, immunosuppressive agents and radiation to head and neck.

15. 4) ACUTE AND CHRONIC DISEASE Acute and chronic diseases such as leukaemia, lymphoma, diabetes mellitus and tuberculosis. 5) MALNUTRITION STATES Malnutrition states such as low serum vitamin A, pyridoxine and iron levels. 6) AGE Infancy, pregnancy and old age, prolonged hospitalization and debilitating diseases. 7) ENDOCRINOPATHY Endocrinopathies such as hypoparathyroidism, hypothyroidism and Addison’s disease.

16. 8) IMMUNODEFICIENCY STATES Primary and acquired immunodeficiency states such as AIDS and hypogammaglobinemia 9) OTHERS Tight and close – fitting garments encourage the growth of candida. Use of intravenous tubes, catheters, heart valves and poorly maintained dentures and heavy smoking.

17. PATHOGENESIS Candida albicans causes thrush when normal host immunity or normal host flora is disrupted, hence it is called ‘opportunistic infection’.

18. PRIMARY ORAL CANDIDIASIS PSEUDOMEMBRANOUS CANDIDIASIS It is a prototype of oral infection caused by yeast – like fungus. It is also known as ‘thrush’ and is one of the most common forms of candidiasis.

19. CLINICAL FEATURES : IN INFANTS SYMPTOMS They are painless and noticed on careful examination. They may be removed with little difficulty .

20. CLINICAL FEATURES : IN ADULTS

21. DIAGNOSIS AND DIFFERENTIAL DIAGNOSIS DIAGNOSIS Clinical Diagnosis : Pseudomembranous lesion which can be scrapped off will diagnose candidiasis. DIFFERENTIAL DIAGNOSIS Plaque form of Lichen planus Leukoplakia Geno dermatoses Gangrenous stomatitis Chemical burns

22. ACUTE ATROPHIC CANDIDIASIS Synonyms : Erythematous candidiasis, Antibiotic sore mouth It is also called ‘antibiotic sore mouth’ and it includes central papillary atrophy of tongue and cheilo candidiasis. CAUSE : It may arise in acute pseudomembranous candidiasis after the white plaques are shed. It occurs as a sequelae to a course of broad-spectrum antibiotics, corticosteroids or any immunosuppressive diseases, more commonly HIV infection.

23. CLINICAL FEATURES :

24. DIAGNOSIS AND DIFFERENTIAL DIAGNOSIS DIAGNOSIS Clinical diagnosis : Erythematous area with condition causing diminished host resistance will diagnose acute atrophic candidiasis. DIFFERENTIAL DIAGNOSIS Chemical burn Drug reaction Syphilitic mucus patches Necrotic ulcer and gangrenous stomatitis Traumatic ulcer

25. CHRONIC HYPERPLASTIC CANDIDIASIS Synonyms : Candidal leukoplakia , Chronic- plaque type, Nodular candidiasis It is also called ‘ candida leukoplakia ’ because of its presentation as firm and adherent white patches occurring in the oral mucosa which appear similar to leukoplakia . It is the least common form of candidiasis. Causon and Binnie have presented data based on their finding that chronic candidiasis itself is a cause of leukoplakia and thus must be regarded as having a possible premalignant potential.

26. CLINICAL FEATURES :

27. DIAGNOSIS AND DIFFERENTIAL DIAGNOSIS DIAGNOSIS A firm white leathery appearance which cannot be rubbed off DIFFERENTIAL DIAGNOSIS Hairy Leukoplakia Lichen Planus Superficial bacterial infection

28. CANDIDA – ASSOCIATED LESIONS DENTURE STOMATITS MEDIAN RHOMBOID GLOSSITIS ANGULAR CHEILITIS

29. DENTURE STOMATITIS (CHRONIC ATROPHIC CANDIDIASIS) Denture stomatitis is now considered synonymous with the condition better known as denture sore mouth, a diffuse erythema and oedema of the denture-bearing area. TYPES : TYPE I – Localized to minor erythematous sites caused by trauma from denture TYPE II – Affects major part of denture covering mucosa TYPE III – Granular mucosa in the central part of the palate

30. CLINICAL FEATURES :

31. DIAGNOSIS AND DIFFERENTIAL DIAGNOSIS DIAGNOSIS Clinical Diagnosis : An erythematous area under the complete denture. DIFFERENTIAL DIAGNOSIS Allergic reaction due to denture base Erosive lichen planus Dermatitis herpetiformis

32. MEDIAN RHOMBOID GLOSSITIS It is also called ‘central papillary atrophy of tongue’. The area of erythema results from the atrophy of filiform papilla. It is a benign lesion of the tongue, characterized by rhomboid or oval in shape, changes occur in the tongue mucosa in the midline, just anterior to the foramen cecum. Candida albicans is many times found in this lesion. This type of lesion is called as posterior midline atrophy candidiasis.

33. ANGULAR CHEILITIS It is also called as ‘Perleche’, ‘Angular Cheilosis’, ‘Cheilocandidiasis’. Causes mainly include Candida albicans , Staphylococci, Streptococci and other factors. Mainly seen in old edentulous patients with denture non – bearer. It presents as a rough triangular area of erythema and oedema at one or more; commonly both the corners of the mouth. Chronic atrophic candidiasis occur with angular cheilitis.

34. SECONDARY ORAL CANDIDIASIS

35. CHRONIC MUCOCUTANEOUS CANDIDIASIS Chronic mucocutaneous candidiasis is a group of different forms of the infection, dome of which may have multiple features in common although they can usually be separated as entities. It is characterized by chronic candida involvement of the skin, scalp, nails and mucous membranes. It is caused by defect in the cellular immunity impaired cell-mediated immunity. Isolated IgA deficiency and reduced serum candidacidal activity. Other factors responsible are diabetes, steroid therapy and in some cases of pregnancy.

36. TYPES Chronic familial mucocutaneous candidiasis Chronic mucocutaneous candidiasis in association with thymoma Chronic localized mucocutaneous candidiasis Endocrinopathy candidiasis syndrome Chronic diffuse mucocutaneous candidiasis

37. ID REACTION It is a hypersensitivity reaction to candida antigen, which manifests as vesicular and papular rash on the skin of patients with chronic candidiasis. A person with chronic candida infection may develop secondarily response characterized by localized or generalized sterile vesicopapular rash that is believed to be an allergic response to candida antigen (also called monolids).

38. LABORATORY DIAGNOSIS The candida organism can be seen microscopically in either an exfoliative cytologic preparator or tissue sections. Fragments of the plaque material may be smeared on a microscopic slide, macerated with 20% potassium hydroxide (KOH) and examined for typical hyphae. Organisms can be cultured in a variety of media including blood agar, cornmeal agar and sabouraud’s broth. Histologic sections of a biopsy from a lesion of oral candidiasis can show the presence of the yeast cells and hyphae or mycelia.

39. CANDIDA ISOLATION IN THE CLINIC AND QUANTIFICATION FROM ORAL SAMPLES METHOD MAIN STEPS ADVANTAGES DISADVANTAGES Smear Scrapping, smearing directly onto slide Simple and quick Low Sensitivity Swab Taken by rubbing cotton-tipped swabs over lesional tissue Relatively simple Selecting sampling sites critical Imprint culture Sterile plastic, foam pads dipped into Sabouraud (Sab) broth, placed on lesion for 60 s; pad pressed on Sab agar plate and incubated; colony – counter used Sensitive and reliable; can discriminate between infected and carrier states Reading above 50 CFU/cm² can be inaccurate; selection of sites difficult if no clinical signs present

40. METHOD MAIN STEPS ADVANTAGES DISADVANTAGES Impression culture Maxillary and mandibular alginate impressions; casting in agar fortified with Sab broth; incubation Useful to determine relative distributions of the yeasts on oral surfaces Useful mostly as a research tool Salivary culture Patient expectorates 2 mL saliva into sterile container; vibration; culture on Sab agar by spiral plating; counting As useful as imprint culture Considerable chairside time; not useful for xerostomics ; cannot identify site of infection Oral rinse Subject rinses for 60 s with PBS at pH 7.2, 0.1 M, and returns it to the original container; concentrated by centrifugation; cultured and counted as previous methods Comparable in sensitivity with imprint method; better results if CFU >50/cm²; simple method Recommended for surveillance cultures in the absence of focal lesions; cannot identify site of infection

41. TREATMENT OF ORAL CANDIDIASIS Oral Candidiasis may be treated either topically or systematically. Treatment should be maintained for 7 days. To identify and eliminate predisposing or precipitating factors; Replacement of the denture and thorough cleaning regularly should be done. Withdrawal or change of antibiotics can be done if feasible.

42. TOPICAL TREATMENT CLOTRIMAZOLE (Primary drug of choice) NYSTATIN Oral Suspension – 5 mL 3 -4 times daily for 2 weeks Oral Suspension- 400,000 – 600,000 units 4 – 5 times daily (swish and swallow) for 7 – 21 days Troche – 10 mg. Slowly dissolve in mouth, apply 5 times daily to affected area bid for 7 days Cream and Ointment – 100,000 U/g. Apply to affected area 4-5 times/day. Powder – 50 million U. Sprinkle on tissue contact area of denture Cream – 1% cream, 2-3 times daily for 3-4 weeks Nystatin tablets ( 1 tablet, 100,000 units, dissolved in mouth 3 times a day). Oral pastille (200,000 unit) 5 times a day

43. TOPICAL TREATMENT AMPHOTERICIN B MICONAZOLE AND KETOCONAZOLE MYCOSTATIN Oral suspension – 100 mg/ mL 3 -4 times after food for 2 weeks Cream – 2% Miconazole/ Ketoconazole gently into the affected area 1-2 times daily. Cream – 100,000 unit or lactose containing tablet kept under the tongue. Troche – 10 mg; slowly dissolve in mouth; apply 3 – 4 times daily to affected area for 2 weeks. Used as a rinse for 7-10 days; 3-4 times a day.

44. SYSTEMIC THERAPY Tab. Ketoconazole – 200 – 400 mg/day as single dose for 7 -14 days. Cap. Fluconazole – 200 mg on day 1 then 100 mg daily for 7 – 14 days ( 1 st drug of choice) Cap. Itraconazole – 100 mg tablets once daily (if not responding to Fluconazole) Cap. Posaconazole – 400 mg bid for 7 – 14 days (if not responding to Itraconazole)

45. REFERENCES Burket’s Oral Medicine (12 th Edition) – Michael Glick Shafer’s textbook of Oral Pathology (8 th Edition) Textbook of Oral Medicine (3 rd Edition) – Anil Govindrao Ghom Textbook of Oral Medicine and Oral Radiology – Peeyush Shivhare