The following are selected presentations of various mycoses.

Candidiasis

In the female genital tract, this fungus causes vaginal itching and swelling. The findings may be notable for the presence of a thick cottage cheese discharge.

Additionally, candiduria is common and typically asymptomatic. This infection is often due to the colonization of the bladder or perineum. The patients at risk are those of older ages, females, diabetics, and those that use antibiotics and have a positive history of surgery. Additionally, use of urinary catheters is another predisposing factor. Hence, it has been reported that removal of the catheter eliminated candiduria in approximately 40% of cases [9].

Aspergillosis

There are three clinical presentations of this disease which are allergic bronchopulmonary aspergillosis (ABPA), invasive aspergillosis, and aspergilloma.

ABPA features asthma as well as specific radiographic and laboratory findings [10]. For example, computed tomography (CT) of chest typically reveals bronchiectasis while the chest x-ray demonstrates fleeting infiltrates.

Further findings include immunoglobulin E (IgE) levels greater than 417 IU/ml and immediate skin reaction to Aspergillus species. Additionally, peripheral blood eosinophilia is typically observed.

Histoplasmosis

This disease can present in a wide range of clinical pictures. For example, patients may be asymptomatic while others can manifest with pulmonary and body-wide dissemination.

Pulmonary histoplasmosis is further classified into acute, subacute, and chronic types. The former presents with fever, sweats, and weight loss. Also, the chest imaging shows interstitial infiltrates.

The subacute disease develops over a period of weeks to months. The imaging reveals infiltrate in patchy or focal patterns as well as hilar or mediastinal lymphadenopathy.

Blastomycosis

Blastomycosis presents in various clinical presentations. In some patients, the febrile illness has nonspecific symptoms. In acute or chronic pulmonary infections, the picture resembles that of pneumonia and malignancy. Blastomycosis may even disseminate to the skin, genitourinary system, and skeletal system.

The cutaneous form occurs in 40% to 80% of patients and is suggestive of the multiorgan disease. Osteolytic lesions of the ribs, vertebrae, and long bones may occur. Septic arthritis is another feature as well.

Coccidioidomycosis

The primary type involves the lungs but is mostly asymptomatic. Patients may experience fever, cough, and chest pain that resembles pneumonia. A majority of cases with the acute form will spontaneously recover.

The laboratory findings reveal elevated erythrocyte sedimentation rate (ESR) and peripheral eosinophilia while the chest x-ray demonstrates infiltrates, nodules, cavitations, and effusions.

The workup is composed of the patient's personal and travel history, clinical assessment, epidemiologic correlation, physical exam, and investigations. Depending on the differential diagnoses, the clinician will select the pertinent studies as described below.

Wood's lamp

Skin lesions are assessed with a Wood's lamp, which would produce characteristic findings.

Imaging

Chest radiograph and CT scans of the chest, abdomen, and brain will yield information and hallmark features of specific diseases.

Culture

The gold standard test is the isolation of the pathogen with culture. Since this may take weeks, more rapid laboratory studies utilize various stains to reveal certain suggestive findings. Examples of stains are the Gomori methenamine silver (GMS), periodic acid–Schiff reagent (PAS), and calcofluor white. Note that Gram stain is useful for Candida only.

C. Albicans can be quickly diagnosed through germ tube formation.

Blood cultures may be negative even in disseminated cases. Furthermore, in patients with disseminated histoplasmosis, blood cultures, and bone marrow are positive for the offending organism in as many as half of all cases.

Note that there are histopathological hallmarks related to different fungi. For example, Candida is associated with budding yeast accompanied by hyphae and pseudohyphae. Aspergillus features unpigmented hyphae with septate and branching (acute angle). Additionally, Histoplasma is characterized by ovoid budding yeast and granulomas. Blastomyces dermatitidis presents as large and thick-walled budding yeast with daughter cells. Furthermore, Coccidioidomycosis immitis is described as thick walled spherules along with endospores.

Serology and immunoassays

Serologic tests utilizing antibody and antigen assays may be helpful. However, these may be limited in immunocompromised individuals since the antibody formation is absent [11].

An immunoassay known as galactomannan can diagnose invasive Aspergillus infections. This polysaccharide is specific for Aspergillus in the serum, urine cerebrospinal (CSF), and bronchoalveolar lavage (BAL) samples. The techniques used to detect galactomannan are enzyme-linked immunosorbent assay (ELISA), enzyme immunoassay (EIA), and immunoblot studies. Overall, the assays have not proven validity yet.

The are four categories of drugs used in the treatment of mycoses.

Azoles

This class functions by inhibiting the synthesis of ergosterol in the cell membrane. Examples of this drug are fluconazole, itraconazole, and ketoconazole. There are also second-generation drugs such as voriconazole.

The potency of azoles differs with various candida. As for Aspergillus, the clinician may select itraconazole, voriconazole, or posaconazole as they are all effective.

Polyenes

The mainstay treatment of fungal infections is amphotericin B deoxycholate as it has the broadest range of activity [12]. Its mechanism of actions is characterized by binding to ergosterol and interrupting the membrane, which results in the death of the fungal cell.

Pyrimidines

Flucytosine (5-fluorocytosine) is a pyrimidine analog that inhibits the synthesis of DNA and protein. It has a narrow spectrum of activity and is restricted to Candida spp., Cryptococcus neoformans, and a few molds.

The adverse effects are nausea, emesis, rash, liver impairment, and bone marrow suppression. Note that there is resistance to this drug. Therefore, it is mainly used as an adjunct to amphotericin B for disseminated illnesses.

Echinocandins

This class targets the cell wall synthesis by inhibiting the β-1,3-d-glucan synthase. Examples are caspofungin, micafungin, and anidulafungin.

Combination therapy

Medications of different classes can be combined. Moreover, invasive aspergillosis can be treated with azoles and echinocandins, as well as echinocandins with amphotericin B.

Most acute infections are asymptomatic although mild cases of fungal infections may feature discomfort such as with vaginal candida infection. Furthermore, all yeast are capable of producing toxins [5] that can cause itching, mucus production, and bowel disturbances. Moreover, these toxins may induce autoimmune reactions such as arthritis.

Certain mycoses are associated with severe outcomes. For example, aspergillosis is one of the predominant causes of morbidity and fatality in immunocompromised individuals. Specifically, the death rate in these patients is up to 88%. Likewise, the mortality of invasive candidiasis is as high as 49% [8].

Fungi are ubiquitous as they are present in the soil, air, and decaying matter. The following is a selection of mycoses.

Candida albicans causes candidiasis [3]. This type of yeast causes infection in numerous organs such as lungs, pancreas, heart, kidneys, sinuses, and the female genital tract.

Furthermore, Aspergillus fumigatus is the predominant etiology of aspergillosis, which is acquired through spore inhalation by immunocompromised individuals.

Blastomycosis results from Blastomyces dermatitidis [4], which is inhaled and disseminated through the vasculature and lymphatics.

The main organism responsible for Coccidioidomycosis is Coccidioides, which is present in hot and dry areas with low altitudes [5]. C. posadasii is found in South America and C. immitis is present in certain parts of California. Furthermore, both coexist in the southwestern United States.

Cryptococcosis is caused by Cryptococcus neoformans [6]. The sources of this organism are soil, trees, and other habitats that contain pigeon droppings.

Finally, histoplasmosis results from Histoplasma capsulatum. The reservoir of this fungus is soil contaminated with bat or bird droppings. There are two variants of histoplasmosis: North American and African. The former is a pulmonary condition while the latter manifests with skin and bones pathologies. Furthermore, immunocompromised individuals are susceptible for disseminated histoplasmosis.

The Candida species is the most predominant pathogenic fungi. In the United States, this is the fourth most common organism typically isolated from blood cultures [7]. In fact, 8% to 10% of nosocomial blood infections are attributed to Candida.

Additionally, aspergillus is the most prevalent invasive mold. It commonly occurs in immunocompromised patients.

Also, cryptococcosis is found worldwide with a predominance in northern Europe.

Pathogenesis

Pathogenic mycoses are transmitted through inhalation or ingestion of spores. The degree of severity is correlated with the immune status of the individual as well as the intensity of the exposure.

A healthy immune system is paramount for the prevention of these diseases. The cell-mediated mechanisms promote granulomatous inflammation and recruit immunomodulators and key immune cells such as macrophages and neutrophils. The findings are remarkable for the presence of caseating or noncaseating granulomas, which are markers of the immune response. The function of these granulomas is to contain the organisms.

Types of mycosis

Skin mycosis

In the superficial form, the infection presents on the outer layers of the skin and hair. Tinea versicolor is one example.

The cutaneous type exists in the epidermis, hair, and nails. When an immune reaction occurs, the skin becomes inflamed. Accounting for cutaneous infections is the Microsporum, Trichophyton, and Epidermophyton genera.

Subcutaneous mycosis may encompass every skin layer as well as fat and muscle beneath the skin. Infection ensues following the entrance of the organisms through traumatized skin. Furthermore, subcutaneous infections may be chronic and necessitate surgical intervention.

Systemic mycosis

Opportunistic pathogens affect immunocompromised patients with weakened immune system secondary to AIDS, cancer, chronic corticosteroid use, etc.

Primarily, pathogens can affect other organs and systems through dissemination.

Preventative strategies include ways to reduce colonization. For example, careful use of catheters, proper utilization of antibiotics, and implementation of infection control protocol are all effective approaches.

Patients at risk of mycosis are advised to avoid certain environmental exposures and may be required to wear respiratory masks especially at constructions sites.

For those exposed to pathogenic molds, the recommended measures are high-efficiency particulate air (HEPA) filters, positive pressure ventilation, etc.

Mycoses encompass a broad spectrum of human infections that are caused by almost 150 types of pathogenic fungi [1] [2]. The diseases can manifest in a variety of presentations that range from asymptomatic to invasive illnesses. Additionally, a fungal species may affect various organs and cause diverse diseases. There are also opportunistic pathogens that infect immunocompromised individuals.

While there are many mycoses, the main ones discussed in the upcoming chapters are candidiasis, histoplasmosis, coccidioidomycosis, blastomycosis, cryptococcosis, and aspergillosis.

The workup of fungal infections includes the assessment of the clinical picture, the presence of risk factors and geography. Additionally, other key components of the patient evaluation are the physical exam and any appropriate imaging and laboratory testing. Imaging modalities will demonstrate the involvement of the lungs and other organs. Serology, blood cultures, staining techniques, and immunoassays are selected based on the overall clinical picture and findings.

Therapy is selected from four classifications of antifungals, which have different mechanisms of actions. A combination of the different classes may be employed in certain cases.

Mycosis refers to human infections caused by fungi.

The infections can occur in:

• Scrapes or cuts in the skin
• Individuals who wear rubber boots as they cause sweating as infection occurs between the toes
• Exposure to areas such as pools, public showers;, and construction sites
• Individuals with a weakened immune system
• Individuals with diabetes mellitus or other metabolic disorders
• Individuals using medications such as antibiotics, corticosteroids, or chemotherapy agents

What are the signs and symptoms?

The signs depend on the type of fungal infection and the condition it causes. Few examples include:

• Lesions that are red, round or oval shaped; they may peel off
• Pustules in areas such as a beard
• White lesions in the mouth, at the genitals, or other mucous membranes
• Vaginal discharge (thick cottage cheese texture)
• Red colored skin in the genitals or anal region such as with diaper rash
• Fissures or cracks between the fingers and toes
• Red, crusty, scaly lesions on the scalp

The following are the symptoms:

• Itching
• Burning sensation
• Staining and coloring of the skin

How are fungal infections diagnosed?

The clinician will ascertain the patient's symptoms, personal history, and risk factors. Also, the clinician will perform a physical exam and use appropriate techniques to determine the cause.

The methods of evaluation include the use of a Wood's lamp to examine the affected skin, obtaining smears of the lesions, use of culture to grow the organism and utilization of stains on smears.

What is the treatment?

There are a number of antifungal medications available. The clinician will select the appropriate drug or combination. Diflucan is a common one and is found in over-the-counter medications.

In patients with systemic fungal diseases, the drug of choice is usually amphotericin B.

1. Chandler F, Watts J. Mycotic, Actinomycotic, and Algal Infections. In Kissane J (ed) Anderson’s Pathology, 9th ed. C.V. Mosby, St. Louis. 1996; 391-432.
2. Larone DH. Medically Important Fungi. American Society for Microbiology, Washington, DC. 1993.
3. Shepherd MG, Poulter RTM, Sullivan PA. Candida albicans: Biology, genetics, and pathogenicity. Ann Rev Microbiol. 1985; 39:579-614.
4. Lane KAG ex. ed. The Merck Manual of Diagnosis and Therapy. Merck Research Laboratories, Whitehouse Station (NJ). 1996.
5. Cotran RS, Kumar V, Collins T. Pathologic Basis of Disease, 6th ed. WB Saunders, Phil. 1999.
6. Berkow R. The Merck Manual of Diagnosis and Therapy, 14th ed. Merck & Company, Rahway (NJ). 1982; 148-159.
7. Wisplinghoff H, Bischoff T, Tallent SM, et al. Nosocomial bloodstream infections in U.S. hospitals: Analysis of 24,179 cases from a prospective nationwide surveillance study. Clin Infect Dis. 2004; 39(3); 309-317.
8. Pappas PG, Rex JH, Lee J, et al. A prospective observation study of candidemia: Epidemiology, therapy, and influences on mortality in hospitalized adult and pediatric patients. Clin Infect Dis. 2003; 37(5): 634-643.
9. Sobel JD, Kauffman CA, McKinsey D, et al. Candiduria: a randomized, double-blind study of treatment with fluconazole and placebo. The National Institute of Allergy and Infectious Diseases (NIAID) Mycoses Study Group. Clin Infect Dis. 2000; 30(1): 19-24.
10. Roseberg M, Patterson R, Mintzer R, et al. Clinical and immunologic criteria for the diagnosis of allergic bronchopulmonary aspergillosis. Ann Intern Med. 1977; 86(4): 405-414.
11. Vojdani, A. et al. Immunological cross reactivity between Candida albicans and human tissue. J Clin Lab Immunol. 1996; 48(1):1-15.
12. Nucci, M. & Marr, K.A. Emerging fungal diseases. Clinical Infectious Diseases. 2005; 41(4): 521-526.