Mucosal Candidiasis Clinical Presentation
- 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...
White patches on the surface of the oral mucosa, tongue, or other parts of the body characterize thrush. Lesions develop into confluent plaques that resemble milk curds and can be wiped off to reveal a raw erythematous and sometimes bleeding base. Note the image below.
Erythematous areas found generally on the dorsum of the tongue, palate, or buccal mucosa are characteristic. Lesions on the dorsum of the tongue present as depapillated areas. Red areas often are seen on the palate of individuals with HIV infection. An associated angular stomatitis may be present. Note the image below.
Chronic hyperplastic candidosis (candidal leukoplakia) 
A chronic, discrete, raised lesion that may vary from a small, palpable, translucent, or whitish area to a large, dense, opaque plaque that is hard and rough to the touch (plaquelike lesion) is observed. Homogeneous or speckled areas, which do not rub off (nodular lesions), can be seen. Speckled leukoplakia accounts for 3-50% of candidal leukoplakias. Candidal leukoplakias usually occur on the inside surface of one or both cheeks; they occur less commonly on the tongue.
Chronic multifocal oral candidosis
In a minority of individuals, chronic candidal infection may be seen in multiple oral sites with various combinations including (1) angular stomatitis, which is unilateral or bilateral and is encountered mostly in denture wearers; (2) retrocommissural leukoplakia, which is the most constant component of the tetrad; (3) median rhomboid glossitis; and (4) palatal lesions.
Additional criteria include (1) lesions of more than 1-month duration; (2) absence of predisposing medical conditions; (3) exclusion of individuals undergoing radiotherapy or administration of the following types of drugs: anti-inflammatory, immunosuppressive, cytotoxic, or psychotropic agents or antibiotics.
This type is most common in male tobacco smokers in their fifth or sixth decade. Antifungal therapy clears the infection and produces clinical improvement; however, recurrence is common, unless smoking can be reduced.
Denture-related stomatitis (denture-induced stomatitis, denture sore mouth, chronic atrophic candidosis) 
Chronic erythema and edema of the mucosa that contacts the fitting surface of the denture are characteristic. The mucosa below the lower denture rarely is involved. Occasional slight soreness is experienced; however, the patient typically is asymptomatic. The typical presenting complaint is angular stomatitis. Note the image below.
Denture-related stomatitis is classified into three clinical types as follows:
Localized simple inflammation or a pinpoint hyperemia
Erythematous or generalized simple type presenting as more diffuse erythema involving a part of, or the entire, denture-covered mucosa
Granular type (inflammatory papillary hyperplasia) commonly involving the central part of the hard palate and the alveolar ridge
Angular stomatitis (perlèche, angular cheilitis)
Lesions affect the angles of the mouth; soreness, erythema, and fissuring are characteristic; diagnosis commonly is associated with denture-related stomatitis. Both yeasts (candidal) and bacteria (especially Staphylococcus aureus) may be involved. Note the image below.
Angular stomatitis commonly is an isolated initial sign of anemia or vitamin deficiency, such as vitamin B-12, and resolves when the underlying disease has been treated. Iron deficiency anemia and other vitamin deficiencies have been cited as other predisposing factors.
In conditions such as Down syndrome or orofacial granulomatosis/Crohn disease, as many as 20% of individuals have angular stomatitis, although candidal species often are not isolated. Angular stomatitis also may be seen in individuals with HIV infection or diabetes.
Median rhomboid glossitis (glossal central papillary atrophy)
Papillary atrophy, which is symmetric and elliptic or rhomboidal in shape, is located centrally at the midline of the tongue, anterior to the circumvallate papillae. Occasionally, median rhomboid glossitis presents with a hyperplastic exophytic or lobulated appearance.
Histopathologically, candidal hyphae infiltrate the superficial layers of the parakeratotic epithelium, and a polymorphonuclear leukocyte infiltrate occupies the epithelium, with elongated hyperplastic rete ridges and a lymphocyte infiltration in the corium. However, the condition frequently shows a mixed bacterial-fungal microflora, as has been documented.
Exfoliative cheilitis may occasionally be associated with Candida species, especially in individuals with HIV infection.
The diagnosis usually is made based on physical examination. Gram stain of a smear (hyphae) or oral rinse may aid in the diagnosis. Differentiate pseudomembranous candidosis from lichen planus. Hairy leukoplakia, leukoplakia, or Fordyce spots occasionally cause confusion. Differentiate erythematous candidosis from other inflammatory stomatitides, lichen planus, and erythroplakia.
Members of the genus Candida are the causal organisms of candidosis. Secretion of antimicrobial proteins and peptides is decreased in saliva of patients with oral candidosis. The following factors affect candidal carriage and infection:
Carriage is more frequent in females than in males; carriage is frequent during the summer months.
Increased carriage rates are seen in immunocompromised states (eg, HIV infection), blood group O, and nonsecreting of blood group antigens in the saliva possibly mediated by an effect on C albicans adhesion to epithelia.
Carriage of yeast is higher in acidic saliva.
Hyposalivation increases the carriage of C albicans.
Use of psychotropic drugs that cause hyposalivation increases carriage of candidal organisms and S aureus.
Candidal counts increase during sleep but are reduced by eating a meal and by brushing the teeth. Counts usually are highest first thing in the morning; the organism frequently cannot be isolated when counts are low, except in the early morning. Early morning saliva sample is the most dependable for making a comparison of the candidal population in individuals.
Denture-wearing habits affect candidal growth. C albicans counts consistently are low in early morning saliva specimens from edentulous patients not wearing dentures. This is attributed to sleeping without dentures and the consequent alteration in the oral environment. When dentures are worn at night, the early morning saliva candidal count is high; when dentures are not worn at night, the early morning count is the lowest. Increased candidal count following reinsertion of the dentures suggests that plaque on the dentures harbors C albicans. Increase in both the frequency of carriage and the density of candidal colonization in denture wearers compared with dentate individuals suggests that prostheses encourage the presence and growth of candidal species.
Smoking affects candidal infection. Some studies have reported that smoking significantly increased carriage from 30-70%. Smoking increased the risk in persons with HIV infection. Smoking commonly underlies multifocal candidosis and median rhomboid glossitis.
Tetracycline therapy affects candidal growth. Candida species can be isolated from the oral cavity with greater prevalence and in greater numbers during tetracycline therapy.
Disruption of the ecologic balance disruption can affect growth patterns. Under normal circumstances, it appears unlikely that candidal organisms establish in the mouths of noncarriers; however, if the ecologic balance is altered (by bacterial suppression, alteration of salivary flow, or immunologic deficit), candidal infection may occur.
Similarities between carriers and noncarriers of C albicans with respect to age, caries experience, periodontal status, and intraoral temperature indicate that these factors do not influence candidal carriage significantly.
Factors predisposing individuals to oral candidal infections are as follows:
Broad-spectrum antimicrobial therapy may predispose individuals to stomatitis or glossitis caused by C albicans.
Topical, systemic, and aerosolized corticosteroid use or other immunosuppressive agents may result in oral yeast infection.
Smoking predisposes individuals to chronic atrophic candidosis and other forms of candidosis.
Drugs with hyposalivation adverse effects (eg, psychopharmaceuticals) are associated with oral candidosis. Hyposalivation (as in Sjögren syndrome and after graft-versus-host disease, radiotherapy or chemotherapy) predisposes individuals to candidosis.
Immunologic disorders may play a role. Candidosis is common in patients with HIV infection and other secondary immunodeficiencies, including blood dyscrasias, diabetes, and malignant disease.
CMC can be a feature of primary immune defects such as severe combined immune deficiency syndrome.
Diabetes may predispose individuals to candidosis.
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].