Onychomycosis And Diabetic Foot Syndrome
Overview
This systematic review aimed to investigate the prevalence of onychomycosis in individuals with diabetes and explore its connection to risk factors, particularly within the context of diabetic foot syndrome. Adhering to the PRISMA guidelines and utilizing the STROBE method, the study searched PubMed and Scopus databases in October 2022 for relevant clinical and observational studies. The review incorporated ten studies, encompassing 5664 diabetes patients, to analyze the prevalence and implications of onychomycosis in individuals with diabetes, as well as its diagnosis and treatment.
The findings revealed that 29.18% of diabetes patients exhibited onychomycosis, primarily attributed to Trichophyton rubrum. Notably, a significant correlation was identified between onychomycosis and diabetic neuropathy (p = .012) and elevated glycosylated hemoglobin levels (p = .039), but no substantial link was established between onychomycosis and ulceration (p = .185). The majority of the studies presented grade 4 evidence with a grade C recommendation, while one study exhibited grade 1b evidence with a grade A recommendation.
The review underscores the current lack of uniform and comprehensive data regarding the association of risk factors and ulceration in diabetic foot patients with the development of onychomycosis. It highlights the necessity to introduce diagnostic testing for onychomycosis beyond solely relying on clinical diagnosis. Additionally, the review calls for further prospective, randomized, and comparative studies to enhance the overall quality of research in this domain.
Introduction
Diabetes is characterized by persistent elevated blood glucose levels, which, if not managed, can lead to complications like retinopathy, nephropathy, and diabetic neuropathy (DN). With a global impact affecting 422 million people, particularly in low-income countries, diabetes carries the risk of various issues including diabetic foot ulcers (DFUs), which bring about increased morbidity, disability, healthcare costs, and mortality. The term “diabetic foot” refers to tissue infection, ulcers, or destruction in individuals with prior diabetes diagnoses, often tied to neuropathy and peripheral arterial disease in the lower limbs.
The diabetic population is prone to various complications, especially neuropathy and peripheral vascular disease, making them susceptible to DFUs. These ulcers occur in 12%–25% of people with diabetes, preceding a significant portion of non-traumatic amputations. Unmanaged diabetic foot problems can lead to partial lower limb amputations. Hyperglycemia, neuropathy, and arterial disease also compromise the immune system, increasing the likelihood of fungal and bacterial skin infections, including fungal nail infections.
Among these complications, onychomycosis stands out. Affecting around 4% of the global population, it accounts for a substantial portion of nail infections, particularly affecting toenails. This fungal infection is marked by nail thickening, discoloration, hyperkeratosis, and detachment. Risk factors for onychomycosis include age, gender, genetics, footwear choices, peripheral arterial disease, and immunodeficiency. Given its prevalence and its impact on physical, psychological, and aesthetic aspects, onychomycosis is a significant health concern.
Dermatophytes and other microorganisms are responsible for onychomycosis, manifesting in various clinical forms like distal and lateral subungual onychomycosis (DLSO) and total dystrophic onychomycosis. Diagnosis requires identifying the causative microorganism’s identity, often through techniques like microbiological culture, polymerase chain reaction (PCR), direct microscopy (e.g., potassium hydroxide [KOH]), and histology.
Treatment options include topical, oral, and external therapies, sometimes requiring combinations based on the specific situation. Although systematic reviews exist for onychomycosis in at-risk patients and children, there’s currently a gap in systematic reviews addressing its prevalence, diagnosis, treatment, and associated risk factors in diabetic foot patients. Therefore, the objective of this study was to provide a comprehensive systematic review of onychomycosis in diabetic patients, examining its prevalence, diagnosis, treatment, and connections to risk factors in those with diabetic foot syndrome.
Method
The systematic review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist, and the included studies were assessed using the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist. The review was registered in PROSPERO with a designated identification code. The search was conducted in October 2022 using PubMed (Medline) and Scopus databases, employing keywords like ‘onychomycosis’ and ‘diabetic foot’ with the operator ‘AND’. Studies published in English, Spanish, French, and German were considered.
The selection process involved reviewing titles and abstracts to eliminate irrelevant studies, followed by a thorough assessment of full texts to ensure adherence to inclusion criteria and exclusion criteria. This evaluation process was executed by two independent reviewers, resolving disagreements with a third reviewer if necessary. Extracted data, including author names, publication year, study design, participant count, diabetes type, onychomycosis prevalence, diagnostic methods, etiological agent, and more, were recorded using a custom Microsoft Excel spreadsheet.
The STROBE guidelines were employed to assess the quality and completeness of observational studies, providing a structured framework for transparent reporting. The STROBE checklist comprises 22 items that encompass various aspects of study presentation, ranging from title and abstract to funding and sponsorship. Each study was independently evaluated by two raters, with a third rater aiding in achieving consensus if discrepancies arose.
To classify the type of study, the Oxford Centre for Evidence-Based Medicine (OCEBM) levels of evidence and grades of recommendation were used. Additionally, the Science Citation Index Expanded (SCIE) quartile and impact level of the publishing journals were noted. Statistical analyses were conducted using SPSS software to assess the prevalence of onychomycosis among different types of diabetes and patient demographics.
The primary focus of this systematic review was to ascertain the prevalence of onychomycosis in diabetes patients, explore its association with diabetic foot ulcers (DFUs), identify relevant factors, and analyze the diagnostic methods employed. This review’s meticulous methodology ensures comprehensive evaluation and reliable findings.
Inclusion Criteria
The eligibility criteria encompassed various study types, including clinical studies, clinical trials, comparative studies, observational studies, and both randomized and controlled clinical trials. These studies were focused on investigating the prevalence and outcomes of onychomycosis in individuals with diabetes, examining diagnoses and treatments. The participants considered for inclusion were of any gender and age. The studies could either feature a control group or not, and they could be either retrospective or prospective in design. The language of publication was restricted to English, French, German, or Spanish, and the timeframe for inclusion covered the past two decades. This comprehensive set of criteria aimed to encompass a range of research approaches and provide insights into onychomycosis within the context of diabetes.
Exclusion Criteria
Studies were excluded based on specific criteria, which included excluding animal studies, pre-clinical or in vitro investigations, and studies lacking sufficient data for meaningful analysis. Additionally, references cited in systematic reviews were scrutinized to identify potential supplementary articles for consideration. By implementing these exclusion criteria, the review aimed to focus on human-centered studies with relevant and substantial data, while also ensuring the overall quality and relevance of the selected articles.
Result
During the systematic review, an initial search yielded a total of 251 articles. After reviewing titles and abstracts, 161 articles were excluded, and a subsequent full-text assessment led to the exclusion of an additional 80 articles due to not meeting the defined selection criteria. Eventually, 10 studies were included in the systematic review. These studies were conducted between 2006 and 2021, enrolling a total of 5664 patients with diabetes. Among these patients, the majority had type 2 diabetes mellitus, followed by type 1 diabetes mellitus. The prevalence of onychomycosis in patients with diabetes was found to be 29.18% after excluding studies that focused on treatment. Various diagnostic tests were used, with the KOH test, conventional culture, and Sabouraud culture being the most common. Trichophyton rubrum was the most frequently identified pathogen. Diabetic neuropathy and elevated glycosylated hemoglobin values were associated with onychomycosis, while no significant link was found between onychomycosis and ulceration. The studies’ completion of certain items in the analysis, such as bias, study size, quantitative variables, and main results, varied in quality. The review underscores the need for more comprehensive and standardized reporting in future research in this domain.
Conclusion
This systematic review stands as the first of its kind to specifically explore the link between onychomycosis and diabetic foot conditions. In contrast to previous indications suggesting a connection between onychomycosis and an increased risk of ulceration in patients with diabetic foot disease, this review found insufficient scientific evidence to substantiate this association. Interestingly, the factors most significantly associated with onychomycosis development were diabetic neuropathy and elevated glycosylated hemoglobin values. Additionally, poor hygiene and reduced perspiration at the plantar foot were identified as contributing to onychomycosis infection. The calculated prevalence of onychomycosis, drawn from eight of the included studies, was approximately 29.18%, aligning closely with the one-third estimate within the diabetes population. However, clinical diagnosis, without supplementary testing for culture, can introduce bias. Only a subset of studies employed diagnostic tests, often failing to identify the causal microorganism. While dermatophyte fungi are typically responsible, the most reliable diagnostic method is PCR. Challenges in diagnosis and clinical inaccuracies may contribute to underestimation. Peripheral vascular disease displayed an association with onychomycosis, while findings regarding diabetic neuropathy yielded conflicting results. The review’s limitations encompassed variable study quality, design, diagnostic methods, and language bias. Future research should encompass control groups, randomized treatments, and valid complementary tests like PCR. In conclusion, the current literature’s inadequacies and inconsistencies regarding risk factors, ulceration, and onychomycosis in diabetic foot patients necessitate further prospective, randomized, and comparative studies to enhance understanding and clinical management.
Additionally, the systematic review acknowledges several limitations that need to be considered. The overall quality of the studies examined in this review was often lacking, contributing to the variability and heterogeneity observed in study designs, diagnostic methodologies, and analyzed variables. This heterogeneity prevented the pooling of data, thereby limiting comprehensive comparisons across most studies. The exclusion of articles not published in English, Spanish, French, or German could introduce language bias and exclude valuable insights from other regions.
To enhance the credibility and comprehensiveness of future investigations, it is recommended that forthcoming studies address these limitations. For instance, studies should incorporate well-defined control groups consisting of patients without diabetes, allowing for meaningful comparisons. If treatments are implemented, a rigorous randomization method should be employed, and adequate sample size calculations should be performed for each treatment arm. Additionally, reporting of outcomes should encompass the total number of patients with cured onychomycosis, detailing treatment sessions, disease duration, follow-up periods, as well as assessment of key risk factors such as diabetic neuropathy, peripheral vascular disease, and long-term glycosylated hemoglobin values. Also, descriptions of nail condition characteristics and disease severity can provide a more comprehensive picture of the patient population.
Furthermore, a pressing need exists for studies evaluating the efficacy and efficiency of antifungal treatments specifically in patients with diabetes, in comparison to patients without diabetes. Validating the diagnosis of onychomycosis through reliable complementary tests, such as PCR, can enhance diagnostic accuracy, thereby providing more accurate prevalence estimates.
In conclusion, the findings of this systematic review underscore the insufficiencies and discrepancies in the current literature regarding the complex relationship between risk factors, ulceration, and onychomycosis in individuals with diabetic foot conditions. The call for more robust prospective, randomized, and comparative studies is resounding. By addressing these gaps in research, healthcare professionals can gain a deeper understanding of the intricate interactions between onychomycosis and diabetic foot syndrome, leading to improved clinical management and patient outcomes.
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