Clinicodemographic and Mycological Profile of Onychomycosis and Its Associated Factors in a Tertiary Care Hospital in Port Elizabeth, South Africa

1. Introduction

Onychomycosis is an invasive fungal infection of the nail unit involving the nail plate, bed, and matrix, caused by dermatophytes, non-dermatophyte mycelial fungi, and yeasts [1,2,3,4,5]. It is the most common nail disorder in clinical practice worldwide, accounting for 50–60% of nail abnormalities and up to 30% of superficial mycoses [4,6,7]. The overall prevalence based on recently published studies ranges from 13.1% to 80.5% [3,8,9,10,11] with a prevalence of 10% in the adult population [12] and 2.4% in children [13]. Although not life-threatening, onychomycosis acts as a fungal reservoir and is associated with substantial morbidity and psychosocial sequelae, including pain, paresthesia, dysesthesia, nail deformities, cosmetic disfigurement, functional impairment, and reduced quality of life [3,6,14,15]. The risk of cross-transmission [16,17], together with a predisposition to systemic spread, ulceration, and complications such as cellulitis, osteomyelitis, and soft-tissue or bone necrosis [6,18], underscores its public health significance.

The clinical presentation is polymorphous, encompassing distal lateral subungual onychomycosis (DLSO), proximal subungual onychomycosis (PSO), superficial white onychomycosis (SWO), endonyx onychomycosis (EO), and total dystrophic onychomycosis (TDO) [2,5,19], with DLSO representing the most common subtype [20,21,22,23,24,25]. These presentations are characterized by nail discoloration, thickening, dystrophy, and subungual hyperkeratosis [21,22,26,27].

The pathogenic spectrum varies geographically, both across regions and even within the same region. Dermatophytes, particularly Trichophyton rubrum and T. mentagrophytes, remain the predominant global causes of onychomycosis [1,8,9,11,12,17,20,22,27,28,29]. However, non-dermatophyte moulds and yeasts are increasingly reported, especially in African and tropical regions, driven by environmental, climatic, and host-related factors [3,10,23,30,31,32]. This evolving spectrum, alongside demographic and clinical variability, underscores the need for region-specific mycological and epidemiological data. Despite this, available data from South Africa, especially the Eastern Cape, remain limited and are largely confined to specific population groups [33,34]. Moreover, recent systematic reviews of onychomycosis in Africa could not identify any studies from South Africa, highlighting a notable absence of available research [29].

Risk factors include advancing age, systemic conditions such as diabetes and immunosuppression, trauma, and environmental exposure, all of which contribute to susceptibility and persistence [1,5,27,35]. Accurate diagnosis requires laboratory confirmation, as clinical features often mimic other nail disorders. Fungal culture remains the gold standard, supported by potassium hydroxide (KOH) microscopy and histopathological methods such as Periodic Acid–Schiff (PAS) staining [27]. Although advanced techniques such as PCR and molecular assays offer improved sensitivity [2,36], their use is limited in resource-constrained settings, where microscopy and culture remain the main diagnostic options [29]. Management remains challenging due to high recurrence rates, treatment failure, and emerging antifungal resistance despite available options including debridement, systemic, topical, and adjunctive therapies [2,7,19,29,37]. Consequently, early diagnosis and context-specific understanding of epidemiology and causative agents are essential.

However, there remains a substantial gap in comprehensive, up-to-date research on onychomycosis in South Africa, with available data scarce, outdated, or limited to specific populations, highlighting the urgent need for region-specific epidemiological studies. This study, therefore, aims to characterize the epidemiology, clinical features, risk factors, and pathogenic spectrum of onychomycosis in a coastal industrial metropolitan region of South Africa to inform improved management and contribute to ongoing surveillance.

2. Materials and Methods

2.1. Study Design

A retrospective cross-sectional study was conducted using clinical and laboratory data from patients with laboratory-confirmed onychomycosis over a five-year period, from 01 January 2019 to 31 December 2023.

2.2. Data Source

Data were sourced from dermatology clinic registers, hospital medical records, and the National Health Laboratory Services database. Onychomycosis cases were identified based on documented laboratory confirmation. Mycological diagnosis was established using direct microscopy (potassium hydroxide preparation), fungal culture, and histopathological examination with Periodic Acid–Schiff staining of nail specimens, all of which constitute established diagnostic modalities.

2.3. Study Setting

The study was conducted in the Department of Dermatology at Livingstone Hospital, a tertiary referral center located in Gqeberha (formerly Port Elizabeth), Eastern Cape, South Africa. The hospital serves a large urban and peri-urban population and receives referrals from surrounding districts, including OR Tambo. Livingstone Hospital provides comprehensive multidisciplinary care, including specialized dermatological services, and functions as a referral, training, and research institution. Its well-established clinical record systems and integrated laboratory databases make it suitable for retrospective epidemiological studies.

2.4. Study Population

The study population comprised all patients with a clinical diagnosis of onychomycosis recorded during the study period. Cases were identified from the dermatology departmental registers and verified against the NHLS laboratory records. Patients were included if they had laboratory-confirmed onychomycosis based on at least one positive diagnostic modality, namely potassium hydroxide (KOH) microscopy, fungal culture, or Periodic Acid–Schiff (PAS) staining. A total of 112 patients met the initial eligibility criteria. A census sampling approach was employed, including all eligible cases to ensure complete representation of the accessible population and to minimize sampling bias. Patients with a clinical diagnosis of onychomycosis but without mycological confirmation, or with negative results across all diagnostic tests, were excluded. This resulted in a final analytic sample of 103 patients with confirmed onychomycosis.

2.5. Data Collection and Measurements

Data were systematically extracted using a structured, pre-defined data collection tool. Variables collected included demographic characteristics (age and sex), clinical features, comorbidities, occupational and lifestyle factors, and laboratory findings. Laboratory variables comprised KOH microscopy results, fungal culture isolates, and PAS staining outcomes. Onychomycosis was further categorized according to etiological subtypes, namely dermatophytes, non-dermatophyte moulds, and yeasts. Where non-dermatophyte organisms were identified, confirmatory culture results were reviewed, where available, to ensure diagnostic accuracy.

2.6. Statistical Analysis

Data were entered into Microsoft Excel and cross-checked against source records to ensure accuracy and completeness prior to analysis. Statistical analyses were performed using Stata version 15 (StataCorp, College Station, TX). Categorical variables were summarized using frequencies and percentages, while continuous variables were described using medians and interquartile ranges. Associations between categorical variables were assessed using Pearson’s chi-square test or Fisher’s exact test, as appropriate. For continuous variables, the Mann–Whitney U test was applied. To identify independent risk factors associated with different pathogenic types of onychomycoses, binary logistic regression analysis was performed. Statistical significance was set at p < 0.05.

3. Results

3.1. Cross-Analysis of the Different Diagnostic Test Methods and Results

A five-year census of 112 patients with onychomycosis based on clinical diagnosis was initially reviewed. Cross-analysis with potassium hydroxide (KOH) microscopy, fungal culture, and Periodic Acid–Schiff (PAS) staining results are presented in Table 1. Named pathogens were identified by fungal culture in 103 (92.0% CI: 85.8% - 95.9%) and none in nine (9; 9.0% CI: 4.1% - 14.2%). A positive PAS stain was observed in 60 (53.6%) patients, while 25 (22.3%) had fungal hyphae based on KOH microscopy. Among culture-positive cases, 50.5% were PAS-positive, and 21.4% were KOH-positive. Of the PAS-positive cases, 26.7% (16/60) were also KOH-positive.

3.2. Common Pathogens Found in Onychomycosis

Non-dermatophytes were the predominant isolates (57.3%, n = 59), followed by yeasts (36.9%, n = 38) and dermatophytes (8.7%, n = 9). Mixed colonies were identified in five cases, including three cases of non-dermatophyte and yeast co-infection and two cases with dual non-dermatophyte species, giving a total of 108 isolates. Among non-dermatophytes, Alternaria species were most common (16.5%, n = 17), followed by Penicillium (12.6%, n = 13) and Aspergillus (8.7%, n = 9). Yeast isolates included Candida (30.1%, n = 31) and Trichosporon (6.8%, n = 7). The only dermatophyte identified was Trichophyton (8.7%, n = 9) of the rubrum species (Table 2).

3.3. Demographic Characteristics of 103 Patients with Culture-Confirmed Onychomycosis

The demographic profile presented in Table 3 shows a slight female predominance, with 54.4% females and 45.6% males, corresponding to a female-to-male ratio of 1.2:1. The median age was 57 years (interquartile range [IQR]: 42–68; range: 13–89). There was no statistically significant difference in age between sexes (p = 0.676).

3.4. Clinical Risk Factors, Environmental Exposures, and Comorbidities in 103 Patients with Culture-Confirmed Onychomycosis

Almost all participants (95.1%, n = 98) were exposed to at least one clinical (59.2%) and/or environmental (23.3%) risk factor for onychomycosis. Smoking (20.4%) was the predominant environmental exposure. The main clinical risk factors included tinea infections (22.3%), followed by diabetes mellitus (16.5%), HIV infection (14.6%), paronychia (7.8%), and neoplastic conditions (3.9%). Systemic (53.4%), dermatologic (25.2%), and neoplastic (5.8%) comorbidities were also common, particularly hypertension (29.1%) and dermatitis (15.5%) (Table 4).

3.5. Clinical Features of Onychomycosis

The most prominent clinical features of onychomycosis were nail discoloration (98.1%), subungual hyperkeratosis (77.7%), onycholysis (59.2%), and nail dystrophy (52.4%). Toenail involvement (70.9%) was more common than fingernail involvement (43.7%), with the big toe most frequently affected (65.8%). Bilateral involvement of the toes (45.2%) and fingers (48.9%) was common, with a median of three nails affected for both toes and fingers. (Table 5).

A significantly higher proportion of males (83.0% vs 60.7%, p = 0.017) had toenail infections than females (Table 6).

3.6. Factors Associated with Pathogenic Forms of Onychomycosis

Dermatophyte infection was significantly associated with age, with the highest proportion observed among the 15–24 years age group (33.3%, p = 0.035), and with the presence of tinea (21.7% vs 5.0%, p = 0.025). Other factors, including male sex, smoking, HIV infection, clinical risk factors, and environmental exposures, showed higher proportions but were not statistically significant (p > 0.05).

Non-dermatophyte onychomycosis was significantly associated with dermatitis (81.3%, p = 0.035) and toenail involvement (64.4%, p = 0.023). Fingernail involvement was less frequent in non-dermatophyte infections (44.4%, p = 0.020). Higher proportions were observed among younger age groups (1–14 years), females, and those with diabetes, neoplastic conditions, or dermatologic comorbidities, although these were not statistically significant.

Paronychia was strongly associated with yeast onychomycosis, with all affected participants testing positive (100.0%, p < 0.001). A significantly higher proportion of yeast infections involved the fingernails (48.9%, p = 0.026), whereas a lower proportion affected the toenails (28.8%, p = 0.013). Although not statistically significant, higher proportions of yeast infection were observed among participants aged >64 years, males, and those with systemic comorbidities, clinical risk factors, or neoplastic conditions (Table 7). Multivariable analysis did not identify any statistically significant independent predictors associated with the different pathogenic forms of onychomycosis.

4. Discussion

Onychomycosis is a common nail disorder with significant functional and psychological impact [15,26], yet its epidemiology and risk profile in the Eastern Cape Province of South Africa remain underexplored. This study aimed to characterize the demographic profile, identify at-risk clinical groups, and determine causative pathogens to guide targeted interventions, resource allocation, and surveillance, thereby contributing to improved health and well-being.

In the study settings, the diagnosis of onychomycosis is confirmed using a combination of microscopy, histopathology, and culture to improve detection. The use of culture for detection was highest, unlike microscopy common in African settings [29]. The results show that fungal culture yielded the highest detection rate (92%), followed by PAS (53.6%) and KOH (22.3%), consistent with findings from India and Nepal [24,27].

The pathogenic spectrum of onychomycosis shows a marked shift toward non-dermatophyte moulds (57.3%), especially Alternaria, with dermatophytes accounting for only 8.7%. This profile is at odds with the traditionally dominant dermatophytes, particularly Trichophyton species [1,8,9,11,12,17,20,22,27,28,29]. It is also contrary to yeast-predominant patterns reported in Iran [38], Madagascar [39], Senegal [23], a rural community in Spain [31], but aligns with findings from Ethiopia [3], Iran [10], Benin [30], Greece [32], India [40], Egypt [41], and Tunisia [42], showing increasing non-dermatophyte involvement.

The predominance of moulds, including Alternaria, Penicillium, and Aspergillus, may reflect environmental and climatic influences such as humidity and temperature, as well as host factors and antimicrobial exposure, which are known to favour non-dermatophyte infections [6,40]. The high proportion of Candida and Trichosporon species further supports the expanding role of yeasts, particularly in cases associated with paronychia. The low dermatophyte burden supports emerging evidence of an evolving, region-specific spectrum driven by environmental and host determinants, challenging the traditional dermatophyte-dominant model and reinforcing the growing importance of mixed infections [34,43].

Across settings, onychomycosis predominantly affects adults, with age distribution shifting by context. In this study, the median age of 57 years reflects older adult predominance, consistent with findings from India and Iran [24,38] and higher-income or clinical populations in the UK, USA, Turkey, Malaysia, and Thailand [44,45,46,47,48], supporting the view that advancing age is a key determinant. This aligns with the reported peak around the fifth decade, attributed to cumulative trauma, reduced nail growth, and impaired circulation [42,49]. However, studies from Eastern Nepal [27], Ethiopia [3], Egypt [41], and broader African settings [29] report higher prevalence among younger adults, highlighting the role of occupational and environmental exposure. These findings suggest that while onychomycosis is age-progressive, exposure drives infection earlier, whereas biological vulnerability dominates later life.

Gender distribution also varies and reflects exposure rather than biology. In this South African setting, a slight female predominance (54.5%) aligns with reports from Poland, Iran, Madagascar, Ethiopia, Indonesia, and Egypt, often linked to moisture exposure and health-seeking behavior [3,12,38,39,41,44,50,51], but contrasts with male dominance in Northern Odisha, Nepal, Turkey, the USA, UK, Thailand, and another South African study [24,27,34,45,47,48,52], often attributed to trauma and occlusive footwear [40]. The observed dominance, minimal or inconsistent gender patterns, reinforce that gender differences are context-dependent, shaped by exposure, behavior, and healthcare utilization rather than inherent susceptibility.

Environmental and behavioral factors are important but context-dependent. In this study, exposures were reported in only 23.3% of participants, with smoking (20.4%) predominating, contrasting with moisture- and trauma-driven patterns emphasizing water exposure, hygiene, and footwear [24,29,47]. This discrepancy likely reflects the inherent under-reporting in retrospective designs. Clinical risk factors were common (59.2%), with tinea co-infections, diabetes, and HIV predominating, consistent with global evidence linking immunosuppression and metabolic disease to increased susceptibility [24,29,43,44,52]. The high burden of tinea (25.7%) reinforces the role of fungal reservoirs in sustaining infection cycles. Comorbidity was universal in this cohort, with systemic conditions most prevalent, followed by dermatologic and neoplastic conditions. The predominance of systemic comorbidity aligns with the comorbidity profile among patients with onychomycosis in the USA [52]. These findings suggest that onychomycosis reflects an interplay between systemic vulnerability and local fungal reservoirs, with the latter playing a more prominent role in this setting.

Clinical features of onychomycosis are largely consistent globally, characterized by nail discoloration, subungual hyperkeratosis, onycholysis, dystrophy, and brittleness [27,47,53]. In this study, these findings were highly prevalent, particularly discoloration (98.1%), hyperkeratosis (77.7%), and onycholysis (59.2%). Toenail involvement was predominant (70.9%), consistent with findings from China [20], India [40], Iran [38], in Malaysia [46], in Tunisia [42], in Poland [12], reflecting the typical distal subungual pattern widely reported [20,24]. This predominance is supported by evidence linking infection to slower nail growth, reduced circulation, and repeated trauma [40]. The significantly higher prevalence of toenail involvement among males may further reflect greater exposure to environmental and mechanical risk factors, particularly given that most male participants were older than 45 years. However, variability exists, with some studies reporting greater fingernail involvement [9,21,41,51]. Concurrent involvement of both fingernail and toenail (13.5%) has also been documented in the literature [40,46]. In terms of anatomical distribution, infections were most observed in the big toe and thumb, which aligns with findings from other settings [40].

Dermatophyte infection was significantly associated with younger age (15–24 years), contrasting with global evidence that emphasizes older age [8,24,45,47], and higher odds of non-dermatophyte in older age [49] suggesting exposure may be more important in this setting. The strong association with coexisting tinea confirms the role of fungal reservoirs [27,44]. Dermatitis and paronychia were key local drivers, linking non-dermatophyte and yeast organisms to skin barrier disruption and periungual inflammation [3,6,29]. The differential distribution of pathogens, with non-dermatophytes predominating in toenails and yeasts in fingernails, may provide valuable insight into the pathophysiological mechanisms underlying onychomycosis. In contrast, systemic factors such as HIV, diabetes, sex, and smoking were not significant, suggesting local conditions may outweigh systemic risk in this cohort.

Strengths and Limitations

This study enhances understanding of onychomycosis by identifying key risk factors, comorbidities, and causative pathogens, and is the first to provide such comprehensive data from this region. The use of a single operator for data collection improved consistency and reliability, while laboratory-confirmed diagnoses minimized misclassification and strengthened the validity of findings. These results provide valuable baseline data for future research.

However, despite including a census of eligible cases, the study period (2019–2023) overlapped with the COVID-19 pandemic, which may have affected healthcare access, case detection, and data completeness. In addition, the retrospective design, incomplete records, and inability to capture key clinical data, such as symptom duration, behavioral exposures, and racial data, may introduce bias and limit generalisability. The single-center setting, together with the lack of treatment and outcome data, further restricts the broader applicability of the findings.

5. Conclusions

This mycologically confirmed study of onychomycosis shows a shift in the pathogenic spectrum, with non-dermatophyte moulds predominating. Onychomycosis rarely occurs in isolation; most cases are associated with tinea, dermatitis, and hypertension. The condition mainly affected older adults with a slight female predominance, presenting with nail discoloration, hyperkeratosis, onycholysis, and dystrophy, predominantly involving the toenails. Dermatophyte infections were associated with younger age and tinea, while dermatitis and paronychia were associated with non-dermatophyte and yeast infections. These findings highlight a multifactorial disease influenced by evolving pathogens, host factors, and environmental exposures, underscoring the need for context-specific diagnosis and management.