Content » Vol 93, Issue 3

Letter to the Editor

Does Anti-Tumour Necrosis Factor-Alpha Increase Oral Candida Colonization? A Case-control Study in Psoriatic Patients

Monica Corazza1, Stefania Zauli1, Michela Ricci1, Alessandro Borghi1, Rita Rossi2 and Anna Virgili1

1Department of Clinical and Experimental Medicine, Section of Dermatology, University of Ferrara, Via Savonarola 9, IT-44100 Ferrara, and 2Section of Microbiology, Arcispedale S. Anna, Ferrara, Italy. E-mail:

Accepted June 25, 2012.

Infliximab, etanercept and adalimumab are biologic agents used in psoriasis treatment that suppress the activity of tumour necrosis factor (TNF)-α, and are associated with a potential increased risk of infection (1). Invasive fungal infections and, rarely, superficial mycoses have been reported (2–7).

Candida spp., a yeast commonly present at low concentration in the oral cavity, can cause disease in immunocompromised hosts (8).

The aim of this study was to determine whether anti-TNF-α drugs, used in psoriatic patients, can affect oral colonization by Candida.


A total of 30 patients affected by psoriasis vulgaris, attending our Psoriasis Unit were consecutively included in the study, after obtaining informed consent.

Male and female patients were enrolled with the following inclusion criteria: >18 years, regardless of the severity of psoriasis, in treatment with anti-TNF-α drugs (group A), or in treat­ment with non-immunosuppressive drugs (group B). Patients in group B had to have interrupted prior immuno­suppressive systemic therapies at least 6 months earlier. Exclusion criteria were: < 18 years of age, pregnant or breastfeeding, in treatment with cyclosporine or methotrexate, immunosuppressed for other reasons, or have forms of psoriasis other than psoriasis vulgaris.

Lifelong history of psoriasis and eventual diagnosis of diabetes mellitus (DM) were collected from hospital clinical records.

All the patients completed a questionnaire concerning oral hygiene habits (time devoted to daily oral hygiene, use of mouth­washes and dental floss) and smoking status (how long they had been smoking and number of cigarettes/day). They underwent clinical examination of the oral cavity to assess oral hygiene and denture wearing. Oral hygiene was globally assessed as good or poor by the same physicians (MC, AV) based on the presence of gingivitis (swelling, bleeding, redness), caries, dental plaque and epulis. All patients underwent oral swab cultured in Sabouraud dextrose broth (BioMèrieux). Candida was researched through observation with phase-contrast microscope. If blastospores were present, identification of Candida species was performed.

Statistical analysis was carried out for all study data using the Fisher’s exact test and Student’s t-test.


Demographic and clinical features and data regarding psoriasis treatments, oral cavity hygiene and habits of the patients enrolled in both the study groups are summarized in Table I.

Table I. Demographic and clinical features and oral swab culture results of study patients

Group A (n = 13)

Group B (n = 17)


4 F (30.8%)

9 M (69.2%)

10 F (58.8%)

7 M (41.2%)

Age, years, mean (SD)

58.2 (45–73)

63.9 (47–89)

Duration of psoriasis, years, mean (SD)

18.4 (6–30)

28.4 (1–50)

Treatment, n

8 etanercept

4 adalimumab

1 infliximab

11 acitretin

6 topicals only

Duration of treatment, months, mean (SD)

9.9 (1–36)

12.5 (1–27)

Diabetes mellitus, n (%)

6 (46.2)

5 (29.4)

Time devoted to daily oral hygiene, min, mean (SD)

8.5 (3–15)

8.9 (1–15)

Use of mouthwash, n (%)

7 (53.9)

10 (58.8)

Use of floss, n (%)

1 (7.7)

4 (23.5)

Oral hygiene, n (%)

10 good (76.9)

3 poor (23.1)

13 good (76.5)

4 poor (23.5)

Use of dentures, n (%)

7 (53.9)

8 (47.1)

Smokers, n (%)

13 (23.1)

6 (35.3)

Number of cigarettes/day

21.7 (15–30)

12 (15–30)

How long they had been smoking, years, median (range)

30 (15–40)

40 (6–60)

Positive Candida oral swab, n (%)

8 (61.5)

7 (41.2)

SD: standard deviation.

The results of oral swab for Candida in group A revealed viable strains in 8 patients (61.5%): 2 had poor oral hygiene, 3 were affected by DM, and 3 were smokers. C. albicans was detected in 7 patients (87.5%), C. glabrata was found in one patient, while C. parapsilosis was present in one case, concomitant with C. albicans.

Regarding ongoing therapies in patients with positive swabs, 5 patients were in treatment with etanercept, 2 with adalimumab and 1 with infliximab. The mean duration of treatment with anti-TNF-α drugs was 8.4 months (range 1–28) among patients with a positive swab and 12.4 months (range 3–36) among patients with negative results. No significant difference in treatment duration was found in patients with positive swabs with respect to patients with negative swabs (p = 0.54). Only 2 patients (25%) with positive oral swabs showed clinical signs of oral candidiasis: pseudomembranous in one case and erythematous in the other. Both were in treatment with etanercept.

In group B Candida-positive swab was found in 7 patients (41.2%): one had poor oral hygiene, 2 were affected by DM, and 3 were smokers. C. albicans was found in 6 patients (85.7%), C. doubliniensis in one patient, while C. krusei was concomitant with C. albicans in only one case.

Only 2 patients (28.6%) with a positive oral swab showed clinical signs of erythematous oral candidiasis. Three patients were in treatment with acitretin (42.9%) and 4 with derivatives of vitamin D (57.1%).

No significant difference was found in the rate of positive swabs between the 2 groups (p = 0.23). The detection of positive oral swab did not correlate with DM (p = 0.41 in group A; p = 0.69 in group B), with the use of dentures (p = 0.25 in group A; p = 0.12 in group B) or with smoking (p = 0.20 in group A; p = 0.63 in group B) in either group.

Considering all the enrolled patients, a significant correlation was found between positive oral swabs and the use of dentures (p = 0.03), but not with DM (p = 0.50) or smoking (p = 0.21).


It could be hypothesized that patients receiving anti-TNF-α therapy are more susceptible to fungal infections, as their immune system may not be able to recognize fungal antigens through toll-like receptor signalling, and in particular through toll-like receptor 4 by host cells (e.g. dendritic cells and macrophages) (3). Moreover, blockage of TNF-α could inhibit the production of interferon-γ, leading to a defective activation of phagocytosis and killing of intracellular pathogens (3).

TNF-α inhibition could be associated with increased apoptosis of peripheral blood monocytes (3). TNF-α can also affect other mediators involved in C. albicans infection, such as E-selectin, vascular cell adhesion molecule 1, and IL-8, which act mainly by recruiting leukocytes at the site of fungal infection (3).

In the literature only 4 cases of oral candidiasis have been reported in patients in treatment with infliximab (5–7), which exert a pronounced effect in T-cell-mediated immunity and almost completely neutralize TNF-α activity (3).

In this study 30 patients, 13 in treatment with anti-TNF-α drugs (group A) and 17 in non-immunosuppressive treatment (group B), underwent oral swabs for testing for Candida.

In group A we found a more frequent colonization by Candida (61.5%) compared with the rate reported in healthy individuals (17.7–60%) (8, 9) and with the rate observed in group B (41.2%). But the difference between groups A and B was not significant (p = 0.23). The restricted number of patients and the presence of only one patient in treatment with infliximab does not allow us to draw definitive conclusions. Further studies on a larger number of patients would provide more data about the implication of anti-TNF-α drugs in the development of oral candidiasis and possible differences between etanercept, adalimumab and infliximab.

Considering other well-known predisposing factors for oral candidiasis in the enrolled population, such as DM, wearing dentures and smoking (9–11), a significant correlation was found only with the use of dentures.

In accordance with literature data, C. albicans was the species most represented in subjects with positive oral swab and a small proportion of patients with positive oral swab had clinical manifestations of oral candidiasis.


The authors would like to thank Silvia Giari for statistical analysis.

The authors declare no conflicts of interest.


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