Mycoses, or fungal infections, are responsible for a broad range of diseases in humans.
Presentation
The following are selected presentations of various mycoses.
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].
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.
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.
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.
Entire Body System
- Pain
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The patient presented with fever, weight loss, numerous painful cutaneous tumors of MF, aseptic pustules, and erythematous painful plaques resembling those of Sweet syndrome (Figure 2A) associated with peripheral neutrophilia (neutrophil count, 10 × 109 [jamanetwork.com]
Fever and pain in the affected bone are cardinal symptoms. This would usually be investigated with x-rays, computed tomography (CT) scanning and an aspiration via a needle to obtain a specimen for culture. [dermnetnz.org]
Management Frontiers in Medicine Coronavirus Climate Crisis and Health Zika Virus Ebola Virus E-Cigarettes and Vaping-Related Disease View all topics Health Policy Medicine and Society Pain Management Ebola Virus Multimedia Multimedia Selected Multimedia [nejm.org]
Painful ulcerations and nodules appear in subcutaneous tissues in sporotrichosis ( Sporothrix ). In systemic fungal infections fungi may invade normal hosts or immunosuppressed hosts (opportunistic infections). [britannica.com]
- Candidiasis
Dermatophytoses, tinea versicolor Terconazole 0.4% and 0.8% cream, 80-mg suppositories Vulvovaginal candidiasis Tioconazole 6.5% ointment Vulvovaginal candidiasis Polyene Nystatin Topical: 100,000 units/g cream, ointment, powder, or vaginal tablet Candidiasis [msdmanuals.com]
We also explore conditions caused by candidiasis including oral intertrigo, vulvovaginitis, diaper rashes, paronychia and chronic mucocutaneous candidiasis. [fungalguide.ca]
It is estimated that at least 70 percent of all people will have a… candidiasis Candidiasis, infectious disease produced by the yeastlike fungus Candida albicans and closely related species. [britannica.com]
- Sepsis
A first-line antiretroviral therapy-resistant HIV patient with rhinoentomophthoromycosis 1 Department of Dermatology, Lokmanya Tilak Municipal Medical College and General Hospital, Mumbai, Maharashtra, India 2 Department of Medical Microbiology, Sepsis [doi.org]
Opportunistic fungal sepsis is seen most often in immunosuppressed patients with severe neutropenia or in postoperative patients with intravenous catheters and usually follows prolonged antibiotic therapy. [icd10data.com]
Two died of infections (disseminated tuberculosis and sepsis) and 1 of brain cancer (glioblastoma multiforme). The cause was unknown in 1 case. Several findings stand out in this patient series. [actasdermo.org]
During the pretransplant phase, he had an episode of pulmonary embolism and SA sepsis, both of which resolved after treatment. [nature.com]
Oral Antibiotics for Neutropenic Sepsis Giving Early Hospital Discharge [ORANGE] Unknown status NCT00445497 Phase 3 amoxicillin-clavulanate potassium;ciprofloxacin 8 Multicenter, Double-Blind, Randomized Study to Compare the Safety and Efficacy of Levofloxacin [malacards.org]
- Surgical Procedure
Predisposing factors include intravenous catheters, use of antibacterial drugs, urinary catheters, surgical procedures, corticosteroid therapy, neutropenia, severe burns, parental nutrition, and chemotherapy induced impairment of oropharyngeal or gastrointestinal [mycology.adelaide.edu.au]
Procedures (NCSP) codes for diagnostic and treatment procedures [9, 10]. [bmchealthservres.biomedcentral.com]
Respiratoric
- Pneumonia
He had a bad pneumonia several weeks ago. His vital signs are stable, and the remainder of his physical examination is benign. The lesion is swabbed and cultured revealing the organism shown in Figure B. [medbullets.com]
Differential diagnosis of allergic bronchopulmonary mycosis is difficult, and it is often misdiagnosed as tuberculosis, pneumonia, bronchiectasis, lung abscess or bronchial asthma. [dictionary.cambridge.org]
It usually occurs as an atypical pneumonia, in the acute form appearing in epidemics with prostration, fever and respiratory symptoms. [patient.info]
Fungal sinusitis Invasive fungal sinusitis Left fungal keratitis Meningitis, fungal Mycosis Mycotic aneurysm Mycotic endocarditis Pneumonia due to fungus Right fungal keratitis Clinical Information An infection caused by a fungus. [icd10data.com]
- Pleural Effusion
Other signs included: lung hilum or mediastinal lymphadenectasis in 25 cases (36.7%), pleural thickening and adhesion in 9 cases and pleural effusion in 8 cases (Figures 1, 2, 3, 4 ). [mrmjournal.biomedcentral.com]
Jaw & Teeth
- Cheilitis
IMG 1884.JPG 562 × 809; 79 KB Peach shot hole disease.jpg 4 160 × 2 340; 629 KB Periorbital fungal infection known as mucormycosis, or phycomycosis PHIL 2831 lores.jpg 700 × 657; 68 KB Photographic Comparison of a Canker Sore, Herpes, Angular Cheilitis [commons.wikimedia.org]
Oropharyngeal candidiasis: including thrush, glossitis, stomatitis and angular cheilitis. Acute oral candidiasis is rarely seen in healthy adults but may occur in up to 5% of newborn infants and 10% of the elderly. [mycology.adelaide.edu.au]
Cardiovascular
- Hypotension
Grade 4 Pneumocystis pneumonia was observed in one patient. and grade 3 anemia, hypotension, hypertension, pulmonary edema, and periorbital edema were each reported in one patient, respectively. [ascopost.com]
One participant in the ECP group withdrew due to hypotension. However, we are unsure of the results due to very low-certainty evidence. [cochrane.org]
Thereafter, her condition deteriorated rapidly; the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) was unresponsive to treatment with fluid restriction, hypotension, and hypothermia. [ajnr.org]
[…] side effects, including cardiac arrhythmias, liver dysfunction, myalgia, flu-like symptoms and capillary leak syndrome (a rare medical condition in which extravasation of fluid through the capillaries from blood to the interstitial space results in hypotension [cancertherapyadvisor.com]
Skin
- Eczema
Mycosis fungoides palmaris et plantaris most often resembles persistent hand eczema and foot eczema [1,2]. It may affect only the hands, only the feet, or both hands and feet. [dermnetnz.org]
Eczema, atopic: Important here is the history with the typical type I allergies; in the eczematoid form there are scaly, partly eroded, scratched and crusted different red plaques. Marked pruritus is always present. Histology: typical eczema morph. [altmeyers.org]
In its early stages, it can look like eczema. [healthline.com]
Types & treatments Childhood eczema Adult eczema Insider secrets Types of hair loss Treatment for hair loss Causes of hair loss Hair care matters Insider secrets What is psoriasis Diagnosis & treatment Skin, hair & nail care Triggers Insider secrets What [aad.org]
- Pruritic Rash
CTCLs are insidious in onset, and sometimes patients initially present with a chronic, pruritic rash that is difficult to diagnose even with biopsies. This prodrome may exist for several years until the diagnosis of CTCL is finally made. [msdmanuals.com]
The patient was a 57-year-old woman with pruritic rash for 5 years. She had several biopsies over a period of 9 months that demonstrated progression of MF. [ajcp.oxfordjournals.org]
- Skin Ulcer
Look for ulceration in the lesions. For lesions in the tumor stage, evaluate the number, size, and sites of the lesions. Look for lymphadenopathy and organomegaly. Skin biopsy The biopsy site must be chosen carefully. [ncbi.nlm.nih.gov]
Management of skin ulcers in a patient with mycosis fungoides. Dermatol Online J 2006;12:16. 148. Mays SR, Bogle MA, Bodey GP. Cutaneous fungal infections in the oncology patient: Recognition and management. Am J Clin Dermatol 2006;7:31-43. 149. [e-ijd.org]
Neurologic
- Neglect
As mycetoma is a badly neglected disease, accurate data on its incidence and prevalence are not available. [who.int]
It is time to stop the neglect and put fungal diseases firmly in the spotlight. References 1. The Burden of Fungal Disease ( LIFE, 2017); http://go.nature.com/2sMKpuN 2. et al. Nature 484, 186–194 (2012). 3. Hawksworth, D. L. Mycol. [doi.org]
It is time to stop the neglect and put fungal diseases firmly in the spotlight. References 1. The Burden of Fungal Disease ( LIFE, 2017); http://go.nature.com/2sMKpuN 2. Fisher, M. C. et al. Nature 484, 186–194 (2012). 3. Hawksworth, D. L. Mycol. [nature.com]
^ "Stop neglecting fungi". Nature Microbiology. 2 (8): 17120. 25 July 2017. doi:10.1038/nmicrobiol.2017.120. ISSN 2058-5276. PMID 28741610. ^ Britt, L. D.; Peitzman, Andrew; Barie, Phillip; Jurkovich, Gregory (2012). Acute Care Surgery. p. 186. [en.wikipedia.org]
- Stroke
Regarding specific causes of death of the patients with CTCL, 1 myocardial infarction and 2 strokes were found. [medicaljournals.se]
Workup
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.
Microbiology
- Candida
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. In fact, 8% to 10% of nosocomial blood infections are attributed to Candida. [symptoma.com]
In general, it is candida, of the yeast family, that is at the origin. Candida albicans, the most common form involved, exists naturally in the human digestive tract and is not responsible for symptoms. [health.ccm.net]
Causative agents: Candida albicans Candida catenulata Candida dubliniensis Candida glabrata complex Candida haemulonii Candida inconspicua Candida parapsilosis complex Candida rugosa Candida tropicalis Clavispora lusitaniae (formerly Candida lusitaniae [mycology.adelaide.edu.au]
Candidiasis (Candida) may be a superficial infection (thrush, vaginitis) or a disseminated infection affecting certain target organs, such as the eyes or kidneys. [britannica.com]
- Aspergillus Niger
Aspergillus niger infection.jpg 1 600 × 1 200; 346 KB Bilateral exophthalmos.jpg 1 366 × 1 020; 191 KB Cladophialophora carrionii.jpg 400 × 457; 63 KB Clivia miniata, choroba (001).jpg 4 416 × 3 312; 4,85 MB Die Parasiten der weiblichen Geschlechtsorgane [commons.wikimedia.org]
Other Pathologies
- Granulomatous Tissue
Granulomatous slack skin: Very rare granulomatous variant (< 100 cases in world literature) of a usually CD4-positive cutaneous T-cell lymphoma characterized by granulomatous tissue formations and loss of elastic fibers. [altmeyers.org]
Pleura
- Pleural Effusion
Other signs included: lung hilum or mediastinal lymphadenectasis in 25 cases (36.7%), pleural thickening and adhesion in 9 cases and pleural effusion in 8 cases (Figures 1, 2, 3, 4 ). [mrmjournal.biomedcentral.com]
Treatment
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.
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.
Prognosis
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].
Etiology
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.
Epidemiology
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.
Pathophysiology
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
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.
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.
Prevention
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.
Summary
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.
Patient Information
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.
References
- 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.
- Larone DH. Medically Important Fungi. American Society for Microbiology, Washington, DC. 1993.
- Shepherd MG, Poulter RTM, Sullivan PA. Candida albicans: Biology, genetics, and pathogenicity. Ann Rev Microbiol. 1985; 39:579-614.
- Lane KAG ex. ed. The Merck Manual of Diagnosis and Therapy. Merck Research Laboratories, Whitehouse Station (NJ). 1996.
- Cotran RS, Kumar V, Collins T. Pathologic Basis of Disease, 6th ed. WB Saunders, Phil. 1999.
- Berkow R. The Merck Manual of Diagnosis and Therapy, 14th ed. Merck & Company, Rahway (NJ). 1982; 148-159.
- 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.
- 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.
- 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.
- 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.
- Vojdani, A. et al. Immunological cross reactivity between Candida albicans and human tissue. J Clin Lab Immunol. 1996; 48(1):1-15.
- Nucci, M. & Marr, K.A. Emerging fungal diseases. Clinical Infectious Diseases. 2005; 41(4): 521-526.