Prevalence of fungal colonization among patients with psoriasis in difficult-to-treat areas: impact of apremilast on mycotic burden and clinical outcomes

Abstract

Introduction: Fungi, including Candida, may be a trigger or exacerbate psoriasis, especially in difficult to treat (DTT) areas, through the activation of IL-17/23 axis.

Methods: In this study, seventy patients with DDT psoriasis were enrolled to evaluate Candida species and/or other opportunistic fungi colonization rate at baseline (T0) and the impact of apremilast on fungal load, clinical outcome, serum cytokine levels and biochemical serum profile of patients after 16, 24 and 52 weeks of treatment.

Results: In our population, 33 (47%) patients were colonized by Candida spp. at baseline. In 24 (34%) individuals Candida was detected in the oral cavity while in the remaining 9 (13%) individuals the fungus was isolated from stool samples. Twenty subjects were colonized by only the species C. albicans, whereas in the remaining 13 a combination of two or more species (C. albicans plus non-albicans strains) was found in the oral cavity. Moreover, 27 (39%) patients were affected by onychomycosis. At 52 weeks, apremilast treatment induced a full recovery from Candida colonization in 83% of patients colonized with a single species of Candida (C. albicans); while in those co-infected by two or more Candida spp. induced a significant reduction (colony counts >10 CFU/mL) in fungal load was observed in comparison to baseline. Among patients with onychomycosis, 78% (21/27) of them presented a complete clinical resolution of nail psoriasis and concomitant nail infections. Finally, improvements in clinical scores i.e., PASI, NAPSI, DLQI, itch VAS, PAIN VAS, scPGA and sPGA-G and biochemical serum profile, as well as a significant decrease in serum IL-17A, TGF-β 1 and IL-10 levels (from 8.51 to 4.16 pg/mL; from 66.10 to 48.70 ng/mL and from 20.05 to 14 pg/mL, respectively) were observed in all patients.

Conclusions: Fungi may play a role in the psoriasis pathogenesis. Apremilast has been shown to ameliorate psoriasis signs and symptoms and counteract fungal overgrowth, probably by dampening inflammation, triggered by the fungal infections themselves. Thus, apremilast may represent an effective therapeutic approach in the treatment of DTT psoriasis and modulate the fungal colonization.

Keywords: Candida species; IL-17; apremilast; cytokines; difficult-to-treat psoriasis areas; fungal infections.

Figure 1

Microscopic examination of positive fungal cultures from nail clipping of psoriasis patients shows the presence of (A) Aspergillus spp. (B) Microsporum canis (C) Alternaria alternata and (D) Trichophyton mentagrophytes complex. Scale bar 50 µm.

Figure 2

(A) Number of patients with positive culture for Candida species at baseline (T0) and 52 weeks of treatment. (B) CFU counts of Candida albicans and (C) non-albicans species at baseline (T0) and at all-time points considered. The graph shows the mean ± SD. *p<0.05 (One-way ANOVA).

Figure 3

(A) Severe 10-nail and nail fold psoriasis before apremilast treatment. (B) Improvement in nail psoriasis after 52 weeks of treatment. Complete remission of psoriasis and concomitant onychomycosis.

Figure 4

PASI, NAPSI, DLQI, ITCH VAS, ScPGA and sPGA-G scores variation during treatment. The graph shows the mean ± 95% CI. ****p<0.001 (Repeated measures ANOVA).

Figure 5

Clinical evaluation at T0 and after 52 weeks of treatment. (A–C) Clinical examination revealed inverse psoriasis in the context of metabolic syndrome, (B–D) resolved after 52 weeks of treatment.

Figure 6

Plasma glucose level value over study period. At week 52, glucose levels decreased from 103.10 to 93.30 mg/dL. In parallel, total cholesterol decreased, from 191.70 to 180.90 mg/dL without diet modification in the population. Ns, not significant; repeated measures ANOVA. Error bars represent 95% CI. CI, Confidence interval.

Figure 7

Serum cytokine levels at different time points of the study. The graph shows the mean ± 95% CI. *p<0.05, **p<0.01, ****p<0.0001 (one-way ANOVA).