Fungal Infection: Diagnosis and Management (2003)

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May appear on the superficial nail plate or emerge from under the nail fold; may be deep penetration of the superficial infection. Previously known as superficial white onychomycosis, but some organisms produce black debris. Complete destruction of the nail from long-standing infection; nail thickens, and nail structure is lost. Can result from any of the other classes, although it is most often from severe distal and lateral subungual onychomycosis. NOTE : Candidal onychomycosis was previously considered a class of onychomycosis.

This condition, which more commonly involves the fingernails, has recently been excluded as a separate type because it was inconsistent to base a class on the organism alone. Information from reference 5. Accurate diagnosis is crucial for successful treatment and requires identification of physical changes and positive laboratory analysis.

Psoriasis, chronic nail trauma, and other causes must also be considered. The differential diagnosis of onychomycosis is presented in Table 2 , 7 and an algorithm outlining a suggested diagnostic approach is shown in Figure 6. Chronic inflammation of the proximal paronychium; cross-striations of the nail; Streptococcus, Staphylococcus , or Candida found on smear and culture; common in children. Localized in nail folds and subungual tissue; longitudinal depressed grooves in the nail plate. Subungual dermatitis, hyperkeratosis, Beau lines, and pitting; thickened nail with corrugated surface.

Dystrophy of all 20 nails; usually resolves in childhood; associated with the lesions of lichen planus eFigure C. Oncholysis, ingrown toenails, subungual keratosis, nail plate discoloration and irregularities; caused by friction against the shoe. Horizontal parallel nail plate grooves, inflammation from Staphylococcus aureus or Pseudomonas infection eFigure D. Squamous cell carcinoma; bleeding, pain, nail deformity, and nail discoloration.

Oval or spherical, white or yellow nodule; causes tunnel-like melanonychia; fibrous dermatofibroma or periungual fibroma. Brown-yellow nail with dark pigment extending into the periungual skin folds; poor prognosis. Information from reference 7. Nail pitting in a patient with psoriasis. The pits are enhanced by the presence of grease. Twenty-nail dystrophy also called sandpaper nails is characterized by longitudinal ridges on all 20 nails. The nails may become discolored. Median nail dystrophy caused by repetitive trauma to the nail from habitual rubbing.

Algorithm for the diagnosis and treatment of onychomycosis. Laboratory analysis involves evaluation of nail clippings and subungual debris from the involved portion of the nail. Clippings should be obtained with a sterile nail clipper or curette, and subungual debris using a No. To improve accuracy, eight to 10 nail shards should be collected. In those with suspected superficial onychomycosis, the superficial aspect of the nail is scraped.

The KOH will dissolve keratin, leaving the fungal cell intact. Identification of hyphae, pseudohyphae, or spores confirms infection but does not identify the organism. To identify the organism, culture can be performed in a laboratory. Histologic evaluation can also be helpful for identification of the organism, and it can provide results within 24 hours.

Periodic acid—Schiff PAS staining and methenamine silver stains are used. In a review of cases in which treatment was initiated before specimens were obtained, PAS staining had the highest sensitivity, and culture had the least. Polymerase chain reaction testing has been shown to be more accurate than culture, and results can be available in three days. However, it is not yet widely available. Onychomycosis is widely believed to be only a cosmetic problem, but it can be uncomfortable and can lead to cellulitis in older adults 17 and foot ulcers in patients with diabetes. Treatment varies depending on the severity of nail changes, the organism involved, and concerns about adverse effects and drug interactions.

Treatments also have varying effectiveness, based on cure parameters that are defined differently among studies. Mycotic cure denotes that no organism is identified on microscopy and culture. It is a subjective measure that is difficult to compare across studies. Antifungals from the azole and allylamine classes are the most widely used oral medications for the treatment of onychomycosis. The azole class includes itraconazole Sporanox , fluconazole Diflucan , and ketoconazole; however, ketoconazole is rarely prescribed because of drug interactions and hepatotoxicity.

The allylamine class is represented by terbinafine Lamisil. These medications and their dosing regimens are shown in Table 3. Periungual erythema, erythema of the proximal nail fold, burning sensation, nail shape changes, ingrown toenails, nail discoloration. Indicated for use in immunocompetent patients with mild to moderate onychomycosis without lunular involvement; patients should not bathe for eight hours after applying nail lacquer; lacquer should be removed once per week, and as much of the damaged nail as possible should be removed using scissors, nail clippers, or a nail file. Not FDA approved for treatment of onychomycosis in children or adults; prescribing guidelines recommend periodic monitoring of liver function, renal function, and potassium levels; use with caution in breastfeeding women and in patients with hepatic or renal disease or porphyria.

Pulse dosing: mg orally two times per day for one week per month, for two months fingernails or three months toenails Continuous dosing: mg orally once per day for six weeks fingernails or 12 weeks toenails. Candida species, dermatophytes, nondermatophyte molds, Aspergillus species. Nausea, vomiting, hypokalemia, elevated transaminase and triglyceride levels, rash. Benzodiazepines, calcium channel blockers, proton pump inhibitors, statins, warfarin Coumadin , zolpidem Ambien. Liver function should be monitored in patients with preexisting hepatic dysfunction, and in all patients being treated for longer than one month; serum drug levels should be monitored because of erratic bioavailability with capsule formulation; renal function should be monitored; use with caution in breastfeeding women and in patients with hepatic or renal disease or porphyria; contraindicated in patients with ventricular dysfunction or congestive heart failure.

Antiarrhythmic agents, beta blockers, selective serotonin reuptake inhibitors, tricyclic antidepressants, warfarin. Liver transaminase levels should be checked before therapy is started; if treatment continues beyond six weeks, complete blood count and liver function testing should be performed; use with caution in breastfeeding women and in patients with hepatic or renal disease, psoriasis, or porphyria.

Information from references 21 through Common adverse effects included headache, gastrointestinal problems, and rash; these drugs also have been associated with Stevens-Johnson syndrome, prolonged QT interval, and ventricular dysfunction. The use of these agents is discouraged in patients with liver, renal, or heart disease, and in those receiving medications with which there may be significant drug-drug interactions.

Several topical agents are used for the treatment of onychomycosis. These agents have few contraindications and no drug-drug interactions. It is a synthetic hydroxypyridine antifungal formulated as a nail lacquer.

What you need to know about fungal infections

Adverse effects include burning, itching, and stinging at the application site. Ciclopirox has also been used in combination with oral agents to improve effectiveness. Nonprescription agents have also been used for treatment of onychomycosis Table 4. Topical mentholated ointment Vicks Vaporub was used in a small study involving 18 patients. Tea tree oil Melaleuca alternifolia has been evaluated in two studies.

Although one trial was favorable, combined data from both studies did not demonstrate significant benefit. It was studied in a randomized trial involving 96 patients who applied the extract or ciclopirox for six months to nails with confirmed infections. Differences between the two treatments were not statistically significant. Ageratina pichinchensis snakeroot extract Apply every third day for the first month, twice per week for the second month, then once per week for the third month. Study of patients; therapeutic effectiveness was similar to that in the control group, which used ciclopirox.

Cyanoacrylate, undecylenic acid, and hydroquinone Renewed Nail Soak and debride affected nails, then apply solution every two weeks for three to four visits; patients may also apply at home. Dual-wavelength near-infrared laser Noveon Melaleuca alternifolia tea tree oil Cochrane review found no evidence of benefit Mentholated ointment Vicks Vaporub Neodymium: yttrium-aluminum-garnet laser Patholase Pinpointe Information from references 31 , and 33 through Nail trimming and debridement are often performed concomitantly with other treatments and appear to offer benefit.

Study groups that received nail debridement with oral terbinafine had higher clinical cure rates than those who received oral terbinafine alone. Although they are expensive, laser and photodynamic therapies have become popular based on the success of in-vitro studies. Food and Drug Administration for treatment of onychomycosis. However, there are only limited data about the use of these therapies in patients.

In one study, Nd:YAG laser light was used to treat 37 nails, with one to three treatments given four to eight weeks apart. Another laser treatment, the dual-wavelength near-infrared laser Noveon , is approved for dermatologic use, but not specifically for treatment of onychomycosis. Photodynamic therapy using photosensitizing drugs and light to destroy fungal cells has shown some success in the treatment of onychomycosis, but further evaluation is needed.

Despite the number of available treatments, not all patients with onychomycosis are cured. Numerous factors have been cited to explain the lack of response to therapy, such as nonadherence to treatment, incorrect diagnosis, or advanced disease. Factors contributing to poor response or nonresponse to treatment are listed in eTable B. Another cause of nail dystrophy; mixed disease e. Dermatophytoma i. Older age; diabetes mellitus; immunosuppression; impaired peripheral circulation. Scher RK, Baran R.

Onychomycosis in clinical practice: factors contributing to recurrence. Br J Dermatol. For those who appear to be cured, recurrent infection is a risk, with a number of factors increasing the chance of recurrence. Risk factors include concomitant disease, genetic factors, immunosuppression, incorrect dosing or duration of treatment, moisture, occlusive footwear, older age, poor hygiene, tinea pedis, and trauma.

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Data Sources: A PubMed search was performed using the term onychomycosis combined with prevalence, classification, diagnosis, and treatment. The search included meta-analyses and systematic reviews, including those from the Cochrane database. The initial search strategy was supplemented by searches for randomized controlled trials of specific treatments identified during the review of meta-analyses and systematic reviews.

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British Society for Medical Mycology best practice recommendations for the diagnosis of serious fungal diseases. Lancet Infect Dis. J Microbiol Immunol Infect. The use of mannan antigen and anti-mannan antibodies in the diagnosis of invasive candidiasis: recommendations from the Third European Conference on Infections in Leukemia.

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Temporal trends, risk factors and outcomes in albicans and non-albicans candidaemia: an international epidemiological study in four multidisciplinary intensive care units. Int J Antimicrob Agents. Risk factors for candidaemia in critically ill patients: a prospective surveillance study. Crit Care Med. Incidence, characteristics and outcome of ICU-acquired candidemia in India.

Candida colonization and subsequent infections in critically ill surgical patients. Ann Surg. Eggimann P, Pittet D. Determinants of candidemia and candidemia-related death in cardiothoracic ICU patients. Candidemia on presentation to the hospital: development and validation of a risk score. Rules for identifying patients at increased risk for candidal infections in the surgical intensive care unit: approach to developing practical criteria for systematic use in antifungal prophylaxis trials. Med Mycol. Multicenter retrospective development and validation of a clinical prediction rule for nosocomial invasive candidiasis in the intensive care setting.

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Fungal infections: Symptoms, types, and treatment

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A similar process was used to establish the MIC breakpoints for voriconazole and Candida species [ 70 ]. A statistically significant correlation was observed between MICs and investigator end-of-treatment assessments of outcome [ 70 ]. The category of susceptible dose dependent was applied to those isolates for which the MIC was determined to be 0.

A similar approach was not useful for amphotericin B because of the narrow range of MIC values 0. Thus, the present lack of correlation between caspofungin MICs and clinical outcome [ ] most likely represents the fact that strains for which MICs are elevated i. The development of breakpoints for caspofungin and other echinocandins is a work in progress but will ultimately take into account all the factors mentioned above for the azole antifungals.

However, on the basis of the 2 case reports of acquired resistance to caspofungin, it appears that increasing MICs in serial isolates of Candida species may signify the development of clinically important resistance [ , ]. Antifungal susceptibility testing is now increasingly and appropriately used as a routine adjunct to the treatment of fungal infections [ 59 , — ].

Guidelines for the use of antifungal testing and other laboratory studies have been developed [ 59 ]. Selective application of antifungal susceptibility testing coupled with broader identification of fungi to the species level should prove to be useful, especially in difficult-to-manage fungal infections [ 59 , ]. Future efforts will be dedicated to further validating the interpretive breakpoints for established antifungal agents and developing them for newly introduced systemically active agents.

In addition, procedures must be optimized for testing non- Candida yeasts e.


The accurate diagnosis of fungal infections by use of conventional mycologic and histopathologic techniques is time consuming and arduous because of the suboptimal sensitivity of these methods. Facilitating an earlier and noninvasive means of diagnosing fungal disease continues to be a major focus for medical microbiologists and clinicians, particularly those who provide care to immunosuppressed patients. Although progress has been made during the past 2 decades—including the standardization of methods for susceptibility testing, the development of more-rapid means of presumptively identifying C.

Future efforts must be directed toward expanding the availability of the new US FDA—approved and CLSI-recommended tests, validating the molecular assays for the diagnosis of fungal disease, and establishing and validating the interpretive breakpoints for all medically important fungi to all licensed antifungal agents. Financial support.

This article is supported by an educational grant from Schering-Plough. Potential conflicts of interest. Oxford University Press is a department of the University of Oxford. It furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide. Sign In or Create an Account. Sign In. Advanced Search. Article Navigation. Close mobile search navigation Article Navigation. Volume Article Contents. Spectrum of Opportunistic Fungal Pathogens.

Identification of Fungi. Antifungal Susceptibility Testing. Figures and Tables. Reprints or correspondence: Dr. Alexander, Div. Oxford Academic. Google Scholar. Michael A. Cite Citation. Permissions Icon Permissions. Abstract Invasive fungal infections have become a major cause of morbidity and mortality over the past 3 decades. Open in new tab Download slide. Rare and emerging opportunistic fungal pathogens: concern for resistance beyond Candida albicans and Aspergillus fumigatus. Search ADS.

Diagnosis and management of invasive candidiasis in the ICU: an updated approach to an old enemy

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Early diagnosis and treatment of pulmonary opportunistic infection by using polymerase chain reaction and beta-glucan in patients with hematological neoplasms. False-positive result in Limulus test caused by Limulus amebocyte lysate-reactive material in immunoglobulin products. False-positive endotoxemia derives from gauze glucan after hepatectomy for hepatocellular carcinoma with cirrhosis. Has antifungal susceptibility testing come of age? National Committee for Clinical Laboratory Standards. Reference method for broth dilution antifungal susceptibility testing of yeasts: approved standard MA.

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Laboratory Investigation Of Fungal Infection --Koh , Calcoflour white ,India ink stain-- Microscopy

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