PATIENT RISK FACTOR	COMMON FUNGAL INFECTION
Human immunodeficiency virus infection (acquired immunodeficiency syndrome)	Candidiasis, cryptococcosis, aspergillosis
Recent organ transplantation	Candidiasis, aspergillosis
Neutropenia	Candidiasis, aspergillosis
High-dose steroids	Zygomycosis, candidiasis
Recent antibiotic treatment	Candidiasis
Diabetes	Candidiasis, zygomycosis
Recent or ongoing hospitalization	Candidiasis, aspergillosis
Recent abdominal surgery or burns (especially with intensive care unit stay)	Candidiasis
Travel to endemic area	Histoplasmosis, blastomycosis, coccidioidomycosis

Depending on the site of infection, presenting symptoms vary. The important signs of fungal infection are indicated by indirect evidence found in the patient’s history. Patients who have a history suggestive of greater risk for fungal infection should be evaluated and treated more extensively. For example, when a patient with acquired immunodeficiency syndrome (AIDS) presents to the emergency department (ED) after a recent admission for pneumonia with recurrent symptoms of pneumonia, the incidence of fungal infection, specifically Candida, is much higher. The patient needs cultures specifically for Candida and requires prompt antifungal therapy in the ED, in addition to broad-spectrum antibiotics covering health care–associated pneumonia.

Organ-Specific Clinical Findings

Pulmonary Disorders

Patients with fungal pneumonia present similarly to patients with other types of pneumonia. They have fever, dry or productive cough, fatigue, shortness of breath, or hemoptysis. The chest radiographic appearance also resembles that of other pneumonias. No specific finding is associated with particular fungal infections; lobar and interstitial infiltrates are both common. Certain fungal infections occasionally manifest with visible masslike lesions (e.g., blastomycosis, aspergillosis), and other infections form cavitary lesions (e.g., sporotrichosis), but these are the exception and not the rule. Fungal pneumonia causes varying symptoms and radiologic appearances. In one review,³ aspergillosis was the most common fungal cause of pneumonia in patients with cancer. Other reviews reported aspergillosis as the most common cause of pneumonia in immunocompromised patients. Healthy, immunocompetent individuals are overwhelmingly more likely to have one of the endemic fungal infections.

Central Nervous System Disorders

Almost all the common fungal pathogens can cause CNS infection. The best known is Cryptococcus because of its propensity to cause meningitis in 50% to 60% of infected, immunocompromised patients. CNS infections may also be seen in much lower proportions in healthy individuals. Histoplasmosis leads to meningitis in approximately 1% of symptomatic individuals. Almost all patients with fungal meningitis present after known fungal infections and are hospitalized patients with severe immunodeficiency. This is not the case in many HIV-infected patients with cryptococcal meningitis. Patients with cryptococcal meningitis have varying presentations, often including a headache for weeks, fever, nausea, or frank mental status decline. Such patients require lumbar puncture and prompt antifungal therapy.

Fungal sepsis is rare, but it is highly fatal. The Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis (PROWESS) trial ⁴ demonstrated a fungal sepsis mortality rate of nearly 56% that was more than double the nonfungal sepsis mortality rate of 28% to 30%. Suspicion is necessary to identify these patients early. A patient with a history of recent hospitalization, immunosuppression from organ transplants, or abdominal surgery has a dramatically increased risk of disseminated fungal infection causing sepsis. Cultures with specific fungal organism media should be sent, followed by initiation of antifungal therapy.

Ear, Nose, and Throat Disorders

Fungal infections in the craniofacial area may be progressive and often fatal (e.g., zygomycosis), or they may be chronic and need referral for eventual diagnosis and treatment (e.g., allergic fungal sinusitis). Zygomycosis is rare, but it is also extremely invasive and may manifest as facial pain and swelling. Patients with diabetes, especially those with diabetic ketoacidosis, require a thorough craniofacial examination to look for the characteristic black exudate. Craniofacial computed tomography (CT) scanning hastens the diagnosis when zygomycosis is suspected. Most patients with fungal sinusitis present with common sinusitis symptoms: facial pressure, congestion or drainage, swelling, and allergic “shiners.” Although most of these patients may be treated conservatively, patients with ongoing symptoms, nasal polyps, or evidence of facial deformity or bone erosion on CT will need rapid ear, nose, and throat follow-up and evaluation for débridement and antifungal therapy.

Rheumatic Disorders

Patients with disseminated fungal infections often complain of polyarthritis. Specifically, sporotrichosis spreads to the elbow or knee, and blastomycosis spreads to the weight-bearing joints or spine. Patients with cutaneous evidence of sporotrichosis or blastomycosis who have joint pain and swelling need aspiration and specific fungal analysis of the synovial fluid.

Cutaneous Disorders

The most common fungal infections in humans are the superficial cutaneous fungal infections (e.g., tinea), which are detailed in Chapter 184. Certain fungal species may start as cutaneous lesions and disseminate to invasive disease, or they may begin as pulmonary disease and disseminate to form cutaneous lesions. The latter type is a form of blastomycosis characterized by a primary pulmonary infection that spreads, leading to cutaneous lesions in 75% of patients with disseminated disease. Sporotrichosis behaves similarly, but in an opposite fashion, because most patients with disseminated disease initially have cutaneous lesions. Both infections manifest as raised verrucous lesions with irregular borders that are painless and are often seen on the face or neck. Either infection can develop into the verrucous form or can become an extremity ulcer. Potassium hydroxide (KOH) scraping identifies these lesions as fungal.

Vulvovaginal Disorders

Candida is well known to cause a vulvovaginal infection that is common among sexually active women. This infection is often seen after a course of antibiotics, or it may appear spontaneously. Patients describe itching, burning of the labia, and a thick, white discharge. The incidence is increased in women taking oral contraceptives and in patients with diabetes. Adequate treatment is usually provided by over-the-counter antifungal creams, but patients may require oral medication if the infection is recurrent or severe.

Diagnostic Testing

Fungi are usually visible in a tissue or fluid sample with the aid of KOH solution, which destroys nonfungal cell structures. This approach identifies only fungi that are easy to sample. In cases of pneumonia or fungemia, this type of testing is not usually possible. Most fungi can be cultured, and species such as Coccidioides and Candida grow readily on most agars. Other species, such as Histoplasma and Aspergillus, are much more difficult to grow and require antigen testing such as enzyme-linked immunosorbent assay to confirm infection. Zygomycetes requires special stains and is often a laboratory contaminant. It may be erroneously discarded if the laboratory is not told that it is a possible pathogen. Emergency physicians should call their particular hospital or outpatient microbiology laboratory to determine the best method of identification.

Specific Fungal Infections

Blastomycosis

Blastomycosis is caused by the fungus Blastomyces dermatitidis. This infection occurs primarily in healthy individuals who are exposed in one of the endemic areas (Table 176.2). Pulmonary infections are typical, especially in the acute phase, and are contracted though inhalation of the dormant form. After attaining body temperature, the organism transforms into the yeast form and develops a greater ability to infect. Many patients acquire the infection and have chronic pneumonia for years, often diagnosed as reactive airway disease, before the infection is discovered. Patients with chronic pulmonary infections often develop extrapulmonary manifestations of the disease. These patients frequently have cutaneous lesions, and frank meningitis occurs in 10% of disseminated cases. If CNS involvement is suspected, a simple lumbar puncture is inadequate because results are routinely negative; ventricular fluid collection is required to confirm the diagnosis.

Table 176.2 Endemic Areas of Common Fungi