**5. Clinical presentation in immunocompetent and immunocompromised patients**

Most CO cases involve fingernails compared to toenails, with an estimated prevalence of up to 50% of onychomycosis cases in fingernails. Women at risk of developing CO are typically wet workers due to the recurrent moist in the hands, exposure to trauma, regular contact with washing liquids, and contamination to vaginal flora during cleansing, which ultimately provides a suitable niche for the development of Candida species [2].

Clinical presentations that are predictive for CO are nail plate dystrophy and off-white discoloration, commonly followed by pigmentation. Melanisation, one of the virulence factors for Candida, suggests an indication of progressive resistance to antifungal treatment. Classification of CO is established because of the complex etiopathogenesis and diverse clinical presentations. The first clinical classification of CO was suggested based on the clinical presentation, the affected location, and the infection route, which are Candida paronychia, Candida granuloma, and Candida onycholysis [2].

The most frequent type of CO is paronychia. Humidity plays an essential role in the development of Candida paronychia. Clinical manifestation of Candida paronychia comprises erythema and swelling in the nail folds followed by gradual dystrophy in the nail plate accompanied by paronychia and Beau lines, which is depicted by an oblique dent in the nail plate suggesting parasite infestation on the nail matrix. The most severe type of CO is granuloma, which is frequently observed in patients with chronic mucocutaneous candidosis. Clinical

manifestation of Candida granuloma displays brittle nails and a deformity resembling drumstick which is also referred to as pseudoclubbing. The last type of CO is onycholysis. Clinical manifestation of Candida onycholysis is characterized by subungual distal hyperkeratosis, which further develops into a group of keratosis separating the nail plate from the bed. Moreover, a recent classification was proposed, including four clinical groups of CO, which are chronic paronychia with secondary nail dystrophy, distal onychomycosis, chronic mucocutaneous candidosis, and secondary candidosis [17].

Chronic paronychia initially emerges from the proximal nail fold, although lateral nail folds are occasionally affected in the beginning. Swelling of the periungual skin and a noticeable gap between the fold and nail plate is observed, followed by the nail plate involvement. Marks with a white, green, or black color can be detected at the lateral and distal parts, respectively. The longitudinal ridges and opaqueness appear on the nail that develops into a brittle and easily detached nail. Pressure and movement on the nail can be painful in contrast to dermatophyte infections. A superimposed infection caused by bacteria into the subcuticular space usually occurs, leading to a vicious cycle. Chronic paronychia usually appears in adults whose occupations regularly contact water and children because of the thumb sucking habit [17].

Distal candida nail infection manifests as subungual hyperkeratosis along with onycholysis. Differentiating the clinical manifestation with dermatophytosis can be challenging, however the candida results in less extent damage to the nail compared to dermatophyte. In addition, the predilection of CO usually affects the fingernails, while most dermatophytes invade the toenails. The prevalence of distal candida nail infection is infrequent and most of the cases are related to vascular problems, such as Raynaud's phenomenon [17].

Total dystrophic onychomycosis occurs in patients with chronic mucocutaneous candidosis. The organism invasion on the nail plate results in hyperkeratotic and gross thickening of the nail. Chronic mucocutaneous candidosis has multifaceted etiology which results in the weakened cell-mediated immunity. The variety of clinical appearance depends on the severity of immunosuppression; however, thickening of the nails can be observed in advanced cases due to the Candida granuloma. In addition, the involvement of the mucous membrane is nearly presented in most cases [17].

Secondary candida onychomycosis results because of other diseases involving the nail apparatus, most commonly psoriasis [17].

### **6. Diagnostic tests**

Common tests utilized in the diagnosis of onychomycosis are potassium hydroxide (KOH) preparation, fungal culture, histopathology, polymerase chain reaction (PCR), and flow cytometry (**Table 4**). The combination tests are usually performed; however, the gold standard of diagnostic tests are microscopy and culture [3].

Onychoscopy can also be used for initial diagnosis of onychomycosis. The most common findings in onychomycosis are jagged edge with spikes of the proximal part of the onycholysis, parallel bands of various color resembling aurora borealis pattern, and ruin appearance at the subungual part [3].

KOH microscopy and fungal culture are presently the gold standards to establish the diagnosis of onychomycosis. However, it remains questionable because KOH microscopy demonstrates a false-negative rate between 5% to 15% and falsepositive for evaluating the medication, given that KOH microscopy visualizes both

#### *Candida Onychomycosis: Mini Review DOI: http://dx.doi.org/10.5772/intechopen.96650*


#### **Table 4.**

*Diagnostic tests for onychomycosis [3].*

live and dead hyphae which are identical through microscope. Furthermore, fungal culture has a wide-ranging sensitivity from 30% to 57% and requires incubation for weeks. Latest studies comparing a variety of diagnostic tests indicate that histopathology staining has higher sensitivity than KOH microscopy or culture, although another study suggests PCR for a quicker and precise alternative for fungal culture, particularly in NDM onychomycosis. Therefore, the combination of diagnostic tests is recommended to diagnosis onychomycosis accurately. A feasible option can be a KOH microscopy and PCR (or culture in a resource-limited setting) if the KOH shows positive results [3].

In the case of CO, obtaining sample for KOH microscopy and culture can be performed from the proximal and lateral parts of the nail. Nevertheless, sample can be obtained from the distal part in the case of onycholysis. Culture result may reveal creamy-whitish colonies on Sabouraud dextrose agar media or primary isolation can also be attained using chromogenic media, for instance CHROMagar Candida®. Anti-fungal susceptibility should be performed following the identification of the isolated strains to achieve the most effective therapy. Histopathological results of

CO usually display hyphae and pseudomycelia on the nail through Schiff's periodic acid stains or Grocott's methenamine silver stains. PCR can also be utilized for further identification [2].
