Mucosal Candidiasis Workup
- Author: Crispian Scully, MD, MRCS, PhD, MDS, CBE, FDSRCS(Eng), FDSRCPS, FFDRCSI, FDSRCSE, FRCPath, FMedSci, FHEA, FUCL, FSB, DSc, DChD, DMed(HC), Dr(HC); Chief Editor: William D James, MD more...
Quantitative saliva culture is useful in the diagnosis of oral candidosis. Carriers and patients with oral candidal infection can be distinguished reliably (95% confidence limits) on the basis of quantitative culture, since they harbor more than 400 colony-forming units of candidal organisms per mL of saliva. Ask the patient to rinse his or her mouth for 60 seconds with 10 mL of sterile phosphate-buffered saline (PBS; pH 7.2) or sterile water; then, return the oral rinse to the universal container. If the patient wears a denture, remove it prior to sampling. A rapid commercial system (Microstix-Candida or Oricult-N test) for diagnosing oral candidosis is useful for screening patients in the clinical setting, particularly when microbiology laboratories are not in easy access.
Because Candida species stain poorly by hematoxylin and eosin, staining with periodic acid-Schiff (PAS), Gridley stain, or Gomori methenamine silver (GMS) stain is used. In both Gridley stain and the PAS procedure, fungi appear pinkish red. GMS technique stains yeast cell walls brown-black as a result of deposition of reduced silver. Presence of blastospores and characteristic pseudohyphae or hyphae in the superficial epithelial tissues identifies the fungus as a species of Candida. GMS staining alone cannot perform the speciation of the organism; therefore, cultural or nucleic acid studies also should be used. Polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) are available.
Blastospores similar to those in Candida species may be seen in histoplasmosis or cryptococcosis, both of which are increasingly prevalent and may manifest orally with increasing frequency in the AIDS epidemic. If only blastospores of candidal organisms are seen in tissue sections of patients in whom infection is suspected, serial sections should be searched carefully for pseudohyphae or hyphae.
As tests of humoral immunity, the candida agglutinin test, candida complement-fixation test, candida precipitin test, immunofluorescence, and enzyme-linked immunoassay (ELISA) have been used. Immunity in superficial candidosis and in oral candidosis is predominantly cell mediated. Cell-mediated immunity to C albicans antigens can be demonstrated in most human subjects both by the appearance of delayed skin hypersensitivity to antigens and by in vitro tests of cellular immunity, such as inhibition of leukocyte migration or stimulation of lymphocyte transformation to candidal antigens.
In the serologic tests, four principal types of Candida antigens have been used, including (1) whole nonviable yeast cells, (2) candidal culture filtrates, (3) cell wall polysaccharides or glycoproteins, and (4) cytoplasmic antigens from mechanically disrupted yeast cells. Serologic tests for candidal organisms are not diagnostic tools, since the diagnosis can be achieved more readily by clinical evaluation and by smear or culture.
With regard to hematologic testing, because oral candidosis frequently is associated with HIV disease, nutritional deficiencies, diabetes, or blood dyscrasias, estimates of corrected whole blood folate, vitamin B-12, serum ferritin, glucose, hemoglobin, lymphocyte, and WBC counts can be important. Tests, such as lymphocyte function, serum immunoglobulins, calcium status, or parathyroid hormone levels, are unnecessary except in chronic mucocutaneous candidosis (CMC). Tests of thyroid or adrenocortical function are warranted in selected individuals, since endocrine disorders may be associated with oral candidosis. HIV testing may be indicated.
Although swabs and smears are essential for a microbiological diagnosis of a number of types of oral candidosis, when candidal leukoplakia (chronic hyperplastic candidosis) is suspected, a biopsy specimen should be taken.
Stoopler ET, Sollecito TP. Oral mucosal diseases: evaluation and management. Med Clin North Am. 2014 Nov. 98 (6):1323-52. [Medline].
Boriollo MF, Bassi RC, dos Santos Nascimento CM, Feliciano LM, Francisco SB, Barros LM. Distribution and hydrolytic enzyme characteristics of Candida albicans strains isolated from diabetic patients and their non-diabetic consorts. Oral Microbiol Immunol. 2009 Dec. 24(6):437-50. [Medline].
Olczak-Kowalczyk D, Daszkiewicz M, Krasuska-Slawinska, Dembowska-Baginska B, Gozdowski D, Daszkiewicz P, et al. Bacteria and Candida yeasts in inflammations of the oral mucosa in children with secondary immunodeficiency. J Oral Pathol Med. 2012 Aug. 41(7):568-76. [Medline].
Meighani G, Aghamohammadi A, Javanbakht H, Abolhassani H, Nikayin S, Jafari SM, et al. Oral and dental health status in patients with primary antibody deficiencies. Iran J Allergy Asthma Immunol. 2011 Dec. 10(4):289-93. [Medline].
Alnuaimi AD, Wiesenfeld D, O'Brien-Simpson NM, Reynolds EC, McCullough MJ. Oral Candida colonization in oral cancer patients and its relationship with traditional risk factors of oral cancer: a matched case-control study. Oral Oncol. 2015 Feb. 51 (2):139-45. [Medline].
Lafleur MD, Qi Q, Lewis K. Patients with long-term oral carriage harbor high-persister mutants of Candida albicans. Antimicrob Agents Chemother. 2010 Jan. 54(1):39-44. [Medline].
Conti HR, Peterson AC, Brane L, Huppler AR, Hernández-Santos N, Whibley N, et al. Oral-resident natural Th17 cells and γδ T cells control opportunistic Candida albicans infections. J Exp Med. 2014 Sep 22. 211 (10):2075-84. [Medline].
Rane HS, Hardison S, Botelho C, Bernardo SM, Wormley F Jr, Lee SA. Candida albicans VPS4 contributes differentially to epithelial and mucosal pathogenesis. Virulence. 2014. 5 (8):810-8. [Medline].
Break TJ, Jaeger M, Solis NV, Filler SG, Rodriguez CA, Lim JK, et al. CX3CR1 is dispensable for control of mucosal Candida albicans infections in mice and humans. Infect Immun. 2015 Mar. 83 (3):958-65. [Medline].
Redding SW, Dahiya MC, Kirkpatrick WR, et al. Candida glabrata is an emerging cause of oropharyngeal candidiasis in patients receiving radiation for head and neck cancer. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2004 Jan. 97(1):47-52. [Medline].
Junqueira JC. Models hosts for the study of oral candidiasis. Adv Exp Med Biol. 2012. 710:95-105. [Medline].
Tinoco-Araujo JE, Araujo DF, Barbosa PG, Santos PS, Medeiros AM. Invasive candidiasis and oral manifestations in premature newborns. Einstein (Sao Paulo). 2013 Jan-Mar. 11(1):71-5. [Medline].
Shephard MK, Schifter M, Palme CE. Multiple oral squamous cell carcinomas associated with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy. Oral Surg Oral Med Oral Pathol Oral Radiol. 2012 Dec. 114(6):e36-42. [Medline].
Sitheeque MA, Samaranayake LP. Chronic hyperplastic candidosis/candidiasis (candidal leukoplakia). Crit Rev Oral Biol Med. 2003. 14(4):253-67. [Medline].
Golecka M, Oldakowska-Jedynak U, Mierzwinska-Nastalska E, Adamczyk-Sosinska E. Candida-associated denture stomatitis in patients after immunosuppression therapy. Transplant Proc. 2006 Jan-Feb. 38(1):155-6. [Medline].
Tanida T, Okamoto T, Okamoto A, et al. Decreased excretion of antimicrobial proteins and peptides in saliva of patients with oral candidiasis. J Oral Pathol Med. 2003 Nov. 32(10):586-94. [Medline].
Moris DV, Melhem MS, Martins MA, Souza LR, Kacew S, Szeszs MW, et al. Prevalence and antifungal susceptibility of Candida parapsilosis complex isolates collected from oral cavities of HIV-infected individuals. J Med Microbiol. 2012 Dec. 61:1758-65. [Medline].
Niimi M, Firth NA, Cannon RD. Antifungal drug resistance of oral fungi. Odontology. Feb 2010. 98(1):15-25.
Karbach J, Ebenezer S, Warnke PH, Behrens E, Al-Nawas B. Antimicrobial effect of Australian antibacterial essential oils as alternative to common antiseptic solutions against clinically relevant oral pathogens. Clin Lab. 2015. 61 (1-2):61-8. [Medline].
Pappas PG, Kauffman CA, Andes DR, Clancy CJ, Marr KA, Ostrosky-Zeichner L, et al. Executive Summary: Clinical Practice Guideline for the Management of Candidiasis: 2016 Update by the Infectious Diseases Society of America. Clin Infect Dis. 2016 Feb 15. 62 (4):409-17. [Medline].
Kraft-Bodi E, Jørgensen MR, Keller MK, Kragelund C, Twetman S. Effect of Probiotic Bacteria on Oral Candida in Frail Elderly. J Dent Res. 2015 Sep. 94 (9 Suppl):181S-6S. [Medline].
Scardina GA, Ruggieri A, Messina P. Chronic hyperplastic candidosis: a pilot study of the efficacy of 0.18% isotretinoin. J Oral Sci. 2009 Sep. 51(3):407-10. [Medline].
Scully C, el-Kabir M, Samaranayake LP. Candida and oral candidosis: a review. Crit Rev Oral Biol Med. 1994. 5(2):125-57. [Medline].